bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Effects of Chemotherapy on Cognitive Function in a Mouse Model: A Prospective Study
Authors: Winocur Gordon , Henkelman Mark , Wojtowicz J. Martin , Zhang Haibo , Binns Malcolm A. , Tannock Ian F. 
Published: March 2012

Abstract
Purpose: Clinical studies indicate that up to 70% of patients with cancer who receive chemotherapy experience cognitive impairment. The present study used a prospective longitudinal design to assess short- and long-term effects of commonly used anticancer drugs on cognitive performance in a mouse model.
Experimental Design: Normal mice received three weekly injections of a combination of methotrexate + 5-fluorouracil (CHEMO group) or an equal volume of saline (SAL group). Cognitive tests, measuring different aspects of learning and memory, were administered before treatment, immediately after treatment, and three months later. Structural MRI scanning was conducted at each stage of cognitive testing.
Results: The CHEMO group exhibited deficits on cognitive tasks acquired pretreatment [spatial memory, nonmatching-to-sample (NMTS) learning, and delayed NMTS], as well as impaired new learning on two tasks (conditional associative learning, discrimination learning) introduced posttreatment. Consistent with clinical evidence, cognitive deficits were pronounced on tests that are sensitive to hippocampal and frontal lobe dysfunction, but the CHEMO group's poor performance on the discrimination learning problem suggests that impairment is more widespread than previously thought. Cognitive deficits persisted for at least three months after treatment but some recovery was noted, particularly on tests thought to be under frontal lobe control. The MRI tests did not detect brain changes that could be attributed to treatment.
Conclusions: Chemotherapeutic agents can have adverse effects on information acquired pretreatment as well as new learning and memory and, despite some recovery, impairment is long lasting. Clin Cancer Res; 18(11); 3112–21. ©2012 AACR.
Novel Immunotherapy for Malignant Melanoma with a Monoclonal Antibody That Blocks CEACAM1 Homophilic Interactions
Authors: Ortenberg Rona , Sapir Yair , Raz Lee , Hershkovitz Liat , Ben Arav Ayelet , Sapoznik Sivan , Barshack Iris , Avivi Camila , Berkun Yackov , Besser Michal J. , Ben-Moshe Tehila , Schachter Jacob , Markel Gal 
Published: March 2012

AbstractCEACAM1 (biliary glycoprotein-1, CD66a) was reported as a strong clinical predictor of poor prognosis in melanoma. We have previously identified CEACAM1 as a tumor escape mechanism from cytotoxic lymphocytes. Here, we present substantial evidence in vitro and in vivo that blocking of CEACAM1 function with a novel monoclonal antibody (MRG1) is a promising strategy for cancer immunotherapy. MRG1, a murine IgG1 monoclonal antibody, was raised against human CEACAM1. It recognizes the CEACAM1-specific N-domain with high affinity (KD ∼ 2 nmol/L). Furthermore, MRG1 is a potent inhibitor of CEACAM1 homophilic binding and does not induce any agonistic effect. We show using cytotoxicity assays that MRG1 renders multiple melanoma cell lines more vulnerable to T cells in a dose-dependent manner, only following antigen-restricted recognition. Accordingly, MRG1 significantly enhances the antitumor effect of adoptively transferred, melanoma-reactive human lymphocytes using human melanoma xenograft models in severe combined immunodeficient/nonobese diabetic (SCID/NOD) mice. A significant antibody-dependent cell cytotoxicity response was excluded. It is shown that MRG1 reaches the tumor and is cleared within a week. Importantly, approximately 90% of melanoma specimens are CEACAM1+, implying that the majority of patients with melanoma could be amenable to MRG1-based therapy. Normal human tissue microarray displays limited binding to luminal epithelial cells on some secretory ducts, which was weaker than the broad normal cell binding of other anticancer antibodies in clinical use. Importantly, MRG1 does not directly affect CEACAM1+ cells. CEACAM1 blockade is different from other immunomodulatory approaches, as MRG1 targets inhibitory interactions between tumor cells and late effector lymphocytes, which is thus a more specific and compartmentalized immune stimulation with potentially superior safety profile. Mol Cancer Ther; 11(6); 1300–10. ©2012 AACR.
Development of Noxa-like BH3 Mimetics for Apoptosis-Based Therapeutic Strategy in Chronic Lymphocytic Leukemia
Authors: Billard Christian 
Published: March 2012

Abstract
Despite real advances made in chemoimmunotherapy, chronic lymphocytic leukemia (CLL) is still an incurable disease. New therapeutic strategies based on the restoration of the cell death program seemed relevant. Some members of the Bcl-2 family are critical players in the defective apoptotic program in CLL cells and/or targets of apoptosis inducers in vitro. The concept of BH3 mimetics has led to the characterization of small molecules mimicking proapoptotic BH3-only members of the Bcl-2 family by their ability to bind and antagonize the prosurvival members. Some putative or actual BH3 mimetics are already being tested in clinical trials with somewhat promising results. However, none of them has a high enough interaction affinity with Mcl-1, a crucial antiapoptotic factor in CLL. It has been suggested that resistance to BH3 mimetics can be overcome by using inhibitors of Mcl-1 expression. An alternative and more direct strategy is to design mimetics of the Noxa BH3 domain, which is a specific antagonistic Mcl-1 ligand. The development of such Noxa-like BH3 mimetics, capable of directly interacting with Mcl-1 and efficiently neutralizing its antiapoptotic activity, is extremely important to evaluate their impact on the clinical outcome of patients with CLL. Mol Cancer Res; 10(6); 673–6. ©2012 AACR.
miR-23a Promotes the Transition from Indolent to Invasive Colorectal Cancer
Authors: Jahid Sohail , Sun Jian , Edwards Robert A. , Dizon Diana , Panarelli Nicole C. , Milsom Jeffrey W. , Sikandar Shaheen S. , Gümüş Zeynep H. , Lipkin Steven M. 
Published: March 2012

Abstract
Colorectal cancer is a classic example of a tumor that progresses through multiple distinct stages in its evolution. To understand the mechanisms regulating the transition from indolent to invasive disease, we profiled somatic copy number alterations in noninvasive adenomas and invasive adenocarcinomas from Apc and DNA mismatch repair (MMR) mutant mouse models. We identified a recurrent amplicon on mouse chromosome 8 that encodes microRNA (miRNA) 23a and -27a (miR). miR-23a and -27a levels are upregulated in mouse intestinal adenocarcinomas, primary tumors from patients with stage I/II colorectal cancers, as well as in human colorectal cancer cell lines and cancer stem cells. Functionally, miR-23a promotes the migration and invasion of colorectal cancer cells and stem cells, whereas miR-27a primarily promotes proliferation. We computationally and experimentally validated that metastasis suppressor 1 (MTSS1) is a direct miR-23a target and similarly validated that the ubiquitin ligase FBXW7 is a direct miR-27a target. Analyses of computationally predicted target genes in microarray data sets of patients with colorectal cancers are consistent with a role for miR-23a, but not miR-27a, specifically in invasive colorectal cancers.
Significance: Understanding the mechanisms regulating the transition from indolent adenomas to invasive and metastatic colorectal cancers is critical to improving patient outcomes. Our study highlights roles of miR-23a and miR-27a in tumor progression and supports a potential mechanistic role for miR-23a in the transition from indolent to invasive colorectal cancers. Cancer Discov; 2(6); 540–53. © 2012 AACR.
This article is highlighted in the In This Issue feature, p. 473
Diastolic Electromechanical Coupling
Authors: Sauer Andrew , Wilcox Jane E. , Andrei Adin-Cristian , Passman Rod , Goldberger Jeffrey J. , Shah Sanjiv J. 
Published: March 2012

Background—
Electromechanical coupling, a well-described phenomenon in systolic dysfunction, has not been well studied in diastole. We hypothesized that the ECG T-peak to T-end (TpTe) interval, representing transmural dispersion of repolarization, is associated with echocardiographic markers of diastolic dysfunction (DD).

Methods and Results—

We performed a prospective, cross-sectional study of the association between TpTe and markers of DD in 84 consecutive, unselected patients referred for exercise echocardiography. We systematically measured TpTe on the resting ECG, and we performed comprehensive assessment of DD at rest and at peak stress. ECGs and echocardiograms were analyzed independently, blinded to each other and to all clinical data. By univariable analysis, increased TpTe was associated with older age, increased E/e’ ratio, and DD (
P
<0.05 for all associations after correcting for multiple comparisons). Increased TpTe was inversely associated with reduced tissue Doppler e’ velocity, a marker of DD (
R
= −0.66,
P
<0.0001). This association persisted after adjusting for age, QTc, exercise-induced wall motion abnormalities, and left ventricular mass index (β= −0.41 [95% confidence interval, −0.70 to −0.12] cm/s per 10-ms increase in TpTe;
P
=0.006). Baseline TpTe was also independently associated with resting DD (adjusted odds ratio, 3.9 [95% confidence interval, 1.4–10.7];
P
=0.009) and peak exercise E/e’ ratio (
P
<0.0001).

Conclusions—
Increased TpTe is associated with both resting and exercise-induced DD. Electromechanical coupling may represent a pathophysiologic link between electrical transmural dispersion of repolarization and abnormal myocardial relaxation, and may be a novel therapeutic target.
Prognostic Implication of Appropriateness Criteria for Pharmacologic Stress Echocardiography Performed in an Outpatient Clinic
Authors: Cortigiani Lauro , Bigi Riccardo , Bovenzi Francesco , Molinaro Sabrina , Picano Eugenio , Sicari Rosa 
Published: March 2012

Background—
Although appropriateness criteria for stress echocardiography have been developed to deliver high-quality care, the prognostic impact of these criteria remains undefined. Therefore, we sought to assess the prognostic implication of the American College of Cardiology/American Society of Echocardiography appropriateness criteria for pharmacological stress echo in a cohort of ambulatory patients.

Methods and Results—

The study population consisted of 1552 ambulatory patients who underwent pharmacological (752 dobutamine, 800 dipyridamole) stress echo for the evaluation of known (n=549) or suspected (n=1003) coronary artery disease at a single cardiology center. Patients were followed up for a median of 36 months. Indications were determined for consecutive studies by 2 reviewers and categorized as follows: 984 (63%) patients had appropriate, 145 (9%) uncertain, and 423 (27%) inappropriate indication for stress echo. Ischemia was present in 15% of patients with appropriate, 8% of those with uncertain, and 5% of those with inappropriate indication (
P
<0.0001). During follow-up, 146 events (89 deaths, 57 nonfatal infarctions) occurred. Annual event rate associated with appropriate, uncertain, and inappropriate study was 3.1%, 3.8%, and 1.3%, respectively. The abnormal test result in patients with appropriate, uncertain, and inappropriate study was associated with 5.0%, 5.6%, and 1.8% annual event rate, respectively, exerting an independent value only in the appropriate and uncertain subset.

Conclusions—
Inappropriate indication for pharmacological stress echo is common, being documented in about 1 of 4 patients evaluated in an ambulatory setting, and is associated with lower rate of positive results and better survival as compared with appropriate and uncertain indication.
Preoperative Incidence of Olfactory Dysfunction in Nasal Surgery Patients
Authors: Jumaily Jeffrey Saad , Fayad Christine , Mardirossian Vartan , Singh Ashok , Stram John , Spiegel Jeffrey 
Published: March 2012

ObjectiveLearn the incidence of olfactory dysfunction in preoperative patients prior to nasal surgery and compare with a control group of patients who are not going to have such surgery. Assess the usefulness of the coffee/tea differentiation test in assessing preoperative dysosmia.Study DesignProspective controlled cohort study.SettingUrban medical center.Subjects and MethodsOne hundred fifty‐one adult patients (aged 18‐65 years) whose olfactory function was tested using the Pocket Smell Test and a coffee/tea differentiation test. A failed test required missing at least 1 item on the card or failure to report a difference between tea and coffee. The statistical analysis using the t test and the Fisher exact test were calculated using MINITAB.ResultsThe study group (n = 55) had 38% men and 62% women compared with 58% men and 42% women in the control group (n = 96). The incidence of dysosmia was 32% in the study group and 14% in the control group. In the study group, 34.5% of patients failed the Pocket Smell Test and 12.4% failed the coffee/tea differentiation test as compared with 12.4% and 0%, respectively, in the control group.ConclusionPatients who are scheduled for nasal surgery for medical or cosmetic indications are more likely to suffer from olfactory dysfunction before surgical intervention. This should be taken into consideration when counseling patients regarding possible postoperative complications.
Reevaluating the Prognostic Significance of Age in Differentiated Thyroid Cancer
Authors: Oyer Samuel L. , Smith Valerie A. , Lentsch Eric J. 
Published: March 2012

ObjectiveTo determine the impact of age on disease‐specific survival in differentiated thyroid cancer.Study DesignRetrospective analysis of a large population database.SettingSurveillance, Epidemiology, and End Results (SEER) database/multiple settings.Subjects and MethodsThe SEER database was examined to identify patients diagnosed with either papillary or follicular carcinoma of the thyroid between the years 1988 and 2003. Information obtained included patient age, sex, tumor type, size, extension, and nodal or distant metastases. Kaplan‐Meier survival analyses were used to estimate disease‐specific survival based on patient age range, and the log‐rank test was used to assess for statistical differences between survival curves. A multivariate analysis was performed including the variables listed above to determine disease‐specific hazard ratios of death for various age cutoffs.ResultsA total of 42,209 patients were identified. Patients 45 years and older had significantly worse survival than younger patients (P <. 0001). A significant decrease in disease‐specific survival was first seen in patients aged 35 years and older, and survival continued to steadily decrease with each additional decade of age (P <. 001). Patients aged 35 years and older were 14 times more likely to die from differentiated thyroid cancer than patients younger than 35 years.ConclusionIncreasing age is associated with poorer survival in differentiated thyroid cancer. This relationship represents a continuum with an initial decrease in survival starting at age 35 years that continues to decline with further advancing age.
The Role of Vestibular Caloric Tests in Cochlear Implantation
Authors: Parmar Amit , Savage Julian , Wilkinson Andrew , Hajioff Daniel , Nunez Desmond A. , Robinson Philip 
Published: March 2012

ObjectiveVestibular function tests are often undertaken before cochlear implantation, in part to help select the side of surgery. The authors aim to determine whether implantation on the side of better vestibular function leads to greater perception of dizziness by patients than implantation on the side of worse or similar function.Study DesignHistorical cohort study.SettingTertiary cochlear implantation center.Subjects and MethodsThe records of 177 adult recipients of a unilateral cochlear implant were reviewed retrospectively in 2 groups. Group A included patients with an implant in the ear with worse or similar caloric responses. Group B included patients with an implant in the ear with the stronger caloric response. All patients underwent preoperative bithermal caloric testing: a clinically significant difference was defined by a 20% lateral canal paresis. They were assessed postoperatively by the Dizziness Handicap Inventory and supplementary questions.ResultsFifty‐seven percent of both groups reported dizziness in the first 7 days postoperatively. At 2 months, 20% of group A and 34% of group B experienced some dizziness. Fourteen percent of group A and 10% of group B felt that cochlear implantation had resulted in impaired balance. The Dizziness Handicap Inventory scores of 86% of group A (median score 0) and 76% of group B (median score 10) corresponded with low handicap. None of these results differed significantly between groups A and B.ConclusionAlthough cochlear implantation may result in dizziness, it is almost always short‐lived and mild, even when the ear with the stronger caloric response is implanted.
Mental health planning for children and youth: is it developmentally appropriate?
Authors: Newman Louise , Birleson Peter 
Published: March 2012

Objectives: We aim to provide an overview of current issues facing child and adolescent mental health services and the provision of developmentally informed and appropriate care. Method: We review developmental models of mental disorder and the impact on service design. Results: Developmental issues can shape service design. Conclusions: Mental health services need to be informed and responsive to changing developmental needs and of the context of child development in terms of family and attachment relationships. Children and adolescents have specific needs in terms of service design.
Integrating Evidence-Based Tobacco Cessation Interventions in Free Medical Clinics
Authors: Foley Kristie L. , Pockey Jessica R. , Helme Donald W. , Song Eun-Young , Stewart Kate , Jones Cindy , Spangler John G. , Sutfin Erin L. 
Published: March 2012

Background. Free medical clinics serve a critical role in health care delivery of America’s uninsured population, who are less likely to receive tobacco cessation counseling and 1½ times more likely than the general population to use tobacco. The authors evaluate the opportunities for and challenges to implementing the U.S. Public Health Service Guidelines for tobacco cessation in free clinics. Methods. Six free clinics participated in this pilot study. Five objectives were targeted: implementation of a tobacco user identification system, education of all clinic staff and volunteers, dedication of a program champion, use of evidence-based treatment, and creation of a supportive environment that reinforces provider behavior. Key informant interviews and focus group data were used to describe the opportunities and barriers of implementing the Public Health Service Guidelines. Results. All clinics adopted a user identification system, dedicated a program champion, adopted evidence-based counseling, and created an environment conducive for cessation. Common challenges included getting volunteers to attend on-site training programs, accessing nicotine replacement therapy, and promoting Quit Line usage, all of which are part of evidence-based treatment. Conclusion. With more than 1,200 free clinics nationwide, it is very important to understand the opportunities and barriers of implementing tobacco cessation services and systems in free clinics.
A mutation at IVS1 + 5 of the von Hippel-Lindau gene resulting in intron retention in transcripts is not pathogenic in a patient with a tongue cancer?: case report
Authors: Asakawa Takeshi , Esumi Mariko , Endo Sohei , Kida Akinori , Ikeda Minoru 
Published: March 2012

Abstract

Background
Von Hippel-Lindau disease (VHL) is a dominantly inherited familial cancer syndrome predisposing the patient to a variety of malignant and benign neoplasms, most frequently hemangioblastoma, renal cell carcinoma, pheochromocytoma, and pancreatic tumors. VHL is caused by mutations of the VHL tumor suppressor gene on the short arm of chromosome 3, and clinical manifestations develop if both alleles are inactivated according to the two-hit hypothesis. VHL mutations are more frequent in the coding region and occur occasionally in the splicing region of the gene. Previously, we reported that the loss of heterozygosity (LOH) of the VHL gene is common in squamous cell carcinoma tissues of the tongue.

Case Presentation
We describe a case of squamous cell carcinoma in the tongue caused by a point mutation in the splicing region of the VHL gene and discuss its association with VHL disease. Sequence analysis of DNA extracted from the tumor and peripheral blood of the patient with squamous cell carcinoma revealed a heterozygous germline mutation (c. 340 + 5 G > C) in the splice donor sequence in intron 1 of the VHL gene. RT-PCR analysis of the exon1/intron1 junction in RNA from tumor tissue detected an unspliced transcript. Analysis of LOH using a marker with a heterozygous mutation of nucleotides (G or C) revealed a deletion of the mutant C allele in the carcinoma tissues.

Conclusions
The fifth nucleotide G of the splice donor site of the VHL gene is important for the efficiency of splicing at that site. The development of tongue cancer in this patient was not associated with VHL disease because the mutation occurred in only a single allele of the VHL gene and that allele was deleted in tumor cells.
Proteomics analysis of differentially expressed proteins in chicken trachea and kidney after infection with the highly virulent and attenuated coronavirus infectious bronchitis virus in vivo
Authors: Cao Zhongzan , Han Zongxi , Shao Yuhao , Liu Xiaoli , Sun Junfeng , Yu Demin , Kong Xiangang , Liu Shengwang 
Published: March 2012

Abstract

Background
Infectious bronchitis virus (IBV) is first to be discovered coronavirus which is probably endemic in all regions with intensive impact on poultry production. In this study, we used two-dimensional gel electrophoresis (2-DE) and two-dimensional fluorescence difference gel electrophoresis (2-DIGE), coupled with matrix-assisted laser desorption/ionization time-of-flight tandem mass spectrometry (MALDI-TOF/TOF-MS), to explore the global proteome profiles of trachea and kidney tissues from chicken at different stages infected in vivo with the highly virulent ck/CH/LDL/97I P5 strain of infectious bronchitis virus (IBV) and the embryo-passaged, attenuated ck/CH/LDL/97I P115 strain.

Results
Fifty-eight differentially expressed proteins were identified. Results demonstrated that some proteins which had functions in cytoskeleton organization, anti-oxidative stress, and stress response, showed different change patterns in abundance from chicken infected with the highly virulent ck/CH/LDL/97I P5 strain and those given the embryo-passaged, attenuated P115 stain. In addition, the dynamic transcriptional alterations of 12 selected proteins were analyzed by the real-time RT-PCR, and western blot analysis confirmed the change in abundance of heat shock proteins (HSP) beta-1, annexin A2, and annexin A5.

Conclusions
The proteomic alterations described here may suggest that these changes to protein expression correlate with IBV virus' virulence in chicken, hence provides valuable insights into the interactions of IBV with its host and may also assist with investigations of the pathogenesis of IBV and other coronavirus infections.