bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of Critical Host Mitochondrion-Associated Genes during Ehrlichia chaffeensis Infections
Authors: Von Ohlen Tonia , Luce-Fedrow Alison , Ortega M. Teresa , Ganta Roman R. , Chapes Stephen K. 
Published: July 2012

ABSTRACT

Ehrlichia chaffeensis
is an obligate intracellular bacterium that causes human monocytic ehrlichiosis (HME). To determine what host components are important for bacterial replication, we performed microarray analysis on
Drosophila melanogaster
S2 cells by comparing host gene transcript levels between permissive and nonpermissive conditions for
E. chaffeensis
growth. Five-hundred twenty-seven genes had increased transcript levels unique to permissive growth conditions 24 h postinfection. We screened adult flies that were mutants for several of the “permissive” genes for the ability to support
Ehrlichia
replication. Three additional
D. melanogaster
fly lines with putative mutations in pyrimidine metabolism were also tested. Ten fly lines carrying mutations in the genes
CG6479
,
separation anxiety
,
chitinase 11
,
CG6364
(
Uck2
),
CG6543
(
Echs1
),
withered
(
whd
),
CG15881
(
Ccdc58
),
CG14806
(
Apop1
),
CG11875
(
Nup37
), and
dumpy
(
dp
) had increased resistance to infection with
Ehrlichia
. Analysis of RNA by quantitative real-time reverse transcription-PCR (qRT-PCR) confirmed that the bacterial load was decreased in these mutant flies compared to wild-type infected control flies. Seven of these genes (
san
,
Cht11
,
Uck2
,
Echs1
,
whd
, C
cdc58
, and
Apop1
) encoded proteins that had mitochondrial functions or could be associated with proteins with mitochondrial functions. Treatment of THP-1 cells with double-stranded RNA to silence the human
UCK2
gene indicates that the disruption of the uridine-cytidine kinase affects
E. chaffeensis
replication in human macrophages. Experiments with cyclopentenyl cytosine (CPEC), a CTP synthetase inhibitor and cytosine, suggest that the nucleotide salvage pathway is essential for
E. chaffeensis
replication and that it may be important for the provision of CTP, uridine, and cytidine nucleotides.
RKI-1447 Is a Potent Inhibitor of the Rho-Associated ROCK Kinases with Anti-Invasive and Antitumor Activities in Breast Cancer
Authors: Patel Ronil A. , Forinash Kara D. , Pireddu Roberta , Sun Ying , Sun Nan , Martin Mathew P. , Schönbrunn Ernst , Lawrence Nicholas J. , Sebti Saïd M. 
Published: July 2012

Abstract
The Rho-associated kinases ROCK1 and ROCK2 are critical for cancer cell migration and invasion, suggesting they may be useful therapeutic targets. In this study, we describe the discovery and development of RKI-1447, a potent small molecule inhibitor of ROCK1 and ROCK2. Crystal structures of the RKI-1447/ROCK1 complex revealed that RKI-1447 is a Type I kinase inhibitor that binds the ATP binding site through interactions with the hinge region and the DFG motif. RKI-1447 suppressed phosphorylation of the ROCK substrates MLC-2 and MYPT-1 in human cancer cells, but had no effect on the phosphorylation levels of the AKT, MEK, and S6 kinase at concentrations as high as 10 μmol/L. RKI-1447 was also highly selective at inhibiting ROCK-mediated cytoskeleton re-organization (actin stress fiber formation) following LPA stimulation, but does not affect PAK-meditated lamellipodia and filopodia formation following PDGF and Bradykinin stimulation, respectively. RKI-1447 inhibited migration, invasion and anchorage-independent tumor growth of breast cancer cells. In contrast, RKI-1313, a much weaker analog in vitro, had little effect on the phosphorylation levels of ROCK substrates, migration, invasion or anchorage-independent growth. Finally, RKI-1447 was highly effective at inhibiting the outgrowth of mammary tumors in a transgenic mouse model. In summary, our findings establish RKI-1447 as a potent and selective ROCK inhibitor with significant anti-invasive and antitumor activities and offer a preclinical proof-of-concept that justify further examination of RKI-1447 suitability as a potential clinical candidate. Cancer Res; 72(19); 5025–34. ©2012 AACR.
Let-7 Expression Is a Significant Determinant of Response to Chemotherapy through the Regulation of IL-6/STAT3 Pathway in Esophageal Squamous Cell Carcinoma
Authors: Sugimura Keijiro , Miyata Hiroshi , Tanaka Koji , Hamano Rie , Takahashi Tsuyoshi , Kurokawa Yukinori , Yamasaki Makoto , Nakajima Kiyokazu , Takiguchi Shuji , Mori Masaki , Doki Yuichiro 
Published: July 2012

Abstract
Purpose: Cisplatin-based chemotherapy is widely used for esophageal cancer, sometimes in combination with surgery/radiotherapy, but poor response to chemotherapy is not uncommon. The aim of this study was to examine whether miRNA expression is useful to predict the response to chemotherapy in patients with esophageal cancer.
Experimental Design: Using pretreatment biopsy samples from 98 patients with esophageal cancer who received preoperative chemotherapy, we measured the expression level of several miRNAs whose expression was altered in cisplatin-resistant esophageal cancer cell lines compared with those parent cell lines and examined the relationship between the miRNA expression and response to chemotherapy. In vitro assays were conducted to clarify the mechanism of miRNA-induced changes in chemosensitivity.
Results: The expression levels of 15 miRNAs were altered in cisplatin-resistant cells. Of these, low expression of let-7b and let-7c in before-treatment biopsies from 74 patients of the training set correlated significantly with poor response to chemotherapy, both clinically and histopathologically. Low expression of let-7c also correlated with poor prognosis (P = 0.032). The relationship between let-7b and let-7c expression and response to chemotherapy was confirmed in the other 24 patients of the validation set. In in vitro assay, transfection of let-7c restored sensitivity to cisplatin and increased rate of apoptosis after exposure to cisplatin. Let-7c directly repressed cisplatin-activated interleukin (IL)-6/STAT3 prosurvival pathway.
Conclusions: Let-7 expression in esophageal cancer can be potentially used to predict the response to cisplatin-based chemotherapy. Let-7 modulates the chemosensitivity to cisplatin through the regulation of IL-6/STAT3 pathway in esophageal cancer. Clin Cancer Res; 18(18); 5144–53. ©2012 AACR.
Phase I Clinical Trial of Mixed Bacterial Vaccine (Coley's Toxins) in Patients with NY-ESO-1 Expressing Cancers: Immunological Effects and Clinical Activity
Authors: Karbach Julia , Neumann Antje , Brand Kathrin , Wahle Claudia , Siegel Ekkehard , Maeurer Markus , Ritter Erika , Tsuji Takamasa , Gnjatic Sacha , Old Lloyd J. , Ritter Gerd , Jäger Elke 
Published: July 2012

AbstractPurpose: Mixed bacterial vaccine (MBV, Coley's toxins) is a historical, vaguely defined preparation of heat-inactivated Streptococcus pyogenes and Serratia marcescens used as nonspecific immunotherapy in the treatment of cancer. The mechanism of action is suspected to have an immunologic basis, yet it is poorly defined up to now. We developed a new, biochemically well defined and current good manufacturing practice–compliant MBV preparation, which has been investigated in patients with NY-ESO-1 expressing cancers.Experimental Design: Patients received MBV subcutaneously at a starting dose of 250 EU (endotoxin units) twice a week. The MBV dose was escalated in each patient until a body temperature of 38°C to 39.5°C was induced or up to the maximum dose of 547.000 EU. Changes in serum cytokine levels were determined and immune responses to NY-ESO-1 were evaluated. Tumor response was assessed according to RECIST.Results: Twelve patients were enrolled and 11 of them developed fever after the administration of MBV. Ten of 12 patients showed a consistent increase in serum IL-6 levels with the highest levels coinciding with the highest body temperature. A subgroup of patients showed increasing levels of TNF-α, IFN-γ, and IL1-β. A patient with metastatic bladder cancer showed a partial tumor response strongly correlated with MBV-induced fever and highly elevated levels of several cytokines.Conclusions: MBV at fever-inducing dose levels can lead to a massive induction of immunoregulatory cytokines that may be involved in inducing tumor regressions. We propose to further explore the role of MBV as a potent immune modulator at higher dose levels and in conjunction with antigen-specific cancer vaccines. Clin Cancer Res; 18(19); 5449–59. ©2012 AACR.
Targeting Subcellular Localization through the Polo-Box Domain: Non-ATP Competitive Inhibitors Recapitulate a PLK1 Phenotype
Authors: McInnes Campbell , Estes Kara , Baxter Merissa , Yang Zhengguan , Farag Doaa Boshra , Johnston Paul , Lazo John S. , Wang Jianjun , Wyatt Michael D. 
Published: July 2012

Abstract
The polo-box domain (PBD) has critical roles in the mitotic functions of polo-like kinase 1 (PLK1). The replacement with partial ligand alternative through computational enrichment (REPLACE) strategy to develop inhibitors of protein–protein interactions has identified alternatives for the N-terminal tripeptide of a Cdc25C substrate. In addition, a peptide structure–activity relationship described key determinants and novel information useful for drug design. Fragment-ligated inhibitory peptides (FLIP) were generated with comparable affinity to peptide PBD inhibitors and possessed antiproliferative phenotypes in cells consistent with the observed decrease in PLK1 centrosomal localization. These FLIPs showed evidence of enhanced PLK1 inhibition in cells relative to peptides and induced monopolar and multipolar spindles, which stands in contrast to previously reported small-molecule PBD inhibitors that display phenotypes only partially representative of PLK1 knockdown. Progress obtained applying REPLACE validates this approach for identifying fragment alternatives for determinants of the Cdc25C-binding motif and extends its applicability of the strategy for discovering protein–protein interaction inhibitors. In addition, the described PBD inhibitors retain high specificity for PLK1 over PLK3 and therefore show promise as isotype selective, non-ATP competitive kinase inhibitors that provide new impetus for the development of PLK1-selective antitumor therapeutics. Mol Cancer Ther; 11(8); 1683–92. ©2012 AACR.
Process and Domain Specificity in Regions Engaged for Face Processing: An fMRI Study of Perceptual Differentiation
Authors: Collins Heather R. , Zhu Xun , Bhatt Ramesh S. , Clark Jonathan D. , Joseph Jane E. 
Published: July 2012

Abstract
The degree to which face-specific brain regions are specialized for different kinds of perceptual processing is debated. This study parametrically varied demands on featural, first-order configural, or second-order configural processing of faces and houses in a perceptual matching task to determine the extent to which the process of perceptual differentiation was selective for faces regardless of processing type (domain-specific account), specialized for specific types of perceptual processing regardless of category (process-specific account), engaged in category-optimized processing (i.e., configural face processing or featural house processing), or reflected generalized perceptual differentiation (i.e., differentiation that crosses category and processing type boundaries). ROIs were identified in a separate localizer run or with a similarity regressor in the face-matching runs. The predominant principle accounting for fMRI signal modulation in most regions was generalized perceptual differentiation. Nearly all regions showed perceptual differentiation for both faces and houses for more than one processing type, even if the region was identified as face-preferential in the localizer run. Consistent with process specificity, some regions showed perceptual differentiation for first-order processing of faces and houses (right fusiform face area and occipito-temporal cortex and right lateral occipital complex), but not for featural or second-order processing. Somewhat consistent with domain specificity, the right inferior frontal gyrus showed perceptual differentiation only for faces in the featural matching task. The present findings demonstrate that the majority of regions involved in perceptual differentiation of faces are also involved in differentiation of other visually homogenous categories.
Can a six-week exercise intervention improve gross motor function for non-ambulant children with cerebral palsy? A pilot randomized controlled trial
Authors: Bryant Elizabeth , Pountney Terry , Williams Heather , Edelman Natalie 
Published: July 2012

Objective: To determine the effect of a six-week exercise intervention on gross motor function for non-ambulant children with cerebral palsy. Design: A parallel arm randomized controlled trial. Setting: Four special schools. Participants: Thirty-five children aged 8–17 with bilateral cerebral palsy; Gross Motor Function Classification System levels IV–V. Method: Participants were randomly allocated to a static bike group, a treadmill group or control group. Participants in the bike and treadmill groups received exercise training sessions, three times weekly for six weeks. The control group received their usual care. Blinded assessments were performed at baseline and six weeks and followed up at 12 and 18 weeks. Outcome measures: Gross Motor Function Measures GMFM-66, GMFM-88D and GMFM-88E. Results: At six weeks significant differences were found in GMFM-88D scores between the bike group and the control group, and the treadmill group and the control group ( P < 0.05). The mean change (SD) in GMFM-88D score was 5.9 (6.8) for the bike group; 3.7 (4.4) for the treadmill group and 0.5 (1.9) for the control group. No significant differences were found for GMFM-66 or GMFM-88E scores between the bike group and control group, or the treadmill group and control group, although trends of improvement were observed for both exercise groups. The improvements observed declined during the follow-up period. Conclusion: This study provides preliminary evidence that exercising on a bike or treadmill may provide short-term improvements in gross motor function for non-ambulant children with cerebral palsy. This needs to be tested in a large-scale randomized trial.
Assessment of total aflatoxin level in red pepper obtained from Istanbul
Authors: Alpsoy Lokman , Kiren Artin , Can Sevde Nur , Koprubasi Ayşenur 
Published: July 2012

Aflatoxins ( Aspergillus flavus toxins (AFT)) are biologically active secondary metabolites mostly produced by some Aspergillus species that causes hepatotoxicity, teratogenicity, immunotoxicity, and cancers in human. The aim of this study is to determine the level of total AFT in powdered red pepper in the retail markets in 40 district of Istanbul using enzyme-linked immunosorbent assay. Of the 36 unpacked powdered red pepper samples, 32 samples (88%) contained AFT in the range of 0.2–106.4 µg/kg; 16 samples (44.4%) were above the regulatory limit which is at 10 µg/kg for total AFT in Turkey. More precautions on the production, transport, harvest, and storage of red pepper should be taken on hygiene to prevent toxic and carcinogenic effects of AFT.
The Ulnar Collateral Ligament Procedure Revisited
Authors: Andrews James R. , Jost Patrick W. , Cain E. Lyle 
Published: July 2012

Context: The ulnar collateral ligament of the elbow (UCL) is frequently injured in throwing athletes, most commonly baseball pitchers. The ligament is reconstructed through bone tunnels using palmaris longus or gracilis autograft. Results: This study highlights the following technique for UCL reconstruction in over 2000 athletes. 2 Conclusion: When conservative management fails, ligament reconstruction can allow the athlete to return to their sport. 1
Utilization of evidence-based treatment in elderly patients with chronic heart failure: using Korean Health Insurance claims database
Authors: Kim Ju-Young , Kim Hwa-Jung , Jung Sun-Young , Kim Kwang-Il , Song Hong Ji , Lee Joong-Yub , Seong Jong-Mi , Park Byung-Joo 
Published: July 2012

Abstract

Background
Chronic heart failure accounts for a great deal of the morbidity and mortality in the aging population. Evidence-based treatments include angiotensin-2 receptor blockers (ARBs), angiotensin-converting enzyme inhibitors (ACE-I), beta-blockers, and aldosterone antagonists. Underutilization of these treatments in heart failure patients were frequently reported, which could lead to increase morbidity and mortality. The aim of this study was to evaluate the utilization of evidence-based treatments and their related factors for elderly patients with chronic heart failure.

Methods
This is retrospective observational study using the Korean National Health Insurance claims database. We identified prescription of evidence based treatment to elderly patients who had been hospitalized for chronic heart failure between January 1, 2005, and June 30, 2006.

Results
Among the 28,922 elderly patients with chronic heart failure, beta-blockers were prescribed to 31.5%, and ACE-I or ARBs were prescribed to 54.7% of the total population. Multivariable logistic regression analyses revealed that the prescription from outpatient clinic (prevalent ratio, 4.02, 95% CI 3.31–4.72), specialty of the healthcare providers (prevalent ratio, 1.26, 95% CI, 1.12–1.54), residence in urban (prevalent ratio, 1.37, 95% CI, 1.23–1.52) and admission to tertiary hospital (prevalent ratio, 2.07, 95% CI, 1.85–2.31) were important factors associated with treatment underutilization. Patients not given evidence-based treatment were more likely to experience dementia, reside in rural areas, and have less-specialized healthcare providers and were less likely to have coexisting cardiovascular diseases or concomitant medications than patients in the evidence-based treatment group.

Conclusions
Healthcare system factors, such as hospital type, healthcare provider factors, such as specialty, and patient factors, such as comorbid cardiovascular disease, systemic disease with concomitant medications, together influence the underutilization of evidence-based pharmacologic treatment for patients with heart failure.
Does the effect of gender modify the relationship between deprivation and mortality?
Authors: Salcedo Natalia , Saez Marc , Bragulat Basili , Saurina Carme 
Published: July 2012

AbstractBackgroundIn this study we propose improvements to the method of elaborating deprivation indexes. First, in the selection of the variables, we incorporated a wider range of both objective and subjective measures. Second, in the statistical methodology, we used a distance indicator instead of the standard aggregating method principal component analysis. Third, we propose another methodological improvement, which consists in the use of a more robust statistical method to assess the relationship between deprivation and health responses in ecological regressions.MethodsWe conducted an ecological small-area analysis based on the residents of the Metropolitan region of Barcelona in the period 1994–2007. Standardized mortality rates, stratified by sex, were studied for four mortality causes: tumor of the bronquial, lung and trachea, diabetes mellitus type II, breast cancer, and prostate cancer. Socioeconomic conditions were summarized using a deprivation index. Sixteen socio-demographic variables available in the Spanish Census of Population and Housing were included. The deprivation index was constructed by aggregating the above-mentioned variables using the distance indicator, DP2. For the estimation of the ecological regression we used hierarchical Bayesian models with some improvements.ResultsAt greater deprivation, there is an increased risk of dying from diabetes for both sexes and of dying from lung cancer for men. On the other hand, at greater deprivation, there is a decreased risk of dying from breast cancer and lung cancer for women. We did not find a clear relationship in the case of prostate cancer (presenting an increased risk but only in the second quintile of deprivation).ConclusionsWe believe our results were obtained using a more robust methodology. First off, we have built a better index that allows us to directly collect the variability of contextual variables without having to use arbitrary weights. Secondly, we have solved two major problems that are present in spatial ecological regressions, i.e. those that use spatial data and, consequently, perform a spatial adjustment in order to obtain consistent estimators.
Intratracheally administered titanium dioxide or carbon black nanoparticles do not aggravate elastase-induced pulmonary emphysema in rats
Authors: Roulet Agnès , Armand Lucie , Dagouassat Maylis , Rogerieux Françoise , Simon-Deckers Angélique , Belade Esther , Van Nhieu Jeanne Tran , Lanone Sophie , Pairon Jean-Claude , Lacroix Ghislaine , Boczkowski Jorge 
Published: July 2012

Abstract

Background
Titanium dioxide (TiO2) and carbon black (CB) nanoparticles (NPs) have biological effects that could aggravate pulmonary emphysema. The aim of this study was to evaluate whether pulmonary administration of TiO2 or CB NPs in rats could induce and/or aggravate elastase-induced emphysema, and to investigate the underlying molecular mechanisms.

Methods
On day 1, Sprague-Dawley rats were intratracheally instilled with 25 U kg−1 pancreatic porcine elastase or saline. On day 7, they received an intratracheal instillation of TiO2 or CB (at 100 and 500 μg) dispersed in bovine serum albumin or bovine serum albumin alone. Animals were sacrificed at days 8 or 21, and bronchoalveolar lavage (BAL) cellularity, histological analysis of inflammation and emphysema, and lung mRNA expression of heme oxygenase-1 (HO-1), interleukin-1β (IL-1β), macrophage inflammatory protein-2, monocyte chemotactic protein-1, and matrix metalloprotease (MMP)-1, and -12 were measured. In addition, pulmonary MMP-12 expression was also analyzed at the protein level by immunohistochemistry.

Results
TiO2 NPs per se did not modify the parameters investigated, but CB NPs increased perivascular/peribronchial infiltration, and macrophage MMP-12 expression, without inducing emphysema. Elastase administration increased BAL cellularity, histological inflammation, HO-1, IL-1β and macrophage MMP-12 expression and induced emphysema. Exposure to TiO2 NPs did not modify pulmonary responses to elastase, but exposure to CB NPs aggravated elastase-induced histological inflammation without aggravating emphysema.

Conclusions
TiO2 and CB NPs did not aggravate elastase-induced emphysema. However, CB NPs induced histological inflammation and MMP-12 mRNA and protein expression in macrophages.
Erratum to: Prospects of implant with locking plate in fixation of subtrochanteric fracture: experimental demonstration of its potential benefits on synthetic femur model with supportive hierarchical nonlinear hyperelastic finite element analysis
Authors: Latifi Mohammed Hadi , Ganthel Kunalan , Rukmanikanthan Shanmugam , Mansor Azura , Kamarul Tunku , Bilgen Mehmet 
Published: July 2012

Abstract
The first publication of the work [1] did not present one of the authors' names. Kunalan Ganthel has now been added to the author list. In addition, Habib Sherkat has been added to the Acknowledgements, with thanks for providing help with the use of hyperelastic module of Abaqus Software.