bluuebunny/crossref_metadata_2025_split huggingface dataset:
Thermodynamic modeling of transcription: sensitivity analysis differentiates biological mechanism from mathematical model-induced effects
Authors: Dresch Jacqueline M , Liu Xiaozhou , Arnosti David N , Ay Ahmet 
Published: October 2010

Abstract

Background
Quantitative models of gene expression generate parameter values that can shed light on biological features such as transcription factor activity, cooperativity, and local effects of repressors. An important element in such investigations is sensitivity analysis, which determines how strongly a model's output reacts to variations in parameter values. Parameters of low sensitivity may not be accurately estimated, leading to unwarranted conclusions. Low sensitivity may reflect the nature of the biological data, or it may be a result of the model structure. Here, we focus on the analysis of thermodynamic models, which have been used extensively to analyze gene transcription. Extracted parameter values have been interpreted biologically, but until now little attention has been given to parameter sensitivity in this context.

Results
We apply local and global sensitivity analyses to two recent transcriptional models to determine the sensitivity of individual parameters. We show that in one case, values for repressor efficiencies are very sensitive, while values for protein cooperativities are not, and provide insights on why these differential sensitivities stem from both biological effects and the structure of the applied models. In a second case, we demonstrate that parameters that were thought to prove the system's dependence on activator-activator cooperativity are relatively insensitive. We show that there are numerous parameter sets that do not satisfy the relationships proferred as the optimal solutions, indicating that structural differences between the two types of transcriptional enhancers analyzed may not be as simple as altered activator cooperativity.

Conclusions
Our results emphasize the need for sensitivity analysis to examine model construction and forms of biological data used for modeling transcriptional processes, in order to determine the significance of estimated parameter values for thermodynamic models. Knowledge of parameter sensitivities can provide the necessary context to determine how modeling results should be interpreted in biological systems.
Continuous glucose monitors prove highly accurate in critically ill children
Authors: Bridges Brian C , Preissig Catherine M , Maher Kevin O , Rigby Mark R 
Published: October 2010

Abstract
Introduction
Hyperglycemia is associated with increased morbidity and mortality in critically ill patients and strict glycemic control has become standard care for adults. Recent studies have questioned the optimal targets for such management and reported increased rates of iatrogenic hypoglycemia in both critically ill children and adults. The ability to provide accurate, real-time continuous glucose monitoring would improve the efficacy and safety of this practice in critically ill patients. The aim of our study is to determine if a continuous, interstitial glucose monitor will correlate with blood glucose values in critically ill children.

Methods
We evaluated 50 critically ill children age 6 weeks to 16 years old with a commercially available continuous glucose monitor (CGM; Medtronic Guardian®). CGM values and standard blood glucose (BG) values were compared. During the study, no changes in patient management were made based on CGM readings alone.

Results
Forty-seven patients had analyzable CGM data. A total of 1,555 CGM and routine BG measurements were compared using Clarke error grid and Bland-Altman analysis. For all readings, 97.9% were within clinically acceptable agreement. The mean absolute relative difference between CGM and BG readings was 15.3%. For the 1,555 paired CGM and BG measurements, there is a statistically significant linear relationship between CGM values and BG (P <.0001). A high degree of clinical agreement existed in three subpopulation analyses based on age, illness severity, and support measures. This included some of our smallest patients (that is, <12 months old), those who required vasopressors, and those who were treated for critical illness hyperglycemia.

Conclusions
In one of the largest studies to date, in a highly vulnerable ICU population, CGM values have a clinically acceptable correlation with the BG values now used diagnostically and therapeutically. Our data contest the theoretical concerns posed by some regarding CGM use in the ICU. The existing medical evidence may now support a role for CGM devices in the identification and management of hyperglycemia in diverse ICU settings.
Phase I Study of Everolimus Plus Weekly Paclitaxel and Trastuzumab in Patients With Metastatic Breast Cancer Pretreated With Trastuzumab
Authors: Andre Fabrice , Campone Mario , O'Regan Ruth , Manlius Corinne , Massacesi Cristian , Tarek Sahmoud , Mukhopadhyay Pabak , Soria Jean-Charles , Naughton Michael , Hurvitz Sara A. 
Published: October 2010

Purpose To determine the recommended dose of everolimus, a mammalian target of rapamycin inhibitor, combined with paclitaxel and trastuzumab in patients with human epidermal growth factor receptor 2 (HER2) –overexpressing metastatic breast cancer pretreated with trastuzumab. Methods In this phase Ib, multicenter, dose-escalation study, patients were treated with everolimus 5 mg/d, 10 mg/d, or 30 mg/wk in combination with paclitaxel (80 mg/m2 days 1, 8, and 15 every 4 weeks) and trastuzumab (2 mg/kg weekly). End points included end-of–cycle 1 dose-limiting toxicity (DLT) rate (primary end point), safety, relative dose intensity of study drugs, overall response rate (ORR), and pharmacokinetics. Results Of 33 patients enrolled, 31 were pretreated with taxanes, and 32 were resistant to trastuzumab. Patients received a median of two lines of chemotherapy in the metastatic setting (range, 0 to 17 lines). Three patients experienced cycle 1 DLTs: febrile neutropenia (5 mg/d), stomatitis (10 mg/d), and confusion (30 mg/wk). Grade 3 to 4 neutropenia was the most common toxicity observed (n = 17 patients [52%]). On the basis of observed DLTs and overall safety, 10 mg/d was recommended for additional development. Twenty-seven patients had measurable disease and were evaluable for efficacy. Among these patients, ORR was 44%. Overall disease was controlled for 6 months or more in 74%. Median progression-free survival was 34 weeks (95% CI, 29.1 to 40.7 weeks). Among 11 patients who were resistant to both trastuzumab and taxane, a similar level of antitumor activity was observed (ORR, 55%). Conclusion Everolimus combined with weekly paclitaxel and trastuzumab was generally well tolerated and had encouraging antitumor activity in patients with trastuzumab-pretreated and -resistant metastatic HER2-overexpressing breast cancer.
Multicenter Phase II Trial of S-1 in Patients With Cytokine-Refractory Metastatic Renal Cell Carcinoma
Authors: Naito Seiji , Eto Masatoshi , Shinohara Nobuo , Tomita Yoshihiko , Fujisawa Masato , Namiki Mikio , Nishikido Masaharu , Usami Michiyuki , Tsukamoto Taiji , Akaza Hideyuki 
Published: October 2010

Purpose This phase II multicenter trial was conducted to evaluate the activity and safety of S-1 in Japanese patients with metastatic renal cell carcinoma (mRCC). We also examined the relation between response and mRNA expression levels of enzymes involved in the metabolism of fluorouracil (FU). Methods Patients with mRCC who had received nephrectomy in whom cytokine-based immunotherapy was ineffective or contraindicated were studied. S-1 was administered orally at 80-, 100-, or 120-mg daily, assigned according to body surface area, on days 1 to 28 of a 42-day cycle. The primary end point was the objective response rate. The mRNA expression levels of FU-related enzymes were measured by reverse-transcriptase polymerase chain reaction in formalin-fixed, paraffin-embedded specimens of tumors obtained at nephrectomy. Results A total of 45 eligible patients were enrolled. Eleven (24.4%) of 45 patients had partial responses to S-1, and 28 (62.2%) had stable disease. Median progression-free survival was 9.2 months. The severity of most adverse events was mild to moderate. The most common grade 3/4 drug-related adverse events were neutropenia (8.9%) and anorexia (8.9%). The expression level of thymidylate synthase (TS) mRNA was significantly lower in patients who responded to treatment (t-test, P = .048), and progression-free survival was significantly longer in patients whose TS mRNA expression levels were below the median value, as compared with those with higher levels (log-rank test, P = .006). Conclusion S-1 is active against cytokine-refractory mRCC. Quantification of TS mRNA levels in tumors before treatment may facilitate prediction of the response of mRCC to S-1.
Testosterone Levels and Quality of Life in Diverse Male Patients With Cancers Unrelated to Androgens
Authors: Fleishman Stewart B. , Khan Hina , Homel Peter , Suhail Mohammad F. , Strebel-Amrhein Rotraud , Mohammad Farhan , Mahajan Divya , Rosenwald Victoria , Guarino Michael J. , Mirzoyev Tahir , Wozniak Timothy F. , Suppiah Kathiresan 
Published: October 2010

Purpose Symptoms secondary to hormonal changes significantly impact quality of life (QoL) in patients with cancer. This cross-sectional study examines prevalence of hypogonadism and its correlation with QoL and sexual dysfunction. Patients and Methods We collected blood and medical histories from 428 male patients with non–testosterone-related cancer at three cancer centers. Serum was analyzed for total testosterone (TT), free testosterone (FT), bioavailable testosterone (BAT), and sex hormone binding globulin (SHBG). The Functional Assessment of Cancer Therapy-Prostate (FACT-P) QoL questionnaire measured physical, social, emotional, and functional domains as well as sexual function. Exclusion criteria were prostate, testicular, or male breast cancer; known hypogonadism; and HIV. Results Mean and median TTs were 337.46 and 310 ng/dL, respectively. The mean age of patients was 62.05 years. The crude prevalence of hypogonadism (ie, TT < 300 ng/dL) was 48%, and mean TT in hypogonadal patients was 176 ng/dL. The prevalences that were based on FT (ie, hypogonadal < 52 pg/dL) and BAT (ie, hypogonadal < 95 ng/dL) were 78% and 66%, respectively. The mean FT and BAT values in hypogonadal patients were 25 pg/dL and 45 ng/dL, respectively. Hypogonadal patients had decreased total QoL scores on FACT-P (P = .01) and decreased three-item sexual function subset (P = .003). Conclusion The prevalence of hypogonadism was unexpectedly high. Measurement of FT or BAT detected a higher prevalence than TT alone, which confirmed previous studies. Correlation of T with FACT-P showed significant reduction of both overall QoL and sexual function for hypogonadal men. BAT and FT levels showed a stronger correlation than TT with overall FACT-P and subscales. The prevalence of symptomatic hypogonadism in male patients with cancer exceeds that found in comparable studies in noncancer populations.
Dose Intensity of Chemotherapy in Patients With Relapsed Hodgkin's Lymphoma
Authors: Josting Andreas , Müller Horst , Borchmann Peter , Baars Joke W. , Metzner Bernd , Döhner Hartmut , Aurer Igor , Smardova Lenka , Fischer Thomas , Niederwieser Dietger , Schäfer-Eckart Kerstin , Schmitz Norbert , Sureda Anna , Glossmann Jan , Diehl Volker , DeJong Daphne , Hansmann Martin-Leo , Raemaekers John , Engert Andreas 
Published: October 2010

Purpose High-dose chemotherapy (HDCT) followed by autologous stem-cell transplantation (PBSCT) has become the standard treatment for patients with relapsed Hodgkin's lymphoma (HL). The intensity of treatment needed is unclear. This European intergroup study evaluated the impact of sequential high-dose chemotherapy (SHDCT) before myeloablative therapy. Patients and Methods Patients with histologically confirmed, relapsed HL were treated with two cycles of dexamethasone, cytarabine, and cisplatin, and those without disease progression were randomly assigned. In the standard arm (A), patients received myeloablative therapy with carmustine, BEAM (carmustine, etoposide, cytarabine, and melphalan) followed by PBSCT. Patients in the experimental arm (B) also received sequential cyclophosphamide, methotrexate, and etoposide in high-doses before BEAM. Freedom from treatment failure (FFTF) was the primary end point. Remission rates, overall survival (OS), and toxicity of treatment were secondary end points. Results From a total of 284 patients included, 241 responding patients were randomly assigned after two cycles of dexamethasone, cytarabine, and cisplatinum. Patients treated in arm B had longer treatment duration and experienced more toxicity and protocol violations (P < .05). Mortality was similar in both arms (20% and 18%). With a median observation time of 42 months, there was no significant difference in terms of FFTF (P = .56) and OS (P = .82) between arms. FFTF at 3 years was 62% (95% CI, 56% to 68%) and OS was 80% (95% CI, 75% to 85%). Patients with stage IV, early relapse, multiple relapse, anemia, or B symptoms had a higher risk of recurrence (P < .001). Conclusion Compared with conventional high-dose chemotherapy, additional SHDCT is associated with more adverse effects and does not improve the prognosis of patients with relapsed HL.
Sexual Behaviors and Sexual Violence: Adolescents With Opposite-, Same-, or Both-Sex Partners
Authors: Pathela Preeti , Schillinger Julia A. 
Published: October 2010

OBJECTIVE:
To describe sexual behaviors, sexual violence, and sexual identity among a population-based sample of adolescents according to the sex of their sex partners, considering separately those with partners of both sexes.

METHODS:
From the 2005–2007 New York City Youth Risk Behavior Surveys, 3805 male and 3456 female adolescents reported having had sex and the sex of their sexual contacts. Subgroups were constructed: only opposite-sex partners; only same-sex partners; and partners of both sexes (both-sex partners). Weighted prevalence, risk behaviors (eg, using drugs/alcohol with sex), and sexual identity among subgroups were described.

RESULTS:
Similar numbers of sexually active male (3.2%) and female adolescents (3.2%) reported only same-sex behavior, but fewer male than female adolescents reported both-sex partners (3.7% vs 8.7%; P &lt; .001). Male adolescents with both-sex partners reported a higher prevalence of sexual risk behaviors than male adolescents with only opposite-sex or only same-sex partners. Female adolescents with both-sex or only same-sex partners reported a higher prevalence of risk behaviors than female adolescents with only opposite-sex partners. Adolescents with both-sex partners reported a marked prevalence of dating violence and forced sex. Many adolescents with only same- or both-sex partners (38.9%) self-identified as straight.

CONCLUSIONS:
Of sexually active adolescents, 9.3% reported a same-sex partner, a higher estimate than other published rates. Those who reported both male and female partners reported behaviors that placed them at risk for sexually transmitted infections (STIs), including HIV. Pediatricians and school health providers must inquire about behaviors, not identity, to determine STI risk, and STI education should be appropriate for youth with same-sex partners.
Effects of Resistance Training in Children and Adolescents: A Meta-analysis
Authors: Behringer Michael , vom Heede Andreas , Yue Zengyuan , Mester Joachim 
Published: October 2010

CONTEXT:
Although physiologic benefits of resistance training for children and adolescents have been well documented, the impact of age and maturity on trainability of muscle strength remains poorly understood.

OBJECTIVE:
To assess the effects of resistance training in different age groups and maturity levels.

METHODS:
We searched electronic bibliographic databases, key journals, and reference lists of reviews, book chapters, and articles. Two independent reviewers evaluated the effects of resistance training on muscle strength for prepubertal and postpubertal healthy children and adolescents (younger than 18 years) by using the results of randomized and nonrandomized controlled trials. Assessments of muscle endurance and motor performance tests (eg, vertical jump) were excluded. The influence of continuous and categorical moderator variables was assessed by meta-regression and subgroup analyses, respectively.

RESULTS:
The overall weighted effect size of 1.12 (95% confidence interval: 0.9–1.3) was significantly greater than 0 (P &lt; .01). Subgroup analyses revealed “maturity” to be a significant categorical moderator variable (z = 2.50; P = .01) and positive correlation coefficients were found for the continuous variables “duration” (r = 0.28; P = .02) and “frequency” (r = 0.26; P = .03).

CONCLUSIONS:
The results of our analysis indicate that the ability to gain muscular strength seems to increase with age and maturational status, but there is no noticeable boost during puberty. Furthermore, study duration and the number of performed sets were found to have a positive impact on the outcome.
Interpreting Complete Blood Counts Soon After Birth in Newborns at Risk for Sepsis
Authors: Newman Thomas B. , Puopolo Karen M. , Wi Soora , Draper David , Escobar Gabriel J. 
Published: October 2010

BACKGROUND:
A complete blood count (CBC) with white blood cell differential is commonly ordered to evaluate newborns at risk for sepsis.

OBJECTIVES:
To quantify how well components of the CBC predict sepsis in the first 72 hours after birth.

METHODS:
For this retrospective cross-sectional study we identified 67 623 term and late-preterm (≥34 weeks gestation) newborns from 12 northern California Kaiser hospitals and 1 Boston, Massachusetts hospital who had a CBC and blood culture within 1 hour of each other at &lt;72 hours of age. We compared CBC results among newborns whose blood cultures were and were not positive and quantified discrimination by using receiver operating characteristic curves and likelihood ratios.

RESULTS:
Blood cultures of 245 infants (3.6 of 1000 tested newborns) were positive. Mean white blood cell (WBC) counts and mean absolute neutrophil counts (ANCs) were lower, and mean proportions of immature neutrophils were higher in newborns with infection; platelet counts did not differ. Discrimination improved with age in the first few hours, especially for WBC counts and ANCs (eg, the area under the receiver operating characteristic curve for WBC counts was 0.52 at &lt;1 hour and 0.87 at ≥4 hours). Both WBC counts and ANCs were most informative when very low (eg, the likelihood ratio for ANC &lt; 1000 was 115 at ≥4 hours). No test was very sensitive; the lowest likelihood ratio (for WBC count ≥ 20 000 at ≥4 hours) was 0.16.

CONCLUSION:
Optimal interpretation of the CBC requires using interval likelihood ratios for the newborn's age in hours.
Reliability of Clinical Examinations for Pediatric Skin and Soft-Tissue Infections
Authors: Marin Jennifer R. , Bilker Warren , Lautenbach Ebbing , Alpern Elizabeth R. 
Published: October 2010

OBJECTIVE:
To determine the interrater reliability of clinical examination by pediatric emergency medicine physicians for the diagnosis of skin and soft-tissue infections (SSTIs).

METHODS:
A cross-sectional study of patients presenting to a pediatric emergency department with SSTIs was performed. Each lesion was examined by a treating physician and a study physician (from a pool of 62 physicians) at the bedside during the emergency department visit. The primary outcome was reliability, as measured with the weighted κ statistic, for determining whether the lesion was an abscess and whether the lesion required a drainage procedure.

RESULTS:
A total of 371 lesions were analyzed for interrater reliability. The weighted κ value for diagnosis of the lesion as an abscess was 0.39 (95% confidence interval: 0.32–0.47), and that for assessment of the need for drainage was 0.43 (95% confidence interval: 0.36–0.51). Agreement was statistically more likely for lesions in children ≥4 years of age but was not more likely for lesions in nonblack patients, lesions in patients with a history of or exposure to a close contact with a SSTI, or lesions examined by 2 experienced pediatric emergency medicine physicians.

CONCLUSIONS:
Among the 62 participating physicians at our site, the reliability of the clinical examination was poor. This may indicate that improved education and/or more-objective means for diagnosing these infections in the acute care setting are warranted. Additional studies are needed to determine whether these results are generalizable to other settings.
The polycystic ovary syndrome (pcos) status and cardiovascular risk in young women
Authors: Ilie Ioana , Pepene Carmen , Marian Ioan , Mocan Teodora , Hazi Georgeta , Drăgotoiu Gheorghe , Ilie Razvan , Mocan Lucian , Duncea Ileana 
Published: October 2010

Abstract
The study investigated the presence of early vascular damage and chronic inflammation, and their relationships with hormonal and metabolic parameters in 45 young women with PCOS in comparison with thirty-two healthy age-matched controls. Hormonal and metabolic profiles, high sensitivity C-reactive protein (hsCRP), tumoral necrosis factor-alpha (TNF-α), endothelin-1 (ET-1), brachial flow-mediated vasodilation (FMD) and carotid intima-media thickness (CIMT) were determined in both groups. Compared with the controls, women with PCOS had significantly lower FMD and respectively higher ET-1 levels (p=0.001). No differences were observed between the groups in terms of CIMT or inflammatory markers. In the PCOS group, ET-1 levels were significantly correlated with only testosterone concentrations (r = 0.31, p = 0.037), whereas the hsCRP levels were independently predicted only by body mass index (BMI). Within the total group, the PCOS status was the sole significant predictor of ET-1 levels and the only independent predictor of FMD. In conclusion, there is evidence of endothelial dysfunction associated with increased levels of androgen hormones in young women with PCOS. The combination of endothelial dysfunction and coexistent obesity promoting inflammation contributes to the progression of atherogenesis in PCOS. The PCOS status should be regarded as a predictor marker of cardiovascular risk, along with well-known cardiovascular risk factors.
Postpartum examination, breastfeeding, and contraception in the postpartum period in the Czech Republic
Authors: Zahumensky Jozef , Sykorova Jana , Sottner Oldrich , Zmrhalova Barbora , Vojtech Jiri , Menzlova Erika , Vasicka Ian , Dvorska Monika , Maxova Katerina , Vlacil Jaromir , Hrubantova Helena , Halaska Michael 
Published: October 2010

Abstract
In the majority of recent textbooks of obstetrics, a routine follow-up examination at the end of the postpartum period is recommended. To date, no studies have been done in the Czech Republic addressing use of contraception and follow-up care in the postpartum period. Questionnaires were sent to 672 participants who gave birth in the year 2008, inquiring about follow-up examinations in the postpartum period and use of contraception. In total, 458 (68.2%) questionnaires were returned. 430 women (93.9%) underwent routine examinations at 6 weeks into the postpartum period. At the time of examination, 36 women were asked about their particular health problems (8.4%). In 130 instances, the question most often addressed by the outpatient gynecologist concerned use of contraception (30.2%). However, only 34 physicians expressed concern about changes in sexual life or other sexually related problems. 426 women (93.0%) were sexually active and 310 women (72.8%) did not use any contraception with the exception of breastfeeding. The current practice of outpatient gynecological visits at 6 weeks postpartum and advice on contraception both seem inadequate.