Miracle-dz/UniFAR-FTUs huggingface dataset:
Metformin as additional therapy in adolescents with poorly controlled type 1 diabetes: randomised placebo-controlled trial with aspects on insulin sensitivity.

OBJECTIVE Metabolic control often deteriorates during puberty in children with type 1 diabetes. The aim of the present study was to investigate whether addition of metformin for 3 Months improves metabolic control and insulin sensitivity. DESIGN Twenty-six of 30 randomised adolescents with type 1 diabetes (18 females, eight males) completed a double-blind placebo-controlled trial. Their mean age was 16.9+/-1.6 (s.d.) Years, mean glycated haemoglobin (HbA(1c)) 9.5+/-1.1% and daily insulin dosage 1.2+/-0.3 U/kg. The participants were randomised to receive oral metformin or placebo for 3 Months. HbA(1c) was measured Monthly, and peripheral insulin sensitivity was assessed by a euglycaemic hyperinsulinaemic clamp at baseline and at the end of the study. RESULTS HbA(1c) decreased significantly in the group treated with metformin, from 9.6 to 8.7% (P<0.05), but was unchanged in the placebo group (9.5 vs 9.2%). Peripheral glucose uptake divided by mean plasma insulin concentration was increased in the metformin group (P<0.05) but not in the placebo group. Initial insulin sensitivity was inversely correlated to changes in HbA(1c) (r=-0.62; P<0.05) and positively correlated to changes in insulin sensitivity (r=0.77; P<0.01). CONCLUSIONS In this double-blind placebo-controlled study we found that metformin improves metabolic control in adolescents with type 1 diabetes. The effect seems to be associated with an increased insulin-induced glucose uptake.
Effects of Liposomes Contained in Thermosensitive Hydrogels as Biomaterials Useful in Neural Tissue Engineering

Advances in the generation of suitable thermosensitive hydrogels for the delivery of cells in neural tissue engineering demonstrate a delicate relationship between physical properties and capabilities to promote cell proliferation and differentiation. To improve the properties of these materials, it is possible to add liposomes for the controlled release of bioactive elements, which in turn can affect the physical and biological properties of the hydrogels. In the present investigation, different hydrogels based on Pluronic F127 have been formulated with the incorporation of chitosan and two types of liposomes of two different sizes. The rheological and thermal properties and their relation with the neurite proliferation and growth of the PC12 cell line were evaluated. Our results show that the incorporation of liposomes modifies the properties of the hydrogels dependent on the concentration of chitosan and the lipid type in the liposomes, which directly affect the capabilities of the hydrogels to promote the viability and differentiation of PC12 cells.
The Use of Botulinum Toxin in Strabismus Treatment

ABSTRACT There is a long and extensive experience with the use of Botulinum Toxin type A (BoNT-A) injection in the treatment of different types of strabismus and oculomotor palsies. The frequency of its use varies depending on the country and institution. It is a short procedure, may reduce general anesthesia exposure, causes minimal scarring compared to surgery, and can be proposed as an early treatment in unstable strabismus. Over many years, the experience of using BoNT-A indications has been refined and new applications have been reported. The use of BoNT-A in the postoperative period, after strabismus surgery or during surgery, can also be beneficial.
Solithromycin Pharmacokinetics in Plasma and Dried Blood Spots and Safety in Adolescents

ABSTRACT We assessed the pharmacokinetics and safety of solithromycin, a fluoroketolide antibiotic, in a phase 1, open-label, multicenter study of 13 adolescents with suspected or confirmed bacterial infections. On days 3 to 5, the mean (standard deviation) maximum plasma concentration and area under the concentration versus time curve from 0 to 24 h were 0.74 μg/ml (0.61 μg/ml) and 9.28 μg · h/ml (6.30 μg · h/ml), respectively. The exposure and safety in this small cohort of adolescents were comparable to those for adults. (This study has been registered at ClinicalTrials.gov under registration no. NCT01966055.)
Attenuation of pentylenetrazole-induced acute status epilepticus in rats by adenosine involves inhibition of the mammalian target of rapamycin pathway

Adenosine (ADO) has been characterized as an endogenous anticonvulsant and alternative therapeutic drug, but its mechanism is not entirely clear. This study aimed to examine the relationship of ADO with the mammalian target of rapamycin (mTOR) in a Wistar rat model of pentylenetetrazole (PTZ)-induced acute status epilepticus. ADO (200 mg/kg) was administered intraperitoneally 30 min before PTZ (55–65 mg/kg) treatment, and Western blot assays and immunohistochemistry were performed 3 h after the onset of acute status epilepticus to detect phospho-TOR and the downstream target of mTOR, phospho-S6. The expression of these phosphoproteins in the hippocampus was significantly increased in PTZ-treated rats, but this increase was attenuated by the addition of ADO. To further verify a role for ADO in attenuating mTOR activity, we also evaluated its ability to suppress mTOR activity in normal rats that were not treated with PTZ. Our results suggest that ADO suppresses mTOR and S6 phosphorylation in normal rats and that this suppression can be reversed by the application of Compound C, an inhibitor of AMP-activated protein kinase, which functions as an upstream suppressor of the mTOR pathway. Thus, our results provide a novel antiepileptic mechanism for ADO in suppressing mTOR pathway activation upon PTZ-induced acute status epilepticus.
Quantification of in Vivo Colonic Short Chain Fatty Acid Production from Inulin

Short chain fatty acids (SCFA), including acetate, propionate, and butyrate, are produced during bacterial fermentation of undigested carbohydrates in the human colon. In this study, we applied a stable-isotope dilution method to quantify the in vivo colonic production of SCFA in healthy humans after consumption of inulin. Twelve healthy subjects performed a test day during which a primed continuous intravenous infusion with [1-13C]acetate, [1-13C]propionate and [1-13C]butyrate (12, 1.2 and 0.6 μmol·kg−1·min−1, respectively) was applied. They consumed 15 g of inulin with a standard breakfast. Breath and blood samples were collected at regular times during the day over a 12 h period. The endogenous rate of appearance of acetate, propionate, and butyrate was 13.3 ± 4.8, 0.27 ± 0.09, and 0.28 ± 0.12 μmol·kg−1·min−1, respectively. Colonic inulin fermentation was estimated to be 137 ± 75 mmol acetate, 11 ± 9 mmol propionate, and 20 ± 17 mmol butyrate over 12 h, assuming that 40%, 10%, and 5% of colonic derived acetate, propionate, and butyrate enter the systemic circulation. In conclusion, inulin is mainly fermented into acetate and, to lesser extents, into butyrate and propionate. Stable isotope technology allows quantifying the production of the three main SCFA in vivo and proved to be a practical tool to investigate the extent and pattern of SCFA production.
Oral Squamous Cell Carcinomas are Associated with Poorer Outcome with Increasing Ages.

Objectives 1.1. Although oral cancers traditionally occur in people between the age of 50 and 70, there are increasing incidences of this disease in younger and very old people. Objectives: to compare the demographics, habits, clinicopathological features, treatment and outcome of oral cancer in three age groups of patients: Young (≤ 45), Traditional (46 to 75), and Old (> 75). Subjects 1.2. Primary oral cancers (393 patients) in a longitudinal study were used. Results 1.3. Significant differences were noted in ethnicity (fewer Caucasian patients in Young), tobacco habit (more non-smokers in Young), location of cancer (more at tongue for Young and more at low-risk sites for Old) and treatment (more surgery for Young). Compared to Young (univariate analysis), Traditional and Old showed a 3- and 4.5-fold increase in local recurrences respectively; 1.9- and 2.7-fold increase in regional metastasis; 3.1- and 5.4-fold increase in death due to disease; and a 3.4- and 6.6-fold decrease in overall survival. Compared to Young (multivariate analysis), Traditional and Old showed a 2.4- and 3.3-fold increase in local recurrence; 2.7- and 5.4-fold increase in disease-specific survival; and 2.8- and 6.5-fold decrease in overall survival. Conclusion 1.4. Oral cancer in different age groups showed differing ethnicity, habit, location, treatment and outcome.
Evaluation of body composition monitoring for assessment of nutritional status in hemodialysis patients

Abstract Background: Body composition monitoring is the only clinically available method for distinguishing among the three body components. This study aimed to determine the relationship between body composition and all-cause mortality in Chinese hemodialysis patients and examine whether the lean tissue index (LTI) derived from body composition monitoring can accurately diagnose malnourished patients. Methods: Hemodialysis patients (n = 123) with nutritional and body composition assessment records in 2015 were examined. Body composition was assessed using a body composition monitor machine. Results: Fifty-seven patients (46.3%) had low LTI (LTI less than the 10th percentile of the respective normal distribution). Significant differences in the fat tissue index (FTI) were observed, with the low LTI group having a higher FTI (10.8 kg/m2 vs. 9.0 kg/m2, p= .007). The kappa coefficient of agreement between LTI and subjective global assessment (SGA) was 0.26 for the presence of malnutrition. During the mean observation period of 26.7 months, 20 of 123 (16.3%) patients died. Low LTI remained highly predictive of survival in the Cox regression analysis (hazard ratio: 3.24, 95% confidence interval 1.06–9.91, p= .04). Malnourishment defined by SGA predicted survival in the Kaplan–Meier analysis (log-rank χ2=4.05; p= .04) but not in the multivariate analysis. Conclusions: LTI is a predictor of mortality, and its predictive power was not affected when FTI, SGA, and hydration status were included in the multivariate analysis. However, SGA may not be adequate to identify patients at a risk of death among Chinese hemodialysis patients.
FtsZ from Divergent Foreign Bacteria Can Function for Cell Division in Escherichia coli

ABSTRACT FtsZs from Mycoplasma pulmonis (MpuFtsZ) and Bacillus subtilis (BsFtsZ) are only 46% and 53% identical in amino acid sequence to FtsZ from Escherichia coli (EcFtsZ). In the present study we show that MpuFtsZ and BsFtsZ can function for cell division in E. coli provided we make two modifications. First, we replaced their C-terminal tails with that from E. coli, giving the foreign FtsZ the binding site for E. coli FtsA and ZipA. Second, we selected for mutations in the E. coli genome that facilitated division by the foreign FtsZs. These suppressor strains arose at a relatively high frequency of 10−3 to 10−5, suggesting that they involve loss-of-function mutations in multigene pathways. These pathways may be negative regulators of FtsZ or structural pathways that facilitate division by slightly defective FtsZ. Related suppressor strains were obtained for EcFtsZ containing certain point mutations or insertions of yellow fluorescent protein. The ability of highly divergent FtsZs to function for division in E. coli is consistent with a two-part mechanism. FtsZ assembles the Z ring, and perhaps generates the constriction force, through self interactions; the downstream division proteins remodel the peptidoglycan wall by interacting with each other and the wall. The C-terminal peptide of FtsZ, which binds FtsA, provides the link between FtsZ assembly and peptidoglycan remodeling.
Mitogen-activated protein kinase kinase signaling promotes growth and vascularization of fibrosarcoma

We hypothesized that signaling through multiple mitogen-activated protein kinase (MAPK) kinase (MKK) pathways is essential for the growth and vascularization of soft-tissue sarcomas, which are malignant tumors derived from mesenchymal tissues. We tested this using HT-1080, NCI, and Shac fibrosarcoma-derived cell lines and anthrax lethal toxin (LeTx), a bacterial toxin that inactivates MKKs. Western blots confirmed that LeTx treatment reduced the levels of phosphorylated extracellular signal-regulated kinase and p38 MAPK in vitro. Although short treatments with LeTx only modestly affected cell proliferation, sustained treatment markedly reduced cell numbers. LeTx also substantially inhibited the extracellular release of angioproliferative factors including vascular endothelial growth factor, interleukin-8, and basic fibroblast growth factor. Similar results were obtained with cell lines derived from malignant fibrous histiocytomas, leiomyosarcomas, and liposarcomas. In vivo, LeTx decreased MAPK activity and blocked fibrosarcoma growth. Growth inhibition correlated with decreased cellular proliferation and extensive necrosis, and it was accompanied by a decrease in tumor mean vessel density as well as a reduction in serum expression of angioproliferative cytokines. Vital imaging using high-resolution ultrasound enhanced with contrast microbubbles revealed that the effects of LeTx on tumor perfusion were remarkably rapid (<24 h) and resulted in a marked reduction of perfusion within the tumor but not in nontumor tissues. These results are consistent with our initial hypothesis and lead us to propose that MKK inhibition by LeTx is a broadly effective strategy for targeting neovascularization in fibrosarcomas and other similar proliferative lesions. [Mol Cancer Ther 2008;7(3):648–58]
TLR7 Is Involved in Sequence-Specific Sensing of Single-Stranded RNAs in Human Macrophages1

Human TLR7 and 8 (hTLR7/8) have been implicated in the sequence-dependent detection of RNA oligonucleotides in immune cells. Although hTLR7 sequence-specific sensing of short RNAs has been inferred from studies of murine TLR7, this has yet to be established for hTLR7. We found that different short ssRNA sequences selectively induced either TNF-α or IFN-α in human PBMCs. The sequence-specific TNF-α response to ssRNAs observed in PBMCs could be replicated in activated human macrophage-like (THP-1) cells pretreated with IFN-γ. Surprisingly, suppression of hTLR7 expression by RNA interference in this model reduced sensing of all immunostimulatory ssRNAs tested. Modulation of the relative expression ratio of hTLR7 to hTLR8 in THP-1 cells correlated with differential sensing of immunostimulatory sequences. Furthermore, the sequence-specific IFN-α induction profile in human PBMCs was accurately modeled by a sequence-specific activation of murine TLR7 in mouse macrophages. Thus, we demonstrate for the first time that hTLR7 is involved in sequence-specific sensing of ssRNAs. We establish a novel cell model for the prediction of TNF-α induction by short RNAs in human macrophages. Our results suggest that differential sequence-specific sensing of RNA oligonucleotides between human and mouse macrophages is due to the modulation of TLR7 sensing by human TLR8.
Role of calnexin in the glycan‐independent quality control of proteolipid protein

The endoplasmic (ER) quality control apparatus ensures that misfolded or unassembled proteins are not deployed within the cell, but are retained in the ER and degraded. A glycoprotein‐specific system involving the ER lectins calnexin and calreticulin is well documented, but very little is known about mechanisms that may operate for non‐glycosylated proteins. We have used a folding mutant of a non‐ glycosylated membrane protein, proteolipid protein (PLP), to examine the quality control of this class of polypeptide. We find that calnexin associates with newly synthesized PLP molecules, binding stably to misfolded PLP. Calnexin also binds stably to an isolated transmembrane domain of PLP, suggesting that this chaperone is able to monitor the folding and assembly of domains within the ER membrane. Notably, this glycan‐independent interaction with calnexin significantly retards the degradation of misfolded PLP. We propose that calnexin contributes to the quality control of non‐glycosylated polytopic membrane proteins by binding to misfolded or unassembled transmembrane domains, and discuss our findings in relation to the role of calnexin in the degradation of misfolded proteins.
Assessment of potential predictive value of peripheral blood inflammatory indexes in 26 cases with soft tissue sarcoma treated by pazopanib: a retrospective study

Purpose The aim of this study was to evaluate the prognostic and predictive value of neutrophil-to-lymphocyte ratio (NLR), derived neutrophil-to-lymphocyte ratio (DNLR), lymphocyte-to-monocyte ratio (LMR), and platelet-to-lymphocyte ratio (PLR) in soft tissue sarcoma (STS) cases treated with pazopanib. Materials and methods The study population included 26 STS cases treated with pazopanib for at least 3 months. NLR, DNLR, LMR, and PLR were evaluated at baseline, and at third month of therapy and also compared with response to pazopanib. Median measurements were taken as cutoff for NLR (4.8), DNLR (3.1), LMR (3.6), and PLR (195). The associations between these cutoff values and survival times (progression-free survival [PFS] and overall survival [OS]) were assessed by Kaplan–Meier curves and Cox proportional models. Results Patients with low pretreatment NLR and DNLR had longer OS (P=0.022, P=0.018), but low PLR was found to be associated only with longer OS. Additionally, decrease in NLR and DNLR after 3 months of therapy as compared with pretreatment measurements was found to be associated with an advantage for OS (P=0.021, P=0.010, respectively) and PFS (P=0.005, P=0.001, respectively). Response to pazopanib; changes in NLR, DNLR, LMR, and PLR; and >3 metastatic sites were found to be independent risk factors in univariate analysis, but NLR was the only independent risk factor in multivariate analysis. Conclusion Low pretreatment and decrease in NLR and DNLR values, and regression/stable disease after 3 months of pazopanib are predictive factors for longer OS and PFS.
Development of a novel task for investigating decision making in a social context following traumatic brain injury

Objective: Examination of social cognition as a target for assessment and intervention is beginning to gain momentum in a number of illnesses and acquired disorders. One facet of social cognition is decision making within interpersonal situations. This skill forms an important part of our everyday lives and is commonly impaired in those with neurological and mental health conditions. A novel task was developed to allow the assessment of decision making specifically within a social context and was examined within a group known to experience this difficulty. Method: Participants with severe traumatic brain injury (TBI) were compared to healthy control participants on the Social Decision Making Task (SDMT), which required the participant to learn who the “friendly” players were in a game of toss. Participants also completed a nonsocial decision-making task, the Iowa Gambling Task (IGT) as well as a battery of neuropsychological tests and social cognition tasks. Current social functioning was also examined. Results: Consistent with predictions, the TBI group made poorer decisions on the SDMT than the control group; however, group differences were not evident on the IGT. No significant relationships were observed between the SDMT and either measures of executive functioning (including working memory and reversal learning) or social cognition (including emotion recognition and theory of mind). Performance on the SDMT and the IGT were not associated, suggesting that the two tasks measure different constructs. Conclusions: The SDMT offers a novel way of examining decision making within a social context following TBI and may also be useful in other populations known to have specific social cognition impairment. Future research should aim to provide further clarification of the mechanisms of action and neuroanatomical correlates of poor performance on this task.
Dynamic Affordances in Embodied Interactive Systems: The Role of Display and Mode of Locomotion

We investigated how the properties of interactive virtual reality systems affect user behavior in full-body embodied interactions. Our experiment compared four interactive virtual reality systems using different display types (CAVE vs. HMD) and modes of locomotion (walking vs. joystick). Participants performed a perceptual-motor coordination task, in which they had to choose among a series of opportunities to pass through a gate that cycled open and closed and then board a moving train. Mode of locomotion, but not type of display, affected how participants chose opportunities for action. Both mode of locomotion and display affected performance when participants acted on their choices. We conclude that technological properties of virtual reality system (both display and mode of locomotion) significantly affected opportunities for action available in the environment (affordances) and discuss implications for design and practical applications of immersive interactive systems.
Mining and Quality Assessment of Mashup Model Patterns with the Crowd

Pattern mining, that is, the automated discovery of patterns from data, is a mathematically complex and computationally demanding problem that is generally not manageable by humans. In this article, we focus on small datasets and study whether it is possible to mine patterns with the help of the crowd by means of a set of controlled experiments on a common crowdsourcing platform. We specifically concentrate on mining model patterns from a dataset of real mashup models taken from Yahoo! Pipes and cover the entire pattern mining process, including pattern identification and quality assessment. The results of our experiments show that a sensible design of crowdsourcing tasks indeed may enable the crowd to identify patterns from small datasets (40 models). The results, however, also show that the design of tasks for the assessment of the quality of patterns to decide which patterns to retain for further processing and use is much harder (our experiments fail to elicit assessments from the crowd that are similar to those by an expert). The problem is relevant in general to model-driven development (e.g., UML, business processes, scientific workflows), in that reusable model patterns encode valuable modeling and domain knowledge, such as best practices, organizational conventions, or technical choices, that modelers can benefit from when designing their own models.
Inhibiting factors in the anaerobic digestion process for biogas production

The production of biogas by utilising the anaerobic digestion process is an economically and ecologically interesting process. However, the microbial community and the chemical balances of the anaerobic digestion process are vulnerable to a range of inhibitors. Determining inhibitors and solving the problems that come along is key to increase methane yields in the biogas production. Several methods have been applied to decrease inhibitory effects in anaerobic digesters including the physical-chemical featured separation method called air-stripping. Air-stripping is a method to reduce concentrations of free ammonia which is a known inhibitor of the biogas production. The effects of air-stripping on other components of the anaerobic digestion process are less heavily studied though. This article presents a summary of factors that are reported to inhibit the biogas production and reviews the effects the air-stripping method could have on the following factors: pH, ammonia, sulphate reducing bacteria, long chain fatty acids, humic acids, salinity, heavy metals and nanomaterials.