bluuebunny/crossref_metadata_2025_split huggingface dataset:
Downregulation of gastrokine-1 in gastric cancer tissues and restoration of its expression induced gastric cancer cells to apoptosis
Authors: Mao Wei , Chen Jie , Peng Tie-Li , Yin Xiao-Fei , Chen Lian-Zhou , Chen Min-Hu 
Published: June 2012

Abstract

Background
Gastrokine-1 (GKN1), a secreted protein, is specifically expressed in gastric mucosa to protect and maintain the integrity of gastric epithelium. The present study investigated differential expression of GKN1 in normal, precancerous, and cancerous gastric tissues, and explored the biological functions of GKN1 protein in gastric cancer cells.

Methods
RT-PCR, Western blot, and immunohistochemistry were performed to detect GKN1 expression in normal, precancerous, cancerous gastric tissues and seven gastric cancer cell lines. Gene transfection was used to restore GKN1 expression in gastric cancer AGS cells. Phenotypic changes (i.e., cell viability, apoptosis, cell cycle modulation, and sensitivity of gastric cancer cells to fluorouracil (5-FU)) were assayed in the transfected cells. DNA microarrays were used to analyze expression changes of apoptosis-related genes.

Results
Significant downregulation or absence of GKN1 expression in seven gastric cancer cell lines were detected and progressive decrease of GKN1 expression from normal mucosa, precancerous tissue, to cancer tissues was observed. Moreover, restoration of GKN1 expression suppressed gastric cancer cell viability and induced the cells to undergo apoptosis. GKN1 expression also enhanced tumor cell sensitivity to 5-FU treatment. Moreover, it was found that GKN1 expression in AGS cells modulated expression of 19 apoptosis-related genes.

Conclusions
Expression of GKN1 is progressively lost from normal mucosa, precancerous to cancerous gastric tissues, while restoration of GKN1 expression induces gastric cancer cells to undergo apoptosis, and enhances sensitivity of gastric cancer cells to 5-FU-induced apoptosis.
Computed tomography and pathological findings of five nasal neurilemmomas
Authors: Hu Jing , Bao Yang-Yang , Cheng Ke-Jia , Zhou Shui-Hong , Ruan Ling-Xiang , Zheng Zhou-Jun 
Published: June 2012

Abstract

Objectives
Neurilemmomas are benign tumors deriving from Schwann cells of the nerve sheath. They occur in all parts of the body. The highest incidence of neurilemmoma is in the head and neck region (38–45%), but involvement of the nose and paranasal sinus is quite rare, with only sporadic cases having been reported in the world literature. Fewer than 4% of these tumors involve the nasal cavity and paranasal sinuses. We describe the clinical, pathologic, and computed tomography (CT) features of five nasal neurilemmomas.

Methodology
CT features of five patients with nasal schwannoma proved by operation and pathology were investigated.

Results
Schwannomas tend to be solitary and are usually well-circumscribed tumors with an oval, round or fusiform shape in the unilateral nasal cavity. The lesions usually have a mottled central lucency with peripheral intensification on contrast-enhanced CT scans. The heterogeneous appearance is related to areas of increased vascularity with adjacent non-enhancing cystic or necrotic regions.

Conclusions
Schwannoma should be considered in the differential of unusual nasal masses. Certain clinical and CT patterns may be of use in the differential diagnosis.
New approaches to investigating social gestures in autism spectrum disorder
Authors: Kishida Kenneth T , Li Jian , Schwind Justin , Montague Pendleton Read 
Published: June 2012

Abstract
The combination of economic games and human neuroimaging presents the possibility of using economic probes to identify biomarkers for quantitative features of healthy and diseased cognition. These probes span a range of important cognitive functions, but one new use is in the domain of reciprocating social exchange with other humans - a capacity perturbed in a number of psychopathologies. We summarize the use of a reciprocating exchange game to elicit neural and behavioral signatures for subjects diagnosed with autism spectrum disorder (ASD). Furthermore, we outline early efforts to capture features of social exchange in computational models and use these to identify quantitative behavioral differences between subjects with ASD and matched controls. Lastly, we summarize a number of subsequent studies inspired by the modeling results, which suggest new neural and behavioral signatures that could be used to characterize subtle deficits in information processing during interactions with other humans.
On the epigenetics of vascular regulation and disease
Authors: Schleithoff Christina , Voelter-Mahlknecht Susanne , Dahmke Indra Navina , Mahlknecht Ulrich 
Published: June 2012

Abstract
Consolidated knowledge is accumulating as to the role of epigenetic regulatory mechanisms in the physiology of vascular development and vascular tone as well as in the pathogenesis of cardiovascular disease. The modulation of gene expression through modification of the epigenome by structural changes of the chromatin architecture without alterations of the associated genomic DNA sequence is part of the cellular response to environmental changes. Such environmental conditions, which are finally being translated into adaptations of the cardiovascular system, also comprise pathological conditions such as atherosclerosis or myocardial infarction. This review summarizes recent findings on the epigenetics of vascular regulation and disease and presents nutritional and pharmacological approaches as novel epigenetic strategies in the prevention and treatment of cardiovascular disease.
Integrative medicine and human health ‐ the role of pre‐, pro‐ and synbiotics
Authors: Bengmark Stig 
Published: June 2012

AbstractWestern lifestyle is associated with a sustained low grade increase in inflammation ‐increased levels of endotoxin in the body and increased activation of Toll‐like receptors and neutrophils, which leads to impaired immunity and reduced resistance to disease, changes which might explain the epidemic of chronic diseases spreading around the globe. The immune system cannot function properly without access to bacteria and raw plants, rich not only in bacteria but also in plant fibre, antioxidants, healthy fats and numerous other nutrients. Modern food technology with plant breeding, separation, condensation of food ingredients, heating, freezing, drying, irradiation, microwaving, are effective tool to counteract optimal immune function, and suspected to be a leading cause of so called Western diseases. Supply of pre‐, pro‐, and synbiotics have sometimes proved to be effective tools to counteract, especially acute diseases, but have often failed, especially in chronic diseases. Thousands of factors contribute to unhealth and numerous alterations in life style and food habits are often needed, in order to prevent and cure “treatment‐resistant” chronic diseases. Such alterations include avoiding processed foods rich in pro‐inflammatory molecules, but also a focus on consuming substantial amounts of foods with documented anti‐inflammatory effects, often raw and fresh green vegetables and tubers such as turmeric/curcumin.
Differential effects of androgens on coronary blood flow regulation and arteriolar diameter in intact and castrated swine
Authors: O’Connor Erin K , Ivey Jan R , Bowles Douglas K 
Published: June 2012

Abstract

Background
Low endogenous testosterone levels have been shown to be a risk factor for the development of cardiovascular disease and cardiovascular benefits associated with testosterone replacement therapy are being advocated; however, the effects of endogenous testosterone levels on acute coronary vasomotor responses to androgen administration are not clear. The objective of this study was to compare the effects of acute androgen administration on in vivo coronary conductance and in vitro coronary microvascular diameter in intact and castrated male swine.

Methods
Pigs received intracoronary infusions of physiologic levels (1–100 nM) of testosterone, the metabolite 5α-dihydrotestosterone, and the epimer epitestosterone while left anterior descending coronary blood flow and mean arterial pressure were continuously monitored. Following sacrifice, coronary arterioles were isolated, cannulated, and exposed to physiologic concentrations (1–100 nM) of testosterone, 5α-dihydrotestosterone, and epitestosterone. To evaluate effects of the androgen receptor on acute androgen dilation responses, real-time PCR and immunohistochemistry for androgen receptor were performed on conduit and resistance coronary vessels.

Results

In vivo, testosterone and 5α-dihydrotestosterone produced greater increases in coronary conductance in the intact compared to the castrated males. In vitro, percent maximal dilation of microvessels was similar between intact and castrated males for testosterone and 5α-dihydrotestosterone. In both studies epitestosterone produced significant increases in conductance and microvessel diameter from baseline in the intact males. Androgen receptor mRNA expression and immunohistochemical staining were similar in intact and castrated males.

Conclusions
Acute coronary vascular responses to exogenous androgen administration are increased by endogenous testosterone, an effect unrelated to changes in androgen receptor expression.
Loss of plakoglobin promotes decreased cell-cell contact, increased invasion, and breast cancer cell dissemination in vivo
Authors: Holen Ingunn , Whitworth Jacob , Nutter Faith , Evans Alyson , Brown Hannah K , Lefley Diane V , Barbaric Ivana , Jones Mark , Ottewell Penelope D 
Published: June 2012

Abstract
Introduction
The majority of deaths from breast cancer are a result of metastases; however, little is understood about the genetic alterations underlying their onset. Genetic profiling has identified the adhesion molecule plakoglobin as being three-fold reduced in expression in primary breast tumors that have metastasized compared with nonmetastatic tumors. In this study, we demonstrate a functional role for plakoglobin in the shedding of tumor cells from the primary site into the circulation.

Methods
We investigated the effects of plakoglobin knockdown on breast cancer cell proliferation, migration, adhesion, and invasion in vitro and on tumor growth and intravasation in vivo. MCF7 and T47D cells were stably transfected with miRNA sequences targeting the plakoglobin gene, or scramble vector. Gene and protein expression was monitored by quantitative polymerase chain reaction (qPCR) and Western blot. Cell proliferation, adhesion, migration, and invasion were measured by cell counting, flow cytometry, and scratch and Boyden Chamber assays. For in vivo experiments, plakoglobin knockdown and control cells were inoculated into mammary fat pads of mice, and tumor growth, shedding of tumor cells into the bloodstream, and evidence of metastatic bone lesions were monitored with caliper measurement, flow cytometry, and microcomputed tomography (μCT), respectively.

Results
Plakoglobin and γ-catenin expression were reduced by more than 80% in all knockdown cell lines used but were unaltered after transfection with the scrambled sequence. Reduced plakoglobin resulted in significantly increased in MCF7 and T47D cell proliferation in vitro and in vivo, compared with control, with significantly more tumor cells being shed into the bloodstream of mice bearing plakoglobin knockdown tumors. In addition, plakoglobin knockdown cells showed a >250% increase in invasion through basement membrane and exhibited reduced cell-to-cell adhesion compared with control cells.

Conclusion
Decreased plakoglobin expression increases the invasive behavior of breast cancer cells. This is the first demonstration of a functional role for plakoglobin/γ-catenin in the metastatic process, indicating that this molecule may represent a target for antimetastatic therapies.
Association of gender with outcomes in critically ill patients
Authors: Mahmood Kamran , Eldeirawi Kamal , Wahidi Momen M 
Published: June 2012

Abstract
Introduction
The influence of gender on mortality and other outcomes of critically ill patients is not clear. Different studies have been performed in various settings and patient populations often yielding conflicting results. We wanted to assess the relationship of gender and intensive care unit (ICU) outcomes in the patients included in the Acute Physiology and Chronic Health Evaluation (APACHE) IV database (Cerner Corporation, USA).

Methods
We performed a retrospective review of the data available in the APACHE IV database. A total of 261,255 consecutive patients admitted to adult ICUs in United States from 1 January 2004 to 31 December 2008 were included. Readmissions were excluded from the analysis. The primary objective of the study was to assess the relationship of gender with ICU mortality. The secondary objective was to evaluate the association of gender with active therapy, mechanical ventilation, length of stay in the ICU, readmission rate and hospital mortality. The gender-related outcomes for disease subgroups including acute coronary syndrome, coronary artery bypass graft (CABG) surgery, sepsis, trauma and chronic obstructive pulmonary disease (COPD) exacerbation were assessed as well.

Results
ICU mortality was 7.2% for men and 7.9% for women, odds ratio (OR) for death for women was 1.07 (95% confidence interval (CI): 1.04 to 1.1). There was a statistically significant interaction between gender and age. In patients <50 years of age, women had a reduced ICU mortality compared with men, after adjustment for acute physiology score, ethnicity, co-morbid conditions, pre-ICU length of stay, pre-ICU location and hospital teaching status (adjusted OR 0.83, 95% CI: 0.76 to 0.91). But among patients ≥50 years of age, there was no significant difference in ICU mortality between men and women (adjusted OR 1.02, 95% CI: 0.98 to 1.06).
A higher proportion of men received mechanical ventilation, emergent surgery, thrombolytic therapy and CABG surgery. Men had a higher readmission rate and longer length of ICU stay. The adjusted mortality of women compared to men was higher with CABG, while it was lower with COPD exacerbation. There was no significant difference in mortality in acute coronary syndrome, sepsis and trauma.

Conclusions
Among the critically ill patients, women less than 50 years of age had a lower ICU mortality compared to men, while 50 years of age or older women did not have a significant difference compared to men. Women had a higher mortality compared to men after CABG surgery and lower mortality with COPD exacerbation. There was no difference in mortality in acute coronary syndrome, sepsis or trauma.
Blood transfusions increase circulating plasma free hemoglobin levels and plasma nitric oxide consumption: a prospective observational pilot study
Authors: Vermeulen Windsant Iris C , de Wit Norbert CJ , Sertorio Jonas TC , Beckers Erik AM , Tanus-Santos Jose E , Jacobs Michael J , Buurman Wim A 
Published: June 2012

Abstract
Introduction
The increasing number of reports on the relation between transfusion of stored red blood cells (RBCs) and adverse patient outcome has sparked an intense debate on the benefits and risks of blood transfusions. Meanwhile, the pathophysiological mechanisms underlying this postulated relation remain unclear. The development of hemolysis during storage might contribute to this mechanism by release of free hemoglobin (fHb), a potent nitric oxide (NO) scavenger, which may impair vasodilation and microcirculatory perfusion after transfusion. The objective of this prospective observational pilot study was to establish whether RBC transfusion results in increased circulating fHb levels and plasma NO consumption. In addition, the relation between increased fHb values and circulating haptoglobin, its natural scavenger, was studied.

Methods
Thirty patients electively received 1 stored packed RBC unit (n = 8) or 2 stored packed RBC units (n = 22). Blood samples were drawn to analyze plasma levels of fHb, haptoglobin, and NO consumption prior to transfusion, and 15, 30, 60 and 120 minutes and 24 hours after transfusion. Differences were compared using Pearson's chi-square test or Fisher's exact test for dichotomous variables, or an independent-sample t test or Mann-Whitney U test for continuous data. Continuous, multiple-timepoint data were analyzed using repeated one-way analysis of variance or the Kruskall-Wallis test. Correlations were analyzed using Spearman or Pearson correlation.

Results
Storage duration correlated significantly with fHb concentrations and NO consumption within the storage medium (r = 0.51, P < 0.001 and r = 0.62, P = 0.002). fHb also significantly correlated with NO consumption directly (r = 0.61, P = 0.002). Transfusion of 2 RBC units significantly increased circulating fHb and NO consumption in the recipient (P < 0.001 and P < 0.05, respectively), in contrast to transfusion of 1 stored RBC unit. Storage duration of the blood products did not correlate with changes in fHb and NO consumption in the recipient. In contrast, pre-transfusion recipient plasma haptoglobin levels inversely influenced post-transfusion fHb concentrations.

Conclusion
These data suggest that RBC transfusion can significantly increase post-transfusion plasma fHb levels and plasma NO consumption in the recipient. This finding may contribute to the potential pathophysiological mechanism underlying the much-discussed adverse relation between blood transfusions and patient outcome. This observation may be of particular importance for patients with substantial transfusion requirements.
Comparative multi-omics systems analysis of Escherichia coli strains B and K-12
Authors: Yoon Sung Ho , Han Mee-Jung , Jeong Haeyoung , Lee Choong Hoon , Xia Xiao-Xia , Lee Dae-Hee , Shim Ji Hoon , Lee Sang Yup , Oh Tae Kwang , Kim Jihyun F 
Published: June 2012

Abstract
Background
Elucidation of a genotype-phenotype relationship is critical to understand an organism at the whole-system level. Here, we demonstrate that comparative analyses of multi-omics data combined with a computational modeling approach provide a framework for elucidating the phenotypic characteristics of organisms whose genomes are sequenced.

Results
We present a comprehensive analysis of genome-wide measurements incorporating multifaceted holistic data - genome, transcriptome, proteome, and phenome - to determine the differences between Escherichia coli B and K-12 strains. A genome-scale metabolic network of E. coli B was reconstructed and used to identify genetic bases of the phenotypes unique to B compared with K-12 through in silico complementation testing. This systems analysis revealed that E. coli B is well-suited for production of recombinant proteins due to a greater capacity for amino acid biosynthesis, fewer proteases, and lack of flagella. Furthermore, E. coli B has an additional type II secretion system and a different cell wall and outer membrane composition predicted to be more favorable for protein secretion. In contrast, E. coli K-12 showed a higher expression of heat shock genes and was less susceptible to certain stress conditions.

Conclusions
This integrative systems approach provides a high-resolution system-wide view and insights into why two closely related strains of E. coli, B and K-12, manifest distinct phenotypes. Therefore, systematic understanding of cellular physiology and metabolism of the strains is essential not only to determine culture conditions but also to design recombinant hosts.
Trauma equals danger—damage control by the immune system
Authors: Stoecklein Veit M , Osuka Akinori , Lederer James A 
Published: June 2012

Abstract
Review on how traumatic injuries influence immune system phenotypes and functions.
Traumatic injuries induce a complex host response that disrupts immune system homeostasis and predisposes patients to opportunistic infections and inflammatory complications. The response to injuries varies considerably by type and severity, as well as by individual variables, such as age, sex, and genetics. These variables make studying the impact of trauma on the immune system challenging. Nevertheless, advances have been made in understanding how injuries influence immune system function as well as the immune cells and pathways involved in regulating the response to injuries. This review provides an overview of current knowledge about how traumatic injuries affect immune system phenotype and function. We discuss the current ideas that traumatic injuries induce a unique type of a response that may be triggered by a combination of endogenous danger signals, including alarmins, DAMPs, self-antigens, and cytokines. Additionally, we review and propose strategies for redirecting injury responses to help restore immune system homeostasis.
Cognitive development in children with 22q11.2 deletion
syndrome
Authors: Duijff Sasja N. , Klaassen Petra W. J. , de Veye Henriette F. N. Swanenburg , Beemer Frits A. , Sinnema Gerben , Vorstman Jacob A. S. 
Published: June 2012

BackgroundPeople with 22q11.2 deletion syndrome (velo-cardio-facial syndrome) have
a 30-fold risk of developing schizophrenia. In the general population the
schizophrenia phenotype includes a cognitive deficit and a decline in
academic performance preceding the first episode of psychosis in a
subgroup of patients. Findings of cross-sectional studies suggest that
cognitive abilities may decline over time in some children with 22q11.2
deletion syndrome. If confirmed longitudinally, this could indicate that
one or more genes within 22q11.2 are involved in cognitive decline.AimsTo assess longitudinally the change in IQ scores in children with 22q11.2
deletion syndrome.MethodSixty-nine children with the syndrome were cognitively assessed two or
three times at set ages 5.5 years, 7.5 years and 9.5 years.ResultsA mean significant decline of 9.7 Full Scale IQ points was found between
ages 5.5 years and 9.5 years. In addition to the overall relative decline
that occurred when results were scored according to age-specific IQ
norms, in 10 out of a group of 29 children an absolute decrease in
cognitive raw scores was found between ages 7.5 years and 9.5 years. The
decline was not associated with a change in behavioural measures.ConclusionsThe finding of cognitive decline can be only partly explained as the
result of ‘growing into deficit’; about a third of 29 children showed an
absolute loss of cognitive faculties. The results underline the
importance of early psychiatric screening in this population and indicate
that further study of the genes at the 22q11.2 locus may be relevant to
understanding the genetic basis of early cognitive deterioration.