Miracle-dz/UniFAR-FTUs huggingface dataset:
Unsupervised Machine Learning Approaches Reveal Distinct Phenotypes of Perceived Bladder Pain: A Pilot Study

Interstitial cystitis/bladder pain syndrome (IC/BPS) is defined as an unpleasant sensation perceived to be related to the bladder with associated urinary symptoms. Due to difficulties discriminating pelvic visceral sensation, IC/BPS likely represents multiple phenotypes with different etiologies that present with overlapping symptomatic manifestations, which complicates clinical management. We hypothesized that unique bladder pain phenotypes or “symptomatic clusters” would be identifiable using machine learning analysis (unsupervised clustering) of validated patient-reported urinary and pain measures. Patients (n = 145) with pelvic pain/discomfort perceived to originate in the bladder and lower urinary tract symptoms answered validated questionnaires [OAB Questionnaire (OAB-q), O'Leary-Sant Indices (ICSI/ICPI), female Genitourinary Pain Index (fGUPI), and Pelvic Floor Disability Index (PFDI)]. In comparison to asymptomatic controls (n = 69), machine learning revealed three bladder pain phenotypes with unique, salient features. The first group chiefly describes urinary frequency and pain with the voiding cycle, in which bladder filling causes pain relieved by bladder emptying. The second group has fluctuating pelvic discomfort and straining to void, urinary frequency and urgency without incontinence, and a sensation of incomplete emptying without urinary retention. Pain in the third group was not associated with voiding, instead being more constant and focused on the urethra and vagina. While not utilized as a feature for clustering, subjects in the second and third groups were significantly younger than subjects in the first group and controls without pain. These phenotypes defined more homogeneous patient subgroups which responded to different therapies on chart review. Current approaches to the management of heterogenous populations of bladder pain patients are often ineffective, discouraging both patients and providers. The granularity of individual phenotypes provided by unsupervised clustering approaches can be exploited to help objectively define more homogeneous patient subgroups. Better differentiation of unique phenotypes within the larger group of pelvic pain patients is needed to move toward improvements in care and a better understanding of the etiologies of these painful symptoms.
Transcriptome Profile During Rabies Virus Infection: Identification of Human CXCL16 as a Potential New Viral Target

Rabies virus (RABV), the causative agent for rabies disease is still presenting a major public health concern causing approximately 60,000 deaths annually. This neurotropic virus (genus Lyssavirus, family Rhabdoviridae) induces an acute and almost always fatal form of encephalomyelitis in humans. Despite the lethal consequences associated with clinical symptoms of rabies, RABV limits neuro-inflammation without causing major histopathological lesions in humans. Nevertheless, information about the mechanisms of infection and cellular response in the central nervous system (CNS) remain scarce. Here, we investigated the expression of inflammatory genes involved in immune response to RABV (dog-adapted strain Tha) in mice, the most common animal model used to study rabies. To better elucidate the pathophysiological mechanisms during natural RABV infection, we compared the inflammatory transcriptome profile observed at the late stage of infection in the mouse brain (cortex and brain stem/cerebellum) with the ortholog gene expression in post-mortem brain biopsies of rabid patients. Our data indicate that the inflammatory response associated with rabies is more pronounced in the murine brain compared to the human brain. In contrast to murine transcription profiles, we identified CXC motif chemokine ligand 16 (CXCL16) as the only significant differentially expressed gene in post-mortem brains of rabid patients. This result was confirmed in vitro, in which Tha suppressed interferon alpha (IFN-α)-induced CXCL16 expression in human CNS cell lines but induced CXCL16 expression in IFN-α-stimulated murine astrocytes. We hypothesize that RABV-induced modulation of the CXCL16 pathway in the brain possibly affects neurotransmission, natural killer (NK) and T cell recruitment and activation. Overall, we show species-specific differences in the inflammatory response of the brain, highlighted the importance of understanding the potential limitations of extrapolating data from animal models to humans.
The Impact of Violence on the Anxiety Levels of Healthcare Personnel During the COVID-19 Pandemic

Introduction: The COVID-19 pandemic stressed the importance of healthcare personnel. However, there is evidence of an increase in violence against them, which brings consequences, such as anxiety. The aim of this study was to analyze the anxiety levels of health professionals who have or not suffered violence during the COVID-19 pandemic, and verify the variables associated with the risk of starting to take medication for anxiety. Methods: We assessed the anxiety profile of health professionals in Brazil through an online questionnaire, using the Generalized Anxiety Disorder 7-item Scale (GAD-7), in relation to groups of participants who have or not suffered violence during the COVID-19 pandemic. We used Cronbach's alpha reliability coefficient to check the consistency of the responses, and the effect size using the r coefficient. Principal Component Analysis was used to verify the differences in anxiety scores between the two groups. Logistic regression analysis was also used to verify the variables associated with the risk of starting medication for anxiety and considered statistically significant when p < 0.05. Results: A total of 1,166 health professionals participated in the study, in which 34.13% had a normal anxiety profile, 40.14% mild, 15.78% moderate, and 9.95% severe. The mean score of the sum of the GAD-7 was 7.03 (SD 5.20). The group that suffered violence had a higher mean (8.40; SD 5.42) compared to the group that did not (5.70; SD 4.60). In addition, the median between both groups was significantly different (7.0 vs. 5.0; p < 0.01). Approximately 18.70% of the participants reported having started taking medication to treat anxiety during the pandemic. The factors that increased the chances of these professionals starting medication for anxiety p < 0.05 were having suffered violence during the pandemic (OR 1.97; 95% CI 1.42–2.77), being nurses (OR 1.61; 95% CI 1.04–2.47) or other types of health professionals (OR 1.58; 95% CI 1.04–2.38), and having a mild (OR 2.11; 95% CI 1.37–3.34), moderate (OR 4.05; 95% CI 2.48–6.71) or severe (OR 9.08; 95% CI 5.39–15.6) anxiety level. Conclusion: Brazilian healthcare professionals who have suffered violence during the pandemic have higher anxiety scores and higher risk to start taking anxiety medication.
Viral-Like Particles Are Associated With Endosymbiont Pathology in Florida Corals Affected by Stony Coral Tissue Loss Disease

Stony coral tissue loss disease (SCTLD) was first documented in 2014 near the Port of Miami, Florida, and has since spread north and south along Florida’s Coral Reef, killing large numbers of more than 20 species of coral and leading to the functional extinction of at least one species, Dendrogyra cylindrus. SCTLD is assumed to be caused by bacteria based on presence of different molecular assemblages of bacteria in lesioned compared to apparently healthy tissues, its apparent spread among colonies, and cessation of spread of lesions in individual colonies treated with antibiotics. However, light microscopic examination of tissues of corals affected with SCTLD has not shown bacteria associated with tissue death. Rather, microscopy shows dead and dying coral cells and symbiotic dinoflagellates (endosymbionts) indicating a breakdown of host cell and endosymbiont symbiosis. It is unclear whether host cells die first leading to death of endosymbionts or vice versa. Based on microscopy, hypotheses as to possible causes of SCTLD include infectious agents not visible at the light microscopy level or toxicosis, perhaps originating from endosymbionts. To clarify this, we examined corals affected with SCTLD and apparently healthy corals using transmission electron microscopy. Endosymbionts in SCTLD-affected and apparently healthy corals consistently had varying degrees of pathology associated with elongated particles compatible in morphology with filamentous positive single-stranded RNA viruses of plants termed anisometric viral-like particles (AVLP). There was apparent progression from early to late replication of AVLP in the cytoplasm of endosymbionts adjacent to or at times within chloroplasts, with morphologic changes in chloroplasts consistent with those seen in plant cells infected by viruses. Coral host cell pathology appeared limited to massive proliferation and lysis of mucus cells. Based on these findings, we hypothesize that SCTLD is a viral disease of endosymbionts leading to coral host death. Efforts to confirm the presence of a virus associated with SCTLD through other means would be appropriate. These include showing the presence of a virus through molecular assays such as deep sequencing, attempts to grow this virus in the laboratory through culture of endosymbionts, localization of virus in tissue sections using immunohistochemistry or in situ hybridization, and experimental infection of known-virus-negative corals to replicate disease at the gross and microscopic level.
Identification and Validation of Immune- and Stemness-Related Prognostic Signature of Melanoma

Purpose: Our aim was to construct a signature that accurately predicted the prognostic and immune response of melanoma. Methods: First, the weighted co-expression network analysis (WGCNA) algorithm was used to identify the hub genes related to clinical phenotypes of melanoma in the cancer genome atlas (TCGA) database. Nest, the least absolute shrinkage and selection operator (LASSO) analysis was used to dimensionality reduction of these hub genes and constructed a prognostic signature to predict the prognosis and immunosuppressive response of melanoma. Result: Through in-depth analysis, we constructed a 5-mRNA prognostic signature and verified its prognostic value in internal (TCGA-SKCM, n = 452) and external independent datasets (GSE53118, n = 79). Based on this signature, the tumor immune microenvironment (TME) of melanoma was characterized, and the result was found that patients in the high-risk group had lower CD8 T cell infiltration and immune checkpoint expression (PD-1, PD-L1, CTLA4), as well as higher M0/M2 macrophage infiltration. Our results also found the risk score based on a 5-mRNA signature was significantly associated with tumor mutational burden (TMB) and tumor stem cell markers (CD20, CD38, ABCB5, CD44, etc.). Lastly, we built a nomogram for clinician prediction for the prognosis of patients with melanoma. Conclusion: Our findings indicated that the 5-mRNA signature has an important predictive value for the overall survival of melanoma. By analyzing the tumor immune microenvironment and tumor stem cell marker between different groups, a new method is provided for the stratified diagnosis and treatment of melanoma.
Loci and Natural Alleles for Low-Nitrogen-Induced Growth Response Revealed by the Genome-Wide Association Study Analysis in Rice (Oryza sativa L.)

Nitrogen is essential for plant growth and yield, and it is, therefore, crucial to increase the nitrogen-use efficiency (NUE) of crop plants in fields. In this study, we measured four major low-nitrogen-induced growth response (LNGR) agronomic traits (i.e., plant height, tiller number, chlorophyll content, and leaf length) of the 225-rice-variety natural population from the Rice 3K Sequencing Project across normal nitrogen (NN) and low nitrogen (LN) environments. The LNGR phenotypic difference between NN and LN levels was used for gene analysis using a genome-wide association study (GWAS) combined with 111,205 single-nucleotide polymorphisms (SNPs) from the available sequenced data from the 3K project. We obtained a total of 56 significantly associated SNPs and 4 candidate genes for 4 LNGR traits. Some loci were located in the candidate regions, such as MYB61, OsOAT, and MOC2. To further study the role of candidate genes, we conducted haplotype analyses to identify the elite germplasms. Moreover, several other plausible candidate genes encoding LN-related or NUE proteins were worthy of mining. Our study provides novel insight into the genetic control of LNGR and further reveals some related novel haplotypes and potential genes with phenotypic variation in rice.
The Differences Between Motor Attempt and Motor Imagery in Brain-Computer Interface Accuracy and Event-Related Desynchronization of Patients With Hemiplegia

Background: Motor attempt and motor imagery (MI) are two common motor tasks used in brain-computer interface (BCI). They are widely researched for motor rehabilitation in patients with hemiplegia. The differences between the motor attempt (MA) and MI tasks of patients with hemiplegia can be used to promote BCI application. This study aimed to explore the accuracy of BCI and event-related desynchronization (ERD) between the two tasks. Materials and Methods: We recruited 13 patients with stroke and 3 patients with traumatic brain injury, to perform MA and MI tasks in a self-control design. The BCI accuracies from the bilateral, ipsilesional, and contralesional hemispheres were analyzed and compared between different tasks. The cortical activation patterns were evaluated with ERD and laterality index (LI). Results: The study showed that the BCI accuracies of MA were significantly (p < 0.05) higher than MI in the bilateral, ipsilesional, and contralesional hemispheres in the alpha-beta (8–30 Hz) frequency bands. There was no significant difference in ERD and LI between the MA and MI tasks in the 8–30 Hz frequency bands. However, in the MA task, there was a negative correlation between the ERD values in the channel CP1 and ipsilesional hemispheric BCI accuracies (r = −0.552, p = 0.041, n = 14) and a negative correlation between the ERD values in channel CP2 and bilateral hemispheric BCI accuracies (r = −0.543, p = 0.045, n = 14). While in the MI task, there were negative correlations between the ERD values in channel C4 and bilateral hemispheric BCI accuracies (r = −0.582, p = 0.029, n = 14) as well as the contralesional hemispheric BCI accuracies (r = −0.657, p = 0.011, n = 14). As for motor dysfunction, there was a significant positive correlation between the ipsilesional BCI accuracies and FMA scores of the hand part in 8–13 Hz (r = 0.565, p = 0.035, n = 14) in the MA task and a significant positive correlation between the ipsilesional BCI accuracies and FMA scores of the hand part in 13–30 Hz (r = 0.558, p = 0.038, n = 14) in the MI task. Conclusion: The MA task may achieve better BCI accuracy but have similar cortical activations with the MI task. Cortical activation (ERD) may influence the BCI accuracy, which should be carefully considered in the BCI motor rehabilitation of patients with hemiplegia.
Modeling and Learning Constraints for Creative Tool Use

Improvisation is a hallmark of human creativity and serves a functional purpose in completing everyday tasks with novel resources. This is particularly exhibited in tool-using tasks: When the expected tool for a task is unavailable, humans often are able to replace the expected tool with an atypical one. As robots become more commonplace in human society, we will also expect them to become more skilled at using tools in order to accommodate unexpected variations of tool-using tasks. In order for robots to creatively adapt their use of tools to task variations in a manner similar to humans, they must identify tools that fulfill a set of task constraints that are essential to completing the task successfully yet are initially unknown to the robot. In this paper, we present a high-level process for tool improvisation (tool identification, evaluation, and adaptation), highlight the importance of tooltips in considering tool-task pairings, and describe a method of learning by correction in which the robot learns the constraints from feedback from a human teacher. We demonstrate the efficacy of the learning by correction method for both within-task and across-task transfer on a physical robot.
RhWRKY33 Positively Regulates Onset of Floral Senescence by Responding to Wounding- and Ethylene-Signaling in Rose Plants

Rose plants are one of the most important horticultural crops, whose commercial value mainly depends on long-distance transportation, and wounding and ethylene are the main factors leading to their quality decline and accelerated senescence in the process. However, underlying molecular mechanisms of crosstalk between wounding and ethylene in the regulation of flower senescence remain poorly understood. In relation to this, transcriptome analysis was performed on rose flowers subjected to various treatments, including control, wounding, ethylene, and wounding- and ethylene- (EW) dual treatment. A large number of differentially expressed genes (DEGs) were identified, ranging from 2,442 between the ethylene- and control-treated groups to 4,055 between the EW- and control-treated groups. Using weighted gene co-expression network analysis (WGCNA), we identified a hub gene RhWRKY33 (rchiobhmchr5g0071811), accumulated in the nucleus, where it may function as a transcription factor. Moreover, quantitative reverse transcription PCR (RT-qPCR) results showed that the expression of RhWRKY33 was higher in the wounding-, ethylene, and EW-treated petals than in the control-treated petals. We also functionally characterized the RhWRKY33 gene through virus-induced gene silencing (VIGS). The silencing of RhWRKY33 significantly delayed the senescence process in the different treatments (control, wounding, ethylene, and EW). Meanwhile, we found that the effect of RhWRKY33-silenced petals under ethylene and EW dual-treatment were stronger than those under wounding treatment in delaying the petal senescence process, implying that RhWRKY33 is closely involved with ethylene and wounding mediated petal senescence. Overall, the results indicate that RhWRKY33 positively regulates the onset of floral senescence mediated by both ethylene and wounding signaling, but relies heavily on ethylene signaling.
Baseline Power of Theta Oscillations Predicts Mystical-Type Experiences Induced by DMT in a Natural Setting

N,N-Dimethyltryptamine (DMT) is a classic psychedelic capable of inducing short-lasting but profound changes in consciousness. As with other psychedelics, the experience induced by DMT strongly depends upon contextual factors, yet the neurobiological determinants of this variability remain unknown. We combined wireless electroencephalography and source imaging to map changes in neural oscillations elicited by inhaled DMT. Furthermore, we found that the power of frontal and temporal theta oscillations was inversely correlated with scales indexing feelings of unity and transcendence, which are an integral part of the phenomenology of mystical-type experiences. Finally, we established the robustness of these results using a machine learning model for regression trained and tested following a cross-validation procedure. Our results are consistent with the observation that the state of mind prior to consuming a psychedelic drug influences the ensuing subjective experience of the user. We also suggest that priming subjects to reduce their theta power before administration of a serotonergic psychedelic could enhance the likelihood of inducing mystical-type experiences, leading to sustained positive effects in well-being and improving the outcome of therapeutic interventions.
In the Model Cell Lines of Moderately and Poorly Differentiated Endometrial Carcinoma, Estrogens Can Be Formed via the Sulfatase Pathway

Endometrial cancer (EC) is the most common gynecological malignancy in resource-abundant countries. The majority of EC cases are estrogen dependent but the mechanisms of estrogen biosynthesis and oxidative metabolism and estrogen action are not completely understood. Here, we evaluated formation of estrogens in models of moderately and poorly differentiated EC: RL95-2 and KLE cells, respectively. Results revealed high expression of estrone-sulfate (E1-S) transporters (SLCO1A2, SLCO1B3, SLCO1C1, SLCO3A1, SLC10A6, SLC22A9), and increased E1-S uptake in KLE vs RL95-2 cells. In RL95-2 cells, higher levels of sulfatase and better metabolism of E1-S to E1 were confirmed compared to KLE cells. In KLE cells, disturbed balance in expression of HSD17B genes led to enhanced activation of E1 to E2, compared to RL95-2 cells. Additionally, increased CYP1B1 expression and down-regulation of genes encoding phase II metabolic enzymes: COMT, NQO1, NQO2, and GSTP1 suggested decreased detoxification of carcinogenic metabolites in KLE cells. Results indicate that in model cell lines of moderately and poorly differentiated EC, estrogens can be formed via the sulfatase pathway.
Remote Optogenetics Using Up/Down-Conversion Phosphors

Microbial rhodopsins widely used for optogenetics are sensitive to light in the visible spectrum. As visible light is heavily scattered and absorbed by tissue, stimulating light for optogenetic control does not reach deep in the tissue irradiated from outside the subject body. Conventional optogenetics employs fiber optics inserted close to the target, which is highly invasive and poses various problems for researchers. Recent advances in material science integrated with neuroscience have enabled remote optogenetic control of neuronal activities in living animals using up- or down-conversion phosphors. The development of these methodologies has stimulated researchers to test novel strategies for less invasive, wireless control of cellular functions in the brain and other tissues. Here, we review recent reports related to these new technologies and discuss the current limitations and future perspectives toward the establishment of non-invasive optogenetics for clinical applications.