Miracle-dz/UniFAR-FTUs huggingface dataset:
Treatment With Calcineurin Inhibitor FK506 Attenuates Noise-Induced Hearing Loss

Attenuation of noise-induced hair cell loss and noise-induced hearing loss (NIHL) by treatment with FK506 (tacrolimus), a calcineurin (CaN/PP2B) inhibitor used clinically as an immunosuppressant, has been previously reported, but the downstream mechanisms of FK506-attenuated NIHL remain unknown. Here we showed that CaN immunolabeling in outer hair cells (OHCs) and nuclear factor of activated T-cells isoform c4 (NFATc4/NFAT3) in OHC nuclei are significantly increased after moderate noise exposure in adult CBA/J mice. Consequently, treatment with FK506 significantly reduces moderate-noise-induced loss of OHCs and NIHL. Furthermore, induction of reactive oxygen species (ROS) by moderate noise was significantly diminished by treatment with FK506. In agreement with our previous finding that autophagy marker microtubule-associated protein light chain 3B (LC3B) does not change in OHCs under conditions of moderate-noise-induced permanent threshold shifts, treatment with FK506 increases LC3B immunolabeling in OHCs after exposure to moderate noise. Additionally, prevention of NIHL by treatment with FK506 was partially abolished by pretreatment with LC3B small interfering RNA. Taken together, these results indicate that attenuation of moderate-noise-induced OHC loss and hearing loss by FK506 treatment occurs not only via inhibition of CaN activity but also through inhibition of ROS and activation of autophagy.
Activities of the Right Temporo-Parieto-Occipital Junction Reflect Spatial Hearing Ability in Cochlear Implant Users

Spatial hearing is critical for us not only to orient ourselves in space, but also to follow a conversation with multiple speakers involved in a complex sound environment. The hearing ability of people who suffered from severe sensorineural hearing loss can be restored by cochlear implants (CIs), however, with a large outcome variability. Yet, the causes of the CI performance variability remain incompletely understood. Despite the CI-based restoration of the peripheral auditory input, central auditory processing might still not function fully. Here we developed a multi-modal repetition suppression (MMRS) paradigm that is capable of capturing stimulus property-specific processing, in order to identify the neural correlates of spatial hearing and potential central neural indexes useful for the rehabilitation of sound localization in CI users. To this end, 17 normal hearing and 13 CI participants underwent the MMRS task while their brain activity was recorded with a 256-channel electroencephalography (EEG). The participants were required to discriminate between the probe sound location coming from a horizontal array of loudspeakers. The EEG MMRS response following the probe sound was elicited at various brain regions and at different stages of processing. Interestingly, the more similar this differential MMRS response in the right temporo-parieto-occipital (TPO) junction in CI users was to the normal hearing group, the better was the spatial hearing performance in individual CI users. Based on this finding, we suggest that the differential MMRS response at the right TPO junction could serve as a central neural index for intact or impaired sound localization abilities.
Influence of iTBS on the Acute Neuroplastic Change After BCI Training

Objective: Brain-computer interface (BCI) training is becoming increasingly popular in neurorehabilitation. However, around one third subjects have difficulties in controlling BCI devices effectively, which limits the application of BCI training. Furthermore, the effectiveness of BCI training is not satisfactory in stroke rehabilitation. Intermittent theta burst stimulation (iTBS) is a powerful neural modulatory approach with strong facilitatory effects. Here, we investigated whether iTBS would improve BCI accuracy and boost the neuroplastic changes induced by BCI training. Methods: Eight right-handed healthy subjects (four males, age: 20–24) participated in this two-session study (BCI-only session and iTBS+BCI session in random order). Neuroplastic changes were measured by functional near-infrared spectroscopy (fNIRS) and single-pulse transcranial magnetic stimulation (TMS). In BCI-only session, fNIRS was measured at baseline and immediately after BCI training. In iTBS+BCI session, BCI training was followed by iTBS delivered on the right primary motor cortex (M1). Single-pulse TMS was measured at baseline and immediately after iTBS. fNIRS was measured at baseline, immediately after iTBS, and immediately after BCI training. Paired-sample t-tests were used to compare amplitudes of motor-evoked potentials, cortical silent period duration, oxygenated hemoglobin (HbO2) concentration and functional connectivity across time points, and BCI accuracy between sessions. Results: No significant difference in BCI accuracy was detected between sessions (p > 0.05). In BCI-only session, functional connectivity matrices between motor cortex and prefrontal cortex were significantly increased after BCI training (p's < 0.05). In iTBS+BCI session, amplitudes of motor-evoked potentials were significantly increased after iTBS (p's < 0.05), but no change in HbO2 concentration or functional connectivity was observed throughout the whole session (p's > 0.05). Conclusions: To our knowledge, this is the first study that investigated how iTBS targeted on M1 influences BCI accuracy and the acute neuroplastic changes after BCI training. Our results revealed that iTBS targeted on M1 did not influence BCI accuracy or facilitate the neuroplastic changes after BCI training. Therefore, M1 might not be an effective stimulation target of iTBS for the purpose of improving BCI accuracy or facilitate its effectiveness; other brain regions (i.e., prefrontal cortex) are needed to be further investigated as potentially effective stimulation targets.
Behavioral Variation in the Pygmy Halfbeak Dermogenys collettei: Comparing Shoals With Contrasting Ecologies

Variation in biotic and abiotic factors among populations affects individual behaviors by transforming the social landscape and shaping mating systems. Consequently, describing behaviors in natural populations requires consideration of the biological and physical factors that different individuals face. Here, we examined variation in socio-sexual and locomotor behaviors in a small, livebearing, freshwater fish, the pygmy halfbeak Dermogenys collettei, across natural populations in Singapore. The pygmy halfbeak is a surface feeding fish that spends most of the time near the water surface, making it ideal for non-invasive behavioral observations. We compared behaviors between sexes among 26 shoals while simultaneously accounting for environmental variation. We demonstrated that sexual interactions and locomotor behaviors differed among shoals with varying levels of canopy cover and water flow. Specifically, in areas with greater canopy cover, sexual interactions decreased, whereas time spent in a stationary position increased. Sexual interactions were more numerous in still water, where fish spent less time swimming. Variation in the expression of socio-sexual and locomotor behaviors were not associated with differences in the amount of aquatic vegetation, water depth or halfbeak shoal size. Agonistic interactions were robust to environmental effects, showing little variation among environments. However, there were strong sex effects, with males performing more agonistic behaviors and spending less time in a stationary position compared to females, regardless of the environment. Moreover, sexual interactions, measured as actively performed by males and passively received by females, were on average more frequent in males than in females. Our findings help us explore the proximal causes of intraspecific behavioral variation and suggest that fundamental information on socio-sexual behaviors from wild populations can lead to a better understanding of how sexual selection operates when the strength of natural selection varies across environments.
Succinate Mediates Tumorigenic Effects via Succinate Receptor 1: Potential for New Targeted Treatment Strategies in Succinate Dehydrogenase Deficient Paragangliomas

Paragangliomas and pheochromocytomas (PPGLs) are chromaffin tumors associated with severe catecholamine-induced morbidities. Surgical removal is often curative. However, complete resection may not be an option for patients with succinate dehydrogenase subunit A-D (SDHx) mutations. SDHx mutations are associated with a high risk for multiple recurrent, and metastatic PPGLs. Treatment options in these cases are limited and prognosis is dismal once metastases are present. Identification of new therapeutic targets and candidate drugs is thus urgently needed. Previously, we showed elevated expression of succinate receptor 1 (SUCNR1) in SDHB PPGLs and SDHD head and neck paragangliomas. Its ligand succinate has been reported to accumulate due to SDHx mutations. We thus hypothesize that autocrine stimulation of SUCNR1 plays a role in the pathogenesis of SDHx mutation-derived PPGLs. We confirmed elevated SUCNR1 expression in SDHx PPGLs and after SDHB knockout in progenitor cells derived from a human pheochromocytoma (hPheo1). Succinate significantly increased viability of SUCNR1-transfected PC12 and ERK pathway signaling compared to control cells. Candidate SUCNR1 inhibitors successfully reversed proliferative effects of succinate. Our data reveal an unrecognized oncometabolic function of succinate in SDHx PPGLs, providing a growth advantage via SUCNR1.
Isolation of the ZmERS4 Gene From Maize and Its Functional Analysis in Transgenic Plants

A gene encoding a protein similar to ethylene receptor was isolated from maize (Zea mays L.), which was named as ZmERS4.The gene was 1,905 bp in length with an open reading frame that encoded a protein consisting of 634 amino acids. The homologous analysis showed that ZmERS4 shared high similarity with the ethylene receptor protein, OsERS1, from rice (Oryza sativa L.). ZmERS4 grouped into the ETR1 subfamily of ethylene receptors based on its conserved domain and phylogenetic status. Tissue-specific and induced expression analyses indicated that ZmERS4 was differentially expressed in maize tissues, predominantly in the stems and leaves, and was induced by salicylic acid (SA). Overexpression of ZmERS4 in Arabidopsis improved resistance against the bacterial pathogen, PstDC3000, by inducing the expression of SA signaling-related genes. Moreover, treatment with flg22 induced the expression of the defense-related gene, PR1, in maize protoplasts that transiently expressed ZmERS4. Furthermore, the ultra-high-performance liquid chromatography (UPLC) analysis showed that the SA contents in ZmERS4-overexpressing Arabidopsis lines were significantly higher than the control lines. Additionally, the improved resistance of ZmERS4-overexpressing Arabidopsis against PstDC3000 was blocked after pretreatment with the SA biosynthetic inhibitor, ABT. Based on the collective findings, we hypothesize that ZmERS4 plays an important role in disease resistance through SA-mediated signaling pathways.
Data-Driven Surveillance: Effective Collection, Integration, and Interpretation of Data to Support Decision Making

The biggest change brought about by the “era of big data” to health in general, and epidemiology in particular, relates arguably not to the volume of data encountered, but to its variety. An increasing number of new data sources, including many not originally collected for health purposes, are now being used for epidemiological inference and contextualization. Combining evidence from multiple data sources presents significant challenges, but discussions around this subject often confuse issues of data access and privacy, with the actual technical challenges of data integration and interoperability. We review some of the opportunities for connecting data, generating information, and supporting decision-making across the increasingly complex “variety” dimension of data in population health, to enable data-driven surveillance to go beyond simple signal detection and support an expanded set of surveillance goals.
Testing Tsunami Inundation Maps for Evacuation Planning in Italy

Inundation maps are a fundamental tool for coastal risk management and in particular for designing evacuation maps and evacuation planning. These in turn are a necessary component of the tsunami warning systems’ last-mile. In Italy inundation maps are informed by a probabilistic tsunami hazard model. Based on a given level of acceptable risk, Italian authorities in charge for this task recommended to consider, as design hazard intensity, the average return period of 2500 years and the 84th percentile of the hazard model uncertainty. An available, regional-scale tsunami hazard model was used that covers the entire Italian coastline. Safety factors based on analysis of run-up variability and an empirical coastal dissipation law on a digital terrain model (DTM) were applied to convert the regional hazard into the design run-up and the corresponding evacuation maps with a GIS-based approach. Since the regional hazard cannot fully capture the local-scale variability, this simplified and conservative approach is considered a viable and feasible practice to inform local coastal risk management in the absence of high-resolution hazard models. The present work is a first attempt to quantify the uncertainty stemming from such procedure. We compare the GIS-based inundation maps informed by a regional model with those obtained from a local high-resolution hazard model. Two locations on the coast of eastern Sicily were considered, and the local hazard was addressed with the same seismic model as the regional one, but using a higher-resolution DTM and massive numerical inundation calculations with the GPU-based Tsunami-HySEA nonlinear shallow water code. This study shows that the GIS-based inundation maps used for planning deal conservatively with potential hazard underestimation at the local scale, stemming from typically unmodeled uncertainties in the numerical source and tsunami evolution models. The GIS-based maps used for planning fall within the estimated “error-bar” due to such uncertainties. The analysis also demonstrates the need to develop local assessments to serve very specific risk mitigation actions to reduce the uncertainty. More in general, the presented case-studies highlight the importance to explore ways of dealing with uncertainty hidden within the high-resolution numerical inundation models, e.g., related to the crude parameterization of the bottom friction, or the inaccuracy of the DTM.
Intervention Implementation of Tools of the Mind for Preschool Children’s Executive Functioning

One of the more prominent early childhood interventions focused on the development of executive function (EF) skills is Tools of the Mind (Tools; Bodrova and Leong, 2019). Intervention studies comparing Tools classrooms with control classrooms, however, reveal inconsistent findings for children’s EF outcomes. The current study utilizes Head Start CARES teachers assigned to the Tools of the Mind enhancement intervention (Tools; N = 75) and the children in their classrooms (N = 738). Relations between teachers’ characteristics (i.e., teaching experience, psychological well-being, and educational background), training attendance and implementation (i.e., coach rated fidelity and observed scaffolding), and the interaction among these factors were examined as predictors of classroom-level gains in EF. Results revealed several significant moderation effects indicating that Tools implementation is related to classroom EF gains for some but not all teachers.
Asthma-Specific Temporal Variability Reveals the Effect of Group Cognitive Behavior Therapy in Asthmatic Patients

Background: Group cognitive behavior therapy (GCBT) is a successful therapy for asthma. However, the neural biomarker of GCBT which could be used in clinic remains unclear. The temporal variability is a novel concept to characterize the dynamic functional connectivity (FC), which has many advantages as biomarker. Therefore, the aim of this study is to explore the potential difference of temporal variability between asthmatic patients and healthy controls, then determine the different patterns of temporal variability between pre- and post-treatment group and reveal the relationship between the variability and the symptoms improvement reduced by GCBT. Methods: At baseline, 40 asthmatic patients and 40 matched controls received resting-state functional magnetic resonance imaging (fMRI) scans and clinical assessments. After 8 weeks of GCBT treatment, 17 patients received fMRI scans, and assessments again. Temporal variability at baseline and post-treatment were calculated for further analysis. Results: Compared with controls, asthmatic patients showed widespread decreases in temporal variability. Moreover, the variability in both right caudate and left putamen were positively correlated with asthma control level. After GCBT, asthma control level and depression of patients were improved. Meanwhile, compared with pre-GCBT, patients after treatment showed lower variability in left opercular of Rolandic, right parahippocampal gyrus and right lingual gyrus, as well as higher variability in left temporal pole. Variability in regions which were found abnormal at baseline did not exhibit significant differences between post-GCBT and controls. Conclusions: Asthma-specific changes of dynamic functional connectivity may serve as promising underpinnings of GCBT for asthma. Clinical Trial Registration: http://www.chictr. org.cn/index.aspx, identifier: Chi-CTR-15007442.
Prognostic Alternative mRNA Splicing in Adrenocortical Carcinoma

Background This paper aims to identify alternative RNA splicing landscape and its prognostic value in adrenocortical carcinoma. Methods The alternative splicing events data with corresponding clinical information data of 79 ACC patients were obtained from the Cancer Genome Atlas and SpliceSeq package. Prognosis-associated AS events by using univariate Cox regression analysis were selected. Gene functional enrichment analysis demonstrated the potential pathways enriched by survival-associated AS. Prognosis-related splicing events were submitted to develop moderate predictors using Lasso regression model. Results One thousand five survival-associated alternative splicing events were identified. The prognostic genes included ATXN2L, MEIS1, IKBKB, COX4I1. Functional enrichment analysis suggested that prognostic splicing events are associated with Wnt signaling pathway. A prediction model including 12 alternative splicing events was constructed by Lasso regression using train set. ROC analysis showed good performance of the prediction model in test set. Then, a nomogram integrating the clinical-pathological factors and riskscore was constructed for predicting 1‐ and 3‐year survival rate. Conclusion Our data provide a comprehensive bioinformatics analysis of AS events in ACC, providing biomarkers for disease progression and a potentially rich source of novel therapeutic targets.
Remedial Training of the Less-Impaired Arm in Chronic Stroke Survivors With Moderate to Severe Upper-Extremity Paresis Improves Functional Independence: A Pilot Study

The ipsilesional arm of stroke patients often has functionally limiting deficits in motor control and dexterity that depend on the side of the brain that is lesioned and that increase with the severity of paretic arm impairment. However, remediation of the ipsilesional arm has yet to be integrated into the usual standard of care for upper limb rehabilitation in stroke, largely due to a lack of translational research examining the effects of ipsilesional-arm intervention. We now ask whether ipsilesional-arm training, tailored to the hemisphere-specific nature of ipsilesional-arm motor deficits in participants with moderate to severe contralesional paresis, improves ipsilesional arm performance and generalizes to improve functional independence. We assessed the effects of this intervention on ipsilesional arm unilateral performance [Jebsen–Taylor Hand Function Test (JHFT)], ipsilesional grip strength, contralesional arm impairment level [Fugl–Meyer Assessment (FM)], and functional independence [Functional independence measure (FIM)] (N = 13). Intervention occurred over a 3 week period for 1.5 h/session, three times each week. All sessions included virtual reality tasks that targeted the specific motor control deficits associated with either left or right hemisphere damage, followed by graded dexterity training in real-world tasks. We also exposed participants to 3 weeks of sham training to control for the non-specific effects of therapy visits and interactions. We conducted five test-sessions: two pre-tests and three post-tests. Our results indicate substantial improvements in the less-impaired arm performance, without detriment to the paretic arm that transferred to improved functional independence in all three posttests, indicating durability of training effects for at least 3 weeks. We provide evidence for establishing the basis of a rehabilitation approach that includes evaluation and remediation of the ipsilesional arm in moderately to severely impaired stroke survivors. This study was originally a crossover design; however, we were unable to complete the second arm of the study due to the COVID-19 pandemic. We report the results from the first arm of the planned design as a longitudinal study.
Land Use Changes Threaten Bird Taxonomic and Functional Diversity Across the Mediterranean Basin: A Spatial Analysis to Prioritize Monitoring for Conservation

Land use changes rank among the highest threats to biodiversity, but assessment of their ecological impact is impaired by data paucity in vast regions of the world. For birds, land use changes may mean habitat loss or fragmentation, changes in resource availability, and disruption of biotic interactions or dispersal pathways. As a result, avian population sizes and assemblage diversity decline in areas subjected to urbanization, agricultural intensification, and land abandonment worldwide. This threat is especially sensitive in hotspots such as the Mediterranean basin, where avifaunas of several biogeographic origins meet, encompassing numerous endemic taxa, and ecological specialists with low resilience to habitat modifications. Here, we correlated several facets of bird taxonomic and functional diversity to a fine-grained land-use change classification, in order to identify priority areas in need for enforced protocoled bird sampling in a conservation prospect. For this, we computed the species richness, functional richness, originality and specificity of 211 bird assemblages based on bird extent-of-occurrence data for 279 species and 10 ecological traits. We used a spatialized regression model to correlate bird diversity patterns with bioclimatic gradients and land use change between 1992 and 2018, assessed from an unsupervised clustering on 2 km resolution data. We showed that species-rich bird assemblages are subjected to agricultural intensification, while functionally diverse assemblages are mainly undergoing desertification and land abandonment. Unfortunately, most of these changes occur in areas where protocoled bird surveys with sufficient spatial and temporal resolution are lacking. In light of these results, we urge for the setting of bird monitoring programs targeted mainly on parts of North-Africa and the Levant, in order to allow a region-level evaluation of the threat posed by recent land use changes on the exceptional avifaunistic diversity of the basin. Fostering such regional-scale evaluations of congruences between human threats and centers of diversity is a necessary preliminary step for a pragmatic response to data deficiencies and ultimately setting appropriate responses to avoid the collapse of avian assemblages.