bluuebunny/crossref_metadata_2025_split huggingface dataset:
Spatial analysis of lung, colorectal, and breast cancer on Cape Cod: An application of generalized additive models to case-control data
Authors: Vieira Verónica , Webster Thomas , Weinberg Janice , Aschengrau Ann , Ozonoff David 
Published: June 2005

Abstract
Background
The availability of geographic information from cancer and birth defect registries has increased public demands for investigation of perceived disease clusters. Many neighborhood-level cluster investigations are methodologically problematic, while maps made from registry data often ignore latency and many known risk factors. Population-based case-control and cohort studies provide a stronger foundation for spatial epidemiology because potential confounders and disease latency can be addressed.

Methods
We investigated the association between residence and colorectal, lung, and breast cancer on upper Cape Cod, Massachusetts (USA) using extensive data on covariates and residential history from two case-control studies for 1983–1993. We generated maps using generalized additive models, smoothing on longitude and latitude while adjusting for covariates. The resulting continuous surface estimates disease rates relative to the whole study area. We used permutation tests to examine the overall importance of location in the model and identify areas of increased and decreased risk.

Results
Maps of colorectal cancer were relatively flat. Assuming 15 years of latency, lung cancer was significantly elevated just northeast of the Massachusetts Military Reservation, although the result did not hold when we restricted to residences of longest duration. Earlier non-spatial epidemiology had found a weak association between lung cancer and proximity to gun and mortar positions on the reservation. Breast cancer hot spots tended to increase in magnitude as we increased latency and adjusted for covariates, indicating that confounders were partly hiding these areas. Significant breast cancer hot spots were located near known groundwater plumes and the Massachusetts Military Reservation.

Discussion
Spatial epidemiology of population-based case-control studies addresses many methodological criticisms of cluster studies and generates new exposure hypotheses. Our results provide evidence for spatial clustering of breast cancer on upper Cape Cod. The analysis suggests further investigation of the potential association between breast cancer and pollution plumes based on detailed exposure modeling.
Variations in societal characteristics of spatial disease clusters: examples of colon, lung and breast cancer in Japan
Authors: Fukuda Yoshiharu , Umezaki Masahiro , Nakamura Keiko , Takano Takehito 
Published: June 2005

Abstract

Background
Spatial analyses and ecological studies are essential for epidemiology and public health. The present study combining these two methods was performed to identify spatial clusters of selected types of cancer in Japan and to determine their societal characteristics focusing on homogeneity among clusters.

Results
Spatial clusters of high mortality rates of male colon and lung cancer and of female breast cancer were identified by the spatial scan statistic using Japanese municipal data (N = 3360) from 1993 to 1998 and also municipalities were divided into four societal clusters based on socioeconomic indicators and population density (urban-rich, suburban, rural-poor, and clutter). Five, seven, and four mortality clusters were identified for lung, colon and breast cancer, respectively. For colon and breast cancer, most municipalities of all except one cluster were included in a single societal cluster (urban-rich). The municipalities associated with mortality clusters for lung cancer belonged to various societal clusters.

Conclusion
Increased mortality rates of colon and breast cancer can be explained by homogenous societal characteristics related to urbanisation, although there were exceptional areas with higher mortality rates. The regional variation in lung cancer mortality rate appeared to be due to heterogeneous factors. These findings and the analysis performed in the present study will contribute to both nationwide and region-specific cancer prevention strategies.
Teaching: the role of active manipulation of three-dimensional scatter plots in understanding the concept of confounding
Authors: Busstra Cora MC , Hartog Rob , van 't Veer Pieter 
Published: June 2005

AbstractIn teaching epidemiology, confounding is a difficult topic. The authors designed active learning objects (LO) based on manipulable three-dimensional (3D) plots to facilitate understanding of confounding. The 3D LOs help illustrate of how confounding can occur, how it generates bias and how to adjust for it. For the development of the LOs, guidelines were formulated based on epidemiology and theories of instructional design. These included integrating the conceptual and empirical aspects: the causal relationships believed to be operating in the study population (conceptual aspect) and data-oriented associations (empirical aspect). Other guidelines based on theories of instructional design included: actively engage the students, use visual methods when possible, and motivate the students about the importance of the topic. Students gave the method strong positive evaluations. Experts in epidemiology agreed that the 3D LOs apply generally accepted scientific views on confounding. Based on their experiences, the authors think that the 3D plots can be useful addition in the teaching of confounding. The article includes links and a downloadable file that provide a demonstration of the 3D LO-based teaching materials.
Genetic loci for ventricular dilatation in the LEW/Jms rat with fetal-onset hydrocephalus are influenced by gender and genetic background
Authors: Jones Hazel C , Totten Crystal F , Mayorga David A , Yue Mei , Carter Barbara J 
Published: June 2005

Abstract
Background
The LEW/Jms rat strain has inherited hydrocephalus, with more males affected than females and an overall expression rate of 28%. This study aimed to determine chromosomal positions for genetic loci causing the hydrocephalus.

Methods
An F1 backcross was made to the parental LEW/Jms strain from a cross with non-hydrocephalic Fischer 344 rats. BC1 rats were generated for two specific crosses: the first with a male LEW/Jms rat as parent and grandparent, [(F × L) × L], designated B group, and the second with a female LEW/Jms rat as the parent and grandparent [L × (L × F)], designated C group. All hydrocephalic and a similar number of non-hydrocephalic rats from these two groups were genotyped with microsatellite markers and the data was analyzed separately for each sex by MAPMAKER.

Results
The frequency of hydrocephalus was not significantly different between the two groups (18.2 and 19.9 %), but there was a significant excess of males in the B group. The mean severity of hydrocephalus, measured as the ventricle-to-brain width ratio, was ranked as B group < C group < LEW/Jms. For the both rat groups, there were several chromosomes that showed possible regions with association between phenotype and genotype significant at the 5% or 1.0% level, but none of these had significant LOD scores. For the C group with a female LEW/Jms parent, there was a fully significant locus on Chr2 with a LOD score of 3.81 that was associated almost exclusively with male rats. Both groups showed possible linkage on Chr17 and the data combined produced a LOD score of 2.71, between suggestive and full significance. This locus was largely associated with male rats with a LEW/Jms male parent.

Conclusion
Phenotypic expression of hydrocephalus in Lew/Jms, although not X-linked, has a strong male bias. One, and possibly two chromosomal regions are associated with the hydrocephalus.
Early detection of breast cancer based on gene-expression patterns in peripheral blood cells
Authors: Sharma Praveen , Sahni Narinder S , Tibshirani Robert , Skaane Per , Urdal Petter , Berghagen Hege , Jensen Marianne , Kristiansen Lena , Moen Cecilie , Sharma Pradeep , Zaka Alia , Arnes Jarle , Sauer Torill , Akslen Lars A , Schlichting Ellen , Børresen-Dale Anne-Lise , Lönneborg Anders 
Published: June 2005

Abstract
Introduction
Existing methods to detect breast cancer in asymptomatic patients have limitations, and there is a need to develop more accurate and convenient methods. In this study, we investigated whether early detection of breast cancer is possible by analyzing gene-expression patterns in peripheral blood cells.

Methods
Using macroarrays and nearest-shrunken-centroid method, we analyzed the expression pattern of 1,368 genes in peripheral blood cells of 24 women with breast cancer and 32 women with no signs of this disease. The results were validated using a standard leave-one-out cross-validation approach.

Results
We identified a set of 37 genes that correctly predicted the diagnostic class in at least 82% of the samples. The majority of these genes had a decreased expression in samples from breast cancer patients, and predominantly encoded proteins implicated in ribosome production and translation control. In contrast, the expression of some defense-related genes was increased in samples from breast cancer patients.

Conclusion
The results show that a blood-based gene-expression test can be developed to detect breast cancer early in asymptomatic patients. Additional studies with a large sample size, from women both with and without the disease, are warranted to confirm or refute this finding.
Thermotropic liquid crystalline drugs
Authors: Bunjes Heike , Rades Thomas 
Published: June 2005

Abstract
Crystalline solids are characterized by long-range positional and orientational order in three dimensions, whereas amorphous liquids lack long-range order in any dimension. Liquid crystals (mesophases) show structural, mechanical and optical properties intermediate to those of crystalline solids and the amorphous, liquid state of matter. There are two principle types of liquid crystals: thermotropic liquid crystals (TLCs) and lyotropic liquid crystals (LLCs). TLCs can be formed by heating a crystalline solid or by cooling an isotropic melt of a TLC-forming molecule (mesogen). In the first part of this review the types of liquid crystals are defined and classified and the structural properties of mesogens are explained. In the second part, ten case studies of thermotropic mesomorphous drugs and pharmaceutically relevant molecules (arsphenamine, nafoxidine hydrochloride, L-660711, palmitoyl propranolol hydrochloride, penbutolol sulfate, itraconazole hydrochloride, fenoprofen sodium, fenoprofen calcium, ciclosporin and cholesteryl esters) are presented and their thermotropic mesomorphism is described. The review closes with a brief discussion of the unusual properties of drug mesophases and a potential use of drugs and excipients in this fourth state of matter.
Phytostanol tablets reduce human LDL-cholesterol
Authors: McPherson Timothy B , Ostlund Richard E , Goldberg Anne C , Bateman Joyce H , Schimmoeller Linda , Spilburg Curtis A 
Published: June 2005

Abstract
The feasibility of using solid dosage forms containing stanol lecithin to lower human LDL-cholesterol was investigated. The particle size distribution of a coarse aqueous dispersion of a stanol lecithin mixture was determined at various weight ratios of the components. At a stanol-to-lecithin weight ratio of 1.00–1.50, dispersions could be spray dried and the solid reconstituted with water to produce a particle size distribution that was similar to that of the aqueous dispersion from which it was derived. Two solid dosage forms containing this spray-dried stanol lecithin preparation had different disintegration times — tablets less than 10 min and capsules greater than 45 min. Each delivery system was then tested for LDL-cholesterol reduction activity in a placebo-controlled, double-blind clinical trial containing a total of 52 subjects. After a six-week treatment period, the group that received rapidly disintegrating stanol lecithin tablets (1.26g stanols daily) experienced a decrease in both LDL-cholesterol and the ratio of LDL-cholesterol to HDL-cholesterol by 10.4% (P=0.01) and 11.5% (P=0.03), respectively, relative to placebo. On the other hand, with slowly disintegrating capsules (1.01 g daily) there was no statistically significant difference in any lipid parameter between the active group and placebo group. Taken together, these studies demonstrate that for maximum LDL-cholesterol reduction activity the stanol lecithin formulation must be delivered in a rapidly dispersible form to reach the site of cholesterol absorption.
Anti-inflammatory and antimicrobial effect of lectin from Lonchocarpus sericeus seeds in an experimental rat model of infectious peritonitis
Authors: Alencar N M N , Cavalcante C F , Vasconcelos M P , Leite K B , Aragão K S , Assreuy A M S , Nogueira N A P , Cavada B S , Vale M R 
Published: June 2005

Abstract
We have investigated the anti-inflammatory and antimicrobial effect of the lectin from Lonchocarpus sericeus seeds (LSL) in a model of infectious peritonitis in adult Wistar rats. Animals were treated with saline or LSL (10mg kg−1, i.v) immediately and 6h after the induction of peritonitis via cecal ligation and single puncture. Twelve hours after surgery, animals were killed and the infectious process was monitored by total and differential count of cells from blood and peritoneal washing liquid, adenosine deaminase activity, antibiogram and the number of viable bacteria of the peritoneal cavity. LSL treatment decreased the inflammatory response evoked by the induction of peritonitis, as seen by the inhibition of neutrophil migration into peritoneal cavities, leucocytosis and reduction of adenosine deaminase activity in the peritoneal fluid. All these effects were reversed by the lectin association to N-acetyl-glucosamine. LSL in-vitro did not show any antimicrobial action, but promoted a marked decrease of the viable bacterial population in peritoneal cavities. In conclusion, LSL inhibited the inflammatory response and the bacterial colonization of infectious peritonitis in rats.
Pharmacodynamic comparison of pantoprazole enantiomers: inhibition of acid-related lesions and acid secretion in rats and guinea-pigs
Authors: Cao Hong , Wang Min-Wei , Sun Li-Xin , Ikejima Takashi , Hu Zhi-Qing , Zhao Wei-Hua 
Published: June 2005

Abstract
Pantoprazole is an irreversible proton pump inhibitor that is administered as a racemic mixture clinically. The effects of pantoprazole sodium (PAN·Na) enantiomers on acid-related lesions were compared using models of pylorus ligation induced ulcer, histamine induced ulcer and reflux oesophagitis in rats and guinea-pigs. Compared with (+)-PAN·Na and (±)-PAN·Na, (-)-PAN·Na showed much stronger inhibitory effects on pylorus ligation induced and histamine induced ulcers, but similar effects on reflux oesophagitis. The doses of (-)-PAN·Na, (+)-PAN·Na and (±)-PAN·Na required for 50% inhibition (ID50) of acid-related lesions were 1.28, 5.03 and 3.40 mg kg−1 against pylorus ligation induced ulcer, 1.20, 4.28 and 3.15 mg kg−1 against histamine induced ulcer, and 2.92, 3.56 and 3.70 mg kg−1 against reflux oesophagitis, respectively. The inhibitory effects of PAN·Na enantiomers on basal gastric acid output were compared in rats with acute fistula. In contrast to inhibitory rates of 89.3% and 83.6% on gastric acid output by (-)-PAN·Na and (±)-PAN·Na at 1.5 mg kg−1, (+)-PAN·Na had an inhibitory rate of only 24.7% at the same dose. The above results indicate that (-)-PAN·Na is more potent than (+)-PAN·Na at inhibiting acid-related lesions owing to its stronger inhibition of acid secretion.
Evaluation of ultrasonic atomization as a new approach to prepare ionically cross-linked chitosan microparticles
Authors: Albertini Beatrice , Passerini Nadia , Rodriguez Lorenzo 
Published: June 2005

Abstract
Ultrasonic atomization was evaluated as a new approach for the preparation of ionically cross-linked controlled-release chitosan microparticles loaded with theophylline as the model drug, using tri-polyphosphate (TPP) as counter-ion. It was possible to nebulize both 2% and 3% (w/v) chitosan solutions as a function of their viscosity, usually not processed by employing the conventional nebulizer. The results of the chitosan molecular characterization using the SEC-MALS analysis revealed that ultrasonic atomization caused a certain depolymerization, probably due to the main chain scission of the 1,4-glycosidic bond; however, Fourier transform-infrared spectroscopy revealed the absence of other chemical modifications. The ultrasonic atomization allowed preparation of TPP cross-linked chitosan microparticles mostly ranging between 50 and 200 μm. As regards manufacturing parameters, the linking time and washing medium were found to affect the properties of the microparticles, while the stirring rate of the TPP solution did not show any influence. The evaluation of the formulation variables revealed that chitosan concentration strongly affected both the feasibility of the ultrasonic atomization and the drug release. All the microparticles showed an encapsulation efficiency of &gt; 50 % and, after an initial burst effect, a controlled release of drug for 48 h. In conclusion, the ultrasonic atomization could be proposed as a robust and innovative single-step procedure with scale-up potential to successfully prepare ionically cross-linked chitosan microparticles.
Comparison of post-emulsification freeze drying or spray drying processes for the microencapsulation of plasmid DNA
Authors: Lane Majella E , Brennan Fiona S , Corrigan Owen I 
Published: June 2005

Abstract
In this work, methods used to microencapsulate plasmid DNA in a biodegradable polymer were compared for their effects on the physicochemical characteristics of DNA-loaded microparticles and on the release and integrity of encapsulated DNA. Microparticles were formulated by either w/o/w emulsification and freeze-drying (EFD) or by w/o/w emulsification and spray-drying (ESD). The influence of both manufacturing processes on particle morphology, charge, release characteristics and biological activity of encapsulated DNA was evaluated. Particles produced by emulsification/spray-drying exhibited more diversity in shape and size than those produced by emulsification/freeze-drying. These particles also exhibited higher plasmid DNA encapsulation efficiency than particles produced by emulsification/freeze-drying. The fractional DNA release rates were similar over the first 25 days for both formulations, release rate declining more rapidly at later times for the ESD product. Mammalian cell transfection assays confirmed the biological activity of encapsulated DNA extracted from both types of particles, with significantly higher transfection levels being observed for ESD particles. Application of a double emulsion (w/o/w) before spray drying resulted in higher encapsulation levels (&gt; 90%) relative to previous literature values, which used single (w/o) emulsions before spray drying. The emulsification/spray-drying technique described here appears to be a rapid and efficient method for the preparation of PLGA microparticles loaded with plasmid DNA.
Design of novel injectable cationic microspheres based on aminated gelatin for prolonged insulin action
Authors: Morimoto Kazuhiro , Chono Sumio , Kosai Tadashi , Seki Toshinobu , Tabata Yasuhiko 
Published: June 2005

Abstract
The aim of this study was to prepare two types of injectable cationized microspheres based on a native gelatin (NGMS) and aminated gelatin with ethylenediamine (CGMS) to prolong the action of insulin. Release of rhodamin B isothiocyanate insulin from CGMS was compared with that from NGMS under in-vitro and in-vivo conditions. Lower release of insulin from CGMS compared with that from NGMS was caused by the suppression of initial release. The disappearance of 125I-insulin from the injection site after intramuscular administration by NGMS and CGMS had a biphasic profile in mice. Almost all the 125I-insulin had disappeared from the injection site one day after administration by NGMS. The remaining insulin at the injection site after administration by CGMS was prolonged, with approximately 59% remaining after one day and 16% after 14 days. The disappearance of CGMS from the injection site was lower than that of NGMS. However, the difference in these disappearance rates was not great compared with those of 125I-insulin from the injection site by NGMS and CGMS. The time course of disappearance of 125I-CGMS from the injection site was similar to that of 125I-insulin by CGMS. The initial hypoglycaemic effect was observed 1h after administration of insulin by NGMS, thereafter its effect rapidly disappeared. The hypoglycaemic effect was observed 2–4h after administration by CGMS and continued to be exhibited for 7 days. The prolonged hypoglycaemic action by CGMS depended on the time profiles of the disappearance of insulin from muscular tissues, which occurs due to the enzymatic degradation of CGMS.
6-Hydroxymelatonin protects against quinolinic-acid-induced oxidative neurotoxicity in the rat hippocampus
Authors: Maharaj D S , Maharaj H , Antunes E M , Maree D M , Nyokong T , Glass B D , Daya S 
Published: June 2005

AbstractMelatonin, a naturally occuring chemical mediator, although assigned a diverse range of functions, has attracted interest because of its ability to function as a free radical scavenger. Its major hepatic metabolite and photoproduct, 6-hydroxymelatonin (6-OHM), also shares this property. Since singlet oxygen and quinolinic acid (QUIN) are critically involved in the pathology of neurotoxicity, the objective of this study was to investigate the ability of 6-OHM to scavenge singlet oxygen and evaluate its ability to scavenge superoxide anions and reduce QUIN-induced neurotoxicity in the hippocampus in-vivo. The results show that 6-OHM is an efficient inhibitor of singlet oxygen formation as indicated by the rate constants and quantum yields reported for 6-OHM and zinc phthalo-cyanine (ZnPc), respectively. 6-OHM, appears to reduce QUIN-induced superoxide anion generation in the hippocampus, which provides some evidence of the neuroprotective effects of 6-OHM.
The sensitivity of the cis/trans-isomerization of enalapril and enalaprilat to solvent conditions
Authors: Ledger Robin , Stellwagen Earle 
Published: June 2005

Abstract
The cis- and trans-isomers of enalapril and enalaprilat can be resolved by HPLC and by capillary electrophoresis. The isomeric content of enalapril is perturbed by the ionization of both its carboxyl and amine groups, while the isomeric content of enalaprilat is only perturbed by the ionization of its amine group. Increasing the hydrophobicity of the analyte solvent, as reflected in its molar polarization, increases the Z (cis) content of enalapril and markedly decreases the kinetics for isomerization. Far UV circular dichroic measurements suggest that the increase in Z (cis) content of enalapril is due to protonation of its carboxylate group. Taken together, the in-vitro properties of enalapril and enalaprilat suggest that the in-vivo transformation of the prodrug enalapril to the inhibitor enalaprilat and its delivery to angiotensin-converting enzyme should not be significantly limited by cis/trans-isomerization.