Miracle-dz/UniFAR-FTUs huggingface dataset:
American Indian/First Nation Place Attachment to Park Lands: The Case of the Nuu-chah-nulth of British Columbia

This article reports the results of a case study of place attachment to park lands among American Indians/First Nations (the Nuu-chah-nulth peoples) in British Columbia, Canada. “First Nations” is the term used for Canada’s aboriginal peoples. Some common values can be identified in nearly all North American aboriginal cultures to a lesser or greater degree. Many share the same cultural values and worldviews, and share the same relationships with lands that once were their traditional areas. Many of today’s national, state and provincial parks were created out of lands that at one time were traditional use areas of aboriginal peoples. Many of these parks now share borders with reservations and reserves, or are located near Indian communities. There is a need for more understanding of American Indian/First Nation views toward the land, and toward parks and protected areas. An examination of place attachment and meanings for the Nuu-chah-nulth can yield information helpful in understanding other North American aboriginal peoples. The article describes the historical relationships the Nuu-chah-nulth people have both with the park and protected lands surrounding their communities and with the government agencies that control these lands. The study uses archive material and contemporary interviews with First Nation people to describe the contemporary meanings of place held by the Nuu-chah-nulth people; examines how historical relationships with park lands influence contemporary place attachment in American Indian/First Nation communities; and, makes recommendations to park management agencies concerning American Indians/First Nations. Recommendations from this research include: park managers need to be aware of the depth of place meanings attached to park lands that used to be in tribal control and more aware of the way lands were obtained for parks and protected areas; managers need to understand that debates over park resources may symbolize cultural reclamation and the ability of a tribal people to determine their own destiny; and park management agencies should consider co-management options for managing parks and protected areas that have cultural and symbolic significance for American Indian/First Nation people, co-management options where American Indian/First Nation people are fully involved in all phases of the management process.
Biomarkers in renal cell carcinoma

Purpose of review To review the latest information on biomarkers in renal cell carcinoma and their use in integrated staging systems. Recent findings The discovery of the Von Hippel-Lindau defect and the hypoxia inducible factor-1α transcripted genes has led to an explosion in the understanding of molecular pathways in renal cell carcinoma. The two most prominent biomarkers are carbonic anhydrase IX and vascular endothelial-derived growth factor. Carbonic anhydrase IX has demonstrated excellent specificity and ability to predict treatment response. Vascular-derived growth factor has good correlation with stage, grade and increased levels with adverse survival. Markers such as CXCL16, ADAM10, B7-H1, Ki-67, survivin, P53, GLUT-1, calveolin-1 and endoglin are continuously being validated. CXCL16 is one of the newest biomarkers, is significantly expressed in papillary renal cell carcinoma and is an independent prognostic marker for better patient survival. The incorporation of biomarkers into integrated staging systems such as UCLA Integrated Staging System, SSIGN and Bioscore are discussed and compared. Summary The use of novel molecular biomarkers are being incorporated into clinical practice. The understanding of molecular pathways will lead to tailored treatment to the individual patient.
Fine‐needle aspiration biopsy findings in sclerosing polycystic adenosis of the parotid gland

Sclerosing polycystic adenosis (SPA) is a recently described, rare lesion of the salivary gland analogous to fibrocystic disease of the breast. Recognition of this benign entity is important since the differential diagnosis includes other more common benign and malignant salivary gland neoplasms, particularly mucoepidermoid carcinoma and tumors with cystic and oncocytic features. While the histomorphology of SPA is well documented, there is only one other cytologic description of SPA in the English‐language literature. Here we describe the fine‐needle aspiration biopsy findings in a case of SPA of the parotid gland in an 84‐year‐old woman. The aspirate was characterized by flat cohesive sheets of epithelial cells with moderate amounts of finely granular oncocytic cytoplasm and enlarged round nuclei with indistinct nucleoli. Some epithelial groups formed glandular structures with lumens, and the background contained small amounts of delicate mucoproteinaceous material. Occasional markedly vacuolated cells were present as well as many cells with apocrine change manifested by well‐defined apical snouting. Familiarity with the cytomorphologic features of SPA, including its characteristic apocrine changes, is important for distinguishing it from other more clinically significant salivary gland lesions. Diagn. Cytopathol. 2007;35:444–447. © 2007 Wiley‐Liss, Inc.
Natural Polymorphisms of Human Immunodeficiency Virus Type 1 Integrase and Inherent Susceptibilities to a Panel of Integrase Inhibitors

ABSTRACT We evaluated the human immunodeficiency virus type 1 (HIV-1) integrase coding region of the pol gene for the presence of natural polymorphisms in patients during early infection (AHI) and with triple-class drug-resistant HIV-1 (MDR). We analyzed selected recombinant viruses containing patient-derived HIV-1 integrase for susceptibility to a panel of strand transfer integrase inhibitors (InSTI). A pretreatment sequence analysis of the integrase coding region was performed for 112 patients identified during acute or early infection and 15 patients with triple-class resistance. A phenotypic analysis was done on 10 recombinant viruses derived from nine patients against a panel of six diverse InSTI. Few of the polymorphisms associated with in vitro InSTI resistance were identified in the samples from newly infected individuals or those patients with MDR HIV-1. We identified polymorphisms V72I, L74I, T97A, V151I, M154I/L, E157Q, V165I, V201I, I203M, T206S, and S230N. V72I was the most common, seen in 63 (56.3%) of the AHI samples. E157Q was the only naturally occurring mutation thought to contribute to resistance to elvitegravir, raltegravir, and L-870,810. None of the patient-derived viruses demonstrated any significant decrease in susceptibility to the drugs tested. In summary, the integrase coding region contains as much natural variation as that seen in protease, but mutations associated with high-level resistance to existing InSTI are rarely, if ever, present in integrase naïve patients, especially those being used clinically. Most of the highly prevalent polymorphisms have little effect on InSTI susceptibility in the absence of specific primary mutations. Baseline testing for integrase susceptibility in InSTI-naïve patients is not currently warranted.
Open-label, multicenter, randomized, phase III study comparing oral topotecan/cisplatin versus etoposide/cisplatin as treatment for chemotherapy-naive patients with extensive-disease small-cell lung cancer.

PURPOSE This open-label, randomized, multicenter phase III study compared oral topotecan/intravenous cisplatin (TC) with intravenous (IV) etoposide/cisplatin (PE) in patients with untreated extensive-disease small-cell lung cancer (ED-SCLC). PATIENTS AND METHODS A total of 784 patients were randomly assigned to either oral topotecan 1.7 mg/m2/d x 5 with IV cisplatin 60 mg/m2 on day 5 (n = 389) or IV etoposide 100 mg/m2/d x 3 with IV cisplatin 80 mg/m2 on day 1 (n = 395) every 21 days. RESULTS Overall survival (primary end point) was similar between groups (P = .48; median: TC, 39.3 weeks v PE, 40.3 weeks). One-year survival was 31% (95% CI, 27% to 36%) in both groups and the difference of -0.03 (95% CI, -6.53 to 6.47) met the predefined criteria of < or = 10% absolute difference for noninferiority of TC relative to PE. Response rates were similar between groups (TC, 63% v PE, 69%). Time to progression was slightly but statistically longer with PE (log-rank P = .02; median: TC, 24.1 weeks v PE, 25.1 weeks). The regimens were similarly tolerable. Grade 3/4 neutropenia occurred more frequently with PE (84% v 59%), whereas grade 3/4 anemia and thrombocytopenia occurred more frequently with TC (38% v 21% and 38% v 23%, respectively). Lung Cancer Symptom Scale scores were statistically better with PE, but the differences were small and of debatable clinical significance. CONCLUSION Oral topotecan with cisplatin provides similar efficacy and tolerability to the standard (etoposide with cisplatin) in untreated ED-SCLC and may provide greater patient convenience compared with intravenous etoposide and cisplatin.
Growth impairment resulting from expression of influenza virus M2 protein in Saccharomyces cerevisiae: identification of a novel inhibitor of influenza virus

The gene encoding M2, the ion channel-forming protein of influenza virus A, was expressed under the control of an inducible promoter in Saccharomyces cerevisiae. By using single and multicopy plasmids containing GAL promoter-M2 fusions, a correlation was observed between plasmid copy number and growth in medium inducing M2 expression. Cells expressing M2 from multicopy plasmids have reduced growth rates, suggesting that high levels of M2 are toxic to growth. The addition of amantadine, a compound known to block the ion channel activity of certain M2 alleles, restores the growth rates to wild-type levels in cells expressing an amantadine-susceptible allele of M2 but not an amantadine-resistant allele of M2, suggesting that M2 expression in S. cerevisiae results in the formation of functional M2 ion channels. Measurements of extracellular acidification by microphysiometry suggest that proton efflux in M2-expressing cells is altered and that the addition of amantadine permits the reestablishment of the proton gradient. The growth impairment phenotype resulting from M2 expression was used to develop a high-capacity screening assay which identified a novel inhibitor possessing an antiviral profile similar to that of amantadine.
NON-INVASIVE ANGIOGRAPHY Original Studies Reproducible Coronary Plaque Quantification by Multislice Computed Tomography

Background: The aim of this study was to investigate reproducibility and accuracy of computer-assisted coronary plaque measurements by multislice computed tomography coronary angiography (QMSCT-CA). Methods and Results: Forty-eight patients undergoing MSCT-CA and coronary arteriography for symptomatic coronary artery disease and quantitative intravascular ultrasound (IVUS, QCU) were examined. Two investigators performed the QMSCT-CA twice and a third investigator performed the QCU, all blinded for each other’s results. There was no difference found for the matched region of interest (ROI) lengths (QCU 29.4 6 13 mm vs. QMSCT-CA 29.6 6 13 mm, P = 0.6; total length = 1,400 mm). The comparison of volumetric measurements showed (lumen QCU 267 6 139 mm vs. mean QMSCT-CA 177 6 91 mm, P < 0.001; vessel 454 6 194 mm vs. 398 6 187 mm, P < 0.001; and plaque 189 6 93 mm vs. 222 6 121 mm; investigator 1, P = 0.02; and investigator 2, P = 0.07) significant differences. Automated lumen detection was also applied for QMSCT-CA (2186 112 mm, P < 0.001 vs. QCU). The interinvestigator variability measurements for QMSCT-CA showed no significant differences. Conclusion: QMSCTCA systematically underestimates absolute coronary lumenand vessel dimensions when compared with QCU. However, repeated measurements of coronary plaque by QMSCT-CA showed no statistically significant differences, although, the outcome showed a scattered result. Automated lumen detection for QMSCT-CA showed improved results when compared with those of human investigators. ' 2007 Wiley-Liss, Inc.
Translating research to clinical practice: a 1-year experience with implementing early goal-directed therapy for septic shock in the emergency department.

OBJECTIVE Early goal-directed therapy (EGDT) has been shown to decrease mortality in patients with severe sepsis and septic shock. Consensus guidelines now advocate EGDT for the first 6 h of sepsis resuscitation. However, EGDT has not yet been widely adopted in practice. A need for effective collaboration between emergency medicine and critical care medicine services has been identified as an obstacle for implementation. We aimed to determine if EGDT end points could reliably be achieved in real-world clinical practice. METHODS EGDT was implemented as a collaborative emergency medicine/critical care quality improvement initiative. EGDT included the following: i.v. fluids (IVF) targeting central venous pressure > or = 8 mm Hg, vasopressors targeting mean arterial pressure > or = 65 mm Hg, and (if necessary) packed RBCs (PRBCs) and/or dobutamine targeting central venous oxygen saturation > or = 70%. A retrospective analysis was performed of emergency department (ED) patients with persistent sepsis-induced hypotension (systolic BP < 90 mm Hg despite 1.5 L of IVF) treated with EGDT during the first year of the initiative. Primary outcome measures included successful achievement of EGDT end points and time to achievement. A secondary analysis was performed comparing EGDT cases to historical control cases (nonprotocolized control subjects without invasive monitoring). RESULTS All end points were achieved in 20 of 22 cases (91%). The median time to reach each end point was < or = 6 h. In the secondary analysis, patients (n = 38; EGDT, n = 22; pre-EGDT, n = 16) had similar age, do-not-resuscitate status, severity scores, hypotension duration, and vasopressor requirement (p = not significant). In the ED, EGDT used more IVF and included PRBC/dobutamine utilization, without any impact on the overall use of these therapies through the first 24 h in the ICU. EGDT was associated with decreased ICU pulmonary artery catheter (PAC) utilization (9.1% vs 43.7%, p = 0.01). CONCLUSIONS With effective emergency medicine/critical care collaboration, we demonstrate that EGDT end points can reliably be achieved in real-world sepsis resuscitation. ED-based EGDT appears to decrease ICU PAC utilization.
Group B Streptococcus and Escherichia coli Infections in the Intensive Care Nursery in the Era of Intrapartum Antibiotic Prophylaxis

Background: Group B Streptococcus (GBS) and Escherichia coli cause serious bacterial infections (SBIs) and are associated with morbidity and mortality in newborn infants. Intrapartum antibiotic prophylaxis reduces early-onset SBIs caused by GBS. The effect of intrapartum antibiotic prophylaxis on late-onset SBIs caused by these organisms is unknown. Methods: We examined all blood, urine and cerebrospinal fluid culture results from infants admitted from 1997 to 2010 to 322 neonatal intensive care units managed by the Pediatrix Medical Group. We identified infants with positive cultures for GBS or E. coli and compared the incidence of early- and late-onset SBI for each organism in the time period before (1997 to 2001) and after (2002 to 2010) universal intrapartum antibiotic prophylaxis recommendations. Results: We identified 716,407 infants with cultures, 2520 (0.4%) with cultures positive for GBS and 2476 (0.3%) with cultures positive for E. coli. The incidence of GBS early-onset SBI decreased between 1997 to 2001 and 2002 to 2010 from 3.5 to 2.6 per 1000 admissions, and the incidence for E. coli early-onset SBI remained stable (1.4/1000 admissions in both time periods). Over the same time period, the incidence of GBS late-onset SBI increased from 0.8 to 1.1 per 1000 admissions, and incidence of E. coli late-onset SBI increased from 2.2 to 2.5 per 1000 admissions. Conclusions: In our cohort, the incidence of GBS early-onset SBI decreased, whereas the incidence of late-onset SBI for E. coli and GBS increased.
Childhood maltreatment, personality disorders and 3-year persistence of adult alcohol and nicotine dependence in a national sample.

BACKGROUND AND AIMS Persistent cases of alcohol and nicotine dependence are associated with considerable morbidity and mortality, and are predicted by childhood maltreatment and personality disorders. Our aim was to test whether personality disorders (individually or conjointly) mediate the relationship between childhood maltreatment and the persistence of dependence. DESIGN Personality disorders, modeled dimensionally, were tested as mediators of the relationship between childhood maltreatment and the 3-year persistence of alcohol and nicotine dependence in participants in the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) who had current alcohol and nicotine dependence in their baseline interview. Individual personality disorders were assessed in separate models. Then, those that were significant were examined jointly in multiple mediator models to determine their total and unique effects. SETTING A large, nationally representative US survey. PARTICIPANTS Participants ≥ 18 years who completed baseline and 3-year follow-up NESARC interviews who had baseline alcohol dependence (n = 1172; 68% male) or nicotine dependence (n = 4017; 52.9% male). MEASUREMENTS Alcohol Use Disorder and Associated Disabilities Interview Schedule (AUDADIS-IV) measures of childhood maltreatment, personality disorders and alcohol/nicotine dependence. FINDINGS Individual models indicated that many personality disorders mediated the relationship between childhood maltreatment and the 3-year persistence of alcohol and nicotine dependence (each explaining 6-46% of the total effect, Ps < 0.05). In multiple mediator models, borderline and antisocial symptoms remained significant mediators, each explaining 20-37% of the total effect (Ps < 0.01). CONCLUSIONS Personality disorder symptoms (especially borderline and antisocial) help explain the association between childhood maltreatment and persistent alcohol and nicotine dependence.
Migraine Associated with Patent Foramen Ovale May Be Caused by Reactivation of Cerebral Toxoplasmosis Triggered by Arterial Blood Oxygen Desaturation

ABSTRACT Approximately two billion people worldwide are chronically infected with T. gondii and yet with largely unknown consequences. On the other hand, several authors reported an association between migraine and patent foramen ovale (PFO), and different types of headaches, including migraine, may be precipitated by various diseased states or medications associated with marked immune irregularities, which sometimes cause reactivation of latent cerebral toxoplasmosis (CT). Recently, in a group of 104 subjects with migraine, 46 individuals (44.2%%) were found to be seropositive for T. gondii. PFO, atrial septal defects, as well as pulmonary right-to-left shunts are usually associated with a various degree of arterial blood oxygen desaturation. Hypoxia is associated with an increase in the generation of several proinflammatory cytokines and other inflammation mediators, such as TNF-α, IL-1-β, IL-6, IL-8, chemokines (monocyte chemoattractant protein-1, CC-chemokine receptor 2, macrophage inflammatory protein-1α, intercellular adhesion molecule-1), acute-phase protein gene expressions, COX-2 gene transcription, induction of iNOS, and reactive oxygen species. Moreover, hypoxia markedly decreased T-lymphocyte IL-2 mRNA, a key cytokine responsible for B-cell proliferation and immunoglobulin secretion, and ischemic tissues demonstrated intravascular neutrophil accumulation, vascular damage, and increased vascular wall permeability. Interestingly, T. gondii activates hypoxia-inducible factor 1 already at physiologically relevant oxygen levels and requires HIF1 for growth and survival. These abnormalities may cause imbalance in the host/T. gondii immune system, which finally results in the reactivation of CT. In addition, hypoxia may participate in paradoxical microembolism because arterial oxygen desaturation enhances expression of plasminogen activator inhibitor-1, an important factor which suppresses fibrinolysis, and this effect may be further amplified by a decreased expression of plasminogen activators, finally causing blood hypercoagulability and paradoxical microembolism. In summary, further studies are required to verify the above-presented pathomechanisms probably responsible for the association between PFO and the development of migraine. It is possible that some migraineurs with PFO may benefit from evaluation and treatment of toxoplasmosis in the future once more information is known.
Wnt/β‐catenin and sonic hedgehog pathways interact in the regulation of the development of the dorsal mesenchymal protrusion

Background: The dorsal mesenchymal protrusion (DMP) is a second heart field (SHF) derived tissue involved in cardiac septation. Molecular mechanisms controlling SHF/DMP development include the Bone Morphogenetic Protein and Wnt/β‐catenin signaling pathways. Reduced expression of components in these pathways leads to inhibition of proliferation of the SHF/DMP precursor population and failure of the DMP to develop. While the Sonic Hedgehog (Shh) pathway has also been demonstrated to be critically important for SHF/DMP development and atrioventricular septation, its role in the regulation of SHF proliferation is contentious. Results: Tissue‐specific deletion of the Shh receptor Smoothened from the SHF resulted in compromised DMP formation and atrioventricular septal defects (AVSDs). Immunohistochemical analysis at critical stages of DMP development showed significant proliferation defect as well as reduction in levels of the Wnt/β‐catenin pathway‐intermediates β‐catenin, Lef1, and Axin2. To determine whether the defects seen in the conditional Smoothened knock‐out mouse could be attributed to reduced Wnt/β‐catenin signaling, LiCl, a pharmacological activator of this Wnt/β‐catenin pathway, was administered. This resulted in restoration of proliferation and partial rescue of the AVSD phenotype. Conclusions: The data presented suggest that the Wnt/β‐catenin pathway interact with the Shh pathway in the regulation of SHF/DMP‐precursor proliferation and, hence, the development of the DMP. Developmental Dynamics 245:103–113, 2016. © 2015 Wiley Periodicals, Inc.
Verification of the protein in the outer membrane of Bdellovibrio bacteriovorus as the OmpF protein of its Escherichia coli prey

Two research groups showed that several Bdellovibrio strains incorporated into their outer membranes intact OmpF porin proteins derived from their Escherichia coli prey. These results could not be reproduced by another group using Bdellovibrio bacteriovorus 109J. They showed that a major protein appearing in the Bdellovibrio Triton X-100-insoluble outer membrane was coded for by the bdellovibrios. We reconciled these results by examining the strain used by this group and by reviving a freeze-dried culture of strain 109J which had been stored for almost 9 years. B. bacteriovorus 109J failed to acquire substantial amounts of the OmpF protein from E. coli ML35, and a protein coded for by the bdellovibrios was expressed in its place. However, B. bacteriovorus 109J incorporated the OmpF protein from rough K-12 strains of E. coli, and the revived 9-year-old culture of B. bacteriovorus 109J incorporated more of the OmpF protein from the smooth E. coli ML35 than did its contemporary counterpart. The protein isolated from the outer membrane of the bdellovibrios was identified as the OmpF protein of E. coli by its protease peptide profile on sodium dodecyl sulfate-polyacrylamide gel electrophoresis and by Western blot analysis. This confirmed that bdellovibrios relocalize outer membrane proteins from their prey, but relocalization may be an unstable trait which can be influenced by the prey.