Miracle-dz/UniFAR-FTUs huggingface dataset:
Liuwei Dihuang formula ameliorates chronic stress-induced emotional and cognitive impairments in mice by elevating hippocampal O-GlcNAc modification

A substantial body of evidence has indicated that intracerebral O-linked N-acetyl-β-D-glucosamine (O-GlcNAc), a generalized post-translational modification, was emerging as an effective regulator of stress-induced emotional and cognitive impairments. Our previous studies showed that the Liuwei Dihuang formula (LW) significantly improved the emotional and cognitive dysfunctions in various types of stress mouse models. In the current study, we sought to determine the effects of LW on intracerebral O-GlcNAc levels in chronic unpredictable mild stress (CUMS) mice. The dynamic behavioral tests showed that anxiety- and depression-like behaviors and object recognition memory of CUMS mice were improved in a dose-dependent manner after LW treatment. Moreover, linear discriminate analysis (LEfSe) of genera abundance revealed a significant difference in microbiome among the study groups. LW showed a great impact on the relative abundance of these gut microbiota in CUMS mice and reinstated them to control mouse levels. We found that LW potentially altered the Uridine diphosphate-N-acetylglucosamine (UDP-GlcNAc) biosynthesis process, and the abundance of O-GlcNAcase (OGA) and O-GlcNAc transferase (OGT) in CUMS mice, which was inferred using PICRUSt analysis. We further verified advantageous changes in hippocampal O-GlcNAc modification of CUMS mice following LW administration, as well as changes in the levels of OGA and OGT. In summary, LW intervention increased the levels of hippocampal O-GlcNAc modification and ameliorated the emotional and cognitive impairments induced by chronic stress in CUMS mice. LW therefore could be considered a potential prophylactic and therapeutic agent for chronic stress.
Functional and effective connectivity analysis of drug-resistant epilepsy: a resting-state fMRI analysis

Objective Epilepsy is considered as a neural network disorder. Seizure activity in epilepsy may disturb brain networks and damage brain functions. We propose using resting-state functional magnetic resonance imaging (rs-fMRI) data to characterize connectivity patterns in drug-resistant epilepsy. Methods This study enrolled 47 participants, including 28 with drug-resistant epilepsy and 19 healthy controls. Functional and effective connectivity was employed to assess drug-resistant epilepsy patients within resting state networks. The resting state functional connectivity (FC) analysis was performed to assess connectivity between each patient and healthy controls within the default mode network (DMN) and the dorsal attention network (DAN). In addition, dynamic causal modeling was used to compute effective connectivity (EC). Finally, a statistical analysis was performed to evaluate our findings. Results The FC analysis revealed significant connectivity changes in patients giving 64.3% (18/28) and 78.6% (22/28) for DMN and DAN, respectively. Statistical analysis of FC was significant between the medial prefrontal cortex, posterior cingulate cortex, and bilateral inferior parietal cortex for DMN. For DAN, it was significant between the left and the right intraparietal sulcus and the frontal eye field. For the DMN, the patient group showed significant EC connectivity in the right inferior parietal cortex and the medial prefrontal cortex for the DMN. There was also bilateral connectivity between the medial prefrontal cortex and the posterior cingulate cortex, as well as between the left and right inferior parietal cortex. For DAN, patients showed significant connectivity in the right frontal eye field and the right intraparietal sulcus. Bilateral connectivity was also found between the left frontal eye field and the left intraparietal sulcus, as well as between the right frontal eye field and the right intraparietal sulcus. The statistical analysis of the EC revealed a significant result in the medial prefrontal cortex and the right intraparietal cortex for the DMN. The DAN was found significant in the left frontal eye field, as well as the left and right intraparietal sulcus. Conclusion Our results provide preliminary evidence to support that the combination of functional and effective connectivity analysis of rs-fMRI can aid in diagnosing epilepsy in the DMN and DAN networks.
Automated detection of myopic maculopathy using five-category models based on vision outlooker for visual recognition

Purpose To propose a five-category model for the automatic detection of myopic macular lesions to help grassroots medical institutions conduct preliminary screening of myopic macular lesions from limited number of color fundus images. Methods First, 1,750 fundus images of non-myopic retinal lesions and four categories of pathological myopic maculopathy were collected, graded, and labeled. Subsequently, three five-classification models based on Vision Outlooker for Visual Recognition (VOLO), EfficientNetV2, and ResNet50 for detecting myopic maculopathy were trained with data-augmented images, and the diagnostic results of the different trained models were compared and analyzed. The main evaluation metrics were sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV), area under the curve (AUC), kappa and accuracy, and receiver operating characteristic curve (ROC). Results The diagnostic accuracy of the VOLO-D2 model was 96.60% with a kappa value of 95.60%. All indicators used for the diagnosis of myopia-free macular degeneration were 100%. The sensitivity, NPV, specificity, and PPV for diagnosis of leopard fundus were 96.43, 98.33, 100, and 100%, respectively. The sensitivity, specificity, PPV, and NPV for the diagnosis of diffuse chorioretinal atrophy were 96.88, 98.59, 93.94, and 99.29%, respectively. The sensitivity, specificity, PPV, and NPV for the diagnosis of patchy chorioretinal atrophy were 92.31, 99.26, 97.30, and 97.81%, respectively. The sensitivity, specificity, PPV, and NPV for the diagnosis of macular atrophy were 100, 98.10, 84.21, and 100%, respectively. Conclusion The VOLO-D2 model accurately identified myopia-free macular lesions and four pathological myopia-related macular lesions with high sensitivity and specificity. It can be used in screening pathological myopic macular lesions and can help ophthalmologists and primary medical institution providers complete the initial screening diagnosis of patients.
Global patterns of plant and microbial biomass in response to CO2 fumigation

Introduction The stimulation of plant and microbial growth has been widely observed as a result of elevated CO2 concentrations (eCO2), however, this stimulation could be influenced by various factors and their relative importance remains unclear. Methods A global meta-analysis was performed using 884 lines of observations collected from published papers, which analyzed the eCO2 impact on plant and microbial biomass. Results A significant positive impact of eCO2 was observed on various biomass measures, including aboveground biomass (20.5%), belowground biomass (42.6%), soil microbial biomass (10.4%), fungal biomass (11.0%), and bacterial biomass (9.2%). It was found that eCO2 levels above 200 ppm had a greater impact on plant biomass compared to concentrations at or below 200 ppm. On the other hand, studies showed that positive effects on microbial biomass were more prominent at lower eCO2 levels (≤200 ppm) than at higher levels (>200 ppm), which could be explained by soil nitrogen limitations. Importantly, our results indicated that aboveground biomass was controlled more by climatic and experimental conditions, while soil properties strongly impacted the stimulation of belowground and microbial biomass. Discussion Our results provided evidence of the eCO2 fertilization effect across various ecosystem types, experimental methods, and climates, and provided a quantitative estimate of plant and soil microbial biomass sensitivity to eCO2. The results obtained in this study suggest that ecosystem models should consider climatic and edaphic factors to more accurately predict the effects of global climate change and their impact on ecosystem functions.
Production, acceptability, and online comprehension of Spanish differential object marking by heritage speakers and L2 learners

We analyzed the production, acceptability and online comprehension of Spanish differential object marking (DOM) by two groups of bilingual speakers living in the U.S.: heritage speakers and L2 learners. DOM is the overt marking of direct objects that are higher on the animacy and referentiality scales, such as animate and specific objects in Spanish, marked by the preposition a (Juan ve a María ‘Juan sees DOM María’). Previous studies have reported variability and high omission rates of obligatory DOM in bilingual situations where Spanish is in contact with a non-DOM language.Our study combined different methodologies to tap knowledge of DOM in the two groups. The results showed that heritage speakers and L2 learners (1) exhibited variability with DOM in production (in two oral tasks), comprehension (in an acceptability judgement task), and processing (in an eye-tracking reading task); (2) can integrate DOM into their production, judgments and processing, but they do so inconsistently, and (3) type of task and type of sentence each have an effect on speakers’ use of DOM.
Stability and flexibility of odor representations in the mouse olfactory bulb

Dynamic changes in sensory representations have been basic tenants of studies in neural coding and plasticity. In olfaction, relatively little is known about the dynamic range of changes in odor representations under different brain states and over time. Here, we used time-lapse in vivo two-photon calcium imaging to describe changes in odor representation by mitral cells, the output neurons of the mouse olfactory bulb. Using anesthetics as a gross manipulation to switch between different brain states (wakefulness and under anesthesia), we found that odor representations by mitral cells undergo significant re-shaping across states but not over time within state. Odor representations were well balanced across the population in the awake state yet highly diverse under anesthesia. To evaluate differences in odor representation across states, we used linear classifiers to decode odor identity in one state based on training data from the other state. Decoding across states resulted in nearly chance-level accuracy. In contrast, repeating the same procedure for data recorded within the same state but in different time points, showed that time had a rather minor impact on odor representations. Relative to the differences across states, odor representations remained stable over months. Thus, single mitral cells can change dynamically across states but maintain robust representations across months. These findings have implications for sensory coding and plasticity in the mammalian brain.
Neurobehavioral risk factors influence prevalence and severity of hazardous substance use in youth at genetic and clinical high risk for psychosis

Background Elevated rates of alcohol, tobacco, and cannabis use are observed in both patients with psychotic disorders and individuals at clinical high risk for psychosis (CHR-P), and strong genetic associations exist between substance use disorders and schizophrenia. While individuals with 22q11.2 deletion syndrome (22qDel) are at increased genetic risk for psychosis, initial evidence suggests that they have strikingly low rates of substance use. In the current study, we aimed to directly compare substance use patterns and their neurobehavioral correlates in genetic and clinical high-risk cohorts. Methods Data on substance use frequency and severity, clinical symptoms, and neurobehavioral measures were collected at baseline and at 12-month follow-up visits in two prospective longitudinal cohorts: participants included 89 22qDel carriers and 65 age and sex-matched typically developing (TD) controls (40.67% male, Mage = 19.26 ± 7.84 years) and 1,288 CHR-P youth and 371 matched TD controls from the North American Prodrome Longitudinal Study-2 and 3 (55.74% male; Mage = 18.71 ± 4.27 years). Data were analyzed both cross-sectionally and longitudinally using linear mixed effects models. Results Controlling for age, sex, and site, CHR-P individuals had significantly elevated rates of tobacco, alcohol, and cannabis use relative to TD controls, whereas 22qDel had significantly lower rates. Increased substance use in CHR-P individuals was associated with increased psychosis symptom severity, dysphoric mood, social functioning, and IQ, while higher social anhedonia was associated with lower substance use across all domains at baseline. These patterns persisted when we investigated these relationships longitudinally over one-year. CHR-P youth exhibited significantly increased positive psychosis symptoms, dysphoric mood, social functioning, social anhedonia, and IQ compared to 22qDel carriers, and lower rates of autism spectrum disorder (ASD) compared to 22qDel carriers, both at baseline and at 1 year follow-up. Conclusion Individuals at genetic and CHR-P have strikingly different patterns of substance use. Factors such as increased neurodevelopmental symptoms (lower IQ, higher rates of ASD) and poorer social functioning in 22qDel may help explain this distinction from substance use patterns observed in CHR-P individuals.
Regulation of eukaryotic mRNA deadenylation and degradation by the Ccr4-Not complex

Accurate and precise regulation of gene expression programmes in eukaryotes involves the coordinated control of transcription, mRNA stability and translation. In recent years, significant progress has been made about the role of sequence elements in the 3′ untranslated region for the regulation of mRNA degradation, and a model has emerged in which recruitment of the Ccr4-Not complex is the critical step in the regulation of mRNA decay. Recruitment of the Ccr4-Not complex to a target mRNA results in deadenylation mediated by the Caf1 and Ccr4 catalytic subunits of the complex. Following deadenylation, the 5′ cap structure is removed, and the mRNA subjected to 5′-3′ degradation. Here, the role of the human Ccr4-Not complex in cytoplasmic deadenylation of mRNA is reviewed, with a particular focus on mechanisms of its recruitment to mRNA by sequence motifs in the 3′ untranslated region, codon usage, as well as general mechanisms involving the poly(A) tail.
Stabilization of the wave equation with boundary or internal distributed delay

We consider the wave equation in a bounded region with a smooth boundary with distributed delay on the boundary or into the domain. In both cases, under suitable assumptions, we prove the expo- nential stability of the solution. These results are obtained by introduc- ing suitable energies and by proving some observability inequalities. For an internal distributed delay, we further show some instability results.
Unveiling behavioral and molecular neuroadaptations related to the antidepressant action of cannabidiol in the unpredictable chronic mild stress model

Introduction: This study aims to further characterize cannabidiol’s pharmacological and molecular profile as an antidepressant. Methods: Effects of cannabidiol (CBD), alone or combined with sertraline (STR), were evaluated in male CD1 mice (n = 48) exposed to an unpredictable chronic mild stress (UCMS) procedure. Once the model was established (4 weeks), mice received CBD (20 mg·kg-1, i.p.), STR (10 mg·kg-1, p.o.) or its combination for 28 days. The efficacy of CBD was evaluated using the light-dark box (LDB), elevated plus maze (EPM), tail suspension (TS), sucrose consumption (SC) and novel object recognition (NOR) tests. Gene expression changes in the serotonin transporter, 5-HT1A and 5-HT2A receptors, BDNF, VGlut1 and PPARdelta, were evaluated in the dorsal raphe, hippocampus (Hipp) and amygdala by real-time PCR. Besides, BDNF, NeuN and caspase-3 immunoreactivity were assessed in the Hipp. Results: CBD exerted anxiolytic and antidepressant-like effects at 4 and 7 days of treatment in the LDB and TS tests, respectively. In contrast, STR required 14 days of treatment to show efficacy. CBD improved cognitive impairment and anhedonia more significantly than STR. CBD plus STR showed a similar effect than CBD in the LBD, TST and EPM. However, a worse outcome was observed in the NOR and SI tests. CBD modulates all molecular disturbances induced by UCMS, whereas STR and the combination could not restore 5-HT1A, BDNF and PPARdelta in the Hipp. Discussion: These results pointed out CBD as a potential new antidepressant with faster action and efficiency than STR. Particular attention should be given to the combination of CBD with current SSRI since it appears to produce a negative impact on treatment.
Survival rate of dental implants installed by postgraduate students attending an implantology program in Brazil: A 52-month retrospective analysis

Objectives The aim of this study was to assess the survival rate and identify possible risk factors for failure of dental implants placed by postgraduate students in Implantology at a Brazilian Dental School. Materials & methods A retrospective observational study was conducted to evaluate 1,164 dental implants placed by postgraduate students in Implantology at São Leopoldo Mandic Dental School (Brazil) during a 3-year time period (2018–2020). Data collected from the patients' medical charts included the following: implant loss, gender, diabetes, smoking, continuous use of medication, type of implant connection system, implant position (maxilla or mandible), previous bone grafting and type of prosthetic provisioning (temporary prosthesis, immediate prosthesis or permanent prosthesis). The association between all the independent variables and implant loss was run using χ2 and G tests (α = 5%). The implant survival rate was estimated using Kaplan-Meier curve. Results Gender, diabetes, smoking, continuous use of medication, type of implant connection system, implant position, previous bone grafting and type of prosthetic provisioning showed no statistically significant association with implant loss. Of the 1,164 implants installed, 29 (2.5%) failed. The overall survival rate of dental implants placed by postgraduate students up to 52 months was 90.5% (IC95%: 74.5%–96.7%). Conclusions Implants placed by postgraduate students in Implantology at São Leopoldo Mandic Dental School showed a high survival rate, with gender, diabetes, smoking, continuous use of medication, type of implant connection system, implant position, previous bone grafting and type of prosthetic provisioning not accounting for the risk of implant failure.
Conditions under which college students cease learning

Introduction Effective learning involves the acquisition of information toward a goal and cessation upon reaching that goal. Whereas the process of learning acquisition is well understood, comparatively little is known about how or when learning ceases under naturalistic, open-ended learning conditions in which the criterion for performance is not specified. Ideally, learning should cease once there is no progress toward the goal, although this has never been directly tested in human learners. The present set of experiments explored the conditions under which college students stopped attempting to learn a series of inductive perceptual discrimination problems. Methods Each problem varied by whether it was solvable and had a criterion for success. The first problem was solvable and involved a pre-determined criterion. The second problem was solvable, but with no criterion for ending the problem so that learners eventually achieved a highly accurate level of performance (overlearning). The third problem was unsolvable as the correct answer varied randomly across features. Measures included the number of trials attempted and the outcome of each problem. Results and Discussion Results revealed that college students rarely ceased learning in the overlearning or unsolvable problems even though there was no possibility for further progress. Learning cessation increased only by manipulating time demands for completion or reducing the opportunity for reinforcement. These results suggest that human learners show laudable, but inefficient and unproductive, attempts to master problems they should cease.
A comprehensive review and update on human fertility cryopreservation methods and tools

The broad conceptualization of fertility preservation and restoration has become already a major concern in the modern western world since a large number of individuals often face it in the everyday life. Driven by different health conditions and/or social reasons, a variety of patients currently rely on routinely and non-routinely applied assisted reproductive technologies, and mostly on the possibility to cryopreserve gametes and/or gonadal tissues for expanding their reproductive lifespan. This review embraces the data present in human-focused literature regarding the up-to-date methodologies and tools contemporarily applied in IVF laboratories' clinical setting of the oocyte, sperm, and embryo cryopreservation and explores the latest news and issues related to the optimization of methods used in ovarian and testicular tissue cryopreservation.
cFOS expression in the prefrontal cortex correlates with altered cerebral metabolism in developing germ-free mice

Introduction The microbiota plays a critical role in modulating various aspects of host physiology, particularly through the microbiota-gut-brain (MGB) axis. However, the mechanisms that transduce and affect gut-to-brain communication are still not well understood. Recent studies have demonstrated that dysbiosis of the microbiome is associated with anxiety and depressive symptoms, which are common complications of metabolic syndrome. Germ-free (GF) animal models offer a valuable tool for studying the causal effects of microbiota on the host. Methods We employed gene expression and nuclear magnetic resonance (NMR)-based metabolomic techniques to investigate the relationships between brain plasticity and immune gene expression, peripheral immunity, and cerebral and liver metabolism in GF and specific pathogen-free (SPF) mice. Results Our principal findings revealed that brain acetate (p = 0.012) was significantly reduced in GF relative to SPF mice, whereas glutamate (p = 0.0013), glutamine (p = 0.0006), and N-acetyl aspartate (p = 0.0046) metabolites were increased. Notably, cFOS mRNA expression, which was significantly decreased in the prefrontal cortex of GF mice relative to SPF mice (p = 0.044), correlated with the abundance of a number of key brain metabolites altered by the GF phenotype, including glutamate and glutamine. Discussion These results highlight the connection between the GF phenotype, altered brain metabolism, and immediate-early gene expression. The study provides insight into potential mechanisms by which microbiota can regulate neurotransmission through modulation of the host’s brain and liver metabolome, which may have implications for stress-related psychiatric disorders such as anxiety.