Miracle-dz/UniFAR-FTUs huggingface dataset:
Concurrent EPA and DHA Supplementation Impairs Brown Adipogenesis of C2C12 Cells

Maternal dietary supplementation of n−3 polyunsaturated fatty acids (n−3 PUFAs), especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), is considered to play positive roles in fetal neuro system development. However, maternal n−3 PUFAs may induce molecular reprogramming of uncommitted fetal myoblasts into adipocyte phenotype, in turn affecting lipid metabolism and energy expenditure of the offspring. The objective of this in vitro study was to investigate the combined effects of EPA and DHA on C2C12 cells undergoing brown adipogenic differentiation. C2C12 myoblasts were cultured to confluency and then treated with brown adipogenic differentiation medium with and without 50 μM EPA and 50 μM DHA. After differentiation, mRNA and protein samples were collected. Gene expression and protein levels were analyzed by real-time PCR and western blot. General Proteomics analysis was conducted using mass spectrometric evaluation. The effect of EPA and DHA on cellular oxygen consumption was measured using a Seahorse XFP Analyzer. Cells treated with n−3 PUFAs had significantly less (P < 0.05) expression of the brown adipocyte marker genes PGC1α, DIO2, and UCP3. Expression of mitochondrial biogenesis-related genes TFAM, PGC1α, and PGC1β were significantly downregulated (P < 0.05) by n−3 PUFAs treatment. Expression of mitochondrial electron transportation chain (ETC)-regulated genes were significantly inhibited (P < 0.05) by n−3 PUFAs, including ATP5J2, COX7a1, and COX8b. Mass spectrometric and western blot evaluation showed protein levels of enzymes which regulate the ETC and Krebs cycle, including ATP synthase α and β (F1F0 complex), citrate synthase, succinate CO-A ligase, succinate dehydrogenase (complex II), ubiquinol-cytochrome c reductase complex subunits (complex III), aconitate hydratase, cytochrome c, and pyruvate carboxylase were all decreased in the n−3 PUFAs group (P < 0.05). Genomic and proteomic changes were accompanied by mitochondrial dysfunction, represented by significantly reduced oxygen consumption rate, ATP production, and proton leak (P < 0.05). This study suggested that EPA and DHA may alter the BAT fate of myoblasts by inhibiting mitochondrial biogenesis and activity and induce white-like adipogenesis, shifting the metabolism from lipid oxidation to synthesis.
Predictors of household food insecurity in the United States during the COVID-19 pandemic

Objective: To examine associations between sociodemographic and mental health characteristics with household food insecurity as a result of the COVID-19 outbreak. Design: Cross-sectional online survey analyzed using univariable tests and a multivariable logistic regression model. Setting: The United States during the week of March 30, 2020. Participants: Convenience sample of 1,965 American adults using Amazon's Mechanical Turk (MTurk) platform. Participants reporting household food insecurity prior to the pandemic were excluded from analyses. Results: 1,517 participants reported household food security before the COVID-19 outbreak. Among this subset, 30% reported food insecurity after the COVID-19 outbreak, 53% were women and 72% were white. On multivariable analysis, race, income, relationship status, anxiety, and depression were significantly associated with incident household food insecurity. Black respondents, Hispanic/Latino respondents, and respondents with annual income less than $100,000 were significantly more likely to experience incident household food insecurity. Individuals experiencing incident household food insecurity were 2.09 (95% CI 1.58-2.83) times more likely to screen positively for anxiety and 1.88 (95% CI 1.37-2.52) times more likely to screen positively for depression. Conclusions: Food insecurity due to the COVID-19 pandemic is common, and certain populations are particularly vulnerable. There are strong associations between food insecurity and anxiety/depression. Public health interventions to increase the accessibility of healthful foods, especially for Black and Hispanic/Latino communities, are crucial to relieving the economic stress of this pandemic.
Inferring Causality from Noninvasive Brain Stimulation in Cognitive Neuroscience

Abstract Noninvasive brain stimulation (NIBS) techniques, such as transcranial magnetic stimulation or transcranial direct and alternating current stimulation, are advocated as measures to enable causal inference in cognitive neuroscience experiments. Transcending the limitations of purely correlative neuroimaging measures and experimental sensory stimulation, they allow to experimentally manipulate brain activity and study its consequences for perception, cognition, and eventually, behavior. Although this is true in principle, particular caution is advised when interpreting brain stimulation experiments in a causal manner. Research hypotheses are often oversimplified, disregarding the underlying (implicitly assumed) complex chain of causation, namely, that the stimulation technique has to generate an electric field in the brain tissue, which then evokes or modulates neuronal activity both locally in the target region and in connected remote sites of the network, which in consequence affects the cognitive function of interest and eventually results in a change of the behavioral measure. Importantly, every link in this causal chain of effects can be confounded by several factors that have to be experimentally eliminated or controlled to attribute the observed results to their assumed cause. This is complicated by the fact that many of the mediating and confounding variables are not directly observable and dose–response relationships are often nonlinear. We will walk the reader through the chain of causation for a generic cognitive neuroscience NIBS study, discuss possible confounds, and advise appropriate control conditions. If crucial assumptions are explicitly tested (where possible) and confounds are experimentally well controlled, NIBS can indeed reveal cause–effect relationships in cognitive neuroscience studies.
Change in the Neural Response to Auditory Deviance Following Cognitive Therapy for Hallucinations in Patients With Schizophrenia

Adjunctive psychotherapeutic approaches recommended for patients with schizophrenia (SZ) who are fully or partially resistant to pharmacotherapy have rarely utilized biomarkers to enhance the understanding of treatment-effective mechanisms. As SZ patients with persistent auditory verbal hallucinations (AVH) frequently evidence reduced neural responsiveness to external auditory stimulation, which may impact cognitive and functional outcomes, this study examined the effects of cognitive behavioral therapy for voices (CBTv) on clinical and AVH symptoms and the sensory processing of auditory deviants as measured with the electroencephalographically derived mismatch negativity (MMN) response. Twenty-four patients with SZ and AVH were randomly assigned to group CBTv treatment or a treatment as usual (TAU) condition. Patients in the group CBTv condition received treatment for 5 months while the matched control patients received TAU for the same period, followed by 5 months of group CBTv. Assessments were conducted at baseline and at the end of treatment. Although not showing consistent changes in the frequency of AVHs, CBTv (vs. TAU) improved patients' appraisal (p = 0.001) of and behavioral/emotional responses to AVHs, and increased both MMN generation (p = 0.001) and auditory cortex current density (p = 0.002) in response to tone pitch deviants. Improvements in AVH symptoms were correlated with change in pitch deviant MMN and current density in left primary auditory cortex. These findings of improved auditory information processing and symptom-response attributable to CBTv suggest potential clinical and functional benefits of psychotherapeutical approaches for patients with persistent AVHs.
Spontaneous Entry into an “Offline” State during Wakefulness: A Mechanism of Memory Consolidation?

Abstract Moments of inattention to our surroundings may be essential to optimal cognitive functioning. Here, we investigated the hypothesis that humans spontaneously switch between two opposing attentional states during wakefulness—one in which we attend to the external environment (an “online” state) and one in which we disengage from the sensory environment to focus our attention internally (an “offline” state). We created a data-driven model of this proposed alternation between “online” and “offline” attentional states in humans, on a seconds-level timescale. Participants (n = 34) completed a sustained attention to response task while undergoing simultaneous high-density EEG and pupillometry recording and intermittently reporting on their subjective experience. “Online” and “offline” attentional states were initially defined using a cluster analysis applied to multimodal measures of (1) EEG spectral power, (2) pupil diameter, (3) RT, and (4) self-reported subjective experience. We then developed a classifier that labeled trials as belonging to the online or offline cluster with >95% accuracy, without requiring subjective experience data. This allowed us to classify all 5-sec trials in this manner, despite the fact that subjective experience was probed on only a small minority of trials. We report evidence of statistically discriminable “online” and “offline” states matching the hypothesized characteristics. Furthermore, the offline state strongly predicted memory retention for one of two verbal learning tasks encoded immediately prior. Together, these observations suggest that seconds-timescale alternation between online and offline states is a fundamental feature of wakefulness and that this may serve a memory processing function.
Temperature Dramatically Shapes Mosquito Gene Expression With Consequences for Mosquito–Zika Virus Interactions

Vector-borne flaviviruses are emerging threats to human health. For successful transmission, the virus needs to efficiently enter mosquito cells, replicate within, and escape several tissue barriers while mosquitoes elicit major transcriptional responses to flavivirus infection. This process will not only be affected by the specific mosquito-pathogen pairing, but also variation in key environmental variables such as temperature. Thus far, few studies have examined the molecular responses triggered by temperature and how these responses modify infection outcomes despite substantial evidence showing strong relationships between temperature and transmission in a diversity of systems. To define the host transcriptional changes associated with temperature variation during the early infection process, we compared the transcriptome of mosquito midgut samples from mosquitoes exposed to Zika virus (ZIKV) and non-exposed mosquitoes housed at three different temperatures (20, 28, and 36°C). While the high temperature samples did not have significant changes from standard rearing conditions (28°C) 48 hr post-exposure, the transcriptome profile of mosquitoes housed at 20°C was dramatically different. The expression of genes most altered by the cooler temperature involved aspects of blood-meal digestion, ROS metabolism, and mosquito innate immunity. Further, we did not find significant differences in the viral RNA copy number between 24 and 48 hr post-exposure at 20°C, suggesting ZIKV replication is limited by cold-induced changes to the mosquito midgut environment. In ZIKV-exposed mosquitoes, vitellogenin, a lipid carrier protein, was the most up-regulated at 20°C. Our results provide a deeper understanding of the temperature-triggered transcriptional changes in Aedes aegypti and can be used to further define the molecular mechanisms driven by environmental temperature variation. Contribution to the Field Statement A variety of methods for engineering refractory mosquitoes are currently being studied and show promise for disease control. Although considerable effort has been put into understanding the immune system of mosquitoes in response to infections, almost nothing is understood about environmental influences in regulating these responses. Here, we used RNA sequencing to study the effect of temperature on the mosquito transcriptome profile, as well as assess the changes in the immune response to ZIKV infection at three different temperatures. We found a remarkable effect of temperature on the transcriptome profile of mosquitoes exposed to cool conditions (20°C) after imbibing a blood meal, as well as accumulation of transcripts involved with different mechanisms associated with blood meal digestion, metabolism, and some components of the immune response in mosquitoes. Our results provide new insights in potential mechanisms that limit temperature-driven pathogen establishment and replication within the mosquito vector.
Characterization of Context-Dependent Effects on Synthetic Promoters

Understanding the composability of genetic elements is central to synthetic biology. Even for seemingly well-known elements such as a sigma 70 promoter the genetic context-dependent variability of promoter activity remains poorly understood. The lack of understanding of sequence to function results in highly limited de novo design of novel genetic element combinations. To address this issue, we characterized in detail concatenated “stacked” synthetic promoters including varying spacer sequence lengths and compared the transcription strength to the output of the individual promoters. The proxy for promoter activity, the msfGFP synthesis from stacked promoters was consistently lower than expected from the sum of the activities of the single promoters. While the spacer sequence itself had no activity, it drastically affected promoter activities when placed up- or downstream of a promoter. Single promoter-spacer combinations revealed a bivalent effect on msfGFP synthesis. By systematic analysis of promoter and spacer combinations, a semi-empirical correlation was developed to determine the combined activity of stacked promoters.
Recognizing Ion Ligand–Binding Residues by Random Forest Algorithm Based on Optimized Dihedral Angle

The prediction of ion ligand–binding residues in protein sequences is a challenging work that contributes to understand the specific functions of proteins in life processes. In this article, we selected binding residues of 14 ion ligands as research objects, including four acid radical ion ligands and 10 metal ion ligands. Based on the amino acid sequence information, we selected the composition and position conservation information of amino acids, the predicted structural information, and physicochemical properties of amino acids as basic feature parameters. We then performed a statistical analysis and reclassification for dihedral angle and proposed new methods on the extraction of feature parameters. The methods mainly included applying information entropy on the extraction of polarization charge and hydrophilic–hydrophobic information of amino acids and using position weight matrices on the extraction of position conservation information. In the prediction model, we used the random forest algorithm and obtained better prediction results than previous works. With the independent test, the Matthew's correlation coefficient and accuracy of 10 metal ion ligand–binding residues were larger than 0.07 and 52%, respectively; the corresponding evaluation values of four acid radical ion ligand–binding residues were larger than 0.15 and 86%, respectively. Further, we classified and combined the phi and psi angles and optimized prediction model for each ion ligand–binding residue.
Novel Insights Into Triple-Negative Breast Cancer Prognosis by Comprehensive Characterization of Aberrant Alternative Splicing

Background Alternative splicing (AS) is important in the regulation of gene expression and aberrant AS is emerging as a major factor in the pathogenesis of human conditions, including cancer. Triple-negative breast cancer (TNBC) is the most challenging subtype of breast cancer with strong invasion, high rate of metastasis, and poor prognosis. Here we report a systematic profiling of aberrant AS in TNBC. Methods The percent spliced in (PSI) values for AS events in 151 TNBC patients were obtained from The Cancer Genome Atlas (TCGA) SpliceSeq database. Univariate Cox and stepwise Multivariate Cox regression analyses were conducted to find the best prognostic AS model. Splicing regulatory networks were constructed by prognosis-related spliceosome and aberrant AS events. Additionally, pathway enrichment and gene set enrichment analysis (GSEA) were further employed to reveal the significant pathways for prognosis-related AS genes. Finally, splicing regulatory networks were constructed via Spearman’s rank correlation coefficients between prognosis-related AS events and splicing factor expressions. Results A total of 1,397 prognosis-associated AS events were identified in TNBC. The majority of the parent genes of prognostic AS events exhibited direct interactions to each other in the STRING gene network. Pathways of focal adhesion (p < 0.001), RNA splicing (p = 0.007), homologous recombination (p = 0.042) and ECM-receptor interaction (p = 0.046) were found to be significantly enriched for prognosis-related AS. Additionally, the area under curve (AUC) of the best AS prognostic predictor model reached 0.949, showing a powerful capability to predict outcomes. The Exon Skip (ES) type of AS events displayed more robust and efficient capacity in predicting performance than any other specific AS events type in terms of prognosis. The ES AS signature might confer a strong oncogenic phenotype in the high-risk group with elevated activities in cell cycle and SUMOylating pathways of tumorigenesis, while programmed cell death and metabolism pathways were found to be enriched in the low-risk group of TNBC. The splicing correlation network also revealed a regulatory mode of prognostic splicing factors (SFs) in TNBC. Conclusion Our analysis of AS events in TNBC could not only contribute to elucidating the tumorigenesis mechanism of AS but also provide clues to uncovering underlying prognostic biomarkers and therapeutic targets for further study.
Early Detection of Non-Small Cell Lung Cancer by Using a 12-microRNA Panel and a Nomogram for Assistant Diagnosis

Background: We previously identified a 12-microRNA (miRNA) panel (miRNA-17, miRNA-146a, miRNA-200b, miRNA-182, miRNA-155, miRNA-221, miRNA-205, miRNA-126, miRNA-7, miRNA-21, miRNA-145, and miRNA-210) that aided in the early diagnosis of non-small cell lung cancer (NSCLC). We validated the diagnostic value of this miRNA panel and compared it with that of traditional tumor markers and radiological diagnosis. We constructed a nomogram based on the miRNA panel's results to predict the risk of NSCLC. Methods: Eighty-two participants with pulmonary nodules on a CT scan and who underwent a pathological examination and surgical treatment were enrolled in our study. Patients were randomly divided into a training group or a validation group. The miRNA concentrations were quantified by RT-PCR and log-transformed for analysis. The cutoff value was determined in the training group and then applied in the validation group. A comparison between the miRNAs and traditional tumor markers [CEA, NSE, and cytokeratin 19 fragment 21-1 (Cyfra21-1)] and radiological diagnosis was performed. A nomogram based on the miRNA panel's results to predict the risk of NSCLC was constructed. Results: The expression level of these 12 miRNAs was significantly higher in NSCLC patients than in benign patients. In the validation group, the specificity and positive predictive value were 96.4 and 95.8%, respectively, which were significantly higher than those using traditional tumor markers or radiological diagnosis. The sensitivity was 42.6%, which was also higher than that using tumor markers. Moreover, the sensitivity increased to 63.6% when the nodule diameters were larger than 2 cm. The miRNAs and seven clinical factors were integrated into the nomogram, and the calibration curves showed optimal agreement between the predicted and actual probabilities. Conclusions: Our miRNA panel has clinical value for the early detection of NSCLC. A nomogram was constructed and internally validated, and the results indicate that it can assist clinicians in making treatment recommendations in the clinic.
Evaluation of Presurgical Serum Cortisol Level in Patients Undergoing Major Maxillofacial Surgery

Background: Stress is an integral part of life. Anxiety levels may increase when it comes to being treated surgically due to road traffic accidents causing facial trauma, other pathologies or burns. The stress that is caused during a surgical procedure as well as during the treatment in debilitated patients or traumatic conditions is bound to cause disturbance in the metabolic and physiologic levels of cortisol. Therefore, a study was carried out to determine the cortisol levels just prior to surgery on the day of operation to quantify the stress levels and also aid in any preanesthetic medication changes for the patient undergoing maxillofacial surgery. Aim: To evaluate and compare pre-surgical serum cortisol levels in patients undergoing major maxillofacial surgery under general anaesthesia. Objective: To evaluate the serum cortisol level of patient 3 days prior to surgery, on the day of surgery and to compare and evaluate the difference seen in both the obtained values. Methods: A prospective, randomized, in- vivo study was carried out in the Department of Oral and Maxillofacial Surgery at a teaching dental hospital. A total of 32 patients were included in this study. Inclusion and Exculsion criteria was made along with pre-opertive assessment of the patient, informed consent was obtained from all patients involved in the study. Patient blood sample, at 8 am three days prior to surgery and on the day of surgery and sent for laboratory investigations. Result: Participants in this clinical study underwent treatment of various ailments like facial trauma, and miscellaneous pathologies like Dentigerous Cyst, Oral submucosa fibrosis, Osteomyelitis, Benign Tumor and Orthognathic surgery. The anxiety of the patients were assessed by serum cortisol level preoperatively and on the day of operation. A total of 32 patients, 26 male and 06 female were included in the study. There was statistically highly significant difference seen between the mean values obtained three days prior to surgery and on the day of surgery.Conclusion: We have concluded from this study that the serum cortisol level shows significant increase on the day of surgery. A future study can focus on association between increased levels of serum cortisol and postoperative wound healing where patients can be divided into two groups one receiving pre-operative stress reduction protocol and other not receiving the same.
Effect of heat on zoospore motility and multiplication of Olpidium radicale and O. brassicae

SUMMARY Whereas zoospores of six cultures of O. brassicae were immobile after treating in glycine solution at 35–40°C for 10 min, those of a cucurbit culture of O. radicale were immobile only after heating at 45°C. Further, O. radicale multiplied in cucumber at 20°, 30° and 35°C, whereas O. brassicae multiplied at 20°, but not 30° or 35°C. Such differences in reaction to temperature might sometimes be useful in separating mixtures of the two species in common hosts such as cucumber.