bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modifying Measures Based on Differential Item Functioning (DIF) Impact Analyses
Authors: Teresi Jeanne A. , Ramirez Mildred , Jones Richard N. , Choi Seung , Crane Paul K. 
Published: March 2012

Objectives: Measure modification can impact comparability of scores across groups and settings. Changes in items can affect the percent admitting to a symptom. Methods: Using item response theory (IRT) methods, well-calibrated items can be used interchangeably, and the exact same item does not have to be administered to each respondent, theoretically permitting wider latitude in terms of modification. Results: Recommendations regarding modifications vary, depending on the use of the measure. In the context of research, adjustments can be made at the analytic level by freeing and fixing parameters based on findings of differential item functioning (DIF). The consequences of DIF for clinical decision making depend on whether or not the patient’s performance level approaches the scale decision cutpoint. High-stakes testing may require item removal or separate calibrations to ensure accurate assessment. Discussion: Guidelines for modification based on DIF analyses and illustrations of the impact of adjustments are presented.
Time-patterns of annualized relapse rates in randomized placebo-controlled clinical trials in relapsing multiple sclerosis: A systematic review and meta-analysis
Authors: Nicholas Richard , Straube Sebastian , Schmidli Heinz , Pfeiffer Sebastian , Friede Tim 
Published: March 2012

Background: Although it is known that the annualized relapse rate (ARR) in patients with multiple sclerosis (MS) changes as disease progresses, in the design and analysis of trials in relapsing multiple sclerosis (RMS) constant ARRs are assumed. Objectives: This paper aims to assess time-patterns of trial ARR by conducting a systematic review of randomized, placebo-controlled trials in RMS. Methods: A systematic literature search was conducted by searching PubMed for randomized, placebo-controlled trials in RMS. In meta-analyses the following comparisons of trial ARR were carried out for the placebo controls and active treatment arms: months 1–6 vs. months 7–12, and months 1–12 vs. months 13–24. Results: A total of 52 trials was identified. Out of these, information on the time-dependence of trial ARR could be extracted from 13 trials. The ARR was by 25% ( p = 0.0005) and 40% ( p < 0.0001) higher in months 1–12 compared with months 13–24 for placebo and active treatments, respectively. Consequently, the treatment effects were by 13% ( p = 0.23) larger in the second year compared with the first year. Within the first year of follow-up the ARR was by 4% ( p = 0.75) and 23% ( p = 0.06) higher in months 1–6 compared with months 7–12 for placebo controls and active arms, respectively. Conclusions: Trial ARR decreases during a trial in RMS, which is in line with epidemiological findings and has implications for design and analysis of future trials. The observed decrease in trial ARR might be at least partially explained by regression to the mean. Individual patient data analyses are warranted.
Favorable effect of priming with granulocyte colony-stimulating factor in remission induction of acute myeloid leukemia restricted to dose escalation of cytarabine
Authors: Pabst Thomas , Vellenga Edo , van Putten Wim , Schouten Harry C. , Graux Carlos , Vekemans Marie-Christiane , Biemond Bart , Sonneveld Peter , Passweg Jakob , Verdonck Leo , Legdeur Marie-Cecile , Theobald Matthias , Jacky Emanuel , Bargetzi Mario , Maertens Johan , Ossenkoppele Gert Jan , Löwenberg Bob 
Published: March 2012

Abstract
The clinical value of chemotherapy sensitization of acute myeloid leukemia (AML) with G-CSF priming has remained controversial. Cytarabine is a key constituent of remission induction chemotherapy. The effect of G-CSF priming has not been investigated in relationship with variable dose levels of cytarabine. We randomized 917 AML patients to receive G-CSF (456 patients) or no G-CSF (461 patients) at the days of chemotherapy. In the initial part of the study, 406 patients were also randomized between 2 cytarabine regimens comparing conventional-dose (199 patients) versus escalated-dose (207 patients) cytarabine in cycles 1 and 2. We found that patients after induction chemotherapy plus G-CSF had similar overall survival (43% vs 40%, P = .88), event-free survival (37% vs 31%, P = .29), and relapse rates (34% vs 36%, P = .77) at 5 years as those not receiving G-CSF. However, patients treated with the escalated-dose cytarabine regimen benefited from G-CSF priming, with improved event-free survival (P = .01) and overall survival (P = .003), compared with patients without G-CSF undergoing escalated-dose cytarabine treatment. A significant survival advantage of sensitizing AML for chemotherapy with G-CSF was not apparent in the entire study group, but it was seen in patients treated with escalated-dose cytarabine during remission induction. The HOVON-42 study is registered under The Netherlands Trial Registry (www.trialregister.nl) as #NTR230.
Phase 2 study of the JAK kinase inhibitor ruxolitinib in patients with refractory leukemias, including postmyeloproliferative neoplasm acute myeloid leukemia
Authors: Eghtedar Alireza , Verstovsek Srdan , Estrov Zeev , Burger Jan , Cortes Jorge , Bivins Carol , Faderl Stefan , Ferrajoli Alessandra , Borthakur Gautam , George Solly , Scherle Peggy A. , Newton Robert C. , Kantarjian Hagop M. , Ravandi Farhad 
Published: March 2012

Abstract
We conducted a phase 2 study of ruxolitinib in patients with relapsed/refractory leukemias. Patients with acceptable performance status (0-2), adequate organ function, and no active infection, received ruxolitinib 25 mg orally twice a day for 4 weeks (1 cycle). Response was assessed after every 2 cycles of treatment, and patients who completed 2 cycles were allowed to continue treatment until disease progression. Dose escalation to 50 mg twice daily was permitted in patients demonstrating a benefit. Thirty-eight patients, with a median age of 69 years (range, 45-88), were treated. The median number of prior therapies was 2 (range, 1-6). Twelve patients had JAK2V617F mutation. Patients received a median of 2 cycles of therapy (range, 1-22). Three of 18 patients with postmyeloproliferative neoplasm (MPN) acute myeloid leukemia (AML) showed a significant response; 2 achieved complete remission (CR) and one achieved a CR with insufficient recovery of blood counts (CRi). The responding patients with palpable spleens also had significant reductions in spleen size. Overall, ruxolitinib was very well tolerated with only 4 patients having grade 3 or higher toxicity. Ruxolitinib has modest antileukemic activity as a single agent, particularly in patients with post-MPN AML. The study was registered at www.clinicaltrials.gov as NCT00674479.
A low protein diet during pregnancy provokes a lasting shift of hepatic expression of genes related to cell cycle throughout ontogenesis in a porcine model
Authors: Oster Michael , Murani Eduard , Metges Cornelia C , Ponsuksili Siriluck , Wimmers Klaus 
Published: March 2012

Abstract

Background
In rodent models and in humans the impact of gestational diets on the offspring's phenotype was shown experimentally and epidemiologically. Adverse environmental conditions during fetal development provoke an intrauterine adaptive response termed 'fetal programming', which may lead to both persistently biased responsiveness to extrinsic factors and permanent consequences for the organismal phenotype. This leads to the hypothesis that the offspring's transcriptome exhibits short-term and long-term changes, depending on the maternal diet. In order to contribute to a comprehensive inventory of genes and functional networks that are targets of nutritional programming initiated during fetal life, we applied whole-genome microarrays for expression profiling in a longitudinal experimental design covering prenatal, perinatal, juvenile, and adult ontogenetic stages in a porcine model. Pregnant sows were fed either a gestational low protein diet (LP, 6% CP) or an adequate protein diet (AP, 12% CP). All offspring was nursed by foster sows receiving standard diets. After weaning, all offspring was fed standard diets ad libitum.

Results
Analyses of the hepatic gene expression of the offspring at prenatal (94 dies post conceptionem, dpc) and postnatal stages (1, 28, 188 dies post natum, dpn) included comparisons between dietary groups within stages as well as comparisons between ontogenetic stages within diets to separate diet-specific transcriptional changes and maturation processes. We observed differential expression of genes related to lipid metabolism (e.g. Fatty acid metabolism, Biosynthesis of steroids, Synthesis and degradation of ketone bodies, FA elongation in mitochondria, Bile acid synthesis) and cell cycle regulation (e.g. Mitotic roles of PLK, G1/S checkpoint regulation, G2/M DNA damage checkpoint regulation). Notably, at stage 1 dpn no regulation of a distinct pathway was found in LP offspring.

Conclusions
The transcriptomic modulations point to persistent functional demand on the liver towards cell proliferation in the LP group but not in the AP group at identical nutritional conditions during postnatal life due to divergent 'programming' of the genome. Together with the observation that the offspring of both groups did not differ in body weight but in body composition and fat content, the data indicate that the activity of various genes led to diverse partitioning of nutrients among peripheral and visceral organs and tissues.
A STAT3-inhibitory hairpin decoy oligodeoxynucleotide discriminates between STAT1 and STAT3 and induces death in a human colon carcinoma cell line
Authors: Souissi Inès , Ladam Patrick , Cognet Jean AH , Le Coquil Stéphanie , Varin-Blank Nadine , Baran-Marszak Fanny , Metelev Valeri , Fagard Remi 
Published: March 2012

Abstract

Background
The Signal Transducer and Activator of Transcription 3 (STAT3) is activated in tumor cells, and STAT3-inhibitors are able to induce the death of those cells. Decoy oligodeoxynucleotides (dODNs), which bind to the DNA Binding Domain (DBD) of STAT3, are efficient inhibitors. However, they also inhibit STAT1, whose activity is essential not only to resistance to pathogens, but also to cell growth inhibition and programmed cell death processes. The aim of this study was to design STAT3-specific dODNs which do not affect STAT1-mediated processes.

Results
New dODNs with a hairpin (hpdODNs) were designed. Modifications were introduced, based on the comparison of STAT3- and STAT1-DBD interactions with DNA using 3D structural analyses. The designed hpdODNs were tested for their ability to inhibit STAT3 but not STAT1 by determining: i) cell death in the active STAT3-dependent SW480 colon carcinoma cell line, ii) absence of inhibition of interferon (IFN) γ-dependent cell death, iii) expression of STAT1 targets, and iv) nuclear location of STAT3 and STAT1. One hpdODN was found to efficiently induce the death of SW480 cells without interfering with IFNγ-activated STAT1. This hpdODN was found in a complex with STAT3 but not with STAT1 using an original in-cell pull-down assay; this hpdODN also did not inhibit IFNγ-induced STAT1 phosphorylation, nor did it inhibit the expression of the STAT1-target IRF1. Furthermore, it prevented the nuclear transfer of STAT3 but not that of IFNγ-activated STAT1.

Conclusions
Comparative analyses at the atomic level revealed slight differences in STAT3 and STAT1 DBDs' interaction with their DNA target. These were sufficient to design a new discriminating hpdODN that inhibits STAT3 and not STAT1, thereby inducing tumor cell death without interfering with STAT1-dependent processes. Preferential interaction with STAT3 depends on oligodeoxynucleotide sequence modifications but might also result from DNA shape changes, known to modulate protein/DNA interactions. The finding of a STAT3-specific hpdODN establishes the first rational basis for designing STAT3 DBD-specific inhibitors.
A novel randomly textured phosphor structure for highly efficient white light-emitting diodes
Authors: Chen Hsin Chu , Chen Kuo Ju , Wang Chao Hsun , Lin Chien Chung , Yeh Chia Chi , Tsai Hsin Han , Shih Min Hsiung , Kuo Hao Chung , Lu Tien Chang 
Published: March 2012

Abstract
We have successfully demonstrated the enhanced luminous flux and lumen efficiency in white light-emitting diodes by the randomly textured phosphor structure. The textured phosphor structure was fabricated by a simple imprinting technique, which does not need an expensive dry-etching machine or a complex patterned definition. The textured phosphor structure increases luminous flux by 5.4% and 2.5% at a driving current of 120 mA, compared with the flat phosphor and half-spherical lens structures, respectively. The increment was due to the scattering of textured surface and also the phosphor particles, leading to the enhancement of utilization efficiency of blue light. Furthermore, the textured phosphor structure has a larger view angle at the full width at half maximum (87°) than the reference LEDs.
ER and HER2 expression are positively correlated in HER2 non-overexpressing breast cancer
Authors: Pinhel Isabel , Hills Margaret , Drury Suzanne , Salter Janine , Sumo Georges , A'Hern Roger , Bliss Judith M , Sestak Ivana , Cuzick Jack , Barrett-Lee Peter , Harris Adrian , Dowsett Mitch ,   the NCRI Adjuvant Breast Cancer Trial Management Group
Published: March 2012

Abstract
Introduction
Estrogen receptor-α (ER) and human epidermal growth factor receptor 2 (HER2) positivity are inversely correlated by standard criteria. However, we investigated the quantitative relation between ER and HER2 expression at both RNA and protein levels in HER2+ve and HER2-ve breast carcinomas.

Methods
ER and HER2 levels were assessed with immunohistochemistry (IHC) and (for HER2) fluorescent in situ hybridization (FISH) and by quantitative reverse transcription-polymerase chain reaction (q-RT-PCR) in formalin-fixed primary breast cancers from 448 patients in the National Cancer Research Institute (NCRI) Adjuvant Breast Cancer Trial (ABC) tamoxifen-only arm. Relations at the RNA level were assessed in 1,139 TransATAC tumors.

Results
ER and HER2 RNA levels were negatively correlated as expected in HER2+ve (IHC 3+ and/or FISH-amplified) tumors (r = -0.45; P = 0.0028). However, in HER2-ve tumors (ER+ve and ER-ve combined), a significant positive correlation was found (r = 0.43; P < 0.0001), HER2 RNA levels being 1.74-fold higher in ER+ve versus ER-ve tumors. This correlation was maintained in the ER+veHER2-ve subgroup (r = 0.24; P = 0.0023) and confirmed in this subgroup in 1,139 TransATAC tumours (r = 0.25; P < 0.0001). The positive relation extended to IHC-detected ER in ABC: mean ± 95% confidence interval (CI) H-scores were 90 ± 19 and 134 ± 19 for 0 and 1+ HER2 IHC categories, respectively (P = 0.0013). A trend toward lower relapse-free survival (RFS) was observed in patients with the lowest levels of ER and HER2 RNA levels within the ER+veHER2-ve subgroup both for ABC and TransATAC cohorts.

Conclusions
ER and HER2 expression is positively correlated in HER2-ve tumors. The distinction between HER2+ve and HER2-ve is greater in ER-ve than in ER+ve tumors. These findings are important to consider in clinical trials of anti-HER2 and anti-endocrine therapy in HER2-ve disease.

Trial Registration
Clinical trial identifier: ISRCTN31514446.
Development by a Large Integrated Health Care System of an Objective Methodology for Evaluation of Medical Oncology Service Sites
Authors: Bjegovich-Weidman Marija , Kahabka Jill , Bock Amy , Frick Jacob , Kowalski Helga , Mirro Joseph 
Published: March 2012

Purpose: Aurora Health Care (AHC) is the largest health care system in Wisconsin, with 14 acute care hospitals. In early 2010, a group of 18 medical oncologists became affiliated with AHC. This affiliation added 13 medical oncology infusion clinics to our existing 12 sites. In the era of health care reform and declining reimbursement, we need an objective method and criteria to evaluate our 25 outpatient medical oncology sites. We developed financial, clinical, and strategic tools for the evaluation and management of our cancer subservice lines and outpatient sites. The key to our success has been the direct involvement of stakeholders with a vested interest in the services in the selection of the criteria and evaluation process. Methods: We developed our objective metrics for evaluation based on strategic, financial, operational, and patient experience criteria. Strategic criteria included: population trends, full-time equivalent (FTE) medical oncologists/primary care physicians, FTE radiation oncologists, FTE oncologic surgeons, new annual cases of patients with cancer, and market share trends. Financial criteria per site included: physician work relative value units, staff FTE by type, staff salaries, and profit and loss. Operational criteria included: facility by type (clinic v hospital based), hours of operation, and facility detail (eg, No. of chairs, No. of procedure and examination rooms, square footage). Patient experience criteria included: nursing model primary/nurse navigators, multidisciplinary support at site, Press Ganey (South Bend, IN; health care performance improvement company) results, and employee engagement score. Results: The outcome of our data analysis has resulted in the development of recommendations for AHC senior leadership and geographic market leadership to consider the consolidation of four sites (phase one, four sites; phase two, two sites) and priority strategic sites to address capacity issues that limit growth. The recommendations if implemented would result in significant cost savings, currently being quantified as a result of consolidation and improved efficiency. A reinvestment of these cost savings would be required to address facility expansion and program enhancement to maximize patient-centered expert care consistently across all of our remaining sites of service.
Development of a Novel Combined Scanning Electrochemical Microscope (SECM) and Scanning Ion-Conductance Microscope (SICM) Probe for Soft Sample Imaging
Authors: Pollard Andrew J. , Faruqui Nilofar , Shaw Michael , Clifford Charles A. , Takahashi Yasufumi , Korchev Yuri E. , Ebejer Neil , Macpherson Julie V. , Unwin Patrick R. , Roy Debdulal 
Published: March 2012

ABSTRACTBy incorporating a localized heating system within a scanning ion-conductance microscopy (SICM) system, we have performed stable ‘hopping-mode’ (HPICM) imaging for live cells maintained at temperatures ranging up to human body temperature. This allows the accurate study of cell volume and morphology variation versus temperature over extended periods of time. The integration of SICM with scanning electrochemical microscopy (SECM) provides the simultaneous mapping of electrochemical and topographic information for soft samples, such as live cells. This combined technique overcomes the limitations of resolution and topographical artifacts typically associated with SECM. However, previously reported SECM-SICM probe production required expensive and time-consuming focused ion beam (FIB) methods and produced pipettes that are typically hundreds of nanometers in diameter. We report a simple and rapid production method for SECM-SICM double-barrel probes with apertures down to 20 nm in diameter. The characterization of these SECM-SICM probes using scanning electron microscopy (SEM) imaging, cyclic voltammetry (CV) and Raman spectroscopy is also detailed. These SECM-SICM probes were subsequently used to study the morphology and electrochemical activity of several samples, ranging from hard metallic/insulating samples to live cells.
Cost performance trade-off in thermoelectric modules with low fractional area coverage
Authors: Yazawa Kazuaki , Shakouri Ali 
Published: March 2012

ABSTRACTWe report a comprehensive study of the cost of materials used in the thermoelectric module as the elements, substrate, and metal interconnect are optimized for maximum output power. The power conversion cost [$/W] is analyzed. The maximum power output is found by matching both thermal and electrical impedances to the external load and heat sink. The fractional area coverage or fill factor of the thermoelement (leg) in the module is a key factor which affects the overall cost of the waste heat recovery system. Thermal spreading resistance is a function of the thermal conductivity and the thickness of the substrates. Also the air gap between the legs contributes to parasitic heat loss from the hot to the cold substrate through heat conduction and radiative heat transfer. The optimum fill factor under atmospheric air-pressure is found to be on the order of a few percent. We also take into account the three-dimensional current flow and the effect of the metallization thickness on the series resistance in the module. Calculations identify the minimum metal trace thickness needed to have a minimum impact on output power generation.
Neuromuscular Electrical Stimulation for Intensive Care Unit–Acquired Weakness: Protocol and Methodological Implications for a Randomized, Sham-Controlled, Phase II Trial
Authors: Kho Michelle E. , Truong Alexander D. , Brower Roy G. , Palmer Jeffrey B. , Fan Eddy , Zanni Jennifer M. , Ciesla Nancy D. , Feldman Dorianne R. , Korupolu Radha , Needham Dale M. 
Published: March 2012

BackgroundAs the population ages and critical care advances, a growing number of survivors of critical illness will be at risk for intensive care unit (ICU)–acquired weakness. Bed rest, which is common in the ICU, causes adverse effects, including muscle weakness. Consequently, patients need ICU-based interventions focused on the muscular system. Although emerging evidence supports the benefits of early rehabilitation during mechanical ventilation, additional therapies may be beneficial. Neuromuscular electrical stimulation (NMES), which can provide some muscular activity even very early during critical illness, is a promising modality for patients in the ICU.ObjectiveThe objectives of this article are to discuss the implications of bed rest for patients with critical illness, summarize recent studies of early rehabilitation and NMES in the ICU, and describe a protocol for a randomized, phase II pilot study of NMES in patients receiving mechanical ventilation.DesignThe study was a randomized, sham-controlled, concealed, phase II pilot study with caregivers and outcome assessors blinded to the treatment allocation.SettingThe study setting will be a medical ICU.ParticipantsThe study participants will be patients who are receiving mechanical ventilation for 1 day or more, who are expected to stay in the ICU for an additional 2 days or more, and who meet no exclusion criteria.InterventionThe intervention will be NMES (versus a sham [control] intervention) applied to the quadriceps, tibialis anterior, and gastrocnemius muscles for 60 minutes per day.MeasurementsLower-extremity muscle strength at hospital discharge will be the primary outcome measure.LimitationsMuscle strength is a surrogate measure, not a patient-centered outcome. The assessments will not include laboratory, genetic, or histological measures aimed at a mechanistic understanding of NMES. The optimal duration or dose of NMES is unclear.ConclusionsIf NMES is beneficial, the results of the study will help advance research aimed at reducing the burden of muscular weakness and physical disability in survivors of critical illness.