Miracle-dz/UniFAR-FTUs huggingface dataset:
Urinary Bladder Weight and Function in a Rat Model of Mild Hyperglycemia and Its Treatment With Dapagliflozin

Hypertrophy and dysfunction of the urinary bladder are consistently observed in animal models of type 1 and less consistently in those of type 2 diabetes. We have tested the effects of mild hyperglycemia (n = 10 per group) in a randomized, blinded study and, in a blinded pilot study, of type 2 diabetes (n = 6 per group) and its treatment with dapagliflozin (1 mg/kg per day) on weight, contraction, and relaxation of the rat bladder. Based on a combination of high-fat diet and a low dose of streptozotocin, animals in the main study reached a mean peak blood glucose level of about 300 mg/dl, which declined to 205 mg/dl at study end. This was associated with a small, if any, increase in bladder weight. In a pooled analysis of all animals of the main and the pilot study, we detected a correlation of moderate strength between blood glucose and bladder weight (r 2 = 0.2013; P = 0.0003 for Pearson correlation coefficient). Neither the main nor the pilot study found evidence for an altered contractility (responses to carbachol or KCl) or relaxation (responses to isoprenaline, fenoterol, CL 316,243, or forskolin). Treatment with dapagliflozin in the absence of hyperglycemia increased diuresis in the main study by 43% relative to control and increased bladder weight by 15% in the pooled groups of both studies (post hoc analysis). We conclude that mild hyperglycemia has no major effects on bladder hypertrophy or function.
Corticofugal Augmentation of the Auditory Brainstem Response With Respect to Cortical Preference

Physiological studies documented highly specific corticofugal modulations making subcortical centers focus processing on sounds that the auditory cortex (AC) has experienced to be important. Here, we show the effects of focal conditioning (FC) of the primary auditory cortex (FCAI) on auditory brainstem response (ABR) amplitudes and latencies in house mice. FCAI significantly increased ABR peak amplitudes (peaks I–V), decreased thresholds, and shortened peak latencies in responses to the frequency tuned by conditioned cortical neurons. The amounts of peak amplitude increases and latency decreases were specific for each processing level up to the auditory midbrain. The data provide new insights into possible corticofugal modulation of inner hair cell synapses and new corticofugal effects as neuronal enhancement of processing in the superior olivary complex (SOC) and lateral lemniscus (LL). Thus, our comprehensive ABR approach confirms the role of the AC as instructor of lower auditory levels and extends this role specifically to the cochlea, SOC, and LL. The whole pathway from the cochlea to the inferior colliculus appears, in a common mode, instructed in a very similar way.
The Potential for Pharmacokinetic Interactions Between Cannabis Products and Conventional Medications.

PURPOSE Increased cannabis use and recent drug approvals pose new challenges for avoiding drug interactions between cannabis products and conventional medications. This review aims to identify drug-metabolizing enzymes and drug transporters that are affected by concurrent cannabis use and, conversely, those co-prescribed medications that may alter the exposure to one or more cannabinoids. METHODS A systematic literature search was conducted utilizing the Google Scholar search engine and MEDLINE (PubMed) database through March 2019. All articles describing in vitro or clinical studies of cannabis drug interaction potential were retrieved for review. Additional articles of interest were obtained through cross-referencing of published bibliographies. FINDINGS After comparing the in vitro inhibition parameters to physiologically achievable cannabinoid concentrations, it was concluded that CYP2C9, CYP1A1/2, and CYP1B1 are likely to be inhibited by all 3 major cannabinoids Δ-tetrahydrocannabinol (THC), cannabidiol (CBD), and cannabinol (CBN). The isoforms CYP2D6, CYP2C19, CYP2B6, and CYP2J2 are inhibited by THC and CBD. CYP3A4/5/7 is potentially inhibited by CBD. Δ-Tetrahydrocannabinol also activates CYP2C9 and induces CYP1A1. For non-CYP drug-metabolizing enzymes, UGT1A9 is inhibited by CBD and CBN, whereas UGT2B7 is inhibited by CBD but activated by CBN. Carboxylesterase 1 (CES1) is potentially inhibited by THC and CBD. Clinical studies suggest inhibition of CYP2C19 by CBD, inhibition of CYP2C9 by various cannabis products, and induction of CYP1A2 through cannabis smoking. Evidence of CBD inhibition of UGTs and CES1 has been shown in some studies, but the data are limited at present. We did not identify any clinical studies suggesting an influence of cannabinoids on drug transporters, and in vitro results suggest that a clinical interaction is unlikely. CONCLUSIONS Medications that are prominent substrates for CYP2C19, CYP2C9, and CYP1A2 may be particularly at risk of altered disposition by concomitant use of cannabis or 1 or more of its constituents. Caution should also be given when coadministered drugs are metabolized by UGT or CES1, on which subject the information remains limited and further investigation is warranted. Conversely, conventional drugs with strong inhibitory or inductive effects on CYP3A4 are expected to affect CBD disposition.
Malignant catarrhal fever: an emerging yet neglected disease in captive sika deer (Cervus nippon) herds in China.

Malignant catarrhal fever (MCF) is a fatal lymphoproliferative disease that represents a serious problem in the deer-rearing industry. To better understand an MCF-like disease that has emerged in northern China since 2015, we investigated ten cases by documenting clinical and epidemiological data and analyzing causative agents and histopathological changes. In addition, a retrospective screen for Macavirus DNA and a questionnaire-based survey were conducted. Epizootic MCF in Chinese sika deer herds has emerged with a low morbidity of 3.8% (95% CI: 2.5-5.1%) and a high mortality of 93.2% (95% CI: 86.6-99.9%). The disease course varied from three to twelve days. Etiologically, OvHV-2 was predominant in the MCFV, accounting for most MCF cases (21/23). In contrast, only two CpHV-2 isolates were phylogenetically closely related to CpHV-2. Diarrhea and nasal discharges were the most frequent manifestations, although clinical signs varied in some cases. Pathologically typical lesions of hemorrhage, necrosis and lymphoid cell infiltration were readily observed in a variety of organs. Vasculitis caused by vascular and perivascular lymphoid cell infiltration was common. The retrospective survey suggested a low positive rate (3/275) of MCFV DNA in peripheral blood lymphocytes (PBL). The questionnaire-based survey suggested the disease was neglected by local veterinarians, who did not acknowledge the risk of co-rearing deer with reservoir species. Collectively, the emerging epizootic MCF in Chinese sika deer herds remains neglected, emphasizing the urgency of initiating full field diagnoses and control strategies. This article is protected by copyright. All rights reserved.
Discourse Measures to Differentiate Between Mild Cognitive Impairment and Healthy Aging

Although subtle discourse declines in people with mild cognitive impairment (MCI) have been reported, heterogeneous measures and tasks among the MCI discourse studies have yielded widely varying outcomes. The present study aimed to first, identify discourse measures that aid the differentiation among people with amnestic MCI (aMCI), people with non-amnestic MCI (naMCI), and cognitively healthy control (HC) participants, and second, delineate the cognitive functions related to such discourse measures. Three discourse tasks (an episodic narrative, a planning task, and a picture description) were performed by 30 aMCI, 22 naMCI, and 21 HC participants. Samples were analyzed using six categories of 15 measures, namely coherence, cohesion, proposition, grammaticality, lexicality, and fluency. The statistical analyses included (1) a multivariate analysis of variance for group comparison; (2) binary simple logistic regression and receiver operating characteristic curve analysis for differentiation between two groups; (3) binary multiple logistic regression for being diagnosed with naMCI or aMCI with the minimum number of predictors; and (4) Pearson correlation analysis for identifying the cognitive functions associated with the discourse measures. The proportion of cohesive words and propositional density in aMCI participants were worse than those in naMCI participants. Global coherence, the proportion of cohesive words, and the proportion of dysfluencies and pauses in naMCI participants were lower than those in the HC participants. Global and local coherence and the proportion of cohesive words, cohesive ties per utterances, propositional density, and dysfluencies and pauses in aMCI participants were worse than those in the HC participants. The aforementioned measures were demonstrated to be effective predictors for classifying groups by receiver operating characteristic curve analysis. In addition, the proportions of cohesive words and pauses were common discourse measures for differentiation between naMCI and HC participants or between aMCI and HC participants using binary multiple logistic regression. According to the correlation analysis, memory and executive functions are needed for coherent, cohesive, and efficient discourse productions in MCI. The detailed description of discourse performances in this study will aid the characterization of the declined language abilities of MCI participants and also the understanding of the cognitive functions involved in discourse performance in MCI.
Microstructural White Matter Characteristics in Parkinson's Disease With Depression: A Diffusion Tensor Imaging Replication Study

Background: Clarifying the neuropathology of depression as a symptom of Parkinson's disease (PD) has been the goal of recent neuroimaging studies; however, results have been conflicting and lack replication. The purpose of the current study was to replicate recent methods that have used diffusion tensor imaging (DTI) to compare individuals with PD with and without depression and to extend previous findings to allow for a better understanding of the results. Methods: Thirty-seven participants with de novo PD were retrieved from the Parkinson's Progression Marker's Initiative (PPMI) and were separated into a depressed PD group (dPD) or a non-depressed PD group (ndPD). Groups were determined based on scores on the Geriatric Depression Scale Short Form (GDS-15). Initially, a replicated cut off score of ≥ 5 for dPD and <5 for ndPD was applied. To better understand the results, we secondarily applied a more extreme group analysis with ≥ 9 for dPD and 0 for ndPD. White matter integrity between groups was compared between groups using tract-based spatial statistics. Results and Conclusion: The current study did not reveal significant differences in white matter microstructure between dPD and ndPD groups at the whole brain level or in specific regions of interest. The extreme group results were consistent. These findings did not replicate previous work that found reduced white matter integrity in limbic prefrontal regions in dPD relative to ndPD. The current study highlights the need for more replications of neuroimaging research.
A Tridimensional Model for NK Cell-Mediated ADCC of Follicular Lymphoma

Follicular lymphoma (FL) is the second most frequent subtype of B non-Hodgkin's lymphomas (NHL) for which the treatment is based on the use of anti-CD20 mAbs. NK cells play a crucial role in their mechanism of action and the number of these cells mediating antibody-dependent cell cycotoxicity (ADCC) in the peripheral blood of FL patients predict the outcome. However, their presence in FL biopsies, their activation and their role have been poorly investigated. Moreover, in vitro studies have not deciphered the exact signaling cascades triggered by NK cells in presence of anti-CD20 mAbs on both effector and target cells in a relevant FL model. We performed in silico analyses and ex vivo functional assays to determine the presence and the activation status of NK cells in FL biopsies. We modelized ADCC phenomenon by developing a co-culture model composed by 3D-cultured FL cells and NK cells. Thus, we investigated the biological effect of anti-CD20 mAbs by fluorescent microscopy and the phosphorylation status of survival pathways by cell bar coding phosphoflow in target cells. In parallel, we measured the status of activation of downstream FcγRIIIa signaling pathways in effector cells and their activation (CD69, perforin, granzyme B, IFNγ) by flow cytometry. We determined by in vivo experiments the effects of anti-CD20 mAbs in presence of NK cells in SCID-Beige engrafted FL mice. Here, we show that functional NK cells infiltrate FL biopsies, and that their presence tends to correlate with the survival of FL patients. Using our 3D co-culture model, we show that rituximab and GA101 are able to promote degranulation, CD69 expression, IFNγ production and activate FcγRIIIa signaling cascade in NK cells, and inhibit survival pathways and induce apoptosis in FL cells. The effect of GA101 seems to be more pronounced as observed in vivo in a xenograft FL model. This study strongly supports the role of NK cells in FL and highlights the application of the 3D co-culture model for in vitro validation.
Plasma Type I IFN Protein Concentrations in Human Tuberculosis

Tuberculosis (TB) remains one of the leading causes of mortality worldwide, and a lack of understanding of basic disease pathogenesis is hampering development of new vaccines and treatments. Multiple studies have previously established a role for type I interferon (IFN) in TB disease. Type I IFNs are critical immune mediators for host responses to viral infection, yet their specific influence in bacterial infection remains unclear. As IFN-stimulated genes (ISGs) can have both stimulatory and inhibitory effects on immune function, clarifying the role of type I interferon in TB remains an important question. The quantification of interferon proteins in the circulation of patients has been restricted until the recent development of digital ELISA. To test the hypothesis that patients with active TB disease have elevated circulating type I IFN we quantified plasma IFNα and β proteins with Simoa digital ELISA in patients with active disease and asymptomatic M. tuberculosis infection. Strikingly no differences were observed between these two groups, while plasma from acute influenza infection revealed significantly higher plasma levels of both IFNα and IFNβ proteins. These results suggest a discordance between ISG mRNA expression by blood leukocytes and circulating type I IFN in TB.
Is the re-use of sterilized implant abutments safe enough? (Implant abutment safety)

Background: The reuse of implant healing abutments is common in dental practice. Effective elimination of bacteria and viruses is accomplished by conventional sterilization. The aim of this work was to explore the eventual survival of microorganisms on sterilized healing abutments and to rule out the presence of transmissible organic material after standard procedures. Material and Methods: A total of 55 healing abutments previously used in patients will be washed and sterilized in a steam autoclave at 121ºC for 15 min. Each healing abutment will be cultured in Brain Heart Infusion broth (BHI) under strict aseptic conditions. Besides, two control groups will be included: one of 3 unused healing abutments, and the other of just medium. After 10 days at 37°C under a 5% CO2 100 µl of the broth will be plated on solid media (Brain Infusion Agar, BHIA) and Columbia Blood agar to test for sterility. The remaining volume will be centrifuged, the sediment fixed, and a Gram stain performed to discard the presence of non-cultivable microorganisms. Moreover, to determine the presence of remaining organic material after the cleaning and sterilizing treatments, the bioburden will be determined by measuring total organic carbon (TOC) in another 10 previously used healing abutments, cleaned and sterilized, that will be submerged in Milli-Q water and sonicated. Results: No bacterial growth was detected on any of the 58 cultured abutments, indicating that the sterilization was completely satisfactory in terms of removal of live bacteria or spores. Nevertheless, significant amounts of organic carbon may still be recovered (up to 125,31 µg/abutment) after they have been sterilized. Conclusions: Significant amounts of the bioburden remained adhered to the surfaces in spite of the cleaning and sterilization procedures. Taking into account our results and data from other authors, the presence of infectious particles on the reused healing abutments such as prions cannot be ruled out. Key words:Healing abutment, abutment surface, peri-implantitis, mucositis, sterilization.
Dissatisfaction about body image and associated factors: a study of young undergraduate students

ABSTRACT Objective: To verify the prevalence of dissatisfaction with body image and its association with socio-demographic, economic, and anthropometric variables, as well as levels of physical activity among undergraduate students. Methods: A cross-sectional study was conducted with 348 undergraduate students at the dining hall of a public Brazilian university located in the state of Mato Grosso do Sul. Body image perception was evaluated using the Silhouette Matching Task. The other variables assessed were sex, age, marital status, housing conditions, socioeconomic class, weight, height, waist circumference and physical activity levels. Multinomial logistic regression was performed to verify the association between the dependent and independent variables. Results: Of the interviewees, 55.7% were men. The prevalence of dissatisfaction with body image was 59.8% among men and 55.2% among women. Dissatisfaction for being overweight, between men and women, was higher in overweight individuals when compared to normal weight individuals, according to the body mass index, and also higher in those at risk for cardiovascular disease when compared to those who were not at risk. The dissatisfaction for being thin was higher among women with low weight when compared to normal weight women, according to body mass index. There was no association between dissatisfaction for being thin and the variables analyzed among men. Conclusion: The prevalence of dissatisfaction with body image was observed in more than half of the individuals evaluated and is associated with nutritional status. Knowing the consequences of dissatisfaction with body image helps highlight the need for intervention strategies to avoid the practice of unhealthy behaviors.
Specificity of Morbillivirus Hemagglutinins to Recognize SLAM of Different Species

Measles virus (MV) and canine distemper virus (CDV) are highly contagious and deadly, forming part of the morbillivirus genus. The receptor recognition by morbillivirus hemagglutinin (H) is important for determining tissue tropism and host range. Recent reports largely urge caution as regards to the potential expansion of host specificities of morbilliviruses. Nonetheless, the receptor-binding potential in different species of morbillivirus H proteins is largely unknown. Herein, we show that the CDV-H protein binds to the dog signaling lymphocyte activation molecule (SLAM), but not to the human, tamarin, or mouse SLAM. In contrast, MV-H can bind to human, tamarin and dog SLAM, but not to that of mice. Notably, MV binding to dog SLAM showed a lower affinity and faster kinetics than that of human SLAM, and MV exhibits a similar entry activity in dog SLAM- and human SLAM-expressing Vero cells. The mutagenesis study using a fusion assay, based on the MV-H–SLAM complex structure, revealed differences in tolerance for the receptor specificity between MV-H and CDV-H. These results provide insights into H-SLAM specificity related to potential host expansion.
Real-Time Photometric Calibrated Monocular Direct Visual SLAM

To solve the illumination sensitivity problems of mobile ground equipment, an enhanced visual SLAM algorithm based on the sparse direct method was proposed in this paper. Firstly, the vignette and response functions of the input sequences were optimized based on the photometric formation of the camera. Secondly, the Shi–Tomasi corners of the input sequence were tracked, and optimization equations were established using the pixel tracking of sparse direct visual odometry (VO). Thirdly, the Levenberg–Marquardt (L–M) method was applied to solve the joint optimization equation, and the photometric calibration parameters in the VO were updated to realize the real-time dynamic compensation of the exposure of the input sequences, which reduced the effects of the light variations on SLAM’s (simultaneous localization and mapping) accuracy and robustness. Finally, a Shi–Tomasi corner filtered strategy was designed to reduce the computational complexity of the proposed algorithm, and the loop closure detection was realized based on the oriented FAST and rotated BRIEF (ORB) features. The proposed algorithm was tested using TUM, KITTI, EuRoC, and an actual environment, and the experimental results show that the positioning and mapping performance of the proposed algorithm is promising.
Fluorescence enhancement of monodisperse carbon nanodots treated with aqueous ammonia and hydrogen peroxide

The treatment of monodisperse carbon nanodots (MCNDs) with a combination of aqueous ammonia and hydrogen peroxide is found to result in a prominent enhancement of their fluorescence efficiency. Depending on the hydrogen peroxide concentration, an increase of the MCNDs quantum yield of up to seven-fold has been achieved. Considering the absence of prominent changes in fluorescence lifetime and fluorescence spectra upon the treatment it is suggested that the observed rise of fluorescence efficiency originates from additional formation of new isolated sp2 domains surrounded by defect sites. The structural modification of MCNDs induced by their treatment with combination of aqueous ammonia and hydrogen peroxide is indicated by both transmission electron microscopy images and infrared spectra. The applied method has insignificant effect on the aggregation properties and size distribution of the studied MCNDs. Taking into account the proposed mechanism, the applied treatment procedure can serve as a basis for a facile approach for modification of emissive properties of various nanocarbon structures.
The TOR pathway modulates cytoophidium formation in Schizosaccharomyces pombe

CTP synthase (CTPS) has been demonstrated to form evolutionarily-conserved filamentous structures termed cytoophidia whose exact cellular functions remain unclear, but they may play a role in intracellular compartmentalization. We have previously shown that the mammalian target of rapamycin complex 1 (mTORC1)–S6K1 pathway mediates cytoophidium assembly in mammalian cells. Here, using the fission yeast Schizosaccharomyces pombe as a model of a unicellular eukaryote, we demonstrate that the target of rapamycin (TOR)-signaling pathway regulates cytoophidium formation (from the S. pombe CTPS ortholog Cts1) also in S. pombe. Conducting a systematic analysis of all viable single TOR subunit–knockout mutants and of several major downstream effector proteins, we found that Cts1 cytoophidia are significantly shortened and often dissociate when TOR is defective. We also found that the activities of the downstream effector kinases of the TORC1 pathway, Sck1, Sck2, and Psk1 S6, as well as of the S6K/AGC kinase Gad8, the major downstream effector kinase of the TORC2 pathway, are necessary for proper cytoophidium filament formation. Interestingly, we observed that the Crf1 transcriptional corepressor for ribosomal genes is a strong effector of Cts1 filamentation. Our findings connect TOR signaling, a major pathway required for cell growth, with the compartmentalization of the essential nucleotide synthesis enzyme CTPS, and we uncover differences in the regulation of its filamentation among higher multicellular and unicellular eukaryotic systems.