Miracle-dz/UniFAR-FTUs huggingface dataset:
Intravenous Glutamine Administration Reduces Lung and Distal Organ Injury in Malnourished Rats With Sepsis

ABSTRACT Malnutrition is a risk factor for infection, compromising immune response. Glutamine (Gln) protects the lungs and distal organs in well-nourished septic and nonseptic conditions; however, no study to date has analyzed the effects of Gln in the presence of sepsis and malnutrition. In the present work, we tested the hypothesis that early therapy with intravenous Gln prevents lung and distal organ damage in septic malnourished rats. Protein-energy malnutrition was induced in male Wistar rats for 4 weeks. At the end of 4 weeks, malnourished animals were assigned to a sepsis-inducing cecal ligation and puncture group or a sham surgery group. One hour after surgery, animals were given saline (Sal) or L-alanyl-L-glutamine (Gln) intravenously. In addition, a control group (C) was set up with rats fed ad libitum, not submitted to surgery or treatment. Forty-eight hours after surgery, in malnutrition-sham rats, Gln therapy lessened neutrophil lung infiltration and apoptosis in lung and liver. In malnutrition–cecal ligation and puncture rats, Gln therapy yielded (a) reduced static lung elastance, alveolar collapse, inflammation (neutrophil infiltration, interleukin 6), and collagen deposition; (b) repair of types I and II epithelial cells; (c) no significant changes in heat shock protein 70 expression or heat shock factor 1 phosphorylation; (d) a greater number of M1 and M2 macrophages in lung tissue; and (e) less apoptosis in the lung, kidney, small intestine, and liver. In conclusion, early therapy with intravenous Gln reduced inflammation, fibrosis, and apoptosis, minimizing lung and distal organ injury, in septic malnourished rats. These beneficial effects may be associated with macrophage activation in the lung.
Comparative Sirolimus Pharmacokinetics After Single‐Dose Administration of Two Prototype 0.5‐mg Tablets in Healthy Volunteers

Availability of a lower dose tablet would add to the dosing flexibility of currently available 1‐ and 2‐mg sirolimus tablets for optimal concentrations and patient compliance. A randomized, 3‐period crossover study was conducted in 30 fasting healthy volunteers (29 men, aged 31 ± 8 years, weight 79 ± 12 kg). Subjects were given 5 mg of sirolimus, either as doses of the 0.5‐mg nonshellac‐core prototype, 0.5‐mg shellac‐core prototype, or approved 1‐mg tablet. Whole blood samples were collected at selected time points for 144 hours after dosing and analyzed using LC/MS/MS assay. Noncompartmental pharmacokinetic analysis was performed, followed by bioequivalence assessment. Twenty‐four subjects completed all dosing periods, and no formulation‐associated adverse events were reported. Ratios of maximum plasma concentration (Cmax), area under the concentration‐time curve to the last measured concentration (AUCT), and area under the concentration‐time curve from time 0 to infinity (AUC) for the nonshellac‐core prototype compared with the 1‐mg tablet were within the 80% to 125% range dictated by bioequivalence conventions. Similar results were observed when comparing the ratios of AUCT and AUC for the shellac‐core prototype, while 90% confidence interval of the ratio of Cmax values was 105% to 129%. Within the context of clinical equivalence standards established by a phase 3 study comparing liquid to tablet formulations, it was concluded that both prototypes were clinically bioequivalent to the reference formulation.
Projections from the paraventricular nucleus of the thalamus to the rat prefrontal cortex and nucleus accumbens shell: Ultrastructural characteristics and spatial relationships with dopamine afferents

The paraventricular nucleus of the thalamus (PVT) participates in the functional integration of limbic cortical and striatal circuitry. In the rat, the PVT projects to the deep layers of the medial prefrontal cortex (PFC) and to the shell of the nucleus accumbens (NAc). However, the synaptic organization of PVT afferents within these regions remains undescribed. Furthermore, although dopamine (DA) modulates excitatory glutamate transmission in both areas, possible anatomic substrates for specific DA modulation of PVT inputs have not yet been investigated. To address these issues, immunoperoxidase labeling for tyrosine hydroxylase (TH) in DA axons was combined with anterograde tract‐tracing, either by biotinylated dextran amine (BDA) labeled with immunogold–silver or by degeneration after lesions of the PVT. In both regions, and with either tracing method, PVT terminals formed primarily asymmetric axospinous synapses; in the NAc, a proportion of PVT terminals also synapsed onto dendrites. PVT profiles in both regions were often seen in direct apposition to TH‐immunoreactive axons; this association was more evident in the NAc where the DA innervation is denser. Within the PFC, PVT profiles and TH‐labeled axons were occasionally apposed to the same dendrites, but synaptic specializations were not typically seen at these seeming points of convergence. Within the NAc, PVT profiles occasionally made synapses onto spines and distal dendrites that received convergent synapses from TH‐immunoreactive varicosities. These findings represent the first demonstration of postsynaptic convergence between DA and thalamic afferents to a striatal region and are consistent with direct synaptic modulation of PVT transmission by DA in the NAc but not the PFC. J. Comp. Neurol. 459:142–155, 2003. © 2003 Wiley‐Liss, Inc.
Institutional Influences on strategic entrepreneurial Behaviours

The purpose of this paper is to examine the existence of cross-level moderating effects between national appropriability conditions, individual level predictors and entrepreneurial growth aspirations. We test a multi-level model that connects the determinants of strategic resource allocation decisions at the individual level with the strength of the intellectual property rights regime at the national level. The results suggest that the strengths of the intellectual property regime will moderate negatively the relationship between an individual's education and her growth aspirations and moderate positively the relationship between an individual's income and her growth aspirations. The findings support claims that strategic entrepreneurial behavior cannot be fully understood without giving attention to the context in which those behaviors are observed.
IgA Antiphospholipid Antibodies and Anti-Domain 1 of Beta 2 Glycoprotein 1 Antibodies are Associated with Livedo Reticularis and Heart Valve Disease in Antiphospholipid Syndrome.

BACKGROUND Antiphospholipid syndrome (APS) is an autoimmune disease associated with venous or arterial thrombosis and pregnancy loss, but also infrequently with non-criteria APS manifestations such as thrombocytopenia, livedo reticularis and heart valve disease. The occurrence of antiphospholipid antibodies is necessary to diagnose APS and includes the presence of lupus anticoagulant and anticardiolipin as well as anti-β2-glycoprotein I antibodies, both in IgM and/or IgG isotype. OBJECTIVES The aim of this study was to evaluate the associations between antiphospholipid antibodies including IgA isotype and IgG anti-domain I of β2-glycoprotein I (β-2GPI-D1) and non-criteria-related manifestations of APS. MATERIAL AND METHODS Thirty-three consecutive APS patients (26 women, 7 men, aged 44.1 ± 15 years), including 23 (69.7%) subjects with primary APS, were enrolled. Together with standard antiphospholipid antibodies, IgA anticardiolipin, IgA anti-β2-glycoprotein I and IgG anti-β-2GPI-D1 antibodies in serum samples were evaluated by chemiluminescence using the QUANTA Flash® System. RESULTS Livedo reticularis (n = 8, 24.2%) was associated with increased levels of IgG anti-β-2GPI-D1 (p = 0.005), IgA anticardiolipin (p = 0.001) and IgA anti-β2-glycoprotein I (p = 0.002) antibodies. Heart valve disease (n = 9, 27.3%) was observed in patients with higher IgG anti-β-2GPI-D1 (p = 0.01). The associations of HVD with increased levels of IgA aCL and IgA anti-β-2GPI tended to be significant (p = 0.07). None of antiphospholipid antibodies showed association with thrombocytopenia (n = 6, 18.2%). CONCLUSIONS Our study suggests that increased IgA antiphospholipid antibodies and IgG anti-β-2GPI-D1 antibodies may be involved in the development of livedo reticularis and heart valve disease in APS patients.
Cardiorespiratory repercussions according to the abdominal circumference measurement of men with obstructive respiratory disorder submitted to respiratory physiotherapy

ABSTRACT Purpose: To examine the effect of respiratory physiotherapy among men with obstructive respiratory disorder, in relation to abdominal circumference (AC). Methods: Quasi-experimental study including 26 men split into two groups according to AC(cm): 1) < 102 (ACrisk-free); and 2) ≥ 102 (ACrisk). Heart rate variability (HRV), diastolic blood pressure (DBP), oxygen saturation (SpO2), FEV1/FVC, slow vital capacity (SVC), inspiratory capacity (IC), maximal inspiratory pressure (PImax), thoracoabdominal amplitude (AI) were measured: before (M1); 5 min after the physiotherapy (i.e. breathing exercises for airway clearance and active kinesiotherapy) (M2); and at follow-up, 30 min after physiotherapy (M3). Results: The groups differed in age, body mass index and body fat %. At M2 IC was different between groups (ACrisk-free< ACrisk). There was an increase in HRV indexes, PImax, SpO2, axillary AI, FEV1/FVC, and reduction in HR for ACrisk-free. There was a decrease in AI and an increase in DBP for ACrisk. Conclusion: In men with obstructive respiratory disorder, increased AC measurement limited the thoracoabdominal expansibility and induced a rise of the DBP. Respiratory physiotherapy promotes an increase of cardiac modulation and inspiratory capacity for men with obstructive respiratory disorder.
Face Recognition using Tensors of Census Transform Histograms from Gaussian Features Maps

This paper presents a new approach for face recognition based on the fusion of tensors of census transform histograms from Local Gaussian features maps. Local Gaussian feature maps encode the most relevant information from Gaussian derivative features. Census Transform (CT) histograms are calculated and concatenated to form a tensor for each class of Gaussian map. Multi-linear Principal Component Analysis (MPCA) is applied to each tensor to reduce the number of dimensions as well as the correlation between neighboring pixels due to the Census Transform. We then train Kernel Discriminative Common Vectors (KDCV) to generate a discriminative vector using the results of the MPCA. Results of recognition using MPCA of tensors-CT histograms from Gaussian features maps with KDCV is shown to compare favorably with competing techniques that use more complex features maps like for example Gabor features maps in the FERET and Yale datasets. Additional experiments were done in the Yale B+ extended Yale B Faces dataset to show the performance of Gaussian features map with hard illumination changes.
Discrete Gaussian Sampling Reduces to CVP and SVP

The discrete Gaussian $D_{L- t, s}$ is the distribution that assigns to each vector $x$ in a shifted lattice $L - t$ probability proportional to $e^{-\pi \|x\|^2/s^2}$. It has long been an important tool in the study of lattices. More recently, algorithms for discrete Gaussian sampling (DGS) have found many applications in computer science. In particular, polynomial-time algorithms for DGS with very high parameters $s$ have found many uses in cryptography and in reductions between lattice problems. And, in the past year, Aggarwal, Dadush, Regev, and Stephens-Davidowitz showed $2^{n+o(n)}$-time algorithms for DGS with a much wider range of parameters and used them to obtain the current fastest known algorithms for the two most important lattice problems, the Shortest Vector Problem (SVP) and the Closest Vector Problem (CVP). Motivated by its increasing importance, we investigate the complexity of DGS itself and its relationship to CVP and SVP. Our first result is a polynomial-time dimension-preserving reduction from DGS to CVP. There is a simple reduction from CVP to DGS, so this shows that DGS is equivalent to CVP. Our second result, which we find to be more surprising, is a polynomial-time dimension-preserving reduction from centered DGS (the important special case when $ t = 0$) to SVP. In the other direction, there is a simple reduction from $\gamma$-approximate SVP for any $\gamma = \Omega(\sqrt{n/\log n})$, and we present some (relatively weak) evidence to suggest that this might be the best achievable approximation factor. We also show that our CVP result extends to a much wider class of distributions and even to other norms.
Molecular Characterization of Chikungunya Virus, Philippines, 2011–2013

During 2011–2013, a nationwide outbreak of chikungunya virus infection occurred in the Philippines. The Asian genotype was identified as the predominant genotype; sporadic cases of the East/Central/South African genotype were detected in Mindanao. Further monitoring is needed to define the transmission pattern of this virus in the Philippines.
Robust Constrained Learning-based NMPC enabling reliable mobile robot path tracking

This paper presents a Robust Constrained Learning-based Nonlinear Model Predictive Control (RC-LB-NMPC) algorithm for path-tracking in off-road terrain. For mobile robots, constraints may represent solid obstacles or localization limits. As a result, constraint satisfaction is required for safety. Constraint satisfaction is typically guaranteed through the use of accurate, a priori models or robust control. However, accurate models are generally not available for off-road operation. Furthermore, robust controllers are often conservative, since model uncertainty is not updated online. In this work our goal is to use learning to generate low-uncertainty, non-parametric models in situ. Based on these models, the predictive controller computes both linear and angular velocities in real-time, such that the robot drives at or near its capabilities while respecting path and localization constraints. Localization for the controller is provided by an on-board, vision-based mapping and navigation system enabling operation in large-scale, off-road environments. The paper presents experimental results, including over 5 km of travel by a 900 kg skid-steered robot at speeds of up to 2.0 m/s. The result is a robust, learning controller that provides safe, conservative control during initial trials when model uncertainty is high and converges to high-performance, optimal control during later trials when model uncertainty is reduced with experience.
Vascular endothelial growth factor promotes tumor dissemination by a mechanism distinct from its effect on primary tumor growth.

Tumor growth is dependent on new blood vessel formation. Inhibition of vascular endothelial growth factor (VEGF), an endothelial cell mitogen and angiogenic factor secreted by a variety of tumors and tumor cell lines, is sufficient to inhibit primary tumor growth. In the present study, we examined the effect of inhibiting VEGF on tumor cell micrometastasis. A transfectant of A431 (a human epidermoid carcinoma cell line) expressing chloramphenicol acetyltransferase (CAT) was injected s.c. into severe combined immunodeficiency (scid) mice, which were then sacrificed after 6 weeks. The presence of A431 metastases at distant sites was demonstrated by detection of CAT activity in whole-organ lysates. Treatment of animals with VEGF-neutralizing antibodies not only inhibited primary tumor growth but also suppressed metastases, as determined by CAT activity in organ lysates. In experiments to determine the mechanism by which anti-VEGF antibody inhibited metastasis, control animals were sacrificed when their tumors had reached the same size as tumors in VEGF antibody-treated animals. Metastases were uniformly present in these control animals. These findings show that inhibition of VEGF alone is sufficient to prevent tumor growth and dissemination in vivo. The inhibitory effect on metastases appears to be distinct from that on primary tumor growth.
Linaclotide activates guanylate cyclase‐C/cGMP/protein kinase‐II‐dependent trafficking of CFTR in the intestine

The transmembrane receptor guanylyl cyclase‐C (GC‐C), expressed on enterocytes along the intestine, is the molecular target of the GC‐C agonist peptide linaclotide, an FDA‐approved drug for treatment of adult patients with Irritable Bowel Syndrome with Constipation and Chronic Idiopathic Constipation. Polarized human colonic intestinal cells (T84, CaCo‐2BBe) rat and human intestinal tissues were employed to examine cellular signaling and cystic fibrosis transmembrane conductance regulator (CFTR)‐trafficking pathways activated by linaclotide using confocal microscopy, in vivo surface biotinylation, and protein kinase‐II (PKG‐II) activity assays. Expression and activity of GC‐C/cGMP pathway components were determined by PCR, western blot, and cGMP assays. Fluid secretion as a marker of CFTR cell surface translocation was determined using in vivo rat intestinal loops. Linaclotide treatment (30 min) induced robust fluid secretion and translocation of CFTR from subapical compartments to the cell surface in rat intestinal loops. Similarly, linaclotide treatment (30 min) of T84 and CaCo‐2BBe cells increased cell surface CFTR levels. Linaclotide‐induced activation of the GC‐C/cGMP/PKGII signaling pathway resulted in elevated intracellular cGMP and pVASPser239 phosphorylation. Inhibition or silencing of PKGII significantly attenuated linaclotide‐induced CFTR trafficking to the apical membrane. Inhibition of protein kinase‐A (PKA) also attenuated linaclotide‐induced CFTR cell surface trafficking, implying cGMP‐dependent cross‐activation of PKA pathway. Together, these findings support linaclotide‐induced activation of the GC‐C/cGMP/PKG‐II/CFTR pathway as the major pathway of linaclotide‐mediated intestinal fluid secretion, and that linaclotide‐dependent CFTR activation and recruitment/trafficking of CFTR from subapical vesicles to the cell surface is an important step in this process.
Validation of the Portuguese version of a questionnaire to measure Quality of Care Through the Eyes of Patients with Inflammatory Bowel Disease (QUOTE-IBD)

Background/aim The patient’s perspective on the healthcare that they receive has become increasingly important in the assessment of healthcare quality, especially in chronic diseases such as inflammatory bowel disease (IBD). In this context, the questionnaire QUOTE-IBD (Quality of Care Through the Patient’s Eyes with Inflammatory Bowel Disease) was created to assess the healthcare quality from the point of view of a patient with IBD. This questionnaire does not yet have a validated Portuguese version (PT-QUOTE-IBD). We aimed to assess the acceptability, validity, and reliability of PT-QUOTE-IBD. Patients and methods This was an observational longitudinal unicentric study with three sequential phases: (a) translation and cultural adaptation of QUOTE-IBD that explores the Importance, Performance and Quality Impact of several dimensions of healthcare; (b) assessment of validity by correlation of the results of PT-QUOTE-IBD and visual analogue scales (VAS); and (c) assessment of the reliability of PT-QUOTE-IBD through a second administration of the questionnaire, with a minimum interval of 4 weeks. Results We included 114 patients with IBD (77 Crohn’s disease and 37 ulcerative colitis). Fifty-nine percent of the patients completed all the questions of QUOTE-IBD and VAS. We obtained positive and significant Pearson’s correlation coefficients between QUOTE-IBD scores and VAS for Performance and Quality Impact of Total Care and dimensions Accessibility and Information. Thirty-four (30%) patients completed the second questionnaire adequately. We obtained positive and significant Pearson’s correlation coefficients between the two questionnaires for Performance and Quality Impact of Total Care, Accessibility, Continuity of Care, Courtesy and Information, and for Performance of Cost. Conclusion PT-QUOTE-IBD is acceptable, valid, and reliable in the assessment of Performance and Quality Impact of Total Care, but not of all dimensions of healthcare.
Coronary stenting versus coronary bypass surgery in patients with multiple vessel disease and significant proximal LAD stenosis: results from the ERACI II study

Purpose: To compare percutaneous coronary intervention (PCI) using stent implantation versus coronary artery bypass graft (CABG) in patients with multiple vessel disease with involvement of the proximal left anterior descending coronary artery (LAD). Methods: 230 patients with multiple vessel disease and severe stenosis of the proximal LAD (113 with PCI, 117 with CABG). They were a cohort of patients from the randomised ERACI (Argentine randomized trial of percutaneous transluminal coronary angioplasty versus coronary artery bypass surgery in multivessel disease) II study. Results: Both groups had similar baseline characteristics. There were no significant differences in 30 day major adverse cardiac events (death, myocardial infarction, stroke, and repeat procedures) between the strategies (PCI 2.7% v CABG 7.6%, p = 0.18). There were no significant differences in survival (PCI 96.4% v CABG 95%, p = 0.98) and survival with freedom from myocardial infarction (PCI 92% v CABG 89%, p = 0.94) at 41.5 (6) months’ follow up. However, freedom from new revascularisation procedures (CABG 96.6% v PCI 73%, p = 0.0002) and frequency of angina (CABG 9.4% v PCI 22%, p = 0.025) were superior in the CABG group. Conclusion: Patients with multivessel disease and significant disease of the proximal LAD randomly assigned in the ERACI II trial to PCI or CABG had similar survival and survival with freedom from myocardial infarction at long term follow up. Repeat revascularisation procedures were higher in the PCI group.
Neuroprotective Role of Liver Growth Factor “LGF” in an Experimental Model of Cerebellar Ataxia

Cerebellar ataxias (CA) comprise a heterogeneous group of neurodegenerative diseases characterized by a lack of motor coordination. They are caused by disturbances in the cerebellum and its associated circuitries, so the major therapeutic goal is to correct cerebellar dysfunction. Neurotrophic factors enhance the survival and differentiation of selected types of neurons. Liver growth factor (LGF) is a hepatic mitogen that shows biological activity in neuroregenerative therapies. We investigate the potential therapeutic activity of LGF in the 3-acetylpiridine (3-AP) rat model of CA. This model of CA consists in the lesion of the inferior olive-induced by 3-AP (40 mg/kg). Ataxic rats were treated with 5 µg/rat LGF or vehicle during 3 weeks, analyzing: (a) motor coordination by using the rota-rod test; and (b) the immunohistochemical and biochemical evolution of several parameters related with the olivo-cerebellar function. Motor coordination improved in 3-AP-lesioned rats that received LGF treatment. LGF up-regulated NeuN and Bcl-2 protein levels in the brainstem, and increased calbindin expression and the number of neurons receiving calbindin-positive projections in the cerebellum. LGF also reduced extracellular glutamate and GABA concentrations and microglia activation in the cerebellum. In view of these results, we propose LGF as a potential therapeutic agent in cerebellar ataxias.