Miracle-dz/UniFAR-FTUs huggingface dataset:
Experimental Chemotherapy against Trypanosoma cruzi Infection Using Ruthenium Nitric Oxide Donors

ABSTRACT The ruthenium NO donors of the group trans-[Ru(NO)(NH3)4L]n+, where the ligand (L) is N-heterocyclic H2O, SO32−, or triethyl phosphite, are able to lyse Trypanosoma cruzi in vitro and in vivo. Using half-maximal (50%) inhibitory concentrations against bloodstream trypomastigotes (IC50try) and cytotoxicity data on mammalian V-79 cells (IC50V79), the in vitro therapeutic indices (TIs) (IC50V79/IC50try) for these compounds were calculated. Compounds that exhibited an in vitro TI of ≥10 and trypanocidal activity against both epimastigotes and trypomastigotes with an IC50try/epi of ≤100 μM were assayed in a mouse model for acute Chagas' disease, using two different routes (intraperitoneal and oral) for drug administration. A dose-effect relationship was observed, and from that, the ideal dose of 400 nmol/kg of body weight for both trans-[Ru(NO)(NH3)4isn](BF4)3 (isn, isonicotinamide) and trans-[Ru(NO)(NH3)4imN](BF4)3 (imN, imidazole) and median (50%) effective doses (ED50) of 86 and 190 nmol/kg, respectively, were then calculated. Since the 50% lethal doses (LD50) for both compounds are higher than 125 μmol/kg, the in vivo TIs (LD50/ED50) of the compounds are 1,453 for trans-[Ru(NO)(NH3)4isn](BF4)3 and 658 for trans-[Ru(NO)(NH3)4imN](BF4)3. Although these compounds exhibit a marked trypanocidal activity and are able to react with cysteine, they exhibit very low activity in T. cruzi-glycosomal glyceraldehyde-3-phosphate dehydrogenase tests, suggesting that this enzyme is not their target. The trans-[Ru(NO)(NH3)4isn](BF4)3 and trans-[Ru(NO)(NH3)4imN](BF4)3 compounds are able to eliminate amastigote nests in myocardium tissue at 400-nmol/kg doses and ensure the survival of all infected mice, thus opening a novel set of therapies to try against trypanosomatids.
Nitro-Aromatic Explosive Sensing Using GaN Nanowire-Titania Nanocluster Hybrids

Globalization of terrorist attacks in recent years calls for advanced technologies to detect the concealed explosives effectively. We demonstrate a highly sensitive and selective detection of traces of nitro-aromatic explosive compounds by functionalizing gallium nitride (GaN) nanowires with titania (TiO2) nanoclusters to address this issue. The ultraviolet light photo-modulated GaN/TiO2 nanowire-nanocluster (NWNC) hybrids show remarkable selectivity to benzene and related aromatic compounds, with no measureable response for other analytes at room temperature. This paper presents the sensing characteristics of GaN/TiO2 NWNC hybrids towards the different aromatic and nitroaromatic compounds at room temperature. The GaN/TiO2 hybrids are able to detect trinitrotoluene (TNT) concentrations as low as 500 ppt in air and dinitrobenzene concentrations as low as 10 ppb in air in approximately 30 s. The noted sensitivity range of the devices for TNT is from 8 ppm down to as low as 500 ppt. The detection limit of dinitrotoluene, nitrobenzene, nitrotoluene, toluene and benzene in air is 100 ppb with a response time of ~ 75 s. The devices showed very sensitive and selective response to TNT when compared to interfering compounds like toluene with good reproducibility. Integration of different NWNC hybrids on the same substrate could lead to tiny, highly sensitive, selective, low-power and smart explosive detectors that could be manufactured cheaply in large numbers.
Contesting Identity: Politics of gays and lesbians in Toronto in the 1970s: Identidad en Conflicto: políticas de gays y lesbianas en Toronto en los años 1970

This article explores a particular moment in the history of Toronto's gay movement politics when the movements' ideological perspectives on the nature of gay and lesbian identities and associated spaces shifted dramatically from the so-called liberationist stance of the mid-1970s to the so-called ethnic minority approach of the late 1970s. This occurred within the context of a particular series of events that prompted gay activists to rework their conceptualization of gay and lesbian identity in order to be recognized as legitimate participants in certain pivotal, public proceedings. Far from being a well-thought-out and deliberate shift in political strategy, the ‘minority’ argument was, in many ways, a reflexive and unexamined response to unanticipated circumstances. Toronto's gay activists, in representing gays and lesbians as a minority fundamentally altered meanings associated with both gay and lesbian identities and with the spaces dominated or controlled by gay and lesbian interests. Este artículo explora un momento particular en la historia de las políticas del movimiento de los gays de Toronto cuando sus perspectivas ideológicas sobre la naturaleza de identidades gay y lesbiana y sus espacios respectivos cambiaron dramáticamente, desde la llamada ‘perceptiva liberacionista’ de los mediados de los años setenta hasta la llamada ‘perspectiva de las minorías étnica’ de los últimos años de los setentas. Esta cambio ocurrió dentro del contexto de una serie particular de eventos que incitaron a los activistas gay a revisar sus conceptualizaciónes sobre su identidad gay y lesbiana con el fin de ser reconocidos como participantes legítimos en ciertos procesos públicos. Lejos de ser un cambio bien planeado y deliberado en la estrategia política, el argumento de la ‘minoría’ consistía, de varios maneras, en una repuesta no reflexiva no examinada a circunstancias inesperadas. Los activistas gay de Toronto, al representar a los gays y lesbianas como minorías, alteraron de manera fundamental los significados asociados tanto a las identidades de gays y lesbianas como los espacios dominados o controlados por intereses de gays y lesbianas.
Goals of Chronic Pain Management: Do Patients and Primary Care Physicians Agree and Does it Matter?

Objective: Assess patient-physician agreement on management goals for chronic musculoskeletal pain and its associations with patient and physician visit experiences. Materials and Methods: Pre-visit and post-visit questionnaires for 87 primary care visits that involved patients taking opioids for chronic musculoskeletal pain and primary care resident physicians. After each visit, patients and physicians independently ranked 5 pain treatment goals from most to least important. Results: In total, 48% of patients ranked reducing pain intensity as their top priority, whereas 22% ranked finding a diagnosis as most important. Physicians ranked improving function as the top priority for 41% of patients, and ranked reducing medication side effects as most important for 26%. The greatest difference between patient and physician rankings was for reducing pain intensity. In regression analyses, neither overall agreement on goals (ie, the physician’s first or second priority included the patient’s top priority) nor difference in patient versus physician ranking of pain intensity was significantly associated with patient-reported visit experience (&bgr; for overall agreement, −0.08; 95% confidence interval [CI], −0.45 to 0.30; P=0.69; &bgr; for intensity, −0.06; 95% CI, −0.17 to 0.04; P=0.24) or physician-reported visit difficulty (&bgr; for overall agreement, 1.92; 95% CI, −2.70 to 6.55; P=0.41; &bgr; for intensity, 0.42; 95% CI, −0.87 to 1.71; P=0.53). Discussion: Patients and physicians prioritize substantially different goals for chronic pain management, but there is no evidence that agreement predicts patient experience or physician-reported visit difficulty. Primary care physicians may have adapted to new recommendations that emphasize functional goals and avoidance of long-term opioid therapy, whereas patients continue to focus on reducing pain intensity.
Age-Related Disparity in Immediate Prognosis of Patients with Triple-Negative Breast Cancer: A Population-Based Study from SEER Cancer Registries

Background Triple-negative breast cancer (TNBC) has been demonstrated to carry poor prognosis, but whether or not there exists any age-related variation in TNBC outcomes has yet to be elucidated. The current population-based study investigated the early survival pattern of elderly women with TNBC and identified outcome-correlated factors. Patients and Methods We searched the Surveillance, Epidemiology, and End Results (SEER) database and enrolled female primary non-metastatic TNBC cases. The patients were subdivided into elderly (≥70 years) and young groups (<70 years). The survival status of elderly patients was compared to that of the younger women. The primary and secondary endpoints were cancer-specific survival (CSS) and overall survival (OS) respectively. Results 9908 female TNBC patients diagnosed from 2010 to 2011 were included in the current study (20.4% elderly). Elderly patients with relatively advanced diseases exhibited distinctly worse cancer-specific (log-rank, p<0.001) and overall survival (log-rank, p<0.001) than their young counterparts. Advanced age at diagnosis (≥70 years) was significantly predictive of poor outcome in terms of CSS (hazard ratio (HR), 2.125; 95% confidence interval (CI), 1.664 to 2.713; p<0.001) and OS (HR, 3.042; 95%CI, 2.474 to 3.740; p<0.001). Underuse of curative treatment especially radiotherapy was more prevalent in elderly women with stage II or III diseases than in younger patients. Conclusion Elderly patients with TNBC displayed elevated early mortality within the first two years of diagnosis compared to the younger individuals. The observed lower rate of loco-regional treatment might be associated with worse cancer-specific outcome for these patients.
Differences in Clinical Presentation and Findings between Idiopathic Dilated and Ischaemic Cardiomyopathy in an Unselected Population of Heart Failure Patients

We explored the differences in epidemiologic, clinical, laboratory and echocardiographic characteristics between idiopathic dilated (IDCM) and ischaemic cardiomyopathy (ICM). Consecutive patients with stable chronic heart failure evaluated at a tertiary cardiac centre were enrolled. Clinical examination, blood tests and echocardiographic study were performed. A total of 76 patients (43 IDCM, 33 ICM) were studied. IDCM patients were younger (p<0.001) and female gender was more prevalent (p=0.022). NYHA class and left ventricular ejection fraction were similar. IDCM patients had lower rates of dyslipidaemia (p<0.001) but smoked more than ICM patients (p=0.023) and had higher rates of family history of sudden cardiac death (p=0.048). Blood pressure was similar but resting heart rate was higher in IDCM patients (p=0.022). IDCM patients presented less frequently with peripheral oedema or ascites (p=0.046 and 0.020, respectively) and showed better right ventricular function on echocardiogram. QRS duration was similar between groups but only in IDCM patients there was a positive correlation between QRS duration and age (r=0.619, p<0.001). Cardiac output was similar but functional capacity assessed by the Duke Activity Status Index was better in IDCM (p=0.036). Despite these differences, IDCM and ICM patients received similar treatments. Patients with IDCM were younger, presented lower rates of right ventricular dysfunction and clinical right ventricular failure and had better functional capacity. Additional differences in clinical and laboratory findings exist pointing to a different patient population with diverse prognosis and potential need for individualized management.
Impact of a comanaged Geriatric Fracture Center on short-term hip fracture outcomes.

BACKGROUND Hip fractures are associated with substantial morbidity and mortality for older adults. Patients sustaining hip fractures usually have comorbid conditions that may benefit from comanagement by geriatricians and orthopedic surgeons. METHODS The Geriatric Fracture Center (GFC) is part of a community teaching hospital. Patients are comanaged daily by a geriatrician and orthopedic surgeon, emphasizing total quality management, timely treatment, and standardized care. We reviewed medical records to compare process and outcome measures in the GFC with a local institution that did not have a fracture management service. Patients 60 years or older admitted for a proximal femur fracture from May 1, 2005, to April 30, 2006, were included; pathological, recurrent, high-energy, periprosthetic, and nonoperative fractures were excluded. RESULTS Geriatric Fracture Center patients (n = 193) were significantly older, were less likely to reside in the community, and had more comorbid conditions and dementia than usual care patients (n = 121). Despite baseline differences, GFC patients, compared with usual care patients, had shorter times to surgery (24.1 vs 37.4 hours), fewer postoperative infections (2.3% vs 19.8%), fewer complications overall (30.6% vs 46.3%), and shorter length of stay (4.6 vs 8.3 days). Compared with GFC patients, physical restraint use was significantly higher in usual care patients (0% vs 14.1%). After we adjusted for baseline characteristics, patients treated in the GFC had shorter times to surgery, shorter length of stay, fewer cardiac complications, and fewer cases of thromboembolism, delirium, and infection. There was no difference in in-hospital mortality or 30-day readmission rate. CONCLUSION Comanagement by geriatricians and orthopedic surgeons, combined with standardized care, leads to improved processes and outcomes for patients with hip fractures.
Cardioprotection and Myocardial Reperfusion: Pitfalls to Clinical Application

Abstract: With the advent of thrombolytic therapy and angioplasty, it has become possible to reduce myocardial infarct size through early reperfusion. Enormous effort has been expended to find therapies that can further reduce infarct size after early intervention. Animal studies have identified many cardioprotective pathways that have the potential to reduce infarct size if activated before the onset of ischemia. More recently, interventions effective at the onset of reperfusion have been described. Although basic research has identified many targets, most has been conducted in rodent models which may not be directly applicable to human disease and even promising agents have been disappointing in large-scale clinical trials. There are many potential explanations for this failure which is the subject of this review. Potential factors include (1) the variability inherent in the patient population, whereas animal studies usually use single sex homogeneous groups maintained on standard diets in carefully controlled environments; (2) the duration of ischemia is generally shorter in animal studies, resulting in potentially more salvageable myocardium than is often the case in patients; (3) that the animals are usually young without comorbidities, whereas the patient population is generally older and has significant comorbidities; (4) animals are not treated with medications a priori, whereas the patient population is often taking medications that may affect ischemic injury; and (5) animal studies may not involve thorough assessment of effects on organs other than the heart, whereas patients can experience adverse effects of treatment in other organs that can preclude clinical use.
Co-Occurrences of Antonymous Adjectives and Their Contexts

Charles and Miller propose that lexical associations between antonymous adjectives are formed via their co-occurences within the same sentence (the co-occurrence hypothesis), rather than via their syntatic substitutability (the substitutability hypothesis), and that such co-occurrences must take place more often than expected by chance. This paper provides empirical support for the co-occurrence hypothesis in a corpus analysis of all high-frequency adjectives and their antonyms and of a major group of morphologically derived antonyms (e.g., impossible, un-happy). We show that very high co-occurrence rates do appear to characterize all antonymous adjective pairs, supporting the precondition for the formation of the association; and we find that the syntactic contexts of these co-occurrences raise the intrinsic associability of antonyms when they do co-occur. We show that via one of these patterns, mutual substitution within otherwise repeated phrases in a sentence, the co-occurrences hypothesis captures the generalizations that were the basis for the substitutability hypothesis for the formation of antonymic associations.
Induction of Adrenomedullin mRNA and Protein by Lipopolysaccharide and Paclitaxel (Taxol) in Murine Macrophages

ABSTRACT Lipopolysaccharide (LPS), a potent inflammatory stimulus derived from the outer membrane of gram-negative bacteria, has been implicated in septic shock. Plasma levels of adrenomedullin (AM), a potent vasorelaxant, are increased in septic shock and possibly contribute to the characteristic hypotension. As macrophages play a central role in the host response to LPS, we studied AM production by LPS-stimulated macrophages. When peritoneal exudate macrophages from C3H/OuJ mice were treated with protein-free LPS (100 ng/ml) or the LPS mimetic paclitaxel (Taxol; 35 μM), an ∼10-fold increase in steady-state AM mRNA levels was observed, which peaked between 2 and 4 h. A three- to fourfold maximum increase in the levels of immunoreactive AM protein was detected after 6 to 8 h of stimulation. While LPS-hyporesponsive C3H/HeJ macrophages failed to respond to protein-free LPS with an increase in steady-state AM mRNA levels, increased levels were observed after stimulation of these cells with a protein-rich (butanol-extracted) LPS preparation. In addition, increased AM mRNA was observed following treatment of either C3H/OuJ or C3H/HeJ macrophages with soluble Toxoplasma gondii tachyzoite antigen or the synthetic flavone analog 5,6-dimethylxanthenone-4-acetic acid. Gamma interferon also stimulated C3H/OuJ macrophages to express increased AM mRNA levels yet was inhibitory in the presence of LPS or paclitaxel. In vivo, mice challenged intraperitoneally with 25 μg of LPS exhibited increased AM mRNA levels in the lungs, liver, and spleen; the greatest increase (>50-fold) was observed in the liver and lungs. Thus, AM is produced, by murine macrophages, and furthermore, LPS induces AM mRNA in vivo in a number of tissues. These data support a possible role for AM in the pathophysiology of sepsis and septic shock.
A New Language for Psychoanalysis

The “action language” for psychoanalysis which Schafer proposes is a welcome comment on Freud’s mode of conceptualization while attempting to dispense with his mechanistic vocabulary. Even more welcome is Schafer’s implicit invitation to philosophers to join the conversation, since we have been talking a long time ourselves about several issues which his work transects. Recalling these, therefore, may help to frame both the strengths and the weaknesses of his account. One of these issues is the nature of reason itself it’s intrinsically interesting, but philosophers have also valued it as a means of illuminating human behavior. Trees don’t do things for reasons and on purpose and in light of certain beliefs: human beings do. This investigation therefore raises a more general question about the place of man and mind in the world order. Human beings do not much resemble lower animals, but there is a kinship to felines and to other primates. Since people have always used their presumed differencesboth from other species and from other human groupsas justification for oppression and celebrations of all kinds, the definition of these differences has profound moral consequences. What is it so peculiar to ourselves that justifies the belief, in this culture, that killing a cow isn’t murder, while killing another human being may be; and taking a bone from a dog isn’t stealing, while taking someone else’s wife or husband may be? More important, whatever this peculiarity is, can we assume that all human beings have it, and to the same degree? The obverse of this question inquires about the meaning of “responsibility. ” In one tone of voice, we sometimes say that mad dogs are as responsible as Englishmen for whatever damage they
Trends in the number of lightning days at major domestic sites based on the observation record of the Japan meteorological agency

The damages caused by lightning on modern electrical and electronic devices that have low resistance against external noise tend to increase yearly. In recent years, though an increase in the frequency of lightning strikes due to global warming is often reported, a demonstration with credible data has not yet been performed. We have consolidated the data on the annual lightning days in each region for approximately the last 100 years published together with other weather data from the website of the Japan Meteorological Agency, and we report the study results.
Effect of Golimumab on Carotid Atherosclerotic Disease Measures and Cardiovascular Events in Inflammatory Arthritides

ObjectiveThe objective of this study was to assess the effect of golimumab on carotid ultrasound measures and cardiovascular serious adverse events (SAEs) in patients with inflammatory arthritides. MethodsAn exploratory carotid artery ultrasound substudy was performed in the GO-BEFORE study of methotrexate (MTX)–naive rheumatoid arthritis patients, with ultrasounds performed at weeks 0, 24, and 52 to measure common carotid artery intima-media thickness, distensibility coefficient, interadventitial diameter, and plaque count. Cardiovascular SAEs reported over 2 years of follow-up were assessed in 5 golimumab phase 3 clinical trials of patients with rheumatoid arthritis (GO-BEFORE, GO-FORWARD, and GO-AFTER), psoriatic arthritis (GO-REVEAL), and ankylosing spondylitis (GO-RAISE). In GO-BEFORE and GO-FORWARD, patients received placebo + MTX, golimumab 50 mg + MTX, or golimumab 100 mg +/− MTX at baseline and every 4 weeks; in the other 3 trials, patients received placebo or golimumab 50 or 100 mg. ResultsThe carotid ultrasound substudy showed inconsistent changes in common carotid artery intima-media thickness in the golimumab + MTX groups over time, and there was large variability in the measurements. Increases in interadventitial diameter were observed in the golimumab 100 mg + placebo group, but not in the golimumab + MTX groups. There were no significant differences in the distensibility coefficient and plaque count between the golimumab and placebo groups. Very few patients overall experienced a cardiovascular SAE, and the incidence of cardiovascular SAEs was not statistically different between the golimumab and placebo groups. ConclusionsThe results of the carotid ultrasound substudy were inconclusive, and no increase or decrease in cardiovascular SAEs was observed following 2 years of treatment with golimumab with or without MTX.
Bmp signaling is necessary and sufficient for ventrolateral endoderm specification in Xenopus

Here we show that Bmp signaling is necessary and sufficient for the specification of ventral endoderm in Xenopus embryos. Overexpression of Bmp4 in ectoderm induces markers of endoderm, including Sox17β, Mixer, and VegT, but cannot induce the expression of the dorsoanterior markers, Xhex and Cerberus. Furthermore, knockdown approaches using overexpression of Bmp antagonists and morpholinos designed against Bmp4, Bmp2, and Bmp7 demonstrate that Bmp signaling is critical for ventral, but not dorsoanterior endoderm formation. This activity is not simply a result of embryonic dorsalization as markers for dorsal endoderm are not expanded. We further show that endodermal cells of either ventral or dorsal character do not form when both Wnt and Bmp signals are abolished. Overall, this report strongly suggests that Bmp plays an essential role in ventral endoderm specification. Developmental Dynamics 237:2177–2186, 2008. © 2008 Wiley‐Liss, Inc.