bluuebunny/crossref_metadata_2025_split huggingface dataset:
Platinum Sensitivity–Related Germline Polymorphism Discovered via a Cell-Based Approach and Analysis of Its Association with Outcome in Ovarian Cancer Patients
Authors: Huang R. Stephanie , Johnatty Sharon E. , Gamazon Eric R. , Im Hae Kyung , Ziliak Dana , Duan Shiwei , Zhang Wei , Kistner Emily O. , Chen Peixian , Beesley Jonathan , Mi Shuangli , O'Donnell Peter H. , Fraiman Yarden S. , Das Soma , Cox Nancy J. , Lu Yi , MacGregor Stuart , Goode Ellen L. , Vierkant Robert A. , Fridley Brooke L. , Hogdall Estrid , Kjaer Susanne K. , Jensen Allan , Moysich Kirsten B. , Grasela Matthew , Odunsi Kunle , Brown Robert , Paul Jim , Lambrechts Diether , Despierre Evelyn , Vergote Ignace , Gross Jenny , Karlan Beth Y. , deFazio Anna , Chenevix-Trench Georgia , Dolan M. Eileen 
Published: June 2011

Abstract
Purpose: Cell-based approaches were used to identify genetic markers predictive of patients' risk for poor response prior to chemotherapy.
Experimental Design: We conducted genome-wide association studies (GWAS) to identify single-nucleotide polymorphisms (SNP) associated with cellular sensitivity to carboplatin through their effects on mRNA expression using International HapMap lymphoblastoid cell lines (LCL) and replicated them in additional LCLs. SNPs passing both stages of the cell-based study were tested for association with progression-free survival (PFS) in patients. Phase 1 validation was based on 377 ovarian cancer patients receiving at least four cycles of carboplatin and paclitaxel from the Australian Ovarian Cancer Study (AOCS). Positive associations were then assessed in phase 2 validation analysis of 1,326 patients from the Ovarian Cancer Association Consortium and The Cancer Genome Atlas.
Results: In the initial GWAS, 342 SNPs were associated with carboplatin-induced cytotoxicity, of which 18 unique SNPs were retained after assessing their association with gene expression. One SNP (rs1649942) was replicated in an independent LCL set (Bonferroni adjusted P &lt; 0.05). It was found to be significantly associated with decreased PFS in phase 1 AOCS patients (Pper-allele = 2 × 10−2), with a stronger effect in the subset of women with optimally debulked tumors (Pper-allele = 4 × 10−3). rs1649942 was also associated with poorer overall survival in women with optimally debulked tumors (Pper-allele = 9 × 10−3). However, this SNP was not significant in phase 2 validation analysis with patients from numerous cohorts.
Conclusion: This study shows the potential of cell-based, genome-wide approaches to identify germline predictors of treatment outcome and highlights the need for extensive validation in patients to assess their clinical effect. Clin Cancer Res; 17(16); 5490–500. ©2011 AACR.
The 12-Month Effects of Early Motivational Interviewing After Acute Stroke
Authors: Watkins Caroline L. , Wathan Jennifer V. , Leathley Michael J. , Auton Malcolm F. , Deans Carol F. , Dickinson Hazel A. , Jack Cathy I.A. , Sutton Christopher J. , van den Broek Martin D. , Lightbody C. Elizabeth 
Published: June 2011

Background and Purpose—
The purpose of this study was to determine whether motivational interviewing (MI), a patient-centered counseling technique, can benefit patients' mood and mortality poststroke.

Methods—
This was a single-center, open, randomized, controlled trial. The setting was a hospital with a stroke unit. Four hundred eleven consecutive patients on the stroke register were >18 years old, not known to be moving out-of-area postdischarge, not receiving psychiatric or clinical psychology intervention, and were without severe cognitive or communication problems preventing participation in interviews. All patients received usual stroke care. Patients in the intervention group also received 4 individual, weekly sessions of MI. The primary outcome was the proportion of patients with normal mood measured by the 28-item General Health Questionnaire (normal <5; low ≥5) using a mailed questionnaire at 12 months poststroke.

Results—

At 12-month follow-up (including imputed data), 37.7% patients in the control group and 48.0% patients in the intervention group had normal mood. Twenty-five (12.8%) of 195 patients in the control group and 13 (6.5%) of 199 patients in the intervention group had died. A significant benefit of motivational interviewing over usual stroke care was found for mood (
P
=0.020; OR, 1.66; 95% CI, 1.08 to 2.55) and mortality (
P
=0.035; OR, 2.14; 95% CI, 1.06 to 4.38).

Conclusions—
Results suggest that motivational interviewing improves patients' mood and reduces mortality 12 months poststroke.

Clinical Trial Registration—

URL:
www.controlled-trials.com
. Unique identifier: ISRCTN54465472.
Effects of Blood Pressure Lowering on Major Vascular Events Among Patients With Isolated Diastolic Hypertension
Authors: Arima Hisatomi , Anderson Craig , Omae Teruo , Woodward Mark , Hata Jun , Murakami Yoshitaka , MacMahon Stephen , Neal Bruce , Chalmers John ,   for the PROGRESS Collaborative Group
Published: June 2011

Background and Purpose—
Despite clear evidence that blood pressure (BP) lowering is effective for prevention of cardiovascular events among patients with isolated systolic hypertension and systolic–diastolic hypertension, there is ongoing uncertainty about its effects in those with isolated diastolic hypertension. The objective of the present analysis is to determine whether BP lowering provides benefits to patients with isolated diastolic hypertension.

Methods—
Patients with cerebrovascular disease and hypertension at baseline (n=4283) were randomly assigned to either active treatment (perindopril in all participants plus indapamide for those with neither an indication for nor a contraindication to a diuretic) or matching placebo(s). The primary outcome was total major vascular events.

Results—

There were 1923 patients with isolated systolic hypertension (systolic BP ≥140 mm Hg and diastolic BP <90 mm Hg), 315 with isolated diastolic hypertension (systolic BP <140 mm Hg and diastolic BP ≥90 mm Hg), and 2045 with systolic–diastolic hypertension (systolic BP ≥140 mm Hg and diastolic BP ≥90 mm Hg) at baseline. Active treatment reduced the relative risk of major vascular events by 27% (95% CI, 10% to 41%) among patients with isolated systolic hypertension, by 28% (−29% to 60%) among those with isolated diastolic hypertension, and by 32% (17% to 45%) among those with systolic–diastolic hypertension. There was no evidence of differences in the magnitude of the effects of treatment among different types of hypertension (
P
homogeneity=0.89).

Conclusions—
BP lowering is likely to provide a similar level of protection against major vascular events for patients with isolated diastolic hypertension as for those with isolated systolic hypertension and systolic–diastolic hypertension.

Clinical Trial Registration Information—
This trial was not registered because patients were enrolled before July 1, 2005.
Successful Microbubble Sonothrombolysis Without Tissue-Type Plasminogen Activator in a Rabbit Model of Acute Ischemic Stroke
Authors: Culp William C. , Flores Rene , Brown Aliza T. , Lowery John D. , Roberson Paula K. , Hennings Leah J. , Woods Sean D. , Hatton Jeff H. , Culp Benjamin C. , Skinner Robert D. , Borrelli Michael J. 
Published: June 2011

Background and Purpose—
Microbubbles (MB) combined with ultrasound (US) have been shown to lyse clots without tissue-type plasminogen activator (tPA) both in vitro and in vivo. We evaluated sonothrombolysis with 3 types of MB using a rabbit embolic stroke model.

Methods—

New Zealand White rabbits (n=74) received internal carotid angiographic embolization of single 3-day-old cylindrical clots (0.6×4.0 mm). Groups included: (1) control (n=11) embolized without treatment; (2) tPA (n=20); (3) tPA+US (n=10); (4) perflutren lipid MB+US (n=16); (5) albumin 3 μm MB+US (n=8); and (6) tagged albumin 3 μm MB+US (n=9). Treatment began 1 hour postembolization. Ultrasound was pulsed-wave (1 MHz; 0.8 W/cm
2
) for 1 hour; rabbits with tPA received intravenous tPA (0.9 mg/kg) over 1 hour. Lipid MB dose was intravenous (0.16 mg/kg) over 30 minutes. Dosage of 3 μm MB was 5×10
9
MB intravenously alone or tagged with eptifibatide and fibrin antibody over 30 minutes. Rabbits were euthanized at 24 hours. Infarct volume was determined using vital stains on brain sections. Hemorrhage was evaluated on hematoxylin and eosin sections.

Results—

Infarct volume percent was lower for rabbits treated with lipid MB+US (1.0%±0.6%;
P
=0.013), 3 μm MB+US (0.7%±0.9%;
P
=0.018), and tagged 3 μm MB+US (0.8%±0.8%;
P
=0.019) compared with controls (3.5%±0.8%). The 3 MB types collectively had lower infarct volumes (
P
=0.0043) than controls. Infarct volume averaged 2.2%±0.6% and 1.7%±0.8% for rabbits treated with tPA alone and tPA+US, respectively (
P
=nonsignificant).

Conclusions—
Sonothrombolysis without tPA using these MB is effective in decreasing infarct volumes. Study of human application and further MB technique development are justified.
Osteopontin Enhances Endogenous Repair After Neonatal Hypoxic–Ischemic Brain Injury
Authors: van Velthoven Cindy T.J. , Heijnen Cobi J. , van Bel Frank , Kavelaars Annemieke 
Published: June 2011

Background and Purpose—
Hypoxic–ischemic (HI) brain injury is a frequent cause of perinatal morbidity and mortality with limited therapeutic options. To identify molecules important for cerebral damage and repair, we investigated the growth factor-related gene expression profile after neonatal cerebral HI. We identified osteopontin (OPN) as the most highly upregulated factor early after HI. We therefore explored the role of endogenous OPN in brain damage and repair.

Methods—

Nine-day-old wild-type mice were exposed to cerebral HI; growth factor-related gene expression profiles were analyzed 1 to 7 days later by reverse transcriptase–polymerase chain reaction arrays. To determine the contribution of OPN to brain damage, we used p9 OPN
−/−
and wild-type mice. HI brain damage, sensorimotor function, and cell proliferation and differentiation were compared.

Results—

Gene expression profiling of 150 genes related to growth factors and neurotrophins showed that expression of 52 genes changed during the first 7 days after HI.
OPN
was the gene with the strongest increase expression at all time points measured. We show here for the first time that in response to neonatal HI, OPN-deficient mice developed increased gray and white matter loss and more pronounced sensorimotor deficits as compared with wild-type littermates. Furthermore, OPN deficiency decreases HI-induced cell proliferation/survival and oligodendrogenesis without affecting neuronal differentiation.

Conclusions—
OPN plays an important role in repairing brain injury after neonatal HI by regulating cerebral cell proliferation/survival and oligodendrocyte differentiation after injury. The observed promyelinative effect of OPN may offer novel possibilities for a therapy targeting white matter injury.
Oxfordshire Community Stroke Project Classification Poorly Differentiates Small Cortical and Subcortical Infarcts
Authors: Asdaghi Negar , Jeerakathil Thomas , Hameed Bilal , Saini Monica , McCombe Jennifer A. , Shuaib Ashfaq , Emery Derek , Butcher Kenneth 
Published: June 2011

Background and Purpose—
The Oxfordshire Community Stroke Project (OCSP) is a common clinical stroke classification tool. We evaluated the accuracy of OCSP classification with a prospective magnetic resonance imaging (MRI) study.

Methods—
Stroke/transient ischemic attack patients presenting within 48 hours of onset were included in the study (n=130). Following computed tomography scan, OCSP classification, total anterior circulation infarcts (TACI), partial anterior circulation infarcts (PACI), lacunar circulation infarcts (LACI), and posterior circulation infarcts (POCI) were performed by 3 independent examiners. All patients underwent diffusion-weighted MRI with planimetric volume measurement and classification into OCSP categories, organized by lesion location.

Results—

Patients were clinically classified as TACI (12 patients), PACI (62 patients), LACI (38 patients), and POCI (18 patients). In 101 patients with diffusion-weighted MRI lesions, correct classification rates were: TACI (83.3%), PACI (83%), LACI (39%), and POCI (86%). OCSP had the following sensitivity (SE), specificity (SP), and positive predictive value (PPV): TACI (SE, 100%; SP, 98%; PPV, 83%), PACI (SE, 73%; SP, 78%; PPV, 83%), LACI (SE, 47%; SP, 83%; PPV, 39%), and POCI (SE, 92%; SP, 98%; PPV, 86%). Sixty-one percent of patients in the LACI group had radiographic appearances consistent with PACI, and 15% of those classified as PACI had lacunar infarcts. No differences in stroke severity existed between patients classified correctly (median National Institutes of Health Stroke Scale [NIHSS]=4; interquartile range [IQR]=7) or incorrectly (median NIHSS=3; IQR=3). Patients classified correctly had larger infarct volume (median=6.75 mL; IQR=33.2) than did those who were incorrectly classified (1.86 mL; IQR=5;
P
=0.008).

Conclusions—
OCSP classification does not permit accurate discrimination between lacunar and small-volume cortical infarcts. Differential patterns of investigation for stroke etiology should not be based solely on clinical criteria.
Proinflammatory role of angiotensin II in a rat nephrosis model induced by adriamycin
Authors: Muñoz Maydelin , Rincón Jaimar , Pedreañez Adriana , Viera Ninoska , Hernández-Fonseca Juan P , Mosquera Jesús 
Published: June 2011

Introduction: Nephrotic syndrome induced by adriamycin (ADR) is an experimental model of glomerulosclerosis in humans. The AT1 receptor for angiotensin II (Ang II) is involved in the renal expression of the nuclear factor-kappa B (NF-ΚB) during this nephrosis. NF-ΚB is a transcription factor for proinflammatory effects of Ang II; however, there is no information about the role of this receptor in the renal proinflammatory events in ADR nephrosis. Materials and methods: To determine the role of Ang II in ADR nephrosis, Sprague-Dawley rats were treated with ADR (6 mg/kg iv). One ADR group received oral losartan treatment (15 mg/kg gavage) 3 days before ADR injection and then daily for 4 weeks, and the other group water. Animals were sacrificed at week 4 and renal macrophage infiltration, ICAM-1, superoxide anion (O2-) and Ang II expressions were analysed by indirect immunofluorescence and histochemical techniques. Results: ADR rats showed increased expression of ICAM-1, Ang II, O2- and macrophage infiltration, events that were diminished by losartan treatment. Ang II expression remained unaltered after antagonist treatment. Proteinuria was reduced after 3 weeks of treatment. Conclusions: These data suggest that Ang II plays a role in the inflammatory events during ADR-induced nephrosis, probably mediated by AT1 receptors.
Intravenous iron for the treatment of fatigue in nonanemic, premenopausal women with low serum ferritin concentration
Authors: Krayenbuehl Pierre-Alexandre , Battegay Edouard , Breymann Christian , Furrer Joerg , Schulthess Georg 
Published: June 2011

AbstractThis is the first study to investigate the efficacy of intravenous iron in treating fatigue in nonanemic patients with low serum ferritin concentration. In a randomized, double-blinded, placebo-controlled study, 90 premenopausal women presenting with fatigue, serum ferritin ≤ 50 ng/mL, and hemoglobin ≥ 120 g/L were randomized to receive either 800 mg of intravenous iron (III)–hydroxide sucrose or intravenous placebo. Fatigue and serum iron status were assessed at baseline and after 6 and 12 weeks. Median fatigue at baseline was 4.5 (on a 0-10 scale). Fatigue decreased during the initial 6 weeks by 1.1 in the iron group compared with 0.7 in the placebo group (P = .07). Efficacy of iron was bound to depleted iron stores: In patients with baseline serum ferritin ≤ 15 ng/mL, fatigue decreased by 1.8 in the iron group compared with 0.4 in the placebo group (P = .005), and 82% of iron-treated compared with 47% of placebo-treated patients reported improved fatigue (P = .03). Drug-associated adverse events were observed in 21% of iron-treated patients and in 7% of placebo-treated patients (P = .05); none of these events was serious. Intravenous administration of iron improved fatigue in iron-deficient, nonanemic women with a good safety and tolerability profile. The efficacy of intravenous iron was bound to a serum ferritin concentration ≤ 15 ng/mL. This study was registered at the International Standard Randomized Controlled Trial Number Register (www.isrctn.org) as ISRCTN78430425.
The conjugative plasmid of a bean-nodulating Sinorhizobium fredii strain is assembled from sequences of two Rhizobium plasmids and the chromosome of a Sinorhizobiumstrain
Authors: Cervantes Laura , Bustos Patricia , Girard Lourdes , Santamaría Rosa Isela , Dávila Guillermo , Vinuesa Pablo , Romero David , Brom Susana 
Published: June 2011

Abstract

Background
Bean-nodulating Rhizobium etli originated in Mesoamerica, while soybean-nodulating Sinorhizobium fredii evolved in East Asia. S. fredii strains, such as GR64, have been isolated from bean nodules in Spain, suggesting the occurrence of conjugative transfer events between introduced and native strains. In R. etli CFN42, transfer of the symbiotic plasmid (pRet42d) requires cointegration with the endogenous self-transmissible plasmid pRet42a. Aiming at further understanding the generation of diversity among bean nodulating strains, we analyzed the plasmids of S. fredii GR64: pSfr64a and pSfr64b (symbiotic plasmid).

Results
The conjugative transfer of the plasmids of strain GR64 was analyzed. Plasmid pSfr64a was self-transmissible, and required for transfer of the symbiotic plasmid. We sequenced pSfr64a, finding 166 ORFs. pSfr64a showed three large segments of different evolutionary origins; the first one presented 38 ORFs that were highly similar to genes located on the chromosome of Sinorhizobium strain NGR234; the second one harbored 51 ORFs with highest similarity to genes from pRet42d, including the replication, but not the symbiosis genes. Accordingly, pSfr64a was incompatible with the R. etli CFN42 symbiotic plasmid, but did not contribute to symbiosis. The third segment contained 36 ORFs with highest similarity to genes localized on pRet42a, 20 of them involved in conjugative transfer. Plasmid pRet42a was unable to substitute pSfr64a for induction of pSym transfer, and its own transfer was significantly diminished in GR64 background. The symbiotic plasmid pSfr64b was found to differ from typical R. etli symbiotic plasmids.

Conclusions

S. fredii GR64 contains a chimeric transmissible plasmid, with segments from two R. etli plasmids and a S. fredii chromosome, and a symbiotic plasmid different from the one usually found in R. etli bv phaseoli. We infer that these plasmids originated through the transfer of a symbiotic-conjugative-plasmid cointegrate from R. etli to a S. fredii strain, and at least two recombination events among the R. etli plasmids and the S. fredii genome. As in R. etli CFN42, the S. fredii GR64 transmissible plasmid is required for the conjugative transfer of the symbiotic plasmid. In spite of the similarity in the conjugation related genes, the transfer process of these plasmids shows a host-specific behaviour.
Myofibrillogenesis regulator 1 (MR-1) is a novel biomarker and potential therapeutic target for human ovarian cancer
Authors: Lu Renquan , Sun Min , Feng Jingjing , Gao Xiang , Guo Lin 
Published: June 2011

Abstract

Background
Myofibrillogenesis regulator 1 (MR-1) is overexpressed in human cancer cells and plays an essential role in cancer cell growth. However, the significance of MR-1 in human ovarian cancer has not yet been explored. The aim of this study was to examine whether MR-1 is a predictor of ovarian cancer and its value as a therapeutic target in ovarian cancer patients.

Methods
Reverse-transcription polymerase chain reaction (PCR) and quantitative real-time PCR were used to detect MR-1 mRNA levels in tissue samples from 26 ovarian cancer patients and 25 controls with benign ovarian disease. Anti-MR-1 polyclonal antibodies were prepared, tested by ELISA and western blotting, and then used for immunohistochemical analysis of the tissue samples. Adhesion and invasion of 292T cells was also examined after transfection of a pMX-MR-1 plasmid. Knockdown of MR-1 expression was achieved after stable transfection of SKOV3 cells with a short hairpin DNA pGPU6/GFP/Neo plasmid against the MR-1 gene. In addition, SKOV3 cells were treated with paclitaxel and carboplatin, and a potential role for MR-1 as a therapeutic target was evaluated.

Results
MR-1 was overexpressed in ovarian cancer tissues and SKOV3 cells. 293T cells overexpressed MR-1, and cellular spread and invasion were enhanced after transfection of the pMX-MR-1 plasmid, suggesting that MR-1 is critical for ovarian cancer cell growth. Knockdown of MR-1 expression inhibited cell adhesion and invasion, and treatment with anti-cancer drugs decreased its expression in cancer cells. Taken together, these results provide the first evidence of the cellular and molecular mechanisms by which MR-1 might serve as a novel biological marker and potential therapeutic target for ovarian cancer.

Conclusions
MR-1 may be a biomarker for diagnosis of ovarian cancer. It may also be useful for monitoring of the effects of anti-cancer therapies. Further studies are needed to clarify whether MR-1 is an early diagnostic marker for ovarian cancer and a possible therapeutic target.
Specific and sensitive quantitative RT-PCR of miRNAs with DNA primers
Authors: Balcells Ingrid , Cirera Susanna , Busk Peter K 
Published: June 2011

Abstract

Background
MicroRNAs are important regulators of gene expression at the post-transcriptional level and play an important role in many biological processes. Due to the important biological role it is of great interest to quantitatively determine their expression level in different biological settings.

Results
We describe a PCR method for quantification of microRNAs based on a single reverse transcription reaction for all microRNAs combined with real-time PCR with two, microRNA-specific DNA primers. Primer annealing temperatures were optimized by adding a DNA tail to the primers and could be designed with a success rate of 94%. The method was able to quantify synthetic templates over eight orders of magnitude and readily discriminated between microRNAs with single nucleotide differences. Importantly, PCR with DNA primers yielded significantly higher amplification efficiencies of biological samples than a similar method based on locked nucleic acids-spiked primers, which is in agreement with the observation that locked nucleic acid interferes with efficient amplification of short templates. The higher amplification efficiency of DNA primers translates into higher sensitivity and precision in microRNA quantification.

Conclusions
MiR-specific quantitative RT-PCR with DNA primers is a highly specific, sensitive and accurate method for microRNA quantification.