Miracle-dz/UniFAR-FTUs huggingface dataset:
Anti-inflammatory effects of a novel iron chelator, DIBI, in experimental sepsis.

BACKGROUND Iron catalyzes the generation of reactive oxygen species (ROS) as part of the innate antimicrobial defense. During sepsis, the dysregulated systemic inflammatory response to infection, iron homeostasis becomes disrupted, generating an excess of ROS causing damage to tissues. This can be potentially suppressed using iron chelators that selectively bind iron to prevent its participation in ROS-related inflammatory reactions. OBJECTIVE We hypothesize that administration of DIBI, a novel iron-chelator, attenuates the dysregulated systemic immune response and reduces tissue damage in experimental endotoxemia. METHODS Five groups of animals (n = 5-10) were included in this study: control, untreated endotoxemia, and endotoxemia animals treated with either DIBI-A, MAHMP, or DIBI-B. Intravital microscopy was performed on the intestine of anesthesized mice to observe leukocyte endothelial interactions and evaluate the intestinal microcirculation. RESULTS Treatment of endotoxemic mice with DIBI-B reduced the number of adhering leukocytes in submucosal collecting (V1) venules by 68%. DIBI-B, MAHMP, and DIBI-A were able to restore functional capillary density (FCD) in the intestinal muscle layer by 74%, 44%, and 11%, respectively. CONCLUSIONS DIBI-B reduces leukocyte recruitment and improves FCD in experimental endotoxemia, outperforming other chelators tested. These findings suggest a potential role for DIBI-B as a candidate drug for sepsis treatment.
Low Energy Turnover of Physically Inactive Participants as a Determinant of Insufficient Mineral and Vitamin Intake in NHANES

Micronutrient requirements do not scale linearly with physical activity-related energy expenditure (AEE). Inactive persons may have insufficient micronutrient intake because of low energy intake (EI). We extracted data from NHANES 2003–2006 on 4015 adults (53 ± 18 years (mean ± SD), 29 ± 6 kg/m2, 48% women) with valid physical activity (accelerometry) and food intake (2 × 24 h-dietary recall) measures. Total energy expenditure (TEE) was estimated by summing the basal metabolic rate (BMR, Harris-Benedict), AEE, and 10% of TEE for the thermic effect of food, to calculate the physical activity levels (PAL = TEE/BMR). Energy intake (EI) was scaled to match TEE assuming energy balance. Adjusted food intake was then analyzed for energy and micronutrient content and compared to estimated average requirements. The NHANES population was physically insufficiently active. There were 2440 inactive (PAL < 1.4), 1469 lightly to moderately active (PAL1.4 < 1.7), 94 sufficiently active (PAL1.7 < 2.0), and 12 very active participants (PAL ≥ 2.0). The inactive vs. active had significantly lower intake for all micronutrients apart from vitamin A, B12, C, K, and copper (p < 0.05). The inactive participants had insufficient intake for 6/19 micronutrients, while the active participants had insufficient intake for 5/19 (p < 0.05) micronutrients. Multiple linear regression indicated a lower risk for insufficient micronutrient intake for participants with higher PAL and BMI (p < 0.001). Symmetrical up-scaling of PAL and EI to recommended physical activity levels reduced the frequency of micronutrient insufficiencies. It follows that prevalence of insufficient micronutrient intake from food in NHANES might be partly determined by low energy turnover from insufficient PAL.
Impedance Measures During in vitro Cochlear Implantation Predict Array Positioning

Objective: Improper electrode placement during cochlear implant (CI) insertion can adversely affect speech perception outcomes. However, the intraoperative methods to determine positioning are limited. Because measures of electrode impedance can be made quickly, the goal of this study was to assess the relationship between CI impedance and proximity to adjacent structures. Methods: An Advanced Bionics CI array was inserted into a clear, plastic cochlea one electrode contact at a time in a saline bath (nine trials). At each insertion depth, response to biphasic current pulses was used to calculate access resistance (Ra), polarization resistance (Rp), and polarization capacitance (Cp). These measures were correlated to actual proximity as assessed by microscopy using linear regression models. Results: Impedance increased with insertion depth and proximity to the inner wall. Specifically, Ra increased, Cp decreased, and Rp slightly increased. Incorporating all impedance measures afforded a prediction model (r = 0.88) while optimizing for sub-mm positioning afforded a model with 78.3% specificity. Conclusion: Impedance in vitro greatly changes with electrode insertion depth and proximity to adjacent structures in a predicable manner. Significance : Assessing proximity of the CI to adjacent structures is a significant first step in qualifying the electrode-neural interface. This information should aid in CI fitting, which should help maximize hearing and speech outcomes with a CI. Additionally, knowledge of the relationship between impedance and positioning could have utility in other tissue implants in the brain, retina, or spinal cord.
Emerging roles of innate lymphoid cells in inflammatory diseases: Clinical implications

Innate lymphoid cells (ILC) represent a group of lymphocytes that lack specific antigen receptors and are relatively rare as compared to adaptive lymphocytes. ILCs play important roles in allergic and nonallergic inflammatory diseases due to their location at barrier surfaces within the airways, gut, and skin, and they respond to cytokines produced by activated cells in their local environment. Innate lymphoid cells contribute to the immune response by the release of cytokines and other mediators, forming a link between innate and adaptive immunity. In recent years, these cells have been extensively characterized and their role in animal models of disease has been investigated. Data to translate the relevance of ILCs in human pathology, and the potential role of ILCs in diagnosis, as biomarkers and/or as future treatment targets are also emerging. This review, produced by a task force of the Immunology Section of the European Academy of Allergy and Clinical Immunology (EAACI), encompassing clinicians and researchers, highlights the role of ILCs in human allergic and nonallergic diseases in the airways, gastrointestinal tract, and skin, with a focus on new insights into clinical implications, therapeutic options, and future research opportunities.
Effects of Commercial Apple Varieties on Human Gut Microbiota Composition and Metabolic Output Using an In Vitro Colonic Model

Apples are a rich source of polyphenols and fiber. A major proportion of apple polyphenols escape absorption in the small intestine and together with non-digestible polysaccharides reach the colon, where they can serve as substrates for bacterial fermentation. Animal studies suggest a synergistic interaction between apple polyphenols and the soluble fiber pectin; however, the effects of whole apples on human gut microbiota are less extensively studied. Three commercial apple varieties—Renetta Canada, Golden Delicious and Pink Lady—were digested and fermented in vitro using a batch culture colonic model (pH 5.5–6.0, 37 °C) inoculated with feces from three healthy donors. Inulin and cellulose were used as a readily and a poorly fermentable plant fiber, respectively. Fecal microbiota composition was measured by 16S rRNA gene Illumina MiSeq sequencing (V3-V4 region) and Fluorescence in Situ Hybridization. Short chain fatty acids (SCFAs) and polyphenol microbial metabolites were determined. The three apple varieties significantly changed bacterial diversity, increased Actinobacteria relative abundance, acetate, propionate and total SCFAs (p < 0.05). Renetta Canada and Golden Delicious significantly decreased Bacteroidetes abundance and increased Proteobacteria proportion and bifidobacteria population (p < 0.05). Renetta Canada also increased Faecalibacterium prausnitzii, butyrate levels and polyphenol microbial metabolites (p < 0.05). Together, these data suggest that apples, particularly Renetta Canada, can induce substantial changes in microbiota composition and metabolic activity in vitro, which could be associated with potential benefits to human health. Human intervention studies are necessary to confirm these data and potential beneficial effects.
Comment on Amézquita et al. (2017) “Conspicuousness, color resemblance, and toxicity in geographically diverging mimicry: The pan‐Amazonian frog Allobates femoralis”

Amézquita et al. (2017) recently concluded that species of the Allobates femoralis group are toxic to mice at levels equivalent to syntopic alkaloid‐containing poison frogs, which they attributed to the presence of alkaloids in skin secretions. However, the chemical composition of skin secretions was not analyzed, and here we present additional data supporting the absence of alkaloids in skin secretions of the Allobates femoralis group. Instead, we suggest the observed toxicity was caused by the anesthetic benzocaine, which was applied to the buccal cavity to euthanize frogs prior to skin removal. We show that orally administered benzocaine is rapidly incorporated into the skin of species that sequester and do not sequester alkaloids, which casts doubt on the conclusion that Allobates femoralis group skin secretions are toxic and makes the results of experiments with alkaloid‐containing species of Adelphobates and Ameerega uninterpretable. To prevent experimental errors and misinterpretations in studies of amphibian chemical defense, we encourage researchers to test the chemical composition of samples prior to experimentation, include all necessary controls to detect false positives, conduct small pilot studies for new methods, and consider the limitations of particular methods and their ability to address the intended research questions.
Oral morphosyntactic competence as a predictor of reading comprehension in children with specific language impairment.

BACKGROUND Children with a diagnosis of specific language impairment (SLI) present impaired oral comprehension. According to the simple view of reading, general amodal linguistic capacity accounts for both oral and reading comprehension. Considering this, we should expect SLI children to display a reading comprehension deficit. However, previous research regarding the association between reading disorders and SLI has yielded inconsistent results. AIMS To study the influence of prior oral comprehension competence over reading comprehension during the first years of reading acquisition of bilingual Catalan-Spanish children with SLI (ages 7-8). METHODS & PROCEDURES We assessed groups of bilingual Catalan-Spanish SLI and matched control children at ages 7 and 8 with standardized reading comprehension tasks including grammatical structures, sentence and text comprehension. Early oral competence and prior non-verbal intelligence were also measured and introduced into regression analyses with the participants' reading results in order to state the relation between the comprehension of oral and written material. OUTCOMES & RESULTS Although we found no significant differences between the scores of our two participant groups in the reading tasks, data regarding their early oral competence, but not non-verbal intelligence measures, significantly influence their reading outcome. CONCLUSIONS & IMPLICATIONS The results extend our knowledge regarding the course of literacy acquisition of children with SLI and provide evidence in support of the theories that assume common linguistic processes to be responsible for both oral and reading comprehension.
Are shoulder counter rotation and hip shoulder separation angle representative metrics of three-dimensional spinal kinematics in cricket fast bowling?

ABSTRACT This study aimed to investigate the relationship between shoulder counter-rotation (SCR), hip shoulder separation (HSS) and three-dimensional spinal kinematics during fast bowling in cricket. Thirty five elite male fast bowlers were analysed using three-dimensional inertial sensors on the spine. Lumbar, thoracic and thoracolumbar kinematics were determined during the delivery stride. Spearman’s pairwise correlations displayed significant associations between SCR, thoracic and thoracolumbar lateral flexion between the back foot impact and max contralateral rotation phase of the delivery stride (rs = −.462 and −.460). HSS and thoracolumbar lateral flexion displayed a significant correlation between back foot impact and max contralateral rotation (rs = −.552). No other significant correlations were observed. These results suggest SCR and HSS are modestly related to lateral flexion, leaving a large component of SCR and HSS unrelated to specific three-dimensional spinal kinematics. It is possible that this represents changes in whole spinal orientation and not resultant spinal motion. Despite this, SCR remains the only metric currently related to injury and therefore is important; however it is only a very modest proxy for more traditional descriptions of spinal motion.
Bone marrow mesenchymal stem cell-derived extracellular vesicles improve the survival of transplanted fat grafts

Autologous fat grafting is a promising surgical technique for soft tissue augmentation, reconstruction and rejuvenation. However, it is limited by the low survival rate of the transplanted fat, due to the slow revascularization of such grafts. Previous studies have demonstrated that bone marrow mesenchymal stem cell-derived extracellular vesicles (BMSC-EVs) are proangiogenic. The present study aimed to investigate whether BMSC-EVs could improve the survival of transplanted fat grafts. Extracellular vesicles were isolated from the supernatant of cultured rat bone marrow mesenchymal stem cells, and characterized by flow cytometry and scanning electron microscopy. Their proangiogenic potential was measured in vitro using tube formation and cell migration assays. Subsequently, human fat tissue grafts, alongside various concentrations of BMSC-EVs, were subcutaneously injected into nude mice. A total of 12 weeks following transplantation, the mice were sacrificed and the grafts were harvested. The grafts from the experimental group had a higher survival rate and an increased number of vessels compared with grafts from the control group, as demonstrated by tissue volume, weight and histological analyses. Reverse transcription-quantitative polymerase chain reaction analysis indicated that the expression levels of proangiogenic factors were increased in the experimental group compared with in the control group, thus suggesting that BMSC-EVs may promote neovascularization by stimulating the secretion of proangiogenic factors. The present study is the first, to the best of our knowledge, to demonstrate that supplementation of fat grafts with BMSC-EVs improves the long-term retention and quality of transplanted fat.
Localization of Felis catus Papillomavirus Type 2 E6 and E7 RNA in Feline Cutaneous Squamous Cell Carcinoma

Findings from polymerase chain reaction–based methods have suggested a role of Felis catus papillomavirus 2 (FcaPV-2) in the development of feline cutaneous squamous cell carcinoma (SCC). However, because polymerase chain reaction cannot localize deoxyribonucleic acid or ribonucleic acid within the lesion, it is difficult to differentiate a coincidental FcaPV-2 infection and a causative association. Given that a key event in the pathogenesis of human papillomavirus–induced cancer is the expression of viral E6 and E7 oncogenes, localization of FcaPV-2 E6 and E7 transcription within neoplastic cells in feline SCCs would support a causative role for this papillomavirus. Therefore, RNAscope in situ hybridization was used to localize FcaPV-2 E6 and E7 transcripts in 18 formalin-fixed paraffin-embedded samples of cutaneous SCC. Positive signals were present within 5 of 9 samples (56%) from ultraviolet-protected sites and 0 of 9 samples from ultraviolet-exposed sites. In the 4 in situ hybridization–positive samples that contained adjacent hyperplastic skin, hybridization patterns in these regions were characterized by intense nuclear signals within the superficial epidermis and punctate signals within the basal epithelial layers. However, within the 5 SCCs, punctate signals were present within all layers of the epidermis, with progressive loss of intense nuclear signals within the superficial epidermis. This hybridization pattern is consistent with unregulated E6 and E7 transcription and decreased viral replication and is similar to the pattern observed in human papillomavirus–induced cancers as they progress from hyperplastic lesions containing productive infections to nonproductive neoplasms. These findings support a causative role for FcaPV-2 in the pathogenesis of feline SCC.
Improved safety margin for embryotoxicity in rats for the new endoperoxide artefenomel (OZ439) as compared to artesunate.

BACKGROUND Combination medicines including an artemisinin are the mainstay of antimalarial therapy. Artemisinins are potent embryotoxicants in animal species due to their trioxane moiety. METHODS As part of its development, the new synthetic trioxolane antimalarial artefenomel (OZ439) was tested in rat whole embryo culture and in rat embryo-fetal toxicity studies with dosing throughout organogenesis or with a single dose on Gestational Day (GD) 12. The single-dose studies included groups treated with artesunate to allow a direct comparison of the embryotoxicity of the two antimalarials and included toxicokinetics hematology and histological examination of embryos. In addition, the distribution of artefenomel-related material in plasma was determined after the administration of 14 C-artefenomel. RESULTS Artefenomel and artesunate showed similar patterns of embryotoxicity including cardiovascular defects and resorption with a steep dose-response. They both also caused a depletion of circulating embryonic erythroblasts both in vitro and in vivo and decreases in maternal reticulocyte count. However, artefenomel was ∼250-fold less potent than the active metabolite of artesunate (dihydroartemisinin) as an embryotoxicant in vitro. The safety margin (based on AUC) for artefenomel administered on GD 12 was approximately 100-fold greater than that for artesunate. Also, unlike artesunate, artefenomel was not a selective developmental toxicant. CONCLUSIONS The lesser embryotoxicity of artefenomel is likely linked to its original design which included two blocking side groups that had been introduced to lower the reactivity with ferrous iron. Our data support the hypothesis that artefenomel's improved safety margin is linked to a lower potential for inhibiting heme biosynthesis in embryonic erythroblasts.
The cancer-testis antigen, sperm protein 17, a new biomarker and immunological target in head and neck squamous cell carcinoma

Head and Neck Squamous Cell Carcinoma is a deadly and locally aggressive malignancy that frequently portends a poor prognosis. Since current treatment modalities including surgery, chemotherapy and radiation are heavily debilitating and often result in recurrence intense efforts have been put into the development of novel less toxic and more lasting treatment strategies. Recently, immunotherapy has been proposed as a promising alternative that could potentially meet these requirements. SP17 is a validated cancer-testis antigen in multiple myeloma, ovarian cancer and non-small cell lung cancer. We aim at studying SP17 expression in HNSCC and its immunogenicity as a possible future target for HNSCC therapeutic vaccines. SP17 expression was evaluated in tissue specimens of HNSCC patients and controls. Moreover, SP17 immunogenicity was studied by generating autologous dendritic cells in vitro from the peripheral blood mononucleated cells of HNSCC patients and testing their ability to induce SP17 specific cytotoxic lymphocytes capable of killing autologous tumor cells in vitro. SP17specific immune responses were also evaluated in HNSCC patients as circulating anti-SP17 autoantibodies. SP17 was expressed in HNSCC tissues of HNSCC patients. Autologous dendritic cells pulsed with SP17 antigen induced powerful SP17 MHC class-I restricted, perforin-dependent, cytotoxic T-cells capable of efficiently killing autologous tumor cells in vitro. SP17-specific autoantibodies were detectable in the serum of HNSCC patients irrespective of tumor site or TNM stage. In conclusion, SP17 is an ideal immunotherapeutic target for HNSCC and a potential serological biomarker of the disease.
Listeriolysin S: A bacteriocin from epidemic Listeria monocytogenes strains that targets the gut microbiota

ABSTRACT Listeria monocytogenes is a Gram-positive food-borne pathogen that in humans may traverse the intestinal, placental and blood/brain barriers, causing gastroenteritis, abortions and meningitis. Crossing of these barriers is dependent on the bacterial ability to enter host cells, and several L. monocytogenes surface and secreted virulence factors are known to facilitate entry and the intracellular lifecycle. The study of L. monocytogenes strains associated to human listeriosis epidemics has revealed the presence of novel virulence factors. One such factor is Listeriolysin S, a thiazole/oxazole modified microcin that displays bactericidal activity and modifies the host microbiota during infection. Our recent results therefore highlight the interaction of L. monocytogenes with gut microbes as a crucial step in epidemic listeriosis. In this article, we will discuss novel implications for this family of toxins in the pathogenesis of diverse medically relevant microorganisms.
Fundamental studies on contrast resolution of ultrasound B-mode images

Fundamental Studies on Contrast Resolution of Ultrasound B-mode Images Pinar Crombie, Ph.D. 1999 Institute of Biomaterials and Biomedical Engineering Department of Electrical and Computer Engineering, University of Toronto The primary objective of this thesis is to study the factors that affect the contrast resolution of ultrasound B-mode images. A cornputer simulation model of B-mode image formation has been developed and validated. The model simulates bearn profiles fiom linear, 1.5-D and curvilinear arrays. An initial study was perforrned to compare the accuracy and computational efficiency of different methods that have been used to calculate the field profile fÎom linear arrays. It was concluded that the far-field approximation for the impulse response method yields the best trade-off between accuracy and efficiency. The model was used to investigate the effects of transducer design, and tissue parameters on the image characteristics, specifically, texture and contrast resolution. It was shown that the scatterer distribution, as well as the transducer geometry, determines the testural appearance and the contrast of an image. It was also demonstrated that postprocessing schemes can significantly alter the image appearance by changing the mean signal levels and speckle statistics. The simulation model can be used to predict optimum values for the parameters used in post-processing algorithms. Different measures of contrast resolution were exarnined, and it was concluded that the contrast-to-speckle ratio is the most accurate measure in defining an imaging system's ability to detect lowcontrast targets in background speckle noise. In order to illustrate the clinical application of the model, a simple, approximate model of a carotid artery wall with fatty plaque was developed and a preliminary study was performed to analyze the B-mode image of this geometry. The simulated image indicates that the wall region is more echogenic than the plaque region as is the case in clinical images. The image aiso reveals sharp reflection signals at the wall-plaque, and plaque-lumen interfaces. It was shown that the signal levels at these interfaces depend on the backscattenng coefficients and the distributions of the scatterers in the neighbouring