bluuebunny/crossref_metadata_2025_split huggingface dataset:
The association of quality of life with potentially remediable disruptions of circadian sleep/activity rhythms in patients with advanced lung cancer
Authors: Grutsch James F , Ferrans Carol , Wood Patricia A , Du-Quiton Jovelyn , Quiton Dinah Faith T , Reynolds Justin L , Ansell Christine M , Oh Eun Young , Daehler Mary Ann , Levin Robert D , Braun Donald P , Gupta Digant , Lis Christopher G , Hrushesky William JM 
Published: May 2011

Abstract

Background
Cancer patients routinely develop symptoms consistent with profound circadian disruption, which causes circadian disruption diminished quality of life. This study was initiated to determine the relationship between the severity of potentially remediable cancer-associated circadian disruption and quality of life among patients with advanced lung cancer.

Methods
We concurrently investigated the relationship between the circadian rhythms of 84 advanced lung cancer patients and their quality of life outcomes as measured by the EORTC QLQ C30 and Ferrans and Powers QLI. The robustness and stability of activity/sleep circadian daily rhythms were measured by actigraphy. Fifty three of the patients in the study were starting their definitive therapy following diagnosis and thirty one patients were beginning second-line therapy. Among the patients who failed prior therapy, the median time between completing definitive therapy and baseline actigraphy was 4.3 months, (interquartile range 2.1 to 9.8 months).

Results
We found that circadian disruption is universal and severe among these patients compared to non-cancer-bearing individuals. We found that each of these patient's EORTC QLQ C30 domain scores revealed a compromised capacity to perform the routine activities of daily life. The severity of several, but not all, EORTC QLQ C30 symptom items correlate strongly with the degree of individual circadian disruption. In addition, the scores of all four Ferrans/Powers QLI domains correlate strongly with the degree of circadian disruption. Although Ferrans/Powers QLI domain scores show that cancer and its treatment spared these patients' emotional and psychological health, the QLI Health/Function domain score revealed high levels of patients' dissatisfaction with their health which is much worse when circadian disruption is severe. Circadian disruption selectively affects specific Quality of Life domains, such as the Ferrans/Powers Health/Function domain, and not others, such as EORTC QLQ C30 Physical Domain.

Conclusions
These data suggest the testable possibility that behavioral, hormonal and/or light-based strategies to improve circadian organization may help patients suffering from advanced lung cancer to feel and function better.
Complementary and alternative medicine use in oncology: A questionnaire survey of patients and health care professionals
Authors: Chang Kah Hoong , Brodie Rachel , Choong Mei Ann , Sweeney Karl J , Kerin Michael J 
Published: May 2011

Abstract

Background
We aimed to investigate the prevalence and predictors of Complementary and Alternative Medicine (CAM) use among cancer patients and non-cancer volunteers, and to assess the knowledge of and attitudes toward CAM use in oncology among health care professionals.

Methods
This is a cross-sectional questionnaire survey conducted in a single institution in Ireland. Survey was performed in outpatient and inpatient settings involving cancer patients and non-cancer volunteers. Clinicians and allied health care professionals were asked to complete a different questionnaire.

Results
In 676 participants including 219 cancer patients; 301 non-cancer volunteers and 156 health care professionals, the overall prevalence of CAM use was 32.5% (29.1%, 30.9% and 39.7% respectively in the three study cohorts). Female gender (p < 0.001), younger age (p = 0.004), higher educational background (p < 0.001), higher annual household income (p = 0.001), private health insurance (p = 0.001) and non-Christian (p < 0.001) were factors associated with more likely CAM use. Multivariate analysis identified female gender (p < 0.001), non-Christian (p = 0.001) and private health insurance (p = 0.015) as independent predictors of CAM use. Most health care professionals thought they did not have adequate knowledge (58.8%) nor were up to date with the best evidence (79.2%) on CAM use in oncology. Health care professionals who used CAM were more likely to recommend it to patients (p < 0.001).

Conclusions
This study demonstrates a similarly high prevalence of CAM use among oncology health care professionals, cancer and non cancer patients. Patients are more likely to disclose CAM usage if they are specifically asked. Health care professionals are interested to learn more about various CAM therapies and have poor evidence-based knowledge on specific oncology treatments. There is a need for further training to meet to the escalation of CAM use among patients and to raise awareness of potential benefits and risks associated with these therapies.
Translation and validation of the Korean confusion assessment method for the intensive care unit
Authors: Heo Eun Young , Lee Byoung-Jo , Hahm Bong-Jin , Song Eun Hee , Lee Han-A , Yoo Chul-Gyu , Kim Young Whan , Han Sung Koo , Shim Young-Soo , Lee Sang-Min 
Published: May 2011

Abstract

Background
Delirium is a common problem and associated with poor outcomes in intensive care unit (ICU) patients. Diagnosis of delirium in ICU patients is limited and usually underdiagnosed by physicians. The Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) is one of the most widely used screening methods for detection of ICU delirium. Our goal was to translate and validate the CAM-ICU for use in the Korean ICU setting.

Methods
Translation of the CAM-ICU was done according to the guidelines suggested by the Translation and Cultural Adaptation Group. For validation and interrater reliability assessment of the Korean CAM-ICU, two nurses independently assessed delirium in ICU patients and the results were compared with the reference evaluation, which was done by a psychiatrist using the Diagnostic and Statistical Manual of Mental Disorders IV (DSM-IV).

Results
Twenty-two patients were evaluated by two nurses and one psychiatrist expert independently. During the study period, we have continuously educated study nurses. Based on DSM-IV criteria, 16 out of 22 (72.7%) patients developed delirium. The sensitivities of the two nurses' evaluations using the Korean CAM-ICU were 89.80% for nurse 1 and 77.40% for nurse 2. Their specificities were 72.40% and 75.80% and their overall accuracy was 83.33% and 88.37% respectively. The Korean CAM-ICU was done with reasonable interrater reliability between nurse 1 and nurse 2 (κ = 0.81, p < 0.001).

Conclusions
The Korean CAM-ICU showed good validity and could be incorporated into clinical practice in Korean ICUs.

Trial registration
ISRCTN: ISRCTN50265663
Adverse effect profile of trichlormethiazide: a retrospective observational study
Authors: Takahashi Yasuo , Nishida Yayoi , Nakayama Tomohiro , Asai Satoshi 
Published: May 2011

Abstract

Background
Trichlormethiazide, a thiazide diuretic, was introduced in 1960 and remains one of the most frequently used diuretics for treating hypertension in Japan. While numerous clinical trials have indicated important side effects of thiazides, e.g., adverse effects on electrolytes and uric acid, very few data exist on serum electrolyte levels in patients with trichlormethiazide treatment. We performed a retrospective cohort study to assess the adverse effects of trichlormethiazide, focusing on serum electrolyte and uric acid levels.

Methods
We used data from the Clinical Data Warehouse of Nihon University School of Medicine obtained between Nov 1, 2004 and July 31, 2010, to identify cohorts of new trichlormethiazide users (n = 99 for 1 mg, n = 61 for 2 mg daily dosage) and an equal number of non-users (control). We used propensity-score matching to adjust for differences between users and control for each dosage, and compared serum chemical data including serum sodium, potassium, uric acid, creatinine and urea nitrogen. The mean exposure of trichlormethiazide of 1 mg and 2 mg users was 58 days and 64 days, respectively.

Results
The mean age was 66 years, and 55% of trichlormethiazide users of the 1 mg dose were female. In trichlormethiazide users of the 2 mg dose, the mean age was 68 years, and 43% of users were female. There were no statistically significant differences in all covariates (age, sex, comorbid diseases, past drugs, and current antihypertensive drugs) between trichlormethiazide users and controls for both doses. In trichlormethiazide users of the 2 mg dose, the reduction of serum potassium level and the elevation of serum uric acid level were significant compared with control, whereas changes of mean serum sodium, creatinine and urea nitrogen levels were not significant. In trichlormethiazide users of the 1 mg dose, all tests showed no statistically significant change from baseline to during the exposure period in comparison with control.

Conclusions
Our study showed adverse effects of decreased serum potassium and increased serum uric acid with trichlormethiazide treatment, and suggested that a lower dose of trichlormethiazide may minimize these adverse effects. These findings support the current trend in hypertension therapeutics to shift towards lower doses of thiazides.
Functional analysis of HOXD9 in human gliomas and glioma cancer stem cells
Authors: Tabuse Masanao , Ohta Shigeki , Ohashi Yohei , Fukaya Raita , Misawa Aya , Yoshida Kazunari , Kawase Takeshi , Saya Hideyuki , Thirant Cécile , Chneiweiss Hérve , Matsuzaki Yumi , Okano Hideyuki , Kawakami Yutaka , Toda Masahiro 
Published: May 2011

AbstractBackgroundHOXgenes encode a family of homeodomain-containing transcription factors involved in the determination of cell fate and identity during embryonic development. They also behave as oncogenes in some malignancies.ResultsIn this study, we found high expression of theHOXD9gene transcript in glioma cell lines and human glioma tissues by quantitative real-time PCR. Using immunohistochemistry, we observed HOXD9 protein expression in human brain tumor tissues, including astrocytomas and glioblastomas. To investigate the role ofHOXD9in gliomas, we silenced its expression in the glioma cell line U87 usingHOXD9-specific siRNA, and observed decreased cell proliferation, cell cycle arrest, and induction of apoptosis. It was suggested thatHOXD9contributes to both cell proliferation and/or cell survival. TheHOXD9gene was highly expressed in a side population (SP) of SK-MG-1 cells that was previously identified as an enriched-cell fraction of glioma cancer stem-like cells.HOXD9siRNA treatment of SK-MG-1 SP cells resulted in reduced cell proliferation. Finally, we cultured human glioma cancer stem cells (GCSCs) from patient specimens found with high expression ofHOXD9in GCSCs compared with normal astrocyte cells and neural stem/progenitor cells (NSPCs).ConclusionsOur results suggest thatHOXD9may be a novel marker of GCSCs and cell proliferation and/or survival factor in gliomas and glioma cancer stem-like cells, and a potential therapeutic target.
Mitochondrial oxidative stress drives tumor progression and metastasis: should we use antioxidants as a key component of cancer treatment and prevention?
Authors: Sotgia Federica , Martinez-Outschoorn Ubaldo E , Lisanti Michael P 
Published: May 2011

Abstract
The functional role of oxidative stress in cancer pathogenesis has long been a hotly debated topic. A study published this month in BMC Cancer by Goh et al., directly addresses this issue by using a molecular genetic approach, via an established mouse animal model of human breast cancer. More specifically, alleviation of mitochondrial oxidative stress, via transgenic over-expression of catalase (an anti-oxidant enzyme) targeted to mitochondria, was sufficient to lower tumor grade (from high-to-low) and to dramatically reduce metastatic tumor burden by >12-fold. Here, we discuss these new findings and place them in the context of several other recent studies showing that oxidative stress directly contributes to tumor progression and metastasis. These results have important clinical and translational significance, as most current chemo-therapeutic agents and radiation therapy increase oxidative stress, and, therefore, could help drive tumor recurrence and metastasis. Similarly, chemo- and radiation-therapy both increase the risk for developing a secondary malignancy, such as leukemia and/or lymphoma. To effectively reduce mitochondrial oxidative stress, medical oncologists should now re-consider the use of powerful anti-oxidants as a key component of patient therapy and cancer prevention.
Please see related research article: http://www.biomedcentral.com/1471-2407/11/191
Predominance of Th2 polarization by Vitamin D through a STAT6-dependent mechanism
Authors: Sloka Scott , Silva Claudia , Wang Jianxiong , Yong V Wee 
Published: May 2011

AbstractBackgroundVitamin D has several reported immunomodulatory properties including the reduced generation of pro-inflammatory CD4+ T helper 1 (Th1) cells and the increase in levels of the anti-inflammatory Th2 subset. Less clear has been the impact of vitamin D on the pro-inflammatory Th17 subset, and whether and how vitamin D may preferentially drive the polarization of one of the T helper subsets.MethodsUsing human peripheral blood-derived mononuclear cells and mouse splenocytes and lymph node cells in culture, we examined whether and how vitamin D preferentially skews T cells towards the Th1, Th2 or Th17 subsets. Mice afflicted with the multiple sclerosis-like condition, experimental autoimmune encephalomyelitis (EAE), were examined in vivo for the relevance of the tissue culture-derived results.ResultsWe report that the biologically active form of vitamin D, 1,25-dihydroxyvitamin D3 {1,25(OH)2D3}, consistently generates human and murine Th2 cells in culture, frequently leaving unchanged the levels of Th1/Th17 cytokines. As a result, the ratio of Th2 to Th1 and Th17 is increased by 1,25(OH)2D3. The upregulation of Th2 to Th1 or Th17 subsets by 1,25(OH)2D3 is enabled by an increase of the GATA-3 transcription factor, which itself is promoted upstream by an elevation of the STAT6 transcription factor. In mice, the alleviation of EAE severity by 1,25(OH)2D3 is accompanied by elevation of levels of GATA-3 and STAT6. Significantly, the efficacy of 1,25(OH)2D3 in ameliorating EAE is completely lost in mice genetically deficient for STAT6, which was accompanied by the inability of 1,25(OH)2D3 to raise GATA-3 in STAT6 null lymphocytes.ConclusionsThese results of vitamin D promoting a Th2 shift through upstream GATA-3 and STAT6 transcription factors shed mechanistic understanding on the utility of vitamin D in MS.
Characterization of Hepatitis C Virus genotype 3a Hypervariable region 1 in patients achieved rapid virological response to alpha interferon and Ribavirin Combination therapy
Authors: Akram Madiha , Idrees Muhammad , Hussain Abrar , Afzal Samia , Ilyas Muhammad , Zafar Shamail , Aftab Mahwish , Badar Sadaf , Khubaib Bushra 
Published: May 2011

Abstract

Background
Hepatitis C virus roots a chronic liver disease. Currently approved treatment strategy includes administration of alpha interferon and ribavirin combined therapy for 24-48 weeks. One of the predictor of sustained virological response is an early virological response to treatment characterized as rapid response. Hyper variable region 1 (HVR1) of E2 protein is responsible for viral entry and acts as a target for neutralizing antibodies. Any mutation in this region would effect virus interaction with target cell and viral persistence.

Methods
Thirty one clones of six pre-treatment samples subjected to combination therapy were investigated. Three of the patients were rapid responders (R1, R2 and R3) and two were breakthrough responders (BT1 and BT2). Envelope 2 gene was amplified, cloned and sequenced. Amino acid substitution, frequency, composition and antigenic properties of HVR 1 of E2 protein were studied.

Results
In both rapid responders (R.R) (14 amino acid sites) and breakthrough responders (BT.R) (13 amino acid sites) half of the amino acid sites were either conserved or resistant to any physiochemical change due to amino acid substitution. It also indicated that average composition of hydrophilic and basic amino acids were comparatively lower in rapid responders than other samples affecting probable interaction of virus with target cells. A central non antigenic region was constant among the breakthrough responders but differed in length significantly among rapid responders reflecting the adaptive nature of HVR1 to the immune response.

Conclusions
We observed that although HVR1is quite variable region in HCV 3a patients responding differently to treatment it still maintains its physiochemical properties for its proper functioning and viability.
Infection by agnoprotein-negative mutants of polyomavirus JC and SV40 results in the release of virions that are mostly deficient in DNA content
Authors: Sariyer Ilker K , Saribas Abdullah S , White Martyn K , Safak Mahmut 
Published: May 2011

Abstract

Background
Human polyomavirus JC (JCV) is the etiologic agent of a brain disease, known as progressive multifocal leukoencephalopathy (PML). The JCV genome encodes a small multifunctional phospho-protein, agnoprotein, from the late coding region of the virus, whose regulatory functions in viral replication cycle remain elusive. In this work, the functional role of JCV and SV40 agnoproteins in virion release was investigated using a point mutant (Pt) of each virus, where the ATG codon of agnoprotein was mutated to abrogate its expression.

Results
Analysis of both viral protein expression and replication using Pt mutant of each virus revealed that both processes were substantially down-regulated in the absence of agnoprotein compared to wild-type (WT) virus. Complementation studies in cells, which are constitutively expressing JCV agnoprotein and transfected with the JCV Pt mutant genome, showed an elevation in the level of viral DNA replication near to that observed for WT. Constitutive expression of large T antigen was found to be not sufficient to compensate the loss of agnoprotein for efficient replication of neither JCV nor SV40 in vivo. Examination of the viral release process for both JCV and SV40 Pt mutants showed that viral particles are efficiently released from the infected cells in the absence of agnoprotein but were found to be mostly deficient in viral DNA content.

Conclusions
The results of this study provide evidence that agnoprotein plays an important role in the polyomavirus JC and SV40 life cycle. Infection by agnoprotein-negative mutants of both viruses results in the release of virions that are mostly deficient in DNA content.
Time series gene expression profiling and temporal regulatory pathway analysis of BMP6 induced osteoblast differentiation and mineralization
Authors: Luo Weijun , Friedman Michael S , Hankenson Kurt D , Woolf Peter J 
Published: May 2011

Abstract

Background
BMP6 mediated osteoblast differentiation plays a key role in skeletal development and bone disease. Unfortunately, the signaling pathways regulated by BMP6 are largely uncharacterized due to both a lack of data and the complexity of the response.

Results
To better characterize the signaling pathways responsive to BMP6, we conducted a time series microarray study to track BMP6 induced osteoblast differentiation and mineralization. These temporal data were analyzed using a customized gene set analysis approach to identify temporally coherent sets of genes that act downstream of BMP6. Our analysis identified BMP6 regulation of previously reported pathways, such as the TGF-beta pathway. We also identified previously unknown connections between BMP6 and pathways such as Notch signaling and the MYB and BAF57 regulatory modules. In addition, we identify a super-network of pathways that are sequentially activated following BMP6 induction.

Conclusion
In this work, we carried out a microarray-based temporal regulatory pathway analysis of BMP6 induced osteoblast differentiation and mineralization using GAGE method. This novel temporal analysis is more informative and powerful than the classical static pathway analysis in that: (1) it captures the interconnections between signaling pathways or functional modules and demonstrates the even higher level organization of molecular biological systems; (2) it describes the temporal perturbation patterns of each pathway or module and their dynamic roles in osteoblast differentiation. The same set of experimental and computational strategies employed in our work could be useful for studying other complex biological processes.
Phase II Study of Aflibercept in Recurrent Malignant Glioma: A North American Brain Tumor Consortium Study
Authors: de Groot John F. , Lamborn Kathleen R. , Chang Susan M. , Gilbert Mark R. , Cloughesy Timothy F. , Aldape Kenneth , Yao Jun , Jackson Edward F. , Lieberman Frank , Robins H. Ian , Mehta Minesh P. , Lassman Andrew B. , DeAngelis Lisa M. , Yung W.K. Alfred , Chen Alice , Prados Michael D. , Wen Patrick Y. 
Published: May 2011

Purpose Antivascular endothelial growth factor (anti-VEGF) therapy is a promising treatment approach for patients with recurrent glioblastoma. This single-arm phase II study evaluated the efficacy of aflibercept (VEGF Trap), a recombinantly produced fusion protein that scavenges both VEGF and placental growth factor in patients with recurrent malignant glioma. Patients and Methods Forty-two patients with glioblastoma and 16 patients with anaplastic glioma who had received concurrent radiation and temozolomide and adjuvant temozolomide were enrolled at first relapse. Aflibercept 4 mg/kg was administered intravenously on day 1 of every 2-week cycle. Results The 6-month progression-free survival rate was 7.7% for the glioblastoma cohort and 25% for patients with anaplastic glioma. Overall radiographic response rate was 24% (18% for glioblastoma and 44% for anaplastic glioma). The median progression-free survival was 24 weeks for patients with anaplastic glioma (95% CI, 5 to 31 weeks) and 12 weeks for patients with glioblastoma (95% CI, 8 to 16 weeks). A total of 14 patients (25%) were removed from the study for toxicity, on average less than 2 months from treatment initiation. The main treatment-related National Cancer Institute Common Terminology Criteria grades 3 and 4 adverse events (38 total) included fatigue, hypertension, and lymphopenia. Two grade 4 CNS ischemias and one grade 4 systemic hemorrhage were reported. Aflibercept rapidly decreases permeability on dynamic contrast enhanced magnetic resonance imaging, and molecular analysis of baseline tumor tissue identified tumor-associated markers of response and resistance. Conclusion Aflibercept monotherapy has moderate toxicity and minimal evidence of single-agent activity in unselected patients with recurrent malignant glioma.