Miracle-dz/UniFAR-FTUs huggingface dataset:
The contribution of gliosis to diffusion tensor anisotropy and tractography following traumatic brain injury: validation in the rat using Fourier analysis of stained tissue sections.

Diffusion tensor imaging is highly sensitive to the microstructural integrity of the brain and has uncovered significant abnormalities following traumatic brain injury not appreciated through other methods. It is hoped that this increased sensitivity will aid in the detection and prognostication in patients with traumatic injury. However, the pathological substrates of such changes are poorly understood. Specifically, decreases in fractional anisotropy derived from diffusion tensor imaging are consistent with axonal injury, myelin injury or both in white matter fibres. In contrast, in both humans and animal models, increases in fractional anisotropy have been suggested to reflect axonal regeneration and plasticity, but the direct histological evidence for such changes remains tenuous. We developed a method to quantify the anisotropy of stained histological sections using Fourier analysis, and applied the method to a rat controlled cortical impact model to identify the specific pathological features that give rise to the diffusion tensor imaging changes in subacute to chronic traumatic brain injury. A multiple linear regression was performed to relate the histological measurements to the measured diffusion tensor changes. The results show that anisotropy was significantly increased (P < 0.001) in the perilesioned cortex following injury. Cortical anisotropy was independently associated (standardized β = 0.62, P = 0.04) with the coherent organization of reactive astrocytes (i.e. gliosis) and was not attributed to axons. By comparison, a decrease in white matter anisotropy (P < 0.001) was significantly related to demyelination (β = 0.75, P = 0.0015) and to a lesser extent, axonal degeneration (β = -0.48, P = 0.043). Gliosis within the lesioned cortex also influenced diffusion tensor tractography, highlighting the fact that spurious tracts in the injured brain may not necessarily reflect continuous axons and may instead depict glial scarring. The current study demonstrates a novel method to relate pathology to diffusion tensor imaging findings, elucidates the underlying mechanisms of anisotropy changes following traumatic brain injury and significantly impacts the clinical interpretation of diffusion tensor imaging findings in the injured brain.
Endoparasite communities of five fish species (Labridae: Cheilininae) from Lizard Island: how important is the ecology and phylogeny of the hosts?

The parasite community of animals is generally influenced by host physiology, ecology, and phylogeny. Therefore, sympatric and phylogenetically related hosts with similar ecologies should have similar parasite communities. To test this hypothesis we surveyed the endoparasites of 5 closely related cheilinine fishes (Labridae) from the Great Barrier Reef. They were Cheilinus chlorourus, C. trilobatus, C. fasciatus, Epibulus insidiator and Oxycheilinus diagramma. We examined the relationship between parasitological variables (richness, abundance and diversity) and host characteristics (body weight, diet and phylogeny). The 5 fishes had 31 parasite species with 9–18 parasite species per fish species. Cestode larvae (mostly Tetraphyllidea) were the most abundant and prevalent parasites followed by nematodes and digeneans. Parasites, body size and diet of hosts differed between fish species. In general, body weight, diet and host phylogeny each explained some of the variation in richness and composition of parasites among the fishes. The 2 most closely related species, Cheilinus chlorourus and C. trilobatus, had broadly similar parasites but the other fish species differed significantly in all variables. However, there was no all-encompassing pattern. This may be because different lineages of parasites may react differently to ecological variables. We also argue that adult parasites may respond principally to host diet. In contrast, larval parasite composition may respond both to host diet and predator-prey interactions because this is the path by which many parasites complete their life-cycles. Finally, variation in parasite phylogeny and parasite life-cycles among hosts likely increase the complexity of the system making it difficult to find all-encompassing patterns between host characteristics and parasites, particularly when all the species in rich parasite communities are considered.
CSF and clinical data are useful in differentiating CNS inflammatory demyelinating disease from CNS lymphoma

Background: It is often difficult to diagnose central nervous system (CNS) inflammatory demyelinating diseases (IDDs) because they are similar to CNS lymphoma and glioma. Objective: To evaluate whether cerebrospinal fluid (CSF) analysis can differentiate CNS IDDs from CNS lymphoma and glioma. Methods: We measured CSF cell counts; concentrations of proteins, glucose, interleukin (IL)-6, IL-10, soluble IL-2 receptor (sIL-2R), and myelin basic protein; and IgG index in patients with multiple sclerosis (MS, n = 64), neuromyelitis optica spectrum disorder (NMOSD, n = 35), tumefactive demyelinating lesion (TDL, n = 17), CNS lymphoma (n = 12), or glioma (n = 10). We detected diagnostic markers using logistic regression and receiver operating characteristic (ROC) analyses. Results: Median CSF IL-10 and sIL-2R levels were higher in CNS lymphoma patients than in MS, NMOSD, or TDL patients. Logistic regression revealed that CSF sIL-2R levels predicted CNS lymphoma. In the ROC analysis of CSF sIL-2R levels, the area under the curve was 0.867, and the sensitivity and specificity were 83.3% and 90.0%, respectively. Conclusion: CSF sIL-2R levels can be used to differentiate CNS lymphoma from CNS IDDs. Further studies may identify other applications of CSF as a diagnostic biomarker.
Protective effect of recombinant human IL-1Ra on CCl4-induced acute liver injury in mice.

AIM To evaluate the effects of positive regulation of recombinant human interleukin 1 receptor antagonist (rhIL-1Ra) on hepatic tissue recovery in acute liver injury in mice induced by carbon tetrachloride (CCl(4)). METHODS Acute liver damage was induced by injecting 8-wk-old mice with CCl(4) 1 mL/kg (1:3 dilution in corn oil) intraperitoneally (ip). Survival after liver failure was assessed by injecting 8-wk-old mice with a lethal dose of CCl(4) 2.6 mL/kg (1:1 dilution in corn oil) ip. Mice were subcutaneously injected with 1 mg/kg recombinant human IL-1Ra twice a day after CCl(4) treatment for 5 d. Serum alanine amino transferase (ALT) and aspartate aminotransferase (AST) levels were determined with a commercial assay kit. Serum IL-1beta, IL-1Ra levels were measured by enzyme-linked immunosorbent assay kit. Quantitative real-time polymerase chain reaction was used to determine liver IL-1beta, IL-1Ra and IL-6 expression during CCl(4)-induced acute liver injury. Liver sections were stained with hematoxylin-eosin. A histology-injury grading system was used to evaluate the degree of necrosis after acute liver injury. Proliferating cell nuclear antigen (PCNA) staining was used to evaluate the role of rhIL-1Ra in promoting hepatocyte proliferation. RESULTS Quantitative analysis showed a higher level of IL-6 mRNA expression and reduced serum AST and ALT levels in the livers of the rhIL-1Ra-treated group at the early phase of CCl(4)-induced acute liver injury. Histological examination indicated a decrease in centrilobular necrotic areas in mice treated with rhIL-1Ra, and a novel role of rhIL-1Ra in promoting hepatocyte proliferation was also supported by an increase of PCNA staining. All these results, accompanied by a strong survival benefit in rhIL-1Ra-treated vs PBS-treated groups, demonstrated that rhIL-1Ra administration ameliorated the histological damage and accelerated the regeneration and recovery process of the liver. CONCLUSION rhIL-1Ra could be further developed as a novel therapeutic agent for the treatment of acute liver injury because of its ability to reduce hepatocellular damage and facilitate liver regeneration.
Development of a substrate-integrated Ku-band cavity-backed microstrip patch sub-array of dual linear/circular polarization for DBS applications

A Ku-band cavity backed microstrip patch antenna sub-array suitable for dual linear/circular polarization is being developed based on substrate integrated waveguide (SIW) technology for DBS applications. SIW cavities have been emulated using vias and the patches are fed using microstrip line feed network. A 3×4 sub-array has been fabricated, tested and its results demonstrated a relatively high efficiency performance along the DBS 12.2–12.7 GHz band. The design for dual polarization could be used for either dual linear or dual circular polarization and provides adequate isolation between them. Larger array designs can be easily modified to use waveguide feeds along with probes to sustain its high efficiency performance.
Extradural Motor Cortex Stimulation in Advanced Parkinson’s Disease: The Turin Experience: Technical Case Report

OBJECTIVE AND IMPORTANCE: At our institution, extradural motor cortex stimulation (EMCS) has recently been applied for treating Parkinson’s disease symptoms. We report our results and review the literature supporting this application of EMCS. CLINICAL PRESENTATION: Since 1998, six patients affected by advanced Parkinson’s disease and not fulfilling inclusion criteria for deep brain stimulation underwent EMCS. INTERVENTION: A quadripolar electrode was introduced in the extradural space over the motor cortex, opposite to the side on which parkinsonian symptoms had begun. Bipolar chronic electrostimulation was delivered at 2.5 to 6 V, 150 to 180 microseconds, and 25 to 40 Hz. Preoperative and postoperative clinical status was assessed by the Unified Parkinson’s Disease Rating Scale (UPDRS) and recorded on videotapes. The follow-up of this series varied from 4 months to 2.5 years. After EMCS, the overall UPDRS score decreased by 42 to 62%; Section III UPDRS score (motility evaluation) by 32 to 83%; and Section IV UPDRS score (therapy complications) by 100% in two patients, by 50 to 67% in four patients, and by 33% in one patient. l-Dopa therapy was reduced by 11 to 33% in three patients and by 70 to 73% in the other two patients. No postoperative complications or negative side effects of electrostimulation were recorded, except for a misplacement of the electrodes in one patient. CONCLUSION: Unilateral EMCS relieves, at least partially, but sometimes dramatically, the whole spectrum of symptoms in advanced Parkinson’s disease. l-Dopa may be reduced up to 70%. The symptoms of long-term l-dopa syndrome are usually markedly improved. The neurophysiological mechanisms involved are still under debate. Our clinical experience adds favorable data to enlarge the series of parkinsonian patients treated by EMCS.
Moderate innovator trap – Does convergence of innovative potential occur?

Based on β and σ convergence analysis, we find high persistence of technological gap for international innovation indices reported by the European Commission. Our research confirms the diverging scientific potential across the analyzed economies. On the other hand, estimation provides the evidence of convergence in case of R&D expenses and relative position on global technological frontier. We propose a simple fixed effect panel regression measuring relative innovativeness potential. Our model suggests that current ranking leaders i.e. Nordic countries (Sweden, Denmark and Finland) and Germany are likely to further outpace the United States. Central and Eastern Europe countries are achieving greatest relative gains, but are unlikely to exceed 70% of US potential. Peripheral Europe countries, South Africa, Turkey and Russia are projected to further lose innovativeness position, despite weaker initial position.
The politics of guarding the Treaties: Commission scrutiny of rule of law compliance

ABSTRACT Commission's expectations on eventual compliance explain its different behaviour when dealing with Rule of Law (RoL) crises in Hungary and Poland. Whilst the Commission activated the first stage of the procedure of article 7 against Poland in December 2017, it resisted to launch the same procedure against the Hungarian government despite mounting criticism and demands from both academics and EU institutions. The Commission considers that compliance depends, on last instance, on the cooperation of domestic authorities. Accordingly, it prefers to engage with them in dialogue and persuasion rather than activating enforcement mechanisms. If engagement strategies fail to obtain compliance, the Commission anticipates the consequence of activating article 7 enforcement: whether it can rely or not on Council support and the effects of not having it and it also anticipates negative consequences such as the future attitude of the affected member state vis-á-vis the EU.
Truncating the Dose Range for Methacholine Challenge Tests: Three Occupational Studies

The methacholine challenge test protocol was assessed in the reanalysis of three occupational studies. We evaluated the impact of truncating the range of methacholine on responsiveness, as defined by slope and PC20. In original analysis, reactivity was similar for apprentices and auto body shop workers, whereas boilermakers were more responsive. Truncating high concentrations did not change the classification of subjects with PC20 <8 or 16 in any population. However, when responsiveness was measured by slope, the mean responsiveness increased, from −7.9 to −15.3 for apprentices and −7.2 to −10.0 for auto-body shop workers. Results support the American Thoracic Society’s recommended maximum of 16 mg/mL and provide evidence that extending the dose range beyond that does not increase sensitivity, whereas stopping before 16 may exaggerate response. Furthermore, to ensure validity, neither slope nor PC20 should be extrapolated beyond data.
Asymmetric Effects of Economic Activityon Inflation

Data for the G-7 countries strongly support the view that economic activity has a nonlinear effect on inflation, with high levels of activity raising inflation by more than low levels decrease it. In the face of such asym­ metries, the average level of output in an economy subject to demand shocks will be below the level of output at which there is no tendency for inflation to rise or fall, contrary to linear model predictions. One implica­ tion is that policy makers can raise the average level of output over time by responding promptly to demand shocks, reducing the variance of output around trend. [JEL C51, £31, E52]
State Agency Discretion and Entrepreneurship in Regulated Markets

Barriers to entry in regulated markets are frequently conceptualized as static features that must be removed or overcome if new entrants are to successfully enter a market. But government institutions regulating markets often comprise multiple levels that exist in tension with one another due to differing incentives and motivations. We argue that the principal–agent tension between elected officials and agency bureaucrats may render regulatory barriers to entry more malleable, even in the absence of formal policy changes. To test this proposition, we bring the administrative state center stage and examine how regulatory discretion—regulatory agencies’ flexibility to interpret and implement public policies created by elected officials—can influence the market entry of new ventures. Using data on regulatory approval of hydroelectric facilities in the United States from 1978 to 2014, we find that increased state agency discretion improves outcomes for new ventures relative to incumbent firms by freeing regulatory agency officials to interpret and implement policies according to a professional motivation of public service and reducing incumbents’ political influence.
Effect of timing and route of administration of furosemide on pulmonary hemorrhage and pulmonary arterial pressure in exercising thoroughbred racehorses.

OBJECTIVES To examine effect of pre-exercise administration of furosemide (FUR) on mean pulmonary arterial pressure (PAP) during work and RBC concentration in bronchoalveolar lavage fluid (BALF) collected 40 minutes after exercise. ANIMALS 10 adult Thoroughbreds. PROCEDURE A modified 10 X 10 crossover design comprising 10 horses during 10 weeks was used. Each horse received each of 5 treatments twice. Treatment structure included a control plus a 2 X 2 factorial and consisted of the following: A, control; B, FUR, 250 mg, IV, 30 minutes before exercise; C, FUR, 250 mg, IV, 240 minutes before exercise; D, FUR, 250 mg, nebulized, 30 minutes before exercise; and E, FUR, 250 mg, nebulized, 240 minutes before exercise. Mean PAP data were collected, and each horse, after a 500-m warm-up, was galloped at maximal speed for 1,600 m. BALF RBC concentration was determined by hemocytometer. RESULTS Interaction between treatment method and time of administration was significant (P = 0.04). Treatment B resulted in significantly (P = 0.01) lower BALF RBC concentration than did treatment C. Only BALF RBC count after treatment B was significantly lower than the control value. Horses that received FUR IV had significantly lower peak mean PAP than did those that received the drug by nebulization, regardless of administration time. Only treatment B resulted in peak mean PAP that was significantly lower than that of control. Exercise time was not influenced by treatment. CONCLUSIONS FUR, administered IV 30 minutes before exercise, significantly reduced peak mean PAP and BALF RBC concentration.
Survival in a cohort of patients with lung cancer: the role of age and gender in prognosis

ABSTRACT Objective: To determine the demographic and clinical characteristics of patients with non-small cell lung cancer (NSCLC), as well as their disease course, by age group and gender. Methods: This was a retrospective cohort study of patients diagnosed with NSCLC from 2000 to 2012 and followed until July 2015 in a tertiary referral hospital in the city of São Paulo, Brazil. Based on the 25th and 75th percentiles of the age distribution, patients were stratified into three age groups: < 55 years; ≥ 55 and < 72 years; and ≥ 72 years. Survival time was evaluated during the follow-up period of the study. Functions of overall and gender-specific survival stratified by age groups (event: all-cause mortality) were calculated using the Kaplan-Meier method. Differences among survival curves were assessed via the log-rank test. Results: We included 790 patients with the following age distribution: < 55 years, 165 patients; ≥ 55 and < 72 years, 423; and ≥ 72 years, 202. In the entire sample, there were 493 men (62.4%). Adenocarcinoma was the most common histological pattern in the < 72-year age groups; 575 patients (73%) presented with advanced disease (stages IIIB-IV). The median 5-year survival was 12 months (95% CI: 4-46 months), with no significant differences among the age groups studied. Conclusions: NSCLC remains more common in men, although we found an increase in the proportion of the disease in women in the < 55-year age group. Adenocarcinoma predominated in women. In men, squamous cell carcinoma predominated in the ≥ 72-year age group. Most patients presented with advanced-stage disease at diagnosis. There were no statistical differences in survival between genders or among age groups.
Lipoxin A4 and Aspirin-Triggered 15-Epi-Lipoxin A4 Antagonize TNF-α-Stimulated Neutrophil-Enterocyte Interactions In Vitro and Attenuate TNF-α-Induced Chemokine Release and Colonocyte Apoptosis in Human Intestinal Mucosa Ex Vivo1

Lipoxins (LXs) are lipoxygenase-derived eicosanoids and putative endogenous braking signals for inflammation in the gastrointestinal tract and other organs. Aspirin triggers the production of 15-epimers during cell-cell interaction in a cytokine-primed milieu, and aspirin-triggered 15-epi-5(S),6(R),15(S)-trihydroxy-7,9,13-trans-11-cis-eicosatetraenoic acid (15-epi-LXA4) may contribute to the bioactivity profile of this prototype nonsteroidal anti-inflammatory drug in vivo. We determined the effect of LXA4, 15-(R/S)-methyl-11,12-dehydro-LXA4 methyl ester (15-(R/S)-methyl-LXA4), and stable analogs of LXA4 on TNF-α-stimulated neutrophil-enterocyte interaction in vitro and TNF-α-stimulated chemokine release, changes in mucosal architecture, and enterocyte apoptosis in cytokine-activated intact human colonic mucosa ex vivo. LXA4, 15-(R/S)-epi-LXA4, and 16-phenoxy-11,12-dehydro-17,18,19,20-tetranor-LXA4 methyl ester (16-phenoxy-LXA4) inhibited TNF-α-stimulated neutrophil adherence to epithelial monolayers at nanomolar concentrations. In parallel experiments involving human colonic mucosa ex vivo, LXA4potently attenuated TNF-α-stimulated release of the C-X-C chemokine IL-8, and the C-C chemokines monocyte-chemoattractant protein-1 (MCP-1) and RANTES. Exposure of strips of normal human colonic mucosa to TNF-α induced disruption of mucosa architecture and enhanced colonocyte apoptosis via a caspase-3-independent mechanism. Prior exposure of the mucosa strips to 15-(R/S)-methyl-LXA4 attenuated TNF-α-stimulated colonocyte apoptosis and protected the mucosa against TNF-α-induced mucosal damage. In aggregate, our data demonstrate that lipoxins and aspirin-triggered 15-epi-LXA4 are potent antagonists of TNF-α-mediated neutrophil-enterocyte interactions in vitro, attenuate TNF-α-triggered chemokine release and colonocyte apoptosis, and are protective against TNF-α-induced morphological disruption in human colonic strips ex vivo. Our observations further expand the anti-inflammatory profile of these lipoxygenase-derived eicosanoids and suggest new therapeutic approaches for the treatment of inflammatory bowel disease.
Dose KRAS Mutation Status Affect on the Effect of VEGF Therapy in Metastatic Colon Cancer Patients?

Purpose Mutations affecting the KRAS gene are an established negative predictor for anti-epidermal growth factor receptor (anti-EGFR) therapies in metastatic colorectal cancer (CRC). However, the role of KRAS mutation as a biomarker for anti-vascular endothelial growth factor (VEGF) remains controversial. Materials and Methods We analyzed retrospective data from 32 CRC patients who were available for KRAS mutation status and received cytotoxic chemotherapy plus bevacizumab as a first-line therapy. Six of 32 patients received anti-EGFR therapies. We used KRAS mutation status as a predictive or prognostic factor in CRC patients receiving bevacizumab. Results We observed mutations in KRAS in 59.4% of patients. Bevacizumab was used in combination with oxaliplatin based regimens. There was no significant difference for progression free survival (PFS) and overall survival (OS) in patients with oxaliplatin based cytotoxic chemotherapy plus bevacizumab according to the status of KRAS mutation. After first-line therapy, 28 patients (87.5%) received second-line therapy. In univariate analysis, KRAS mutations did not have a major prognostic value for PFS (hazard ratio, 1.007; 95% confidence interval [CI], 0.469 to 2.162; p>0.05) or OS (hazard ratio, 0.548; 95% CI, 0.226 to 1.328; p>0.05). In addition, anti-EGFR therapies did not affect the impact on OS. Conclusion KRAS mutation is neither a predictive for bevacizumab nor a prognostic for OS in CRC patients receiving anti-VEGF therapy.