bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bioengineering a Unique Deimmunized Bispecific Targeted Toxin That Simultaneously Recognizes Human CD22 and CD19 Receptors in a Mouse Model of B-Cell Metastases
Authors: Vallera Daniel A. , Oh Seunguk , Chen Hua , Shu Yanqun , Frankel Arthur E. 
Published: June 2010

Abstract
A drug of high potency and reduced immunogenicity is needed to develop a targeted biological drug that when injected systemically can penetrate to malignant B cells. Therefore, a novel deimmunized bispecific ligand-directed toxin targeted by dual high-affinity single-chain Fvs (scFv) spliced to PE38 with a KDEL COOH-terminus was genetically engineered. The aims were to reduce toxin immunogenicity using mutagenesis, measure the ability of mutated drug to elicit antitoxin antibody responses, and show that mutated drug was effective against systemic B-cell lymphoma in vivo. Both human anti-CD22 scFv and anti-CD19 scFv were cloned onto the same single-chain molecule with truncated pseudomonas exotoxin (PE38) to create the drug. Site-specific mutagenesis was used to mutate amino acids in seven key epitopic toxin regions that dictate B-cell generation of neutralizing antitoxin antibodies. Bioassays were used to determine whether mutation reduced potency, and ELISAs were done to determine whether antitoxin antibodies were reduced. Finally, a powerful genetically altered luciferase xenograft model was used that could be imaged in real time to determine the effect on systemic malignant human B-cell lymphoma, Raji-luc. Patient B-lineage acute lymphoblastic leukemia, B-cell chronic lymphocytic leukemia, and B lymphoma were high in CD22 and CD19 expression. 2219KDEL7mut was significantly effective against systemic Raji-luc in mice and prevented metastatic spread. Mutagenesis reduced neutralizing antitoxin antibodies by ∼80% with no apparent loss in in vitro or in vivo activity. Because 2219KDEL7mut immunogenicity was significantly reduced and the drug was highly effective in vivo, we can now give multiple drug treatments with targeted toxins in future clinical trials. Mol Cancer Ther; 9(6); 1872–83. ©2010 AACR.
Ethno-Religious Communities: To the Problem of Identity Markers
Authors: Arakelova Victoria 
Published: June 2010

AbstractThe paper focuses on the phenomenon of ethno-religiousness and, particularly, on the process of the formation of ethno-religious communities. In the spotlight of the research is the Yezidi identity—the stages of its formation from the new syncretic mentality, initially exclusively with the religious vector, and later having acquired the drive to ethnicity. The similar processes can be traced in other cases of ethno-religious identities, e.g., the Mandaeans and the Druzes, both cases being used as comparative material.
A Remnant Remaining: Armenians amid Northern Iraq's Christian Minority
Authors: Logan Darren 
Published: June 2010

AbstractNorthern Mesopotamia is the source for numerous ethnicities and religions. Each has played a role in forming a fragile, beautiful, yet sometimes painful cultural, religious and social montage in the region. Over the course of millennia, under numberless rulers and regimes, and through successive conflicts, many of these once historic majorities gradually faded into the ascending Arab and Islamic milieu. Within this ethnic and religious mosaic comprising Iraq, one finds a relatively large Christian community. Digging deeper still one discovers a small remaining remnant of Armenians. Long ago this ancient Christian people dominated the Armenian Highland, territory now located in Eastern Turkey. Historical evidence indicates an Armenian presence in Mesopotamia for well over several thousand years. With this as background, the paper is a brief consideration of the Christian minorities—chiefly the small Armenian community—located in Iraqi territory officially under the control of the Kurdistan Regional Government (KRG), generally based on the author's field-work in Iraqi Kurdistan from December 2009 to March 2010.
Feasibility and Effectiveness of a Pilot Health Promotion Program for Adults With Type 2 Diabetes
Authors: Kluding Patricia M. , Singh Rupali , Goetz Jeanine , Rucker Jason , Bracciano Sarah , Curry Natasha 
Published: June 2010

Purpose The purpose of this pilot study was to assess the feasibility and effectiveness of an intense health promotion program in older adults with diabetes. The program combined individually prescribed and supervised exercise with nutrition and education programs on glycemic control and aerobic fitness. Methods Various recruitment and retention strategies were analyzed for effectiveness. Out of 28 potential subjects assessed for eligibility, 6 subjects with type 2 diabetes (2 male and 4 female; all white; age, 60.2 ± 4.7 years) participated in the 10-week intervention. Aerobic and resistance exercise was performed on alternate days (3-4 days per week), with individualized nutrition counseling and diabetes health education sessions once weekly. The primary outcome measures were aerobic fitness and glycemic control (A1C), and secondary outcome measures included body mass index (BMI), self-efficacy, and symptoms of neuropathy. Changes in outcomes were assessed using descriptive statistics and paired t test analysis (α = .05). Results Following the intervention, subjects had improvements that approached significance in A1C and pain, with significant improvements in self-efficacy. Conclusions A systematic approach to analysis of feasibility revealed issues with recruitment and retention that would need to be addressed for future studies or clinical implementation of this program. However, for the subset of subjects who did complete the intervention, adherence was excellent, and satisfaction with the program was confirmed by exit interview comments. Following participation in this pilot health promotion program, subjects had meaningful improvements in glycemic control, pain, and self-efficacy.
Efficacy of exercise and ultrasound in patients with lumbar spinal stenosis: a prospective randomized controlled trial
Authors: Goren Ahmet , Yildiz Necmettin , Topuz Oya , Findikoglu Gulin , Ardic Fusun 
Published: June 2010

Objective: To assess the effectiveness of therapeutic exercises alone and in combination with a single physical agent — ultrasound — in patients with lumbar spinal stenosis. Design: Randomized, prospective, controlled trial. Setting: Department of Physical Medicine and Rehabilitation, University Hospital. Subjects: Forty-five patients presenting with symptoms of neurological claudication and magnetic resonance image-proven lumbar spinal stenosis were assigned to one of three groups: ultrasound plus exercise group (group 1, n =15), sham ultrasound plus exercise group (group 2, n= 15) and no exercise — no treatment group (control group, n = 15). Interventions: Stretching and strengthening exercises for lumbar, abdominal, leg muscles as well as low-intensity cycling exercises were given as therapeutic exercises. Ultrasound was applied with 1 mHz, 1.5 W/cm2 intensity, in continuous mode on the back muscle for 10 minutes in group 1 while ultrasound on/off mode was applied in group 2. Main outcome measures: Before and after a three-week period, all subjects were evaluated by pain, disability, functional capacity and consumption of analgesic. Results: Thirty-two of the participants were women and 13 were men, with an average age of 53.2 ± 12.68 years (range 25—82 years). After a three-week treatment period, leg pain decreased in group 1 (—1.47 ± 3.02) and group 2 (—2.47 ± 3.75) compared with the control group (P<0.05). Disability score decreased in group 1 (—3.94 ± 7.20) and group 2 (—7.80 ± 10.26) compared with control group (P<0.05). We did not find any statistically significant difference between groups 1 and 2 (P>0.05). The amount of analgesic consumption is significantly less in the group with ultrasound application compared to that in the control group (P<0.05). Conclusion: The results of our study suggest that therapeutic exercises are effective for pain and disability in patients with lumbar spinal stenosis and that addition of ultrasound to exercise therapy lowers the analgesic intake substantially.
Elastic instabilities in dry, mesoporous minerals and their relevance to geological applications
Authors: Salje E. K. H. , Koppensteiner J. , Schranz W. , Fritsch E. 
Published: June 2010

AbstractThe collapse of minerals and mineral assemblies under external stress is modelled using a master curve where the stress failure is related to the relative, effective elastic moduli which are in turn related to the porosity of the sample. While a universal description is known not to be possible, we argue that for most porous materials such as shales, silica, cement phases, hydroxyapatite, zircon and also carbonates in corals and agglomerates we can estimate the critical porosity ϕc at which small stresses will lead to the collapse of the sample. For several samples we find ϕc ~0.5 with an almost linear decay of the bulk moduli with porosity at ϕc <0.5. The second scenario involves the persistence of elasticity for porosities until almost 1 whereby the bulk modulus decreases following a power law κ ~ (1–ϕm, m>2, between ϕ = 0.5 and ϕ = 1.
The endocytic adaptor Numb regulates thymus size by modulating pre-TCR signaling during asymmetric division
Authors: Aguado Rocio , Martin-Blanco Nadia , Caraballo Michael , Canelles Matilde 
Published: June 2010

AbstractStem cells must proliferate and differentiate to generate the lineages that shape mature organs; understanding these 2 processes and their interaction is one of the central themes in current biomedicine. An intriguing aspect is asymmetric division, by which 2 daughter cells with different fates are generated. Several cell fate determinants participate in asymmetric division, with the endocytic adaptor Numb as the best-known example. Here, we have explored the role of asymmetric division in thymocyte development, visualizing the differential segregation of Numb and pre-TCR in thymic precursors. Analysis of mice where Numb had been inhibited by expressing a dominant negative revealed enhanced pre–T-cell receptor (TCR) signaling and a smaller thymus. Conversely, Numb overexpression resulted in loss of asymmetric division and a larger thymus. The conclusion is that Numb determines the levels of pre-TCR signaling in dividing thymocytes and, ultimately, the size of the pool from which mature T lymphocytes are selected.
High mortality from Plasmodium falciparum malaria in children living with sickle cell anemia on the coast of Kenya
Authors: McAuley Charlotte F. , Webb Clare , Makani Julie , Macharia Alexander , Uyoga Sophie , Opi Daniel H. , Ndila Carolyne , Ngatia Antony , Scott John Anthony G. , Marsh Kevin , Williams Thomas N. 
Published: June 2010

AbstractAlthough malaria is widely considered a major cause of death in young children born with sickle cell anemia (SCA) in sub-Saharan Africa, this is poorly quantified. We attempted to investigate this question through 4 large case-control analyses involving 7164 children living on the coast of Kenya. SCA was associated with an increased risk of admission to hospital both with nonmalaria diseases in general (odds ratio [OR] = 4.17; 95% confidence interval [CI], 1.95-8.92; P < .001) and with invasive bacterial diseases in particular (OR = 8.73; 95% CI, 4.51-16.89; P < .001). We found no evidence for a strongly increased risk of either uncomplicated malaria (OR = 0.43; 95% CI, 0.09-2.10; P = .30) or malaria complicated by a range of well-described clinical features of severity (OR = 0.80; 95% CI, 0.25-2.51; P = .70) overall; nevertheless, mortality was considerably higher among SCA than non-SCA children hospitalized with malaria. Our findings highlight both the central role that malaria plays in the high early mortality seen in African children with SCA and the urgent need for better quantitative data. Meanwhile, our study confirms the importance of providing all children living with SCA in malaria-endemic areas with effective prophylaxis.
Unsuspected diversity of Niphargus amphipods in the chemoautotrophic cave ecosystem of Frasassi, central Italy
Authors: Flot Jean-François , Wörheide Gert , Dattagupta Sharmishtha 
Published: June 2010

AbstractBackgroundThe sulfide-rich Frasassi caves in central Italy contain a rare example of a freshwater ecosystem supported entirely by chemoautotrophy.Niphargus ictus, the sole amphipod species previously reported from this locality, was recently shown to host the first known case of a freshwater chemoautotrophic symbiosis. Since the habitat ofN. ictusis highly fragmented and is comprised of streams and lakes with various sulfide concentrations, we conducted a detailed study to examine the potential genetic diversity of this species within Frasassi.ResultsBy sequencing one nuclear (ITS) and two mitochondrial (COI and 12S) regions, we show that four partially sympatricNiphargusclades are present in Frasassi. Morphological and behavioral data obtained for three of these clades are perfectly congruent with this molecular delineation and make it possible to distinguish them in the field. Phylogenetic analyses of 28S ribosomal DNA sequences reveal that, among the four clades, only two are closely related to each other. Moreover, these four clades occupy distinct niches that seem to be related to the chemical properties and flow regimes of the various water bodies within Frasassi.ConclusionsOur results suggest that four distinctNiphargusspecies are present in Frasassi and that they originated from three or four independent invasions of the cave system. At least two among the four species harborThiothrixepibionts, which paves the way for further studies of the specificity and evolutionary history of this symbiosis.
Periostin is up-regulated in high grade and high stage prostate cancer
Authors: Tischler Verena , Fritzsche Florian R , Wild Peter J , Stephan Carsten , Seifert Hans-Helge , Riener Marc-Oliver , Hermanns Thomas , Mortezavi Ashkan , Gerhardt Josefine , Schraml Peter , Jung Klaus , Moch Holger , Soltermann Alex , Kristiansen Glen 
Published: June 2010

Abstract

Background
Expression of periostin is an indicator of epithelial-mesenchymal transition in cancer but a detailed analysis of periostin expression in prostate cancer has not been conducted so far.

Methods
Here, we evaluated periostin expression in prostate cancer cells and peritumoural stroma immunohistochemically in two independent prostate cancer cohorts, including a training cohort (n = 93) and a test cohort (n = 325). Metastatic prostate cancers (n = 20), hormone refractory prostate cancers (n = 19) and benign prostatic tissues (n = 38) were also analyzed.

Results
In total, strong epithelial periostin expression was detectable in 142 of 418 (34.0%) of prostate carcinomas and in 11 of 38 benign prostate glands (28.9%). Increased periostin expression in carcinoma cells was significantly associated with high Gleason score (p < 0.01) and advanced tumour stage (p < 0.05) in the test cohort. Whereas periostin expression was weak or absent in the stroma around normal prostate glands, strong periostin expression in tumour stroma was found in most primary and metastatic prostate cancers. High stromal periostin expression was associated with higher Gleason scores (p < 0.001). There was a relationship between stromal periostin expression and shortened PSA relapse free survival times in the training cohort (p < 0.05).

Conclusions
Our data indicate that periostin up-regulation is related to increased tumour aggressiveness in prostate cancer and might be a promising target for therapeutical interventions in primary and metastatic prostate cancer.
Obesity induced by a pair-fed high fat sucrose diet: methylation and expression pattern of genes related to energy homeostasis
Authors: Lomba Almudena , Milagro Fermín I , García-Díaz Diego F , Marti Amelia , Campión Javier , Martínez J Alfredo 
Published: June 2010

Abstract

Background
The expression of some genes controlling energy homeostasis could be regulated by epigenetic mechanisms that may play a role in body weight regulation. Thus, it is known that various nutritional factors affect DNA methylation. In order to assess whether the macronutrient composition of the diet could be related to the epigenetic regulation of gene expression and with obesity development, we investigated the effects on methylation and expression patterns of two pair-fed isocaloric diets in rats: control (rich in starch) and HFS (rich in fat and sucrose).

Results
The pair-fed HFS diet induced higher weight gain and adiposity as compared to the controls as well as liver triglyceride accumulation and oxidative stress. Feeding the HFS diet impaired glucose tolerance and serum triglycerides and cholesterol. Liver glucokinase expression, a key glycolytic gene, remained unaltered, as well as the mRNA values of fatty acid synthase and NADH dehydrogenase (ubiquinone) 1 beta subcomplex, 6 (NDUFB6) in liver and visceral adipocytes, which regulate lipogenesis and mitochondrial oxidative metabolism, respectively. Liver expression of hydroxyacyl-coenzyme A dehydrogenase (HADHB), a key gene of β-oxidation pathway, was higher in the HFS-fed animals. However, the methylation status of CpG islands in HADHB and glucokinase genes remained unchanged after feeding the HFS diet.

Conclusions
These results confirm that the distribution and type of macronutrients (starch vs. sucrose, and percent of fat) influence obesity onset and the associated metabolic complications. HFS diets produce obesity independently of total energy intake, although apparently no epigenetic (DNA methylation) changes accompanied the modifications observed in gene expression.
Controversies Surrounding the Use of Etomidate for Rapid Sequence Intubation in Patients with Suspected Sepsis
Authors: Edwin Stephanie B , Walker Pamela L 
Published: June 2010

Objective: To evaluate the risk of adrenal insufficiency following a single dose of etomidate in patients with suspected sepsis requiring rapid sequence intubation. Data Sources: A literature search was conducted using PubMed, MEDLINE, EMBASE, and International Pharmaceutical Abstracts from the dates of database inception until April 2010, utilizing the terms adrenal insufficiency, etomidate, and sepsis. Study Selection and Data Extraction: Data were synthesized in a qualitative manner, as variable study designs were identified. All studies that evaluated the clinical association between etomidate-induced adrenal insufficiency and sepsis in adults were reviewed and included. Data Synthesis: A search of the literature revealed 7 studies that specifically evaluated clinical endpoints in septic adults receiving etomidate for induction prior to intubation. Three of the studies evaluated risk factors associated with adrenal insufficiency in critically ill patients. Each of these studies determined that etomidate exposure was independently associated with an inappropriate response to cosyntropin stimulation testing (CST). Two studies found no significant difference in hospital mortality rates when evaluating patients receiving induction with etomidate compared with alternative regimens. Three studies found an increased risk of adrenal insufficiency in patients exposed to etomidate. The majority of studies that evaluated the use of etomidate in sepsis were underpowered, leading to difficulty in establishing a causal relationship between drug-related adrenal insufficiency, morbidity, and mortality. Conclusions: Until further studies are available, etomidate should be reserved for hemodynamically unstable patients who cannot tolerate an alternative induction agent despite the administration of fluids or vasoactive agents.
Befriending for mental health problems: Processes of helping
Authors: Mitchell Gemma , Pistrang Nancy 
Published: June 2010

Background. One avenue for addressing the social consequences of mental health problems is through befriending, a supportive relationship in which one‐to‐one companionship is provided on a regular basis. Although there is some evidence that befriending can improve psychological and social functioning, little is known about how it works. Objective. This qualitative study aimed to understand the helping processes occurring in befriending relationships, from the perspectives of both befriendees and befrienders. Method. Semi‐structured interviews were conducted individually and jointly with eight befriendees and their corresponding befrienders. Thematic analysis was carried out on the data set of 23 interviews. Results. The analysis generated nine themes concerning qualities of the relationship valued by befriendees and befrienders (e.g., empathy and mutuality), processes of making meaning (e.g., considering alternative perspectives), and how change was effected in befriendees' lives (e.g., learning how to have healthier relationships with others). The accounts emphasized the importance of the quality of the relationship itself, and highlighted aspects of the relationship that were sometimes difficult to negotiate. Conclusions. The findings suggest that befriending shares commonalities with other types of psychological help. However, it is also characterized by some particular challenges, such as establishing an empathic relationship and managing boundaries and endings.
High Pre-β1 HDL Concentrations and Low Lecithin: Cholesterol Acyltransferase Activities Are Strong Positive Risk Markers for Ischemic Heart Disease and Independent of HDL-Cholesterol
Authors: Sethi Amar A , Sampson Maureen , Warnick Russell , Muniz Nehemias , Vaisman Boris , Nordestgaard Børge G , Tybjærg-Hansen Anne , Remaley Alan T 
Published: June 2010

AbstractBackground: We hypothesized that patients with high HDL-cholesterol (HDL-C) and ischemic heart disease (IHD) may have dysfunctional HDL or unrecognized nonconventional risk factors.Methods: Individuals with IHD (Copenhagen University Hospital) and either high HDL-C (n = 53; women ≥735 mg/L; men ≥619 mg/L) or low HDL-C (n = 42; women ≤387 mg/L; men ≤341 mg/L) were compared with individuals without IHD (Copenhagen City Heart Study) matched by age, sex, and HDL-C concentrations (n = 110). All participants had concentrations within reference intervals for LDL-C (&lt;1600 mg/L) and triglyceride (&lt;1500 mg/L), and none were treated with lipid-lowering medications. Pre-β1 HDL and phospholipid transfer protein concentrations were measured by using commercial kits and lecithin:cholesterol acyltransferase (LCAT) activity by using a proteoliposome cholesterol esterification assay.Results: Pre-β1 HDL concentrations were 2-fold higher in individuals with IHD vs no IHD in both the high [63 (5.7) vs 35 (2.3) mg/L; P &lt; 0.0001] and low HDL-C [49 (5.0) vs 27 (1.5) mg/L; P = 0.001] groups. Low LCAT activity was also associated with IHD in the high [95.2 (6.7) vs 123.0 (5.3) μmol · L−1 · h−1; P = 0.002] and low [93.4 (8.3) vs 113.5 (4.9) μmol · L−1 · h−1; P = 0.03] HDL-C groups. ROC curves for pre-β1 HDL in the high–HDL-C groups yielded an area under the curve of 0.71 (95% CI: 0.61–0.81) for predicting IHD, which increased to 0.92 (0.87–0.97) when LCAT was included. Similar results were obtained for low HDL-C groups. An inverse correlation between LCAT activity and pre-β1 HDL was observed (r2 = 0.30; P &lt; 0.0001) in IHD participants, which was stronger in the low HDL-C group (r2 = 0.56; P &lt; 0.0001).Conclusions: IHD was associated with high pre-β1 HDL concentrations and low LCAT levels, yielding correct classification in more than 90% of the IHD cases for which both were measured, thus making pre-β1 HDL concentration and LCAT activity level potentially useful diagnostic markers for cardiovascular disease.