bluuebunny/crossref_metadata_2025_split huggingface dataset:
Levels of adiponectin, a marker for PPAR-gamma activity, correlate with skin fibrosis in systemic sclerosis: potential utility as biomarker?
Authors: Lakota Katja , Wei Jun , Carns Mary , Hinchcliff Monique , Lee Jungwha , Whitfield Michael L , Sodin-Semrl Snezna , Varga John 
Published: May 2012

Abstract

Introduction

Progressive fibrosis in systemic sclerosis (SSc) is linked to aberrant transforming growth factor beta (TGF-beta) signaling. Peroxisome proliferator-activated receptor gamma (PPAR-gamma) blocks fibrogenic TGF-beta responses in vitro and in vivo. Reduced expression and function of PPAR-gamma in patients with SSc may contribute to progression of fibrosis. Here we evaluated the levels of adiponectin, a sensitive and specific index of PPAR-gamma activity, as a potential fibrogenic biomarker in SSc.

Methods

Adiponectin levels were determined in the sera of 129 patients with SSc and 86 healthy controls, and serial determinations were performed in 27 patients. Levels of adiponectin mRNA in skin biopsies from SSc patients were assessed in an expression profiling microarray dataset. Regulation of adiponectin gene expression in explanted human subcutaneous preadipocytes and fibroblasts was examined by real-time quantitative PCR.

Results

Patients with diffuse cutaneous SSc had reduced serum adiponectin levels. A significant inverse correlation between adiponectin levels and the modified Rodnan skin score was observed. In longitudinal studies changes in serum adiponectin levels were inversely correlated with changes in skin fibrosis. Skin biopsies from a subset of SSc patients showed reduced adiponectin mRNA expression which was inversely correlated with the skin score. An agonist ligand of PPAR-gamma potently induced adiponectin expression in explanted mesenchymal cells in vitro.

Conclusions

Levels of adiponectin, reflecting PPAR-gamma activity, are correlated with skin fibrosis and might have potential utility as a biomarker in SSc.
Variants in the vitamin D pathway, serum levels of vitamin D, and estrogen receptor negative breast cancer among African-American women: a case-control study
Authors: Yao Song , Zirpoli Gary , Bovbjerg Dana H , Jandorf Lina , Hong Chi Chen , Zhao Hua , Sucheston Lara E , Tang Li , Roberts Michelle , Ciupak Gregory , Davis Warren , Hwang Helena , Johnson Candace S , Trump Donald L , McCann Susan E , Ademuyiwa Foluso , Pawlish Karen S , Bandera Elisa V , Ambrosone Christine B 
Published: May 2012

Abstract
Introduction
American women of African ancestry (AA) are more likely than European Americans (EA) to have estrogen receptor (ER)-negative breast cancer. 25-hydroxyvitamin D (25OHD) is low in AAs, and was associated with ER-negative tumors in EAs. We hypothesized that racial differences in 25OHD levels, as well as in inherited genetic variations, may contribute, in part, to the differences in tumor characteristics.

Methods
In a case (n = 928)-control (n = 843) study of breast cancer in AA and EA women, we measured serum 25OHD levels in controls and tested associations between risk and tag single nucleotide polymorphisms (SNPs) in VDR, CYP24A1 and CYP27B1, particularly by ER status.

Results
More AAs had severe vitamin D deficiency (< 10 ng/ml) than EAs (34.3% vs 5.9%), with lowest levels among those with the highest African ancestry. Associations for SNPs differed by race. Among AAs, VDR SNP rs2239186, associated with higher serum levels of 25OHD, decreased risk after correction for multiple testing (OR = 0.53, 95% CI = 0.31-0.79, p by permutation = 0.03), but had no effect in EAs. The majority of associations were for ER-negative breast cancer, with seven differential associations between AA and EA women for CYP24A1 (p for interaction < 0.10). SNP rs27622941 was associated with a > twofold increased risk of ER-negative breast cancer among AAs (OR = 2.62, 95% CI = 1.38-4.98), but had no effect in EAs. rs2209314 decreased risk among EAs (OR = 0.38, 95% CI = 0.20-0.73), with no associations in AAs. The increased risk of ER-negative breast cancer in AAs compared to EAs was reduced and became non-significant (OR = 1.20, 95% CI = 0.80-1.79) after adjusting for these two CYP24A1 SNPs.

Conclusions
These data suggest that genetic variants in the vitamin D pathway may be related to the higher prevalence of ER-negative breast cancer in AA women.
Neurocognitive problems in epilepsy
Authors: Lodhi Shruti , Agrawal Niruj 
Published: May 2012

SummaryCognitive dysfunction is one of the major contributors to the burden of epilepsy. It can significantly disrupt intellectual development in children and functional status and quality of life in adults. Epilepsy affects cognition through a number of mechanisms in complex interrelationship. Cognitive deficits in epilepsy may be treated indirectly through aggressive seizure control using anti-epileptic drugs or surgery, and by treating comorbid conditions such as depression. The beneficial effects of reducing seizures may offset the adverse cognitive side-effects of these therapies. Direct treatment of cognitive impairment in epilepsy mainly involves memory rehabilitation. Other direct treatments are mostly experimental and their evidence base is currently poor.
Use of Health of the Nation Outcome Scales in psychiatry
Authors: Delaffon Vijay , Anwar Zarina , Noushad Fabida , Ahmed Ayesha S. , Brugha Traolach S. 
Published: May 2012

SummaryRoutine outcome measures are essential to chart individual patient progress and evaluate models of service provision. The Health of the Nation Outcome Scales (HoNOS) were commissioned by the Royal College of Psychiatrists as a simple, brief measure for this purpose. It is one of the most widely used outcome measures in mental health services globally and has been translated into at least seven languages. Its use has broadened beyond its original purpose and in several countries collection of HoNOS data is mandatory. We review 585 potential articles to chart the development and evolution of HoNOS, as well as its psychometric properties, qualitative attributes and uses in clinical practice and research. The potential barriers to implementation of HoNOS on a wide scale are considered and its future role in evaluating effectiveness and benchmarking of services are discussed.
Severe mental illness in 33 588 prisoners worldwide: systematic review and meta-regression analysis
Authors: Fazel Seena , Seewald Katharina 
Published: May 2012

BackgroundHigh levels of psychiatric morbidity in prisoners have been documented in many countries, but it is not known whether rates of mental illness have been increasing over time or whether the prevalence differs between low–middle-income countries compared with high-income ones.AimsTo systematically review prevalence studies for psychotic illness and major depression in prisoners, provide summary estimates and investigate sources of heterogeneity between studies using meta-regression.MethodStudies from 1966 to 2010 were identified using ten bibliographic indexes and reference lists. Inclusion criteria were unselected prison samples and that clinical examination or semi-structured instruments were used to make DSM or ICD diagnoses of the relevant disorders.ResultsWe identified 109 samples including 33 588 prisoners in 24 countries. Data were meta-analysed using random-effects models, and we found a pooled prevalence of psychosis of 3.6% (95% CI 3.1–4.2) in male prisoners and 3.9% (95% CI 2.7–5.0) in female prisoners. There were high levels of heterogeneity, some of which was explained by studies in low–middle-income countries reporting higher prevalences of psychosis (5.5%, 95% CI 4.2–6.8;P=0.035 on meta-regression). The pooled prevalence of major depression was 10.2% (95% CI 8.8–11.7) in male prisoners and 14.1% (95% CI 10.2–18.1) in female prisoners. The prevalence of these disorders did not appear to be increasing over time, apart from depression in the USA (P=0.008).ConclusionsHigh levels of psychiatric morbidity are consistently reported in prisoners from many countries over four decades. Further research is needed to confirm whether higher rates of mental illness are found in low- and middle-income nations, and examine trends over time within nations with large prison populations.
Strengths and Difficulties Questionnaire scores and mental
health in looked after children
Authors: Goodman Anna , Goodman Robert 
Published: May 2012

SummaryBritish local authorities are required to monitor the mental health of
looked after children using mean Strengths and Difficulties Questionnaire
(SDQ) scores from parents or carers. This assumes that differences in mean
SDQ scores reflect genuine differences in child mental health in this group,
something we examined using nationally representative surveys
(n = 1391, age 5–16). We found that the SDQ was a
genuinely dimensional measure of mental health in these children and
provided accurate estimates of disorder prevalence.
Emergency department junior medical staff's knowledge, skills and confidence with psychiatric patients: a survey
Authors: Gordon Jacqueline Therese 
Published: May 2012

Aims and methodTo determine knowledge, skills and confidence of junior medical emergency department staff in managing mental health patients. Over a 2-year period new emergency department junior doctors were given a questionnaire to complete early on in their post and prior to any mental health training. The questionnaire asked about knowledge, confidence, concerns and skills in the management of mental health patients in accident and emergency services.ResultsMore than half of the 32 doctors surveyed said they lacked knowledge, skills and confidence when assessing mental health patients.Clinical implicationsThe survey has demonstrated a need for mental health training of new doctors working in the emergency department. Effective training for such doctors can be offered by a liaison psychiatry service. This should be embedded in their teaching programme and be continually responsive to their perceived training needs.
Motivational reserve: does it help our understanding of cognitive impairment? Commentary on … Healthy brain ageing
Authors: Woods Bob 
Published: May 2012

SummaryMotivational reserve is being proposed as an additional component of reserve capacities which may prevent, or ameliorate the effects of, cognitive impairment in later life. This is consistent with an understanding of the presentation of dementia which goes beyond neuropathological and neuropsychological changes. The construct may help make sense of findings relating to the potentially preventative qualities of a diverse range of ‘cognitive’ activities and of social networks, as well as of education. However, caution is required in relation to how cognitive impairment is evaluated and defined, to avoid confounds such as has been the case with level of education.
Deferasirox Reduces Serum Ferritin and Labile Plasma Iron in RBC Transfusion–Dependent Patients With Myelodysplastic Syndrome
Authors: List Alan F. , Baer Maria R. , Steensma David P. , Raza Azra , Esposito Jason , Martinez-Lopez Noelia , Paley Carole , Feigert John , Besa Emmanuel 
Published: May 2012

Purpose This 3-year, prospective, multicenter trial assessed the safety and efficacy of deferasirox in low- or intermediate-1–risk myelodysplastic syndrome (MDS). Patients and Methods Eligible patients had serum ferritin ≥ 1,000 μg/L and had received ≥ 20 units of RBCs with ongoing transfusion requirements. The starting dose of deferasirox was 20 mg/kg/d, with dose escalation up to 40 mg/kg/d permitted. Results A total of 176 patients were enrolled, and 173 patients received therapy. Median serum ferritin decreased 23% in the 53% of patients who completed 12 months of treatment (n = 91), 36.7% in patients who completed 2 years (n = 49), and 36.5% in patients who completed 3 years (n = 33) despite continued transfusion requirement. Reduction in serum ferritin significantly correlated with ALT improvement (P < .001). Labile plasma iron (LPI) was measured quarterly during the first year of the study. Sixty-eight patients (39.3%) had elevated LPI at baseline. By week 13, LPI levels normalized in all patients with abnormal baseline level. Fifty-one (28%) of 173 patients experienced hematologic improvement by International Working Group 2006 criteria; of these, only seven patients received growth factors or MDS therapy. Over the 3-year study, 138 (79.8%) of 173 patients discontinued therapy, 43 patients (24.8%) because of adverse events or disease progression and 23 patients (13.2%) because of abnormal laboratory values. The most common drug-related adverse events were gastrointestinal disturbances and increased serum creatinine. There were 28 deaths, none of which were considered related to deferasirox. Conclusion Deferasirox reduces serum ferritin and LPI in transfusion-dependent patients with MDS. A subset of patients had an improvement in hematologic and hepatic parameters.
Ipilimumab in Combination With Paclitaxel and Carboplatin As First-Line Treatment in Stage IIIB/IV Non–Small-Cell Lung Cancer: Results From a Randomized, Double-Blind, Multicenter Phase II Study
Authors: Lynch Thomas J. , Bondarenko Igor , Luft Alexander , Serwatowski Piotr , Barlesi Fabrice , Chacko Raju , Sebastian Martin , Neal Joel , Lu Haolan , Cuillerot Jean-Marie , Reck Martin 
Published: May 2012

Purpose Ipilimumab, which is an anti–cytotoxic T-cell lymphocyte-4 monoclonal antibody, showed a survival benefit in melanoma with adverse events (AEs) managed by protocol-defined guidelines. A phase II study in lung cancer assessed the activity of ipilimumab plus paclitaxel and carboplatin. Patients and Methods Patients (N = 204) with chemotherapy-naive non–small-cell lung cancer (NSCLC) were randomly assigned 1:1:1 to receive paclitaxel (175 mg/m2) and carboplatin (area under the curve, 6) with either placebo (control) or ipilimumab in one of the following two regimens: concurrent ipilimumab (four doses of ipilimumab plus paclitaxel and carboplatin followed by two doses of placebo plus paclitaxel and carboplatin) or phased ipilimumab (two doses of placebo plus paclitaxel and carboplatin followed by four doses of ipilimumab plus paclitaxel and carboplatin).Treatment was administered intravenously every 3 weeks for ≤ 18 weeks (induction). Eligible patients continued ipilimumab or placebo every 12 weeks as maintenance therapy. Response was assessed by using immune-related response criteria and modified WHO criteria. The primary end point was immune-related progression-free survival (irPFS). Other end points were progression-free survival (PFS), best overall response rate (BORR), immune-related BORR (irBORR), overall survival (OS), and safety. Results The study met its primary end point of improved irPFS for phased ipilimumab versus the control (hazard ratio [HR], 0.72; P = .05), but not for concurrent ipilimumab (HR, 0.81; P = .13). Phased ipilimumab also improved PFS according to modified WHO criteria (HR, 0.69; P = .02). Phased ipilimumab, concurrent ipilimumab, and control treatments were associated with a median irPFS of 5.7, 5.5, and 4.6 months, respectively, a median PFS of 5.1, 4.1, and 4.2 months, respectively, an irBORR of 32%, 21% and 18%, respectively, a BORR of 32%, 21% and 14%, respectively, and a median OS of 12.2, 9.7, and 8.3 months. Overall rates of grade 3 and 4 immune-related AEs were 15%, 20%, and 6% for phased ipilimumab, concurrent ipilimumab, and the control, respectively. Two patients (concurrent, one patient; control, one patient) died from treatment-related toxicity. Conclusion Phased ipilimumab plus paclitaxel and carboplatin improved irPFS and PFS, which supports additional investigation of ipilimumab in NSCLC.
Chromosomal Instability (CIN) Phenotype, CIN High or CIN Low, Predicts Survival for Colorectal Cancer
Authors: Watanabe Toshiaki , Kobunai Takashi , Yamamoto Yoko , Matsuda Keiji , Ishihara Soichiro , Nozawa Keijiro , Yamada Hideki , Hayama Tamuro , Inoue Eisuke , Tamura Junko , Iinuma Hisae , Akiyoshi Takashi , Muto Tetsuichiro 
Published: May 2012

Purpose To examine whether chromosomal instability (CIN) phenotype, determined by the severity of CIN, can predict survival for stages II and III colorectal cancer (CRC). Patients and Methods We determined microsatellite instability (MSI) and loss of heterozygosity (LOH) status in 1,103 patients (training [n = 845] and validation [n = 258] sets with stages II and III CRC). The LOH ratio was defined as the frequency of LOH in chromosomes 2p, 5q, 17p, and 18q. According to the LOH ratio, non–MSI high tumors were classified as CIN high (LOH ratio ≥ 33%) or CIN low (LOH ratio < 33%). CIN-high tumors were subclassified as CIN high (mild type; LOH ratio < 75%) or CIN high (severe type; LOH ratio ≥ 75%). We used microarrays to identify a gene signature that could classify the CIN phenotype and evaluated its ability to predict prognosis. Results CIN high showed the worst survival (P < .001), whereas there was no significant difference between CIN low and MSI high. CIN high (severe type) showed poorer survival than CIN high (mild type; P < .001). Multivariate analysis revealed that CIN phenotype was an independent risk factor for disease-free and overall survival, respectively, in both the training (P < .001 and P = .0155) and validation sets (P < .001 and P = .0076). Microarray analysis also revealed that survival was significantly poorer in those with the CIN-high than in the CIN-low gene signature (P = .0203). In a validation of 290 independent CRCs (GSE14333), the CIN-high gene signature showed significantly poorer survival than the CIN-low signature (P = .0047). Conclusion The CIN phenotype is a predictive marker for survival and may be used to select high-risk patients with stages II and III CRC.
Phase I Pharmacologic and Pharmacodynamic Study of the Gamma Secretase (Notch) Inhibitor MK-0752 in Adult Patients With Advanced Solid Tumors
Authors: Krop Ian , Demuth Tim , Guthrie Tina , Wen Patrick Y. , Mason Warren P. , Chinnaiyan Prakash , Butowski Nicholas , Groves Morris D. , Kesari Santosh , Freedman Steven J. , Blackman Samuel , Watters James , Loboda Andrey , Podtelezhnikov Alexei , Lunceford Jared , Chen Cong , Giannotti Maxine , Hing Jeremy , Beckman Robert , LoRusso Patricia 
Published: May 2012

Purpose Aberrant Notch signaling has been implicated in the pathogenesis of many human cancers. MK-0752 is a potent, oral inhibitor of γ-secretase, an enzyme required for Notch pathway activation. Safety, maximum-tolerated dose, pharmacokinetics (PKs), pharmacodynamics, and preliminary antitumor efficacy were assessed in a phase I study of MK-0752. Patients and Methods MK-0752 was administered in three different schedules to patients with advanced solid tumors. Hair follicles were collected at higher dose levels to assess a gene signature of Notch inhibition. Results Of 103 patients who received MK-0752, 21 patients received a continuous once-daily dosing at 450 and 600 mg; 17 were dosed on an intermittent schedule of 3 of 7 days at 450 and 600 mg; and 65 were dosed once per week at 600, 900, 1,200, 1,500, 1,800, 2,400, 3,200, and 4,200 mg. The most common drug-related toxicities were diarrhea, nausea, vomiting, and fatigue. PKs (area under the concentration-time curve and maximum measured plasma concentration) increased in a less than dose proportional manner, with a half-life of approximately 15 hours. Significant inhibition of Notch signaling was observed with the 1,800- to 4,200-mg weekly dose levels, confirming target engagement at those doses. One objective complete response and an additional 10 patients with stable disease longer than 4 months were observed among patients with high-grade gliomas. Conclusion MK-0752 toxicity was schedule dependent. Weekly dosing was generally well tolerated and resulted in strong modulation of a Notch gene signature. Clinical benefit was observed, and rational combination trials are currently ongoing to maximize clinical benefit with this novel agent.
Improving dosing of gentamicin in the obese patient: a 3-cycle drug chart and case note audit
Authors: Manjaly Joseph G , Reece-Smith Alexander M , Sivaloganathan Sivan S , Thuraisamy Christina , Smallwood Katie Lm , Jonas Elizabeth , Longman Robert J 
Published: May 2012

Summary Objectives To assess the use of an electronic dose calculator to improve accuracy in the use of a complex Gentamicin prescription policy and assess turnaround time of blood sampling to dose delivery in an NHS hospital. Design Retrospective review of drug chart, case notes and hospital antibiotic database. Setting University Hospitals Bristol, UK Participants Patients receiving once daily intravenous gentamicin using the trust protocol, during the same time window for 3 consecutive years. Main outcome measures i) Accuracy of dose and frequency prescription of Gentamicin. ii) Time frame for measurement of serum Gentamicin levels. Results Following the introduction of the online calculator, prescribing errors in obese patients dropped from 43% to 20%, a similar level as in non-obese patients. Errors in frequency calculations dropped from 12.8% to 4%. On average, drug doses could be administered within 2.5 hours of a blood sample being taken. Conclusions Online tools can be used to improve prescribing for the complex dosing policies that will increasingly been required to tailor prescribing in obese patients. Serum gentamicin levels can be measured within a 2.5 hour time frame in the environment of an NHS hospital.
Home Care of Children and Youth With Complex Health Care Needs and Technology Dependencies
Authors: Elias Ellen Roy , Murphy Nancy A. ,   the COUNCIL ON CHILDREN WITH DISABILITIES, Liptak Gregory S. , Adams Richard C. , Burke Robert , Friedman Sandra L. , Houtrow Amy , Kalichman Miriam , Kuo Dennis , Levy Susan E. , Norwood Kenneth W. , Turchi Renee M. , Wiley Susan E. 
Published: May 2012

This Clinical Report was reaffirmed May 2017 and December 2022.
Children and youth with complex medical issues, especially those with technology dependencies, experience frequent and often lengthy hospitalizations. Hospital discharges for these children can be a complicated process that requires a deliberate, multistep approach. In addition to successful discharges to home, it is essential that pediatric providers develop and implement an interdisciplinary and coordinated plan of care that addresses the child’s ongoing health care needs. The goal is to ensure that each child remains healthy, thrives, and obtains optimal medical home and developmental supports that promote ongoing care at home and minimize recurrent hospitalizations. This clinical report presents an approach to discharging the child with complex medical needs with technology dependencies from hospital to home and then continually addressing the needs of the child and family in the home environment.
The Effects of Sentence Writing on Second Language French and Korean Lexical Retention
Authors: Wong Wynne , Pyun Danielle O. 
Published: May 2012

Abstract:This study investigates the effects of sentence writing (SW) on second language (L2) lexical retention by comparing two word-learning conditions: writing new words in sentences and repeated word-picture viewing. L2 learners of French and Korean attempted to learn 24 new words: 12 words with one condition and 12 words with another condition. Dependent measures were one immediate and two delayed posttests that required participants to produce target word forms. Results for both language groups revealed negative effects for SW, suggesting that SW can impede word-form learning during the initial stages of L2 vocabulary learning. Furthermore, the finding that the Korean learners' scores were much lower than the French learners' scores under the SW condition suggests that SW may result in even less retention when the L2 script is far more distant from one's first language (L1), thereby supporting the impact of L1–L2 orthographic distance on L2 word learning and retention.