Miracle-dz/UniFAR-FTUs huggingface dataset:
Mannose receptor high, M2 dermal macrophages mediate nonhealing Leishmania major infection in a Th1 immune environment

The origin and functional specialization of dermal macrophages in cutaneous infections have been little studied. In this paper, we show that a strain of Leishmania major (L. major Seidman [LmSd]) that produces nonhealing cutaneous lesions in conventionally resistant C57BL/6 mice was more efficiently taken up by M2-polarized bone marrow (BM)–derived macrophages (BMDMs) in vitro and by mannose receptor (MR)hi dermal macrophages in vivo compared with a healing strain (L. major Friedlin V1). Both in steady and in T helper type 1 (Th1) cell–driven inflammatory states, the MRhi dermal macrophages showed M2 characteristics. The dermal macrophages were radio resistant and not replaced by monocytes or adult BM-derived cells during infection, but were locally maintained by IL-4 and IL-10. Notably, the favored infection of M2 BMDMs by LmSd in vitro was MR dependent, and genetic deletion of MR or selective depletion of MRhi dermal macrophages by anti–CSF-1 receptor antibody reversed the nonhealing phenotype. We conclude that embryonic-derived, MRhi dermal macrophages are permissive for parasite growth even in a strong Th1-immune environment, and the preferential infection of these cells plays a crucial role in the severity of cutaneous disease.
Prognostic Utility of 90Y Radioembolization Dosimetry Based on Fusion 99mTc-Macroaggregated Albumin–99mTc-Sulfur Colloid SPECT

Planning hepatic 90Y radioembolization activity requires balancing toxicity with efficacy. We developed a dual-tracer SPECT fusion imaging protocol that merges data on radioactivity distribution with physiologic liver mapping. Methods: Twenty-five patients with colorectal carcinoma and bilobar liver metastases received whole-liver radioembolization with resin microspheres prescribed as per convention (mean administered activity, 1.69 GBq). As part of standard treatment planning, all patients underwent SPECT imaging after intraarterial injection of 37 MBq of 99mTc-macroaggregated albumin (99mTc-MAA) to simulate subsequent 90Y distribution. Immediately afterward, patients received 185 MBq of labeled sulfur colloid (99mTc-SC) intravenously as a biomarker for normal hepatic reticuloendothelial function and SPECT was repeated. The SPECT images were coregistered and fused. A region-based method was used to predict the 90Y radiation absorbed dose to functional liver tissue (DFL) by calculation of 99mTc-MAA activity in regions with 99mTc-SC uptake. Similarly, the absorbed dose to tumor (DT) was predicted by calculation of 99mTc-MAA activity in voxels without 99mTc-SC uptake. Laboratory data and radiographic response were measured for 3 mo, and the survival of patients was recorded. SPECT-based DT and DFL were correlated with parameters of toxicity and efficacy. Results: Toxicity, as measured by increase in serum liver enzymes, correlated significantly with SPECT-based calculation of DFL at all time points (P < 0.05) (mean DFL, 27.9 Gy). Broad biochemical toxicity (>50% increase in all liver enzymes) occurred at a DFL of 24.5 Gy and above. In addition, in uni- and multivariate analysis, SPECT-based calculation of DT (mean DT, 44.2 Gy) correlated with radiographic response (P < 0.001), decrease in serum carcinoembryonic antigen (P < 0.05), and overall survival (P < 0.01). The cutoff value of DT for prediction of 1-y survival was 55 Gy (area under the receiver-operating-characteristic curve = 0.86; P < 0.01). Patients who received a DT of more than 55 Gy had a median survival of 32.8 mo, compared with 7.2 mo in patients who received less (P < 0.05). Conclusion: Dual-tracer 99mTc-MAA–99mTc-SC fusion SPECT offers a physiology-based imaging tool with significant prognostic power that may lead to improved personalized activity planning.
A New Technique for Integrating MEMS-Based Low-Cost IMU and GPS in Vehicular Navigation

In providing acceptable navigational solutions, Location-Based Services (LBS) in land navigation rely mostly on integration of Global Positioning System (GPS) and Inertial Navigation System (INS) measurements for accuracy and robustness. The GPS/INS integrated system can provide better land-navigation solutions than the ones any standalone system can provide. Low-cost Inertial Measurement Units (IMUs), based on Microelectromechanical Systems (MEMS) technology, revolutionized the land-navigation system by virtue of their low-cost miniaturization and widespread availability. However, their accuracy is strongly affected by their inherent systematic and stochastic errors, which depend mainly on environmental conditions. The environmental noise and nonlinearities prevent obtaining optimal localization estimates in Land Vehicular Navigation (LVN) while using traditional Kalman Filters (KF). The main goal of this paper is to effectively eliminate stochastic errors of MEMS-based IMUs. The proposed solution is divided into two main components: (1) improving noise cancellation, using advanced stochastic error models in MEMS-based IMUs based on combined Autoregressive Processes (ARP) and first-order Gauss-Markov Process (1GMP), and (2) modeling the low-cost GPS/INS integration, using a hybrid Fuzzy Inference System (FIS) and Second-Order Extended Kalman Filter (SOEKF). The results obtained show that the proposed methods perform better than the traditional techniques do in different stochastic and dynamic situations.
Methylglyoxal, cognitive function and cerebral atrophy in older people.

BACKGROUND The effects of advanced glycation endproducts on cognition and brain structure are poorly understood. We studied associations of the advanced glycation endproduct precursor methylglyoxal (MGO) with cognitive function and brain volumes in older people. METHODS Nondemented participants in the Tasmanian Study of Cognition and Gait underwent cognitive testing and brain magnetic resonance imaging scans. Brain volumes were obtained by magnetic resonance imaging scan segmentation and statistical parametric mapping procedures. Serum MGO was measured after derivatization to methylquinoxaline by high pressure liquid chromatography and UV detection. Linear regression was used to examine associations of log-transformed MGO with cognitive scores and brain volumes adjusting for potential confounding by age, sex, education, mood, insulin resistance, history of stroke, vascular risk factors, alcohol intake, and psychoactive medication use. RESULTS There were 378 participants, mean age 72.1 years (SD 7.1), 55% male. Greater MGO was associated with poorer memory (β = -.12, 95% confidence interval: -0.22, -0.02, p = .02) and executive function, the latter being greater among those with a history of stroke (MGO × stroke β = .48, 95% confidence interval: 0.17, 0.79, p = .002). Greater MGO was associated with lower grey matter volume (β = -6.42, 95% confidence interval -11.82, -1.11, p = .02) but not with white matter volume, white matter lesion volume, or hippocampal volume. CONCLUSIONS These results support the investigation of the role of the advanced glycation endproduct precursor methylglyoxal in cognitive decline and neurodegeneration in older people.
Cultural Heterogeneity and Law: Pornography, Blasphemy, and the First Amendment

Feminists have recently sought the regulation of pornography on the grounds that pornography injures women as a group. This feminist challenge raises a vital constitutional question about the kinds of values the first amendment should protect. Professor Post here considers that question in light of three alternative means by which a legal order might be structured for a society made up of heterogenous groups: (1) assimilationism, which seeks social uniformity by imposing on all individuals the values of a dominant cultural group: (2) pluralism, which nurtures social diversity by protecting the values of competing cultural groups; and (3) individualism, which favors the choices of individuals over the values of any cultural group. He identifies the differences and connections among these perspectives by comparing the English and American laws against blasphemy. That comparison reveals the profoundly individualist character of American first amendment doctrine. Professor Post argues that the feminist challenge against pornography is controversial because it represents a pluralist challenge to our first amendment individualism, and he concludes that the success of the feminist challenge depends on its proponents' ability to offer a convincing vision of the first amendment that is consistent with pluralist values. Twenty-five years ago legal academics viewed the law of obscenity as the regulation of sex. Laws prohibiting obscenity were understood to stem from "traditional notions, rooted in this country's religious antecedents, of governmental responsibility for communal and individual 'decency' and 'morality. ' "" They protected our common cultural "environment. "2 The constitutional issue posed by such laws, therefore, was whether the first amendment permitted expression to be suppressed for the purpose of preserving "the purity of the community and . the
Characterization of visually similar diffuse diseases from B-scan liver images with the nonseparable wavelet transform

This paper describes the application of the nonseparable wavelet decomposition for the discrimination of diffuse diseases of liver. The proposed feature extraction algorithm uses the filter bank performing the quincunx transform and characterizes textures by a set of channel variances estimated at the output of each filter. Classification experiments on a set of three different tissue types show that this approach could be a reliable method for analysis of B-scan liver images.
Immediate changes in biochemical markers of bone turnover and circulating interleukin-6 after parathyroidectomy for primary hyperparathyroidism.

OBJECTIVE The time course of the immediate change in bone turnover after parathyroidectomy (PTX) for primary hyperparathyroidism (PHPT) is not clear. It is uncertain whether circulating interleukin-6 (IL-6) plays a role in mediating the acute withdrawal of the effects of parathyroid hormone (PTH) on bone turnover after PTX. The aims of this study were to determine the time course of immediate changes in biochemical markers of bone turnover after PTX and whether circulating IL-6 is involved in the immediate changes of bone turnover after PTX. DESIGN AND METHODS IL-6 and bone turnover markers were measured in eight women (aged 55+/-11 years, mean+/-s.d. ) with PHTP at baseline and at 1-2h, and 1, 2, 5, 7 and 12 days after PTX. We compared the results with those from eight individually matched women (healthy controls) and five subjects undergoing major surgery (surgical controls). RESULTS At baseline, serum levels of IL-6 and bone turnover markers were higher in PHPT than those in healthy controls (P<0.05). Serum levels of procollagen propeptides increased by 22 and 27% at days 2 and 5, respectively, compared with baseline (P<0.05). Serum tartrate-resistant acid phosphatase decreased by 2 days after PTX, and urinary collagen crosslinks decreased significantly by 21-41% within 24h (P<0.05). Serum IL-6 levels increased immediately in both PHPT and surgical controls at postoperative follow-up (repeated measures ANOVA). CONCLUSIONS (1) PTX decreases bone resorption immediately and (2) circulating IL-6 is not involved in the changes in bone turnover immediately after PTX.
The emerging roles of liver X receptors and their ligands in cancer

Introduction: Liver X receptors (LXRs) are nuclear receptors with well-known functions in cholesterol transport, fatty acid and glucose metabolism, and modulation of immune responses. Natural and synthetic ligands have been identified and are under development for the treatment of metabolic and inflammatory conditions and diseases. There is mounting evidence pointing to functional roles for LXRs in a variety of malignancies and the potential therapeutic efficacy of their ligands. Areas covered: This review summarizes the discovery and characterization of LXRs and their ligands, surveys their effects and mechanisms of action in cell-based and animal models of cancer, and proposes the future direction of basic and translational studies of LXRs and their ligands in cancer research and therapeutics. Expert opinion: Targeting LXRs is a promising strategy for cancer treatment, particularly for those cancers which do not have effective treatment options. Key questions remain, however, regarding the specific mechanisms of action, effects on other target cells within the tumor microenvironment, and receptor status in patient populations. Moreover, LXR ligands optimized for disease-specific functions and cancer-related endpoints are currently not available. These issues represent both challenges and significant opportunities for future research and development efforts.
H2O2 Induces a Transient Multi-phase Cell Cycle Arrest in Mouse Fibroblasts through Modulating Cyclin D and p21Cip1 Expression*

To defend against the potential damages induced by reactive oxygen species, proliferating cells enter a transient cell cycle arrest. We treated mouse fibroblasts with H2O2 and found that sublethal doses of H2O2 induced a transient multi-phase cell cycle arrest at the G1, S, and G2 phases but not the M phase. Western blot analysis demonstrated that this transient cell cycle arrest is associated with the down-regulation of cyclins D1 and D3 and up-regulation of the CKI p21Cip1 expression. We also demonstrate that the induction in p21Cip1 expression by H2O2 is at least partially mediated at the transcriptional level and can occur in the absence of p53 function. Further immunoprecipitation kinase and immunodepletion assays indicated that in response to H2O2 treatment, the down-regulation of cyclin Ds expression are associated with repression of cyclin D-CDK4, whereas the accumulation of p21Cip1 is responsible for the inhibition of cyclin E and A-CDK2 activity and associated with the down-regulation of cyclin B-CDC2 activity. These data could account for the cell cycle arrest at the G1, S, and G2 phases following H2O2stimulation. Deletion of p21Cip1, restoration of cyclin D expression, or overexpression of cyclin E alone is insufficient to effectively overcome the cell cycle arrest caused by sublethal doses of H2O2. By contrast, overexpression of the humanHerpesvirus 8 K cyclin, which can mimic the function of cyclin D and E, is enough to override this transient cell cycle arrest. On the basis of our findings, we propose a model in which moderate levels of H2O2 induce a transient multi-phase cell cycle arrest at least partially through up-regulation of p21Cip1 and down-regulation of cyclin D expression.
A special kind of married man: notions of marriage and married men in the Swedish gay press, 1954–1986.

There has long been ambivalence in the LGBT movement and related research as to the meaning of gay identity in relation to marriage. The article explores changing homonormative discourses of marriage and married men within the Swedish gay press from the mid 1950s to the mid 1980s. Expressions of the changes are a shift in language and in views of extramarital relationships, openness, and gay male identity. As a result of the shift, “married men,” including both “married homosexuals” and “bisexuals,” came to be distinguished from “gays. ”
MDR1 gene C3435T polymorphism is associated with clinical outcomes in gastric cancer patients treated with postoperative adjuvant chemotherapy.

OBJECTIVE To evaluate the impact of the multi-drug resistance 1(MDR1) C3435T polymorphism on clinical outcomes in gastric cancer patients treated with postoperative adjuvant chemotherapy. METHODS From January 2005 to December 2008, 102 patients with surgically resected gastric cancers were enrolled into this study in the Affiliated Jiangsu Cancer Hospital of Nanjing Medical University. The polymorphism was tested using real time polymerase chain reaction (RT-PCR) cycling probes and the relationship with clinical outcomes after postoperative adjuvant chemotherapy was analyzed by SPSS 17.0. RESULTS The CT/TT genotype of C3435T was significantly associated with a shorter progression-free survival (PFS) and overall survival (OS) compared with the CC genotype [PFS: adjusted hazard ratio (HR) = 2.01, 95% confidence intervals (CI): 1.17-3.45, P = 0.012; OS: adjusted HR = 2.37, 95% CI: 1.31-4.28, P = 0.004]. TNM stage was also associated with PFS (adjusted HR = 2.33, 95% CI: 1.34-4.05, P = 0.003) and OS (adjusted HR = 2.62, 95% CI: 1.44-4.76, P = 0.002) in gastric cancer patients treated with postoperative adjuvant chemotherapy. CONCLUSION Our results suggest that the MDR1 gene C3435T polymorphism is associated with clinical outcomes in gastric cancer patients treated with postoperative adjuvant chemotherapy. This now needs to be confirmed by a randomized prospectively controlled study.
Factors Affecting Survival in Patients with Anal Melanoma

Anal melanoma is an aggressive tumor with a predilection for early infiltration and distant spread, resulting in poor overall survival. Because anal melanoma is rare, only small case series are reported in the literature, making it difficult to draw conclusions about optimal treatment and outcome. The Surveillance, Epidemiology, and End Results database was used to identify patients with anal melanomas from 1973 to 2001. In addition to demographics, disease extent at presentation, treatment administered, overall survival, and survival by decade of diagnosis were collected. A total of 126 patients with a mean age of 69.2 years was diagnosed with anal melanoma. Sixty-one per cent were female. Median follow-up was 22.5 months. Median survival was 10 months for those with distant disease, 13 months for patients with regional spread, and 34 months for patients with local disease (P = 0.0001). Five-year survival was 32 per cent, 17 per cent, and 0 per cent for patients presenting with local, regional, and distant disease, respectively (P = 0.0001). Neither age at diagnosis, operation performed, nor use of radiation significantly affected survival. Anal melanoma remains an uncommon but lethal disease. Extent of disease correlates with overall survival. Survival is improving, but the use and extent of operation are not associated with improved overall survival.
Fibroblast Growth Factor 2 Is More Dynamic than Vascular Endothelial Growth Factor A During the Follicle-Luteal Transition in the Cow1

Abstract Luteal inadequacy is a major cause of infertility in a number of species. During the early luteal phase, progesterone production requires the rapid growth of the corpus luteum (CL), which is in turn dependent on angiogenesis. In the present study, we examined the temporal changes in vascular endothelial growth factor A (VEGFA), fibroblast growth factor 2 (FGF2) and secreted protein, acidic, cysteine-rich (osteonectin) (SPARC) during the follicular-luteal transition and CL development in the cow. Luteal VEGFA concentrations increased as the CL developed but were lower in the regressing CL. Conversely, luteal FGF2 concentrations were highest immediately postovulation in the collapsed follicle and declined as the CL developed. Furthermore, three FGF2 isoforms were present in the collapsed follicle, but only one isoform was detected in older CL. Interestingly, FGF2 concentrations increased in the regressing CL. Western blot analysis for SPARC showed the presence of two isoforms, which were constitutively expressed throughout CL development. Further studies investigated the regulation of FGF2 by LH, which showed that FGF2 concentrations in preovulatory follicular fluid were higher in those animals that had experienced an LH surge. Moreover, LH stimulated FGF2 production in dispersed luteal cells. Conversely, the LH surge had no effect on follicular fluid VEGFA concentrations. In conclusion, FGF2 was more dynamic than VEGFA and SPARC during the follicular-luteal transition, which suggests that FGF2 plays a key role in the initiation of angiogenesis at this time. Furthermore, it is likely that this is stimulated by the LH surge. The results also suggest that VEGFA and SPARC have a more constitutive, but essential, role in the development of the CL vasculature.
Ghrelin Protects against Experimental Sepsis by Inhibiting High-Mobility Group Box 1 Release and by Killing Bacteria12

Sepsis, a life-threatening complication of infections and the most common cause of death in intensive care units, is characterized by a hyperactive and out-of-balance network of endogenous proinflammatory cytokines. None of the current therapies are entirely effective, illustrating the need for novel therapeutic approaches. Ghrelin (GHR) is an orexigenic peptide that has emerged as a potential endogenous anti-inflammatory factor. In this study, we show that the delayed administration of GHR protects against the mortality in various models of established endotoxemia and sepsis. The therapeutic effect of GHR is mainly mediated by decreasing the secretion of the high mobility box 1 (HMGB1), a DNA-binding factor that acts as a late inflammatory factor critical for sepsis progression. Macrophages seem to be the major cell targets in the inhibition of HMGB1 secretion, in which GHR blocked its cytoplasmic translocation. Interestingly, we also report that GHR shows a potent antibacterial activity in septic mice and in vitro. Remarkably, GHR also reduces the severity of experimental arthritis and the release of HMGB1 to serum. Therefore, by regulating crucial processes of sepsis, such as the production of early and late inflammatory mediators by macrophages and the microbial load, GHR represents a feasible therapeutic agent for this disease and other inflammatory disorders.
Loss of Heterozygosity on Chromosome 10p14–p15 in Colorectal Carcinoma

High frequencies of loss of heterozygosity (LOH) on chromosome 10p14–p15 have been reported in various tumors, including gliomas, pulmonary carcinoid tumors and cervical, hepatic, prostatic and esophageal carcinomas. However, LOH on chromosome 10p14–p15 in colorectal tumors has not been reported. Therefore, we examined LOH on chromosome 10p14–p15 in 60 colorectal carcinomas (21 superficial and 39 advanced types) by microsatellite assay. Three microsatellite loci, D10S191 (10p14), D10S558 and D10S249 (10p15) were examined by polymerase chain reaction [early colorectal carcinomas, LOH of markers D10S191 (36%), D10S558 (7%) and D10S249 (11%), and in advanced colorectal carcinomas, LOH of markers D10S191 (20%), D10S558 (13%) and D10S249 (33%)]. There were no significant associations between LOH on chromosome 10p14–p15 and clinicopathologic features, including patient age, sex, tumor location, depth of invasion, histologic type, lymph node metastasis and prognosis. These data suggest that a putative tumor suppressor gene associated with colorectal carcinogenesis may be located on chromosome 10p14–p15 and that alteration of this gene may be involved in the development but not progression of colorectal tumors.