tbuckley/cabot-search huggingface dataset:
Prevalence, associations, and predictors of apathy in adult survivors of infantile (&lt;5 years of age) posterior fossa brain tumors†
Authors: Cliodhna Carroll, Peter Watson, Helen A. Spoudeas, Michael M. Hawkins, David A. Walker, Isabel C. H. Clare, Anthony J. Holland, Howard A. Ring
Journal: Neuro-Oncology (2013)

Apathy is associated with pervasive and disadvantageous effects on daily functioning. It has been observed transiently in some children after surgery for posterior fossa tumors. In this study, our objective was to examine prevalence, associations, and predictors of apathy in adult survivors of an infantile posterior fossa brain tumor (PFT). One hundred seventeen adult survivors of a childhood PFT diagnosed before age 5 years and 60 of their siblings were assessed in a cross-sectional study a mean of 32 years (range, 18–53 years) after survivors' initial tumor diagnoses, using the Marin Apathy Evaluation Scale (AES), the Weschler Abbreviated Scale of Intelligence and the Composite International Diagnostic Interview for psychiatric disorders. Marin Apathy Evaluation Scale, the Weschler Abbreviated Scale of Intelligence reached or exceeded a criterion score for clinically significant apathy in 35% of survivors, compared with 18% in a sibling comparison group. In both siblings and survivors, apathy was associated with lower verbal and full-scale IQ and, among survivors, with having undergone partial rather than total tumor resection (independent of irradiation status). Apathy was not related to presence of concurrent International Classification of Diseases, 10th Revision, depression. Female sex was associated with late apathy after a PFT, with increased likelihood of women reaching the apathy criterion relative to men if they were survivors. Clinically significant and potentially treatable apathy occurs relatively commonly in adult survivors of an infantile childhood PFT, particularly women. Clinicians, including those managing posterior fossa pathology in very young children, should be aware of this association, and future research should clarify whether specific treatment-related variables are implicated in increasing this risk of apathy.
New perspectives in the therapy of chronic hepatitis B
Authors: Pietro Lampertico, Yun Fan Liaw
Journal: Gut (2012)

Since approval of the first nucleos(t)ide analogue (NUC) in 1998, remarkable advances have been made in antiviral treatment of chronic hepatitis B virus (HBV) infection. Both interferon-based therapy and treatment with NUCs have evolved to the stage that pegylated interferon (Peg-IFN) has replaced conventional IFN, and entecavir (ETV) and tenofovir disoproxil fumarate (TDF) have become the first-line oral treatments.1–3 As the therapeutic outcomes are still far from satisfactory, many attempts have been made to optimise antiviral therapy of chronic HBV infection. Along with the evolution of drug therapy, quantitation of hepatitis B surface antigen (HBsAg) has gained popularity as a clinically useful seromarker for assessing the natural course and response to therapy of chronic HBV infection. In addition, the discovery of IL28B polymorphism, which has shed new light on the treatment of hepatic C virus (HCV) infection, has been applied in the study of the response of patients with HBV to IFN regimens. These recent developments are reviewed in this article, focusing on the following topics: IL28B and response to IFN or Peg-IFN therapy; response-guided therapy of Peg-IFN treatment; ETV and TDF in field practice naive patients.

### IL28B as a baseline host factor in the response to IFN- or Peg-IFN-based therapy

Peg-IFN treatment remains an attractive anti-HBV strategy because it provides higher rates of off-therapy immune control (normal alanine aminotransferase (ALT) levels coupled with HBV DNA <2000 IU/ml and anti-HBe positivity) compared with NUCs.1–3 These benefits, however, are restricted to a subgroup of patients, ∼30%, and the tolerability, although significantly improved compared with standard IFN, is suboptimal, and also there are significant costs. There have been many attempts to identify pretreatment predictors of a response, resulting in the identification of high ALT levels, low HBV DNA, and virus genotype as significant predictors.1–3 However, these factors have limited applicability in clinical practice, the most important …
Combat Duty in Iraq and Afghanistan, Mental Health Problems, and Barriers to Care
Authors: Charles W. Hoge, Carl A. Castro, Stephen C. Messer, Dennis McGurk, Dave I. Cotting, Robert L. Koffman
Journal: New England Journal of Medicine (2004)

The current combat operations in Iraq and Afghanistan have involved U.S. military personnel in major ground combat and hazardous security duty. Studies are needed to systematically assess the mental health of members of the armed services who have participated in these operations and to inform policy with regard to the optimal delivery of mental health care to returning veterans.We studied members of four U.S. combat infantry units (three Army units and one Marine Corps unit) using an anonymous survey that was administered to the subjects either before their deployment to Iraq (n=2530) or three to four months after their return from combat duty in Iraq or Afghanistan (n=3671). The outcomes included major depression, generalized anxiety, and post-traumatic stress disorder (PTSD), which were evaluated on the basis of standardized, self-administered screening instruments.Exposure to combat was significantly greater among those who were deployed to Iraq than among those deployed to Afghanistan. The percentage of study subjects whose responses met the screening criteria for major depression, generalized anxiety, or PTSD was significantly higher after duty in Iraq (15.6 to 17.1 percent) than after duty in Afghanistan (11.2 percent) or before deployment to Iraq (9.3 percent); the largest difference was in the rate of PTSD. Of those whose responses were positive for a mental disorder, only 23 to 40 percent sought mental health care. Those whose responses were positive for a mental disorder were twice as likely as those whose responses were negative to report concern about possible stigmatization and other barriers to seeking mental health care.This study provides an initial look at the mental health of members of the Army and the Marine Corps who were involved in combat operations in Iraq and Afghanistan. Our findings indicate that among the study groups there was a significant risk of mental health problems and that the subjects reported important barriers to receiving mental health services, particularly the perception of stigma among those most in need of such care.
Management of actinic cheilitis using diclofenac 3% gel: a report of six cases
Authors: C. Ulrich, T. Forschner, M. Ulrich, E. Stockfleth, W. Sterry, C. Termeer
Journal: British Journal of Dermatology (2007)

Actinic cheilitis is a frequent manifestation of actinic dysplasia and requires early therapy to prevent its progression into invasive squamous cell carcinoma (SCC). Several therapies are used, ranging from unspecific lesion-adapted destructive techniques (i.e. laser) to ambitious surgical field-management (vermillionectomy). There is increasing awareness of the effectiveness of field adapted, non destructive therapies, such as photodynamic therapy or 5% imiquimod. Diclofenac 3% gel is used in the treatment of actinic keratosis (AK), but it has not been evaluated for the treatment of actinic cheilitis.This non-blinded, uncontrolled case series study evaluated the effects of diclofenac 3% gel in the treatment of actinic cheilitis.Six patients with histologically verified actinic cheilitis were treated with diclofenac 3% gel, twice daily for 6 weeks. Clinical assessment was performed 2-4 weeks after the end of treatment.Four out of six patients showed clinical clearing of actinic cheilitis 2-4 weeks after the end of treatment. Biopsies were taken from the treated areas at the final visit to verify clinical clearance. Side effects in most of the patients included mild erythema and mild to moderate swelling of the lips.Topical therapy with diclofenac 3% gel may be an efficient, cosmetically more appealing alternative treatment for actinic cheilitis than currently used destructive therapies. However, future studies and long-term follow-up of patients will be needed to compare its efficacy with established forms of therapy.
Mutant WT1 is associated with DNA hypermethylation of PRC2 targets in AML and responds to EZH2 inhibition
Authors: Subarna Sinha, Daniel Thomas, Linda Yu, Andrew J. Gentles, Namyoung Jung, M. Ryan Corces-Zimmerman, Steven M. Chan, Andreas Reinisch, Andrew P. Feinberg, David L. Dill, Ravindra Majeti
Journal: Blood (2014)
IGF1 Gene Polymorphism and Risk for Hereditary Nonpolyposis Colorectal Cancer
Authors: Maja Zecevic, Christopher I. Amos, Xiangjun Gu, Imelda M. Campos, J. Shawn Jones, Patrick M. Lynch, Miguel A. Rodriguez-Bigas, Marsha L. Frazier
Journal: JNCI Journal of the National Cancer Institute (2006)

Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominant disorder caused by germline mutations in DNA mismatch repair (MMR) genes. Insulin-like growth factor-I (IGF-I) is involved in colorectal carcinogenesis, and elevated plasma IGF-I levels are associated with sporadic colorectal cancer (CRC) risk. We investigated the relationship between IGF1 promoter cytosine-adenine (CA) dinucleotide-repeat polymorphism length and CRC risk in 121 MMR gene mutation carriers using Cox regression and Kaplan-Meier analysis. All statistical tests were two-sided. Time to onset for CRC increased for each decrease in CA-repeat number (median = 19 repeats, range = 12-22 repeats; hazard ratio [HR] = 1.17, 95% confidence interval [CI] = 1.05 to 1.31; P = .006). Patients carrying a CA(< or = 17) repeat allele had a statistically significantly higher CRC risk (HR = 2.36; 95% CI = 1.28 to 4.36; P = .006) than all others and were younger at onset (44 years versus 56.5 years; P = .023). These findings indicate a statistically significant association between shorter IGF1 CA-repeat lengths and increased risk for CRC in HNPCC. This is the first report, to our knowledge, to show that IGF1 variant genotypes modify risk of a hereditary form of cancer.
Small molecule antagonist of the bone morphogenetic protein type I receptors suppresses growth and expression of Id1 and Id3 in lung cancer cells expressing Oct4 or nestin
Authors: Elaine Langenfeld, Malik Deen, Emmanuel Zachariah, John Langenfeld
Journal: Molecular Cancer (2013)

Bone morphogenetic proteins (BMP) are embryonic morphogens that are aberrantly expressed in lung cancer. BMPs mediate cell fate decisions and self-renewal of stem cells, through transcription regulation of inhibitor of differentiation protein/DNA binding proteins (Id1-3). Inhibition of BMP signaling decreases growth and induces cell death of lung cancer cells lines by downregulating the expression of Id proteins. It is not known whether the BMP signaling cascade regulates growth and the expression of Id proteins of lung cancer cells expressing the stem cell markers Oct4 and/or nestin.Lung cancer cells expressing Oct4 or nestin were isolated from lung cancer cell lines by stably transfecting the Oct4 promoter or nestin promoter expression vectors that induce expression of the green fluorescent protein reporter.Our studies suggest that lung cancer cells expressing Oct4 or nestin are different cell populations. Microarray and quantitative RT-PCR demonstrated that the expression of specific stem cell markers were different between isolated Oct4 and nestin cells. Both the Oct4 and nestin populations were more tumorigenic than controls but histologically they were quite different. The isolated Oct4 and nestin cells also responded differently to inhibition of BMP signaling. Blockade of BMP signaling with the BMP receptor antagonist DMH2 caused significant growth inhibition of both the Oct4 and nestin cell populations but only increased cell death in the nestin population. DMH2 also induced the expression of nestin in the Oct4 population but not in the nestin cells. We also show that BMP signaling is an important regulator of Id1 and Id3 in both the Oct4 and nestin cell populations. Furthermore, we show that NeuN is frequently expressed in NSCLC and provide evidence suggesting that Oct4 cells give rise to cancer cells expressing nestin and/or NeuN.These studies show that although biologically different, BMP signaling is growth promoting in cancer cells expressing Oct4 or nestin. Inhibition of BMP signaling decreases expression of Id proteins and suppresses growth of cancer cells expressing Oct4 or Nestin. Small molecule antagonists of the BMP type I receptors represent potential novel drugs to target the population of cancer cells expressing stem cell markers.
Inverse association between soy intake and non-Hodgkin lymphoma risk among women: a case–control study in Japan
Authors: D. Chihara, K. Matsuo, J. Kanda, S. Hosono, H. Ito, S. Nakamura, M. Seto, Y. Morishima, K. Tajima, H. Tanaka
Journal: Annals of Oncology (2011)
FOCAL LESIONS OF THE CORTEX OF THE LEFT ANGULAR GYRUS IN TWO CASES OF LATE CATATONIA
Authors: E. E. SOUTHARD, M. M. CANAVAN
Journal: American Journal of Psychiatry (1916)

I. Introduction. Relation of the two angular gyrus cases to previous anatomical work on dementia præox. Former work did not include focally destructive lesions. "Late" catatonia and presenile psychoses. Arteriosclerotic mental disease. Melancholia. Campbell on parietal lobes, angular gyrus. Question of visual function of angular gyrus. Alexia and the angular gyrus. Conjugate deviation. II. Case A. Clinical history. Autopsy. Microscopic study of focal arteriosclerotic lesion of angular gyrus. III. Case B. Clinical history. Autopsy. Miscroscopic study of solitary tubercie of angular gyrus. IV. Summary. V. Conclusions.
Abstinence and Safer Sex HIV Risk-Reduction Interventions for African American Adolescents
Authors: J B Jemmott, L S Jemmott, G T Fong
Journal: JAMA (1998)

Context.—African American adolescents are at high risk of contracting sexually transmitted infection with human immunodeficiency virus (HIV), but which behavioral interventions to reduce risk are most effective and who should conduct them is not known.Objective.—To evaluate the effects of abstinence and safer-sex HIV risk-reduction interventions on young inner-city African American adolescents' HIV sexual risk behaviors when implemented by adult facilitators as compared with peer cofacilitators.Design.—Randomized controlled trial with 3-, 6-, and 12-month follow-up.Setting.—Three middle schools serving low-income African American communities in Philadelphia, Pa.Participants.—A total of 659 African American adolescents recruited for a Saturday program.Interventions.—Based on cognitive-behavioral theories and elicitation research, interventions involved 8 1-hour modules implemented by adult facilitators or peer cofacilitators. Abstinence intervention stressed delaying sexual intercourse or reducing its frequency; safer-sex intervention stressed condom use; control intervention concerned health issues unrelated to sexual behavior.Main Outcome Measures.—Self-reported sexual intercourse, condom use, and unprotected sexual intercourse.Results.—Mean age of the enrollees was 11.8 years; 53% were female and 92.6% were still enrolled at 12 months. Abstinence intervention participants were less likely to report having sexual intercourse in the 3 months after intervention than were control group participants (12.5% vs 21.5%, P=.02), but not at 6- or 12-month follow-up (17.2% vs 22.7%, P=.14; 20.0% vs 23.1%, P=.42, respectively). Safer-sex intervention participants reported significantly more consistent condom use than did control group participants at 3 months (odds ratio [OR]=3.38; 95% confidence interval [CI], 1.25-9.16) and higher frequency of condom use at all follow-ups. Among adolescents who reported sexual experience at baseline, the safer-sex intervention group reported less sexual intercourse in the previous 3 months at 6- and 12-month follow-up than did control and abstinence intervention (adjusted mean days over prior 3 months, 1.34 vs 3.77 and 3.03, respectively; P≤.01 at 12-month follow-up) and less unprotected intercourse at all follow-ups than did control group (adjusted mean days, 0.04 vs 1.85, respectively, P&lt;.001, at 12-month follow-up). There were no differences in intervention effects with adult facilitators as compared with peer cofacilitators.Conclusion.—Both abstinence and safer-sex interventions can reduce HIV sexual risk behaviors, but safer-sex interventions may be especially effective with sexually experienced adolescents and may have longer-lasting effects.
Association of IFN-γ Signal Transduction Defects with Impaired HLA Class I Antigen Processing in Melanoma Cell Lines
Authors: Annedore Respa, Juergen Bukur, Soldano Ferrone, Graham Pawelec, Yingdong Zhao, Ena Wang, Francesco M. Marincola, Barbara Seliger
Journal: Clinical Cancer Research (2011)

Abstract Purpose: Abnormalities in the constitutive and IFN-γ–inducible HLA class I surface antigen expression of tumor cells is often associated with an impaired expression of components of the antigen processing machinery (APM). Hence, we analyzed whether there exists a link between the IFN-γ signaling pathway, constitutive HLA class I APM component expression, and IFN-γ resistance. Experimental Design: The basal and IFN-γ–inducible expression profiles of HLA class I APM and IFN-γ signal transduction cascade components were assessed in melanoma cells by real-time PCR (RT-PCR), Western blot analysis and/or flow cytometry, the integrity of the Janus activated kinase (JAK) 2 locus by comparative genomic hybridization. JAK2 was transiently overexpressed in JAK2− cells. The effect of IFN-γ on the cell growth was assessed by XTT [2,3-bis(2-methoxy-4-nitro-S-sulfophenynl)-H-tetrazolium-5-carboxanilide inner salt] assay. Results: The analysis of 8 melanoma cell lines linked the IFN-γ unresponsiveness of Colo 857 cells determined by lack of inducibility of HLA class I surface expression on IFN-γ treatment to a deletion of JAK2 on chromosome 9, whereas other IFN-γ signaling pathway components were not affected. In addition, the constitutive HLA class I APM component expression levels were significantly reduced in JAK2− cells. Furthermore, JAK2-deficient cells were also resistant to the antiproliferative effect of IFN-γ. Transfection of wild-type JAK2 into JAK2− Colo 857 not only increased the basal APM expression but also restored their IFN-γ sensitivity. Conclusions: Impaired JAK2 expression in melanoma cells leads to reduced basal expression of MHC class I APM components and impairs their IFN-γ inducibility, suggesting that malfunctional IFN-γ signaling might cause HLA class I abnormalities. Clin Cancer Res; 17(9); 2668–78. ©2011 AACR.
Nox4 Is Critical for Hypoxia-Inducible Factor 2-α Transcriptional Activity in von Hippel-Lindau–Deficient Renal Cell Carcinoma
Authors: Jodi K. Maranchie, Ye Zhan
Journal: Cancer Research (2005)

Abstract Inactivation of the von Hippel-Lindau tumor suppressor (VHL) is an early event in &amp;gt;60% of sporadic clear cell renal cell carcinoma (RCC). Loss of VHL E3 ubiquitin ligase function results in accumulation of the α-subunit of the hypoxia-inducible heterodimeric transcription factor (HIF-α) and transcription of an array of genes including vascular endothelial growth factor, transforming growth factor-α, and erythropoietin. Studies have shown that HIF-α can be alternatively activated by reactive oxygen species. Nox4 is an NADP(H) oxidase that generates signaling levels of superoxide and is found in greatest abundance in the distal renal tubules. To determine if Nox4 contributes to HIF activity in RCC, we examined the impact of Nox4 expression on HIF-α expression and transactivation. We report here that small inhibitory RNA (siRNA) knockdown of Nox4 in 786-0 human renal tumor cells expressing empty vector (PRC) or wild-type VHL (WT) results in 50% decrease in intracellular reactive oxygen species as measured by a fluorescent 2′,7′-dichlorofluorescin diacetate assay, and &amp;gt;85% reduction in HIF2-α mRNA and protein levels by quantitative reverse transcription-PCR and Western blot analysis. Furthermore, expression of the HIF target genes, vascular endothelial growth factor, transforming growth factor-α, and Glut-1 was abrogated by 93%, 74%, and 99%, respectively, after stable transfection with Nox4 siRNA relative to nontargeting siRNA, as determined by quantitative reverse transcription-PCR. Thus, renal Nox4 expression is essential for full HIF2-α expression and activity in 786-0 renal tumor cells, even in the absence of functional VHL. We propose the use of Nox4 as a target in the treatment of clear cell RCC.
Expression analysis of mitotic spindle checkpoint genes in breast carcinoma: role of NDC80/HEC1 in early breast tumorigenicity, and a two-gene signature for aneuploidy
Authors: Ivan Bièche, Sophie Vacher, François Lallemand, Sengül Tozlu-Kara, Hind Bennani, Michèle Beuzelin, Keltouma Driouch, Etienne Rouleau, Florence Lerebours, Hugues Ripoche, Géraldine Cizeron-Clairac, Frédérique Spyratos, Rosette Lidereau
Journal: Molecular Cancer (2011)

Aneuploidy and chromosomal instability (CIN) are common abnormalities in human cancer. Alterations of the mitotic spindle checkpoint are likely to contribute to these phenotypes, but little is known about somatic alterations of mitotic spindle checkpoint genes in breast cancer.To obtain further insight into the molecular mechanisms underlying aneuploidy in breast cancer, we used real-time quantitative RT-PCR to quantify the mRNA expression of 76 selected mitotic spindle checkpoint genes in a large panel of breast tumor samples.The expression of 49 (64.5%) of the 76 genes was significantly dysregulated in breast tumors compared to normal breast tissues: 40 genes were upregulated and 9 were downregulated. Most of these changes in gene expression during malignant transformation were observed in epithelial cells.Alterations of nine of these genes, and particularly NDC80, were also detected in benign breast tumors, indicating that they may be involved in pre-neoplastic processes.We also identified a two-gene expression signature (PLK1 + AURKA) which discriminated between DNA aneuploid and DNA diploid breast tumor samples. Interestingly, some DNA tetraploid tumor samples failed to cluster with DNA aneuploid breast tumors.This study confirms the importance of previously characterized genes and identifies novel candidate genes that could be activated for aneuploidy to occur. Further functional analyses are required to clearly confirm the role of these new identified genes in the molecular mechanisms involved in breast cancer aneuploidy. The novel genes identified here, and/or the two-gene expression signature, might serve as diagnostic or prognostic markers and form the basis for novel therapeutic strategies.