bluuebunny/crossref_metadata_2025_split huggingface dataset:
HIV Status Does Not Influence Outcome in Patients With Classical Hodgkin Lymphoma Treated With Chemotherapy Using Doxorubicin, Bleomycin, Vinblastine, and Dacarbazine in the Highly Active Antiretroviral Therapy Era
Authors: Montoto Silvia , Shaw Kate , Okosun Jessica , Gandhi Shreyans , Fields Paul , Wilson Andrew , Shanyinde Milensu , Cwynarski Kate , Marcus Robert , de Vos Johannes , Young Anna Marie , Tenant-Flowers Melinda , Orkin Chloe , Johnson Margaret , Chilton Daniella , Gribben John G. , Bower Mark 
Published: October 2012

Purpose The prognosis of HIV-infected patients with non-Hodgkin lymphoma in the highly active antiretroviral therapy (HAART) era approaches that of the general population when they are treated with the same protocols. We analyzed the outcome of patients with Hodgkin lymphoma (HL) treated with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) in the HAART era according to HIV serostatus to establish whether this also holds true for HL. Patients and Methods From 1997 to 2010, 224 patients newly diagnosed with HL, of whom 93 were HIV positive, were consecutively treated with ABVD chemotherapy. HIV-positive patients had more high-risk disease according to the International Prognostic Score (IPS) than HIV-negative patients (IPS ≥ 3: 68% v 26%, respectively; P < .001). Forty-seven HIV-positive patients had a CD4 count less than 200/μL, and 92 patients received HAART during chemotherapy. Results The complete response rate was 74% for HIV-positive patients and 79% for HIV-negative patients (P = not significant). After a median follow-up of 60 months (range, 8 to 174 months), 23 patients (16 HIV-negative and seven HIV-positive patients) have experienced relapse at a median time of 6 months (range, 1 to 106 months). Five-year event-free survival (EFS) was 59% (95% CI, 47% to 70%) for HIV-positive patients and 66% (95% CI, 57% to 74%) for HIV-negative patients (P = not significant). Five-year overall survival (OS) was 81% (95% CI, 69% to 89%) and 88% (95% CI, 80% to 93%) for HIV-positive and HIV-negative patients, respectively (P = not significant). HIV status did not predict OS or EFS on multivariate analysis including IPS and HIV status. Conclusion This mature study demonstrates that HIV-positive patients with HL have more extensive disease with more adverse prognostic factors than HIV-negative patients, but when treated with ABVD, HIV infection does not adversely affect OS or EFS.
Bruton Tyrosine Kinase Inhibitor Ibrutinib (PCI-32765) Has Significant Activity in Patients With Relapsed/Refractory B-Cell Malignancies
Authors: Advani Ranjana H. , Buggy Joseph J. , Sharman Jeff P. , Smith Sonali M. , Boyd Thomas E. , Grant Barbara , Kolibaba Kathryn S. , Furman Richard R. , Rodriguez Sara , Chang Betty Y. , Sukbuntherng Juthamas , Izumi Raquel , Hamdy Ahmed , Hedrick Eric , Fowler Nathan H. 
Published: October 2012

Purpose Survival and progression of mature B-cell malignancies depend on signals from the B-cell antigen receptor, and Bruton tyrosine kinase (BTK) is a critical signaling kinase in this pathway. We evaluated ibrutinib (PCI-32765), a small-molecule irreversible inhibitor of BTK, in patients with B-cell malignancies. Patients and Methods Patients with relapsed or refractory B-cell lymphoma and chronic lymphocytic leukemia received escalating oral doses of ibrutinib. Two schedules were evaluated: one, 28 days on, 7 days off; and two, once-daily continuous dosing. Occupancy of BTK by ibrutinib in peripheral blood was monitored using a fluorescent affinity probe. Dose escalation proceeded until either the maximum-tolerated dose (MTD) was achieved or, in the absence of MTD, until three dose levels above full BTK occupancy by ibrutinib. Response was evaluated every two cycles. Results Fifty-six patients with a variety of B-cell malignancies were treated over seven cohorts. Most adverse events were grade 1 and 2 in severity and self-limited. Dose-limiting events were not observed, even with prolonged dosing. Full occupancy of the BTK active site occurred at 2.5 mg/kg per day, and dose escalation continued to 12.5 mg/kg per day without reaching MTD. Pharmacokinetic data indicated rapid absorption and elimination, yet BTK occupancy was maintained for at least 24 hours, consistent with the irreversible mechanism. Objective response rate in 50 evaluable patients was 60%, including complete response of 16%. Median progression-free survival in all patients was 13.6 months. Conclusion Ibrutinib, a novel BTK-targeting inhibitor, is well tolerated, with substantial activity across B-cell histologies.
Water Aerosol Formation upon Irradiation of Air Using KrF Laser at 248 nm
Authors: Yoshihara Keitaro , Takatori Yoshiki , Kajii Yoshizumi 
Published: October 2012

Abstract
We report water aerosol formation upon irradiation of wet air with a KrF laser at 248 nm. It occurred at temperatures ranging from 0 to 50 °C and at relative humidity values from ca. 10% to 100%. Aerosols were detected either by light scattering or by differential mobility analyses, and particle growth from 10 nm to sub-micrometers was observed. Photodissociation of oxygen was proposed as the initial step of the reactions leading to formation of the final stable molecule of hydrogen peroxide as a nucleus with a low vapor pressure. Simulations of the chemical kinetics by considering wet air revealed that the amount of the final product could be controlled by laser operational conditions such as laser repetition rates and pulse energies. KrF laser light can reach a few kilometers in the atmosphere owing to a small absorption cross section of oxygen and yet can produce water aerosol.
Theory of Quadrupole Contributions from Interface and Bulk in Second-Order Optical Processes
Authors: Shiratori Kazuya , Morita Akihiro 
Published: October 2012

Abstract
A unified treatment of the dipole and quadrupole contributions to the second-order optical response is developed. The concept of the effective susceptibility is expanded to incorporate both the surface and bulk contributions. This treatment allows us to quantitatively evaluate both surface and bulk contributions in experimental SFG/SHG spectra. The present theory clarifies a number of qualitative features in the quadrupole contribution, and is thereby utilized to settle recent confusions about the quadrupole and/or bulk effects on the surface nonlinear spectroscopy.
Dynamic Experiments for Estimating Preferences: An Adaptive Method of Eliciting Time and Risk Parameters
Authors: Toubia Olivier , Johnson Eric , Evgeniou Theodoros , Delquié Philippe 
Published: October 2012

We present a method that dynamically designs elicitation questions for estimating risk and time preference parameters. Typically these parameters are elicited by presenting decision makers with a series of static choices between alternatives, gambles, or delayed payments. The proposed method dynamically (i.e., adaptively) designs such choices to optimize the information provided by each choice, while leveraging the distribution of the parameters across decision makers (heterogeneity) and capturing response error. We explore the convergence and the validity of our approach using simulations. The simulations suggest that the proposed method recovers true parameter values well under various circumstances. We then use an online experiment to compare our approach to a standard one used in the literature that requires comparable task completion time. We assess predictive accuracy in an out-of-sample task and completion time for both methods. For risk preferences, our results indicate that the proposed method predicts subjects' willingness to pay for a set of out-of-sample gambles significantly more accurately, while taking respondents about the same time to complete. For time preferences, both methods predict out-of-sample preferences equally well, while the proposed method takes significantly less completion time. For risk and time preferences, average completion time for our approach is approximately three minutes. Finally, we briefly review three applications that used the proposed methodology with various populations, and we discuss the potential benefits of the proposed methodology for research and practice. This paper was accepted by Teck Ho, decision analysis.
TMPRSS2-ERG Fusion Transcripts in Matched Urine and Needle Rinse Material after Biopsy for the Detection of Prostate Cancer
Authors: Bories Phuong-Nhi , Younes Patrick , Zerbib Marc , Denjean Lydie , Popovici Theodora , Cynober Luc , Delongchamps Nicolas Barry 
Published: October 2012

BACKGROUND
Current methods for detecting TMPRSS2-ERG fusion transcript in the urine of patients with suspected prostate cancer lack diagnostic sensitivity. We combined urine and prostate biopsy rinse material (BRM) assays to improve the fusion gene detection rate.

METHODS
Eighty patients with clinical and/or prostate-specific antigen suspicion of prostate cancer were prospectively included in the study. Urine samples were collected before and after prostate biopsy, and BRM was collected from the biopsy needle. We used reverse-transcription PCR (RT-PCR) for the detection of fusion transcripts. Microfocal cancer (MFC) on biopsy was defined by a single core involved with ≤3 mm of cancer with Gleason score 3 + 3. We statistically assessed the association between RT-PCR and biopsy results.

RESULTS
Urine alone, BRM alone, and both samples were obtained in 4, 19, and 57 patients, respectively. Three patients were excluded because of insufficient material. In the remaining 77 patients, cancer was detected on biopsy in 42 (55%). The diagnostic sensitivity of the assay for cancer detection was 62% (95% CI 47%–78%), 69% (53%–85%), and 89% (73%–99%) with BRM alone, urine alone, and paired samples, respectively. The lowest values were obtained with the urine assay in patients with MFC or Gleason score &gt;3 + 3 cancer. Assays of paired samples provided increased diagnostic sensitivity in all subgroups of patients.

CONCLUSIONS
TMPRSS2-ERG fusion gene detection may be improved by performing assays in both urine and BRM. Insufficient cell numbers in urine samples and cell lysis during centrifugation may explain the low diagnostic sensitivity of the urine assay.
Homozygous mutation of the IGF1 receptor gene in a patient with severe pre- and postnatal growth failure and congenital malformations
Authors: Gannagé-Yared Marie-Hélène , Klammt Jürgen , Chouery Eliane , Corbani Sandra , Mégarbané Hala , Abou Ghoch Joelle , Choucair Nancy , Pfäffle Roland , Mégarbané André 
Published: October 2012

BackgroundHeterozygous mutations in the IGF1 receptor (IGF1R) gene lead to partial resistance to IGF1 and contribute to intrauterine growth retardation (IUGR) with postnatal growth failure. To date, homozygous mutations of this receptor have not been described.SubjectA 13.5-year-old girl born from healthy first-cousin parents presented with severe IUGR and persistent short stature. Mild intellectual impairment, dysmorphic features, acanthosis nigricans, and cardiac malformations were also present.MethodsAuxological and endocrinological profiles were measured. All coding regions of theIGF1Rgene including intron boundaries were amplified and directly sequenced. Functional characterization was performed by immunoblotting using patient's fibroblasts.ResultsIGF1 level was elevated at 950 ng/ml (+7s.d.). Fasting glucose level was normal associated with high insulin levels at baseline and during an oral glucose tolerance test. Fasting triglyceride levels were elevated. Sequencing of theIGF1Rgene led to the identification of a homozygous variation in exon 2: c.119G>T (p.Arg10Leu). As a consequence, IGF1-dependent receptor autophosphorylation and downstream signaling were reduced in patient's fibroblasts. Both parents were heterozygous for the mutation.ConclusionThe homozygous mutation of theIGF1Ris associated with severe IUGR, dysmorphic features, and insulin resistance, while both parents were asymptomatic heterozygous carriers of the same mutation.
Suppression Analysis ofesa1Mutants inSaccharomyces cerevisiaeLinksNAB3to Transcriptional Silencing and Nucleolar Functions
Authors: Chang Christie S , Clarke Astrid , Pillus Lorraine 
Published: October 2012

AbstractThe acetyltransferase Esa1 is essential in the yeast Saccharomyces cerevisiae and plays a critical role in multiple cellular processes. The most well-defined targets for Esa1 are lysine residues on histones. However, an increasing number of nonhistone proteins have recently been identified as substrates of Esa1. In this study, four genes (LYS20, LEU2, VAP1, and NAB3) were identified in a genetic screen as high-copy suppressors of the conditional temperature-sensitive lethality of an esa1 mutant. When expressed from a high-copy plasmid, each of these suppressors rescued the temperature-sensitivity of an esa1 mutant. Only NAB3 overexpression also rescued the rDNA-silencing defects of an esa1 mutant. Strengthening the connections between NAB3 and ESA1, mutants of nab3 displayed several phenotypes similar to those of esa1 mutants, including increased sensitivity to the topoisomerase I inhibitor camptothecin and defects in rDNA silencing and cell-cycle progression. In addition, nuclear localization of Nab3 was altered in the esa1 mutant. Finally, posttranslational acetylation of Nab3 was detected in vivo and found to be influenced by ESA1.
Light-Inducible System for Tunable Protein Expression inNeurospora crassa
Authors: Hurley Jennifer M , Chen Chen-Hui , Loros Jennifer J , Dunlap Jay C 
Published: October 2012

AbstractFilamentous fungi are important model systems for understanding eukaryotic cellular processes, including the study of protein expression. A salient feature of fungi is the ability of the protein-processing machinery to perform all of the extensive posttranslational modifications needed in the complex world of eukaryotic organisms, making them great hosts for production of eukaryotic proteins. In the model organism Neurospora crassa, several regulatable promoters have been used for heterologous gene expression but all suffer from leaky expression absent stimuli or an inability to induce protein expression at levels greater than those seen in vivo. To increase and better control in vivo protein expression in Neurospora, we have harnessed the light-induced vvd promoter. vvd promoter-driven mRNA expression is dependent upon light, shows a graded response, and is rapidly shut off when returned to the dark. The vvd promoter is a highly tunable and regulatable system, which could be a useful instrument for those interested in efficient and controllable gene expression.
Second-Generation Genetic Linkage Map of Catfish and Its Integration with the BAC-Based Physical Map
Authors: Ninwichian Parichart , Peatman Eric , Liu Hong , Kucuktas Huseyin , Somridhivej Benjaporn , Liu Shikai , Li Ping , Jiang Yanliang , Sha Zhenxia , Kaltenboeck Ludmilla , Abernathy Jason W , Wang Wenqi , Chen Fei , Lee Yoona , Wong Lilian , Wang Shaolin , Lu Jianguo , Liu Zhanjiang 
Published: October 2012

Abstract
Construction of high-density genetic linkage maps is crucially important for quantitative trait loci (QTL) studies, and they are more useful when integrated with physical maps. Such integrated maps are valuable genome resources for fine mapping of QTL, comparative genomics, and accurate and efficient whole-genome assembly. Previously, we established both linkage maps and a physical map for channel catfish, Ictalurus punctatus, the dominant aquaculture species in the United States. Here we added 2030 BAC end sequence (BES)-derived microsatellites from 1481 physical map contigs, as well as markers from singleton BES, ESTs, anonymous microsatellites, and SNPs, to construct a second-generation linkage map. Average marker density across the 29 linkage groups reached 1.4 cM/marker. The increased marker density highlighted variations in recombination rates within and among catfish chromosomes. This work effectively anchored 44.8% of the catfish BAC physical map contigs, covering ∼52.8% of the genome. The genome size was estimated to be 2546 cM on the linkage map, and the calculated physical distance per centimorgan was 393 Kb. This integrated map should enable comparative studies with teleost model species as well as provide a framework for ordering and assembling whole-genome scaffolds.
Performance Metrics After Changes in Screening Protocol for Congenital Hypothyroidism
Authors: Korzeniewski Steven J. , Grigorescu Violanda , Kleyn Mary , Young William , Birbeck Gretchen L. , Todem David , Romero Roberto , Chaiworapongsa Tinnakorn , Paneth Nigel 
Published: October 2012

OBJECTIVE:
To evaluate Michigan newborn screening for congenital hypothyroidism (CH) protocol changes.

METHODS:
This population-based study includes infants born and screened in Michigan (January 1, 1994–June 30, 2010). Screening performance is compared across 4 periods defined by the dried blood spot testing method: (1) thyroxine (T4) with backup thyrotropin, (2) tandem T4 and thyrotropin, (3) primary thyrotropin testing without serial testing, and (4) primary thyrotropin plus serial testing for births weighing &lt;1800 g. Logistic regression is used to test for differences across periods.

RESULTS:
Thyrotropin testing exhibited greater specificity overall and greater likelihood of detection with serial testing relative to primary T4 testing. Tandem T4 and thyrotropin testing appeared more sensitive relative to other protocols, yet it produced significantly more false-positives, and detection may have been affected by overdiagnosis and misclassification. Central CH was no longer detected once T4 testing ceased.

CONCLUSIONS:
Primary thyrotropin plus serial testing for infants at risk for later rising thyrotropin outperformed other newborn screening strategies for classic CH, although 2 false-negatives occurred among normal birth weight infants admitted to the NICU during this testing period. Tandem T4 and thyrotropin screening outperformed other strategies for detection of both classic and central CH combined, although it is associated with increased operating costs. Additional research is necessary to weigh the benefits of increased sensitivity against additional program operating costs.
Prevention of Invasive Cronobacter Infections in Young Infants Fed Powdered Infant Formulas
Authors: Jason Janine 
Published: October 2012

BACKGROUND:
Invasive Cronobacter infection is rare, devastating, and epidemiologically/microbiologically linked to powdered infant formulas (PIFs). In 2002–2004, the US Food and Drug Administration advised health care professionals to minimize PIF and powdered human milk fortifier (HMF)’s preparation, feeding, and storage times and avoid feeding them to hospitalized premature or immunocompromised neonates. Labels for PIF used at home imply PIF is safe for healthy, term infants if label instructions are followed.

METHODS:
1) Medical, public health, Centers for Disease Control and Prevention, US Food and Drug Administration, and World Health Organization records, publications, and personal communications were used to compare 68 (1958–2003) and 30 (2004–2010) cases of invasive Cronobacter disease in children without underlying disorders. 2) The costs of PIFs and ready-to-feed formulas (RTFs) were compared.

RESULTS:
Ninety-nine percent (95/96) of all infected infants were &lt;2 months old. In 2004–2010, 59% (17/29) were term, versus 24% (15/63) in 1958–2003; 52% (15/29) became symptomatic at home, versus 21% (13/61). Of all infected infants, 26% (22/83) had received breast milk (BM), 23% (19/82) RTF, and 90% (76/84) PIF or HMF. Eight percent received BM and not PIF/HMF; 5%, RTF without PIF/HMF. For at least 10 PIF-fed infants, label instructions were reportedly followed. Twenty-four ounces of milk-based RTF cost $0.84 more than milk-based PIF; 24 ounces of soy-based RTF cost $0.24 less than soy-based PIF.

CONCLUSIONS:
Cronobacter can infect healthy, term (not just hospitalized preterm) young infants. Invasive Cronobacter infection is extremely unusual in infants not fed PIF/HMF. RTFs are commercially sterile, require minimal preparation, and are competitively priced. The exclusive use of BM and/or RTF for infants &lt;2 months old should be encouraged.
Drug Shortage–Associated Increase in Catheter-Related Blood Stream Infection in Children
Authors: Ralls Matthew W. , Blackwood R. Alexander , Arnold Meghan A. , Partipilo M. Luisa , Dimond James , Teitelbaum Daniel H. 
Published: October 2012

BACKGROUND:
Ethanol lock therapy (ELT) has been shown to reduce the incidence of catheter-related blood stream infections (CRBSI) in intestinal failure (IF) patients. Dosing and frequency remains undefined. Scrutiny of pharmaceutical facilities by the Food and Drug Administration led to the voluntary shutdown of the sole supplier of ethanol, resulting in a nationwide shortage. To conserve supply, we reduced ELT frequency from a daily regimen. We examined the impact that reduction in ELT frequency had on CRBSI in pediatric IF patients.

METHODS:
We retrospectively reviewed our parenteral nutrition–dependent IF children. Primary outcome measure was CRBSI per 1000 catheter days after ELT frequency reduction. Data were compared (paired t test) to the same group over 1 year before ethanol shortage and to historical controls.

RESULTS:
During the shortage 13 outpatients received ELT. Eight met study criteria. Mean ± SD age was 9.1 ± 7.8 years. Mean CRBSI rate per 1000 catheter days was 0.7 ± 1.3 before ELT shortage. This increased to 6.2 ± 2.5 after frequency reduction (P &lt; .001). This CRBSI rate was similar to historical IF children not on ELT (8.0 ± 5.4). Seven children developed CRBSI after frequency reduction, 6 requiring hospitalization, 2 to the ICU. Mean length of stay (15.5 days) averaged $104,783(± 111,034) in hospital charges. Organisms included Gram-negatives (6), methicillin-resistant Staphylococcus aureus (1), and Candida spp (1).

CONCLUSIONS:
ELT frequency reduction resulted in complete failure in CRBSI prophylaxis. The nationwide shortage of this drug has been costly both financially and in patient morbidity.
Measuring Adverse Events and Levels of Harm in Pediatric Inpatients With the Global Trigger Tool
Authors: Kirkendall Eric S. , Kloppenborg Elizabeth , Papp James , White Denise , Frese Carol , Hacker Deborah , Schoettker Pamela J. , Muething Stephen , Kotagal Uma 
Published: October 2012

OBJECTIVES:
To evaluate and characterize the Global Trigger Tool’s (GTT's) utility in a pediatric population; to measure the rate of harm at our institution and compare it with previously established trigger tools and benchmark rates; and to describe the distribution of harm of the detected events.

METHODS:
Per the GTT methodology, 240 random inpatient charts were retrospectively reviewed over a 12-month pilot period for the presence of 53 predefined safety triggers. When triggers were detected, the reviewers investigated the chart more thoroughly to decide whether an adverse event occurred. Agreement with a physician reviewer was then reached, and a level of harm was assigned.

RESULTS:
A total of 404 triggers were detected (1.7 triggers per patient), and 88 adverse events were identified. Rates of 36.7 adverse events per 100 admissions and 76.3 adverse events per 1000 patient-days were calculated. Sixty-two patients (25.8%) had at least 1 adverse event during their hospitalization, and 18 (7.5%) had &gt;1 event identified. Three-quarters of the events were category E (temporary harm). Two events required intervention to sustain life (category H). Two of the 6 trigger modules identified 95% of the adverse events.

CONCLUSIONS:
The GTT demonstrated utility in the pediatric inpatient setting. With the use of the trigger tool, we identified a rate of harm 2 to 3 times higher than previously published pediatric rates. Modifications to the trigger tool to address pediatric-specific issues could increase the test characteristics of the tool.