bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of in uteroexposure to diethylstilbestrol on lumbar and femoral bone, articular cartilage, and the intervertebral disc in male and female adult mice progeny with and without swimming exercise
Authors: Rowas Sora Al , Haddada Rami , Gawri Rahul , Al Ma'awi Abdul Aziz , Chalifour Lorraine E , Antoniou John , Mwale Fackson 
Published: January 2012

Abstract

Introduction

Developmental exposure to estrogens has been shown to affect the musculoskeletal system. Furthermore, recent studies have shown that environmental exposure to estrogen-like compounds is much higher than originally anticipated. The aim of this study was to determine the effects of diethylstilbestrol (DES), a well-known estrogen agonist, on articular cartilage, intervertebral disc (IVD), and bone phenotype.

Methods

C57Bl/6 pregnant mice were dosed orally with vehicle (peanut oil) or 0.1, 1.0, and 10 μg/kg/day of DES on gestational days 11 to 14. Male and female pups were allowed to mature without further treatment until 3 months of age, when swim and sedentary groups were formed. After euthanasia, bone mineral density (BMD), bone mineral content (BMC), bone area (BA), and trabecular bone area (TBA) of the lumbar vertebrae and femur were measured by using a PIXImus Bone Densitometer System. Intervertebral disc proteoglycan was measured with the DMMB assay. Histologic analysis of proteoglycan for IVD and articular cartilage was performed with safranin O staining, and degeneration parameters were scored.

Results

The lumbar BMC was significantly increased in female swimmers at both the highest and lowest dose of DES, whereas the femoral BMC was increased only at the highest. The males, conversely, showed a decreased BMC at the highest dose of DES for both lumbar and femoral bone. The female swim group had an increased BA at the highest dose of DES, whereas the male counterpart showed a decreased BA for femoral bone. The TBA showed a similar pattern. Proteoglycan analysis of lumbar IVDs showed a decrease at the lowest doses but a significant increase at the highest doses for both males and females. Histologic examination showed morphologic changes of the IVD and articular cartilage for all doses of DES.

Conclusions

DES significantly affected the musculoskeletal system of adult mice. Results suggest that environmental estrogen contaminants can have a detrimental effect on the developmental lumbar bone growth and mineralization in mice. Further studies measuring the impact of environmental estrogen mimics, such as bisphenol A, are then warranted.
Alkaline phosphatase for treatment of sepsis-induced acute kidney injury: a prospective randomized double-blind placebo-controlled trial
Authors: Pickkers Peter , Heemskerk Suzanne , Schouten Jeroen , Laterre Pierre-François , Vincent Jean-Louis , Beishuizen Albertus , Jorens Philippe G , Spapen Herbert , Bulitta Michael , Peters Wilbert HM , van der Hoeven Johannes G 
Published: January 2012

Abstract
Introduction
To evaluate whether alkaline phosphatase (AP) treatment improves renal function in sepsis-induced acute kidney injury (AKI), a prospective, double-blind, randomized, placebo-controlled study in critically ill patients with severe sepsis or septic shock with evidence of AKI was performed.

Methods
Thirty-six adult patients with severe sepsis or septic shock according to Systemic Inflammatory Response Syndrome criteria and renal injury defined according to the AKI Network criteria were included. Dialysis intervention was standardized according to Acute Dialysis Quality Initiative consensus. Intravenous infusion of alkaline phosphatase (bolus injection of 67.5 U/kg body weight followed by continuous infusion of 132.5 U/kg/24 h for 48 hours, or placebo) starting within 48 hours of AKI onset and followed up to 28 days post-treatment. The primary outcome variable was progress in renal function variables (endogenous creatinine clearance, requirement and duration of renal replacement therapy, RRT) after 28 days. The secondary outcome variables included changes in circulating inflammatory mediators, urinary excretion of biomarkers of tubular injury, and safety.

Results
There was a significant (P = 0.02) difference in favor of AP treatment relative to controls for the primary outcome variable. Individual renal parameters showed that endogenous creatinine clearance (baseline to Day 28) was significantly higher in the treated group relative to placebo (from 50 ± 27 to 108 ± 73 mL/minute (mean ± SEM) for the AP group; and from 40 ± 37 to 65 ± 30 mL/minute for placebo; P = 0.01). Reductions in RRT requirement and duration did not reach significance. The results in renal parameters were supported by significantly more pronounced reductions in the systemic markers C-reactive protein, Interleukin-6, LPS-binding protein and in the urinary excretion of Kidney Injury Molecule-1 and Interleukin-18 in AP-treated patients relative to placebo. The Drug Safety Monitoring Board did not raise any issues throughout the trial.

Conclusions
The improvements in renal function suggest alkaline phosphatase is a promising new treatment for patients with severe sepsis or septic shock with AKI.

Trial Registration
www.clinicaltrials.gov: NCTNCT00511186
Statins and the Risk of Hepatocellular Carcinoma in Patients With Hepatitis B Virus Infection
Authors: Tsan Yu-Tse , Lee Chang-Hsing , Wang Jung-Der , Chen Pau-Chung 
Published: January 2012

Purpose Statins have potential protective effects against cancers, but no studies have focused on patients with chronic hepatitis B virus (HBV) infection. The purpose of this study was to investigate the association between the use of statins in HBV-infected patients and the risk of hepatocellular carcinoma (HCC). Patients and Methods We conducted a population-based cohort study from the Taiwan National Health Insurance Research Database. A total of 33,413 HBV-infected patients were included as the study cohort. Each patient was individually tracked from 1997 to 2008 to identify incident cases of HCC since 1999. Subsequent use of statin, other lipid-lowering agents, aspirin, and angiotensin-converting enzyme inhibitors was identified. Cox proportional hazards regression was used to calculate the hazard ratios (HRs) and 95% CIs for the association between the use of statins and the occurrence of HCC in the HBV-infected cohort. Results There were 1,021 HCCs in the HBV cohort during the follow-up period of 328,946 person-years; the overall incidence rate was 310.4 HCCs per 100,000 person-years. There was a dose-response relationship between statin use and the risk of HCC in the HBV cohort. The adjusted HRs were 0.66 (95% CI, 0.44 to 0.99), 0.41 (95% CI, 0.27 to 0.61), and 0.34 (95% CI, 0.18 to 0.67) for statin use of 28 to 90, 91 to 365, and more than 365 cumulative defined daily doses (cDDDs), respectively, relative to no statin use (< 28 cDDDs). Conclusion Statin use may reduce the risk for HCC in HBV-infected patients in a dose-dependent manner. Further mechanistic research is needed.
PI3K/AKT/mTOR Inhibitors in Patients With Breast and Gynecologic Malignancies Harboring PIK3CA Mutations
Authors: Janku Filip , Wheler Jennifer J. , Westin Shannon N. , Moulder Stacy L. , Naing Aung , Tsimberidou Apostolia M. , Fu Siqing , Falchook Gerald S. , Hong David S. , Garrido-Laguna Ignacio , Luthra Rajyalakshmi , Lee J. Jack , Lu Karen H. , Kurzrock Razelle 
Published: January 2012

Purpose Mutations of the PIK3CA gene may predict response to phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) inhibitors. Concomitant mutations in the mitogen-activated protein kinase (MAPK) pathway may mediate resistance. Patients and Methods Tumors from patients with breast, cervical, endometrial, and ovarian cancer referred to the Clinical Center for Targeted Therapy (Phase I Program) were analyzed for PIK3CA, KRAS, NRAS, and BRAF mutations. Patients with PIK3CA mutations were treated, whenever feasible, with agents targeting the PI3K/AKT/mTOR pathway. Results Of 140 patients analyzed, 25 (18%) had PIK3CA mutations, including five of 14 patients with squamous cell cervical, seven of 29 patients with endometrial, six of 29 patients with breast, and seven of 60 patients with ovarian cancers. Of the 25 patients with PIK3CA mutations, 23 (median of two prior therapies) were treated on a protocol that included a PI3K/AKT/mTOR pathway inhibitor. Two (9%) of 23 patients had stable disease for more than 6 months, and seven patients (30%) had a partial response. In comparison, only seven (10%) of 70 patients with the same disease types but with wild-type PIK3CA treated on the same protocols responded (P = .04). Seven patients (30%) with PIK3CA mutations had coexisting MAPK pathway (KRAS, NRAS, BRAF) mutations (ovarian cancer, n = 5; endometrial cancer, n = 2), and two of these patients (ovarian cancer) achieved a response. Conclusion PIK3CA mutations were detected in 18% of tested patients. Patients with PIK3CA mutations treated with PI3K/AKT/mTOR inhibitors demonstrated a higher response rate than patients without mutations. A subset of patients with ovarian cancer with simultaneous PIK3CA and MAPK mutations responded to PI3K/AKT/mTOR inhibitors, suggesting that not all patients demonstrate resistance when the MAPK pathway is concomitantly activated.
Randomized Phase III Study of Thoracic Radiation in Combination With Paclitaxel and Carboplatin With or Without Thalidomide in Patients With Stage III Non–Small-Cell Lung Cancer: The ECOG 3598 Study
Authors: Hoang Tien , Dahlberg Suzanne E. , Schiller Joan H. , Mehta Minesh P. , Fitzgerald Thomas J. , Belinsky Steven A. , Johnson David H. 
Published: January 2012

PurposeThe primary objective of this study was to compare the survival of patients with unresectable stage III non–small-cell lung cancer (NSCLC) treated with combined chemoradiotherapy with or without thalidomide.Patients and MethodsPatients were randomly assigned to the control arm (PC) involving two cycles of induction paclitaxel 225 mg/m2and carboplatin area under the curve (AUC) 6 followed by 60 Gy thoracic radiation administered concurrently with weekly paclitaxel 45 mg/m2and carboplatin AUC 2, or to the experimental arm (TPC), receiving the same treatment in combination with thalidomide at a starting dose of 200 mg daily. The protocol allowed an increase in thalidomide dose up to 1,000 mg daily based on patient tolerability.ResultsA total of 546 patients were eligible, including 275 in the PC arm and 271 in the TPC arm. Median overall survival, progression-free survival, and overall response rate were 15.3 months, 7.4 months, and 35.0%, respectively, for patients in the PC arm, in comparison with 16.0 months (P = .99), 7.8 months (P = .96), and 38.2% (P = .47), respectively, for patients in the TPC arm. Overall, there was higher incidence of grade 3 toxicities in patients treated with thalidomide. Several grade 3 or higher events were observed more often in the TPC arm, including thromboembolism, fatigue, depressed consciousness, dizziness, sensory neuropathy, tremor, constipation, dyspnea, hypoxia, hypokalemia, rash, and edema. Low-dose aspirin did not reduce the thromboembolic rate.ConclusionThe addition of thalidomide to chemoradiotherapy increased toxicities but did not improve survival in patients with locally advanced NSCLC.
Randomized Phase III Study Comparing Paclitaxel–Bleomycin, Etoposide, and Cisplatin (BEP) to Standard BEP in Intermediate-Prognosis Germ-Cell Cancer: Intergroup Study EORTC 30983
Authors: de Wit Ronald , Skoneczna Iwona , Daugaard Gedske , De Santis Maria , Garin August , Aass Nina , Witjes Alfred J. , Albers Peter , White Jeffery D. , Germa-Lluch José R. , Marreaud Sandrine , Collette Laurence 
Published: January 2012

Purpose To compare the efficacy of four cycles of paclitaxel–bleomycin, etoposide, and cisplatin (T-BEP) to four cycles of bleomycin, etoposide, and cisplatin (BEP) in previously untreated patients with intermediate-prognosis germ-cell cancer (GCC). Patients and Methods Patients were randomly assigned to receive either T-BEP or standard BEP. Patients assigned to the T-BEP group received paclitaxel 175 mg/m2 in a 3-hour infusion. Patients who were administered T-BEP received primary granulocyte colony-stimulating factor (G-CSF) prophylaxis. The study was designed as a randomized open-label phase II/III study. To show a 10% improvement in 3-year progression-free survival (PFS), the study aimed to recruit 498 patients but closed with 337 patients as a result of slow accrual. Results Accrual was from November 1998 to April 2009. A total of 169patients were administered BEP, and 168 patients were administered T-BEP. Thirteen patients in both arms were ineligible, mainly as a result of a good prognosis of GCC (eight patients administered BEP; six patients administered T-BEP) or a poor prognosis of GCC (one patient administered BEP; four patients administered T-BEP). PFS at 3 years (intent to treat) was 79.4% in the T-BEP group versus 71.1% in the BEP group (hazard ratio [HR], 0.73; CI, 0.47 to 1.13; P [log-rank test] = 0.153). PFS at 3 years in all eligible patients was 82.7% versus 70.1%, respectively (HR, 0.60; CI: 0.37 to 0.97) and was statistically significant (P = 0.03). Overall survival was not statistically different. Conclusion T-BEP administered with G-CSF seems to be a safe and effective treatment regimen for patients with intermediate-prognosis GCC. However, the study recruited a smaller-than-planned number of patients and included 7.7% ineligible patients. The primary analysis of the trial could not demonstrate statistical superiority of T-BEP for PFS. When ineligible patients were excluded, the analysis of all eligible patients demonstrated a 12% superior 3-year PFS with T-BEP, which was statistically significant.
Accuracy of Genomic Selection Methods in a Standard Data Set of Loblolly Pine (Pinus taedaL.)
Authors: Resende M F R , Muñoz P , Resende M D V , Garrick D J , Fernando R L , Davis J M , Jokela E J , Martin T A , Peter G F , Kirst M 
Published: January 2012

AbstractGenomic selection can increase genetic gain per generation through early selection. Genomic selection is expected to be particularly valuable for traits that are costly to phenotype and expressed late in the life cycle of long-lived species. Alternative approaches to genomic selection prediction models may perform differently for traits with distinct genetic properties. Here the performance of four different original methods of genomic selection that differ with respect to assumptions regarding distribution of marker effects, including (i) ridge regression–best linear unbiased prediction (RR–BLUP), (ii) Bayes A, (iii) Bayes Cπ, and (iv) Bayesian LASSO are presented. In addition, a modified RR–BLUP (RR–BLUP B) that utilizes a selected subset of markers was evaluated. The accuracy of these methods was compared across 17 traits with distinct heritabilities and genetic architectures, including growth, development, and disease-resistance properties, measured in a Pinus taeda (loblolly pine) training population of 951 individuals genotyped with 4853 SNPs. The predictive ability of the methods was evaluated using a 10-fold, cross-validation approach, and differed only marginally for most method/trait combinations. Interestingly, for fusiform rust disease-resistance traits, Bayes Cπ, Bayes A, and RR–BLUB B had higher predictive ability than RR–BLUP and Bayesian LASSO. Fusiform rust is controlled by few genes of large effect. A limitation of RR–BLUP is the assumption of equal contribution of all markers to the observed variation. However, RR-BLUP B performed equally well as the Bayesian approaches.The genotypic and phenotypic data used in this study are publically available for comparative analysis of genomic selection prediction models.
A National Profile of Childhood Epilepsy and Seizure Disorder
Authors: Russ Shirley A. , Larson Kandyce , Halfon Neal 
Published: January 2012

OBJECTIVE:To determine sociodemographics, patterns of comorbidity, and function of US children with reported epilepsy/seizure disorder.METHODS:Bivariate and multivariable cross-sectional analysis of data from the National Survey of Children’s Health (2007) on 91 605 children ages birth to 17 years, including 977 children reported by their parents to have been diagnosed with epilepsy/seizure disorder.RESULTS:Estimated lifetime prevalence of epilepsy/seizure disorder was 10.2/1000 (95% confidence interval [CI]: 8.7–11.8) or 1%, and of current reported epilepsy/seizure disorder was 6.3/1000 (95% CI: 4.9–7.8). Epilepsy/seizure disorder prevalence was higher in lower-income families and in older, male children. Children with current reported epilepsy/seizure disorder were significantly more likely than those never diagnosed to experience depression (8% vs 2%), anxiety (17% vs 3%), attention-deficit/hyperactivity disorder (23% vs 6%), conduct problems (16% vs 3%), developmental delay (51% vs 3%), autism/autism spectrum disorder (16% vs 1%), and headaches (14% vs 5%) (all P &lt; .05). They had greater risk of limitation in ability to do things (relative risk: 9.22; 95% CI: 7.56–11.24), repeating a school grade (relative risk: 2.59; CI: 1.52–4.40), poorer social competence and greater parent aggravation, and were at increased risk of having unmet medical and mental health needs. Children with prior but not current seizures largely had intermediate risk.CONCLUSIONS:In a nationally representative sample, children with seizures were at increased risk for mental health, developmental, and physical comorbidities, increasing needs for care coordination and specialized services. Children with reported prior but not current seizures need further study to establish reasons for their higher than expected levels of reported functional limitations.
Urinary Proteome Analysis to Exclude Severe Vesicoureteral Reflux
Authors: Drube Jens , Schiffer Eric , Lau Esther , Petersen Claus , Kirschstein Martin , Kemper Markus J. , Lichtinghagen Ralf , Ure Benno , Mischak Harald , Pape Lars , Ehrich Jochen H.H. 
Published: January 2012

OBJECTIVES:
High-grade vesicoureteral reflux (VUR, grade IV or V) is a risk factor for renal scarring, impaired renal function, and arterial hypertension. Voiding cystourethrography is the gold standard for detecting the severity of VUR. High-grade VUR is present in the minority of children with urinary tract infection (UTI), thus exposing the majority to invasive diagnostics that have no surgical consequence. We therefore aimed at establishing a noninvasive test to identify children with high-grade VUR.

METHODS:
In a case-control study, a specific urinary proteome pattern was established by capillary electrophoresis coupled to mass spectrometry in 18 patients with primary VUR grade IV or V, distinguishing these from 19 patients without VUR after UTI. This proteome pattern was independently validated in a blinded cohort of 17 patients with VUR grade IV or V and 19 patients without VUR.

RESULTS:
Sensitivity in detecting VUR grade IV or V in the blinded study was 88%, specificity was 79%. The test’s accuracy was independent of age, gender, and grade of VUR in the contralateral kidney. The odds ratio of suffering from VUR grade IV or V when tested positive was 28 (95% confidence interval: 4.5 to 176.0).

CONCLUSIONS:
This noninvasive test is ready for prospective validation in large cohorts with the aim of identifying those children with UTI and hydronephrosis in need of further invasive diagnostics, such as voiding cystourethrography, thus sparing most children without pathologic urinary proteome patterns from additional diagnostics.
Predictors of Cognitive Function and Recovery 10 Years After Traumatic Brain Injury in Young Children
Authors: Anderson Vicki , Godfrey Celia , Rosenfeld Jeffrey V. , Catroppa Cathy 
Published: January 2012

BACKGROUND AND OBJECTIVES:
Childhood traumatic brain injury (TBI) has implications for functional outcomes, but few studies have documented long-term outcomes. The purpose of this study was to plot recovery of cognitive and functional skills after early childhood TBI to 10 years postinjury and to identify the contribution of injury, environment, preinjury characteristics, and acute functional recovery.

METHODS:
Subjects were recruited consecutively to this prospective, longitudinal study, which used a between-factor design, with injury severity as the independent variable. Forty children with TBI aged 2 and 7 years were recruited on admission to a tertiary pediatric hospital, divided according to injury severity, and compared with 16 healthy controls acutely and 12 and 30 months and 10 years postinjury. Cognition, adaptive ability, executive function, and social/behavioral skills were examined.

RESULTS:
Children with severe TBI had poorest outcomes, with deficits greatest for cognition. Recovery trajectories were similar across severity groups but with significant gains in verbal skills from 12 and 30 months to 12 months and 10 years. Predictors of outcome included preinjury ability (for adaptive function) and family function (social/behavioral skills).

CONCLUSIONS:
Results confirm a high risk of persisting deficits after severe TBI in early childhood. Children with less severe TBI appear to recover to function normally. Contrary to speculation about “growing into deficits,” after protracted recovery to 30 months, young children make age-appropriate progress at least to 10 years postinsult. Environmental factors were found to contribute to adaptive and social/behavioral recovery.
Perioperative Methylprednisolone and Outcome in Neonates Undergoing Heart Surgery
Authors: Pasquali Sara K. , Li Jennifer S. , He Xia , Jacobs Marshall L. , O’Brien Sean M. , Hall Matthew , Jaquiss Robert D. B. , Welke Karl F. , Peterson Eric D. , Shah Samir S. , Gaynor J. William , Jacobs Jeffrey P. 
Published: January 2012

BACKGROUND:
Recent studies have called into question the benefit of perioperative corticosteroids in children undergoing heart surgery, but have been limited by the lack of placebo control, limited power, and grouping of various steroid regimens together in analysis. We evaluated outcomes across methylprednisolone regimens versus no steroids in a large cohort of neonates.

METHODS:
Clinical data from the Society of Thoracic Surgeons Database were linked to medication data from the Pediatric Health Information Systems Database for neonates (≤30 days) undergoing heart surgery (2004–2008) at 25 participating centers. Multivariable analysis adjusting for patient and center characteristics, surgical risk category, and within-center clustering was used to evaluate the association of methylprednisolone regimen with outcome.

RESULTS:
A total of 3180 neonates were included: 22% received methylprednisolone on both the day before and day of surgery, 12% on the day before surgery only, and 28% on the day of surgery only; 38% did not receive any perioperative steroids. In multivariable analysis, there was no significant mortality or length-of-stay benefit associated with any methylprednisolone regimen versus no steroids, and no difference in postoperative infection. In subgroup analysis by surgical-risk group, there was a significant association of methylprednisolone with infection consistent across all regimens (overall odds ratio 2.6, 95% confidence interval 1.3–5.2) in the lower-surgical-risk group.

CONCLUSIONS:
This multicenter observational analysis did not find any benefit associated with methylprednisolone in neonates undergoing heart surgery and suggested increased infection in certain subgroups. These data reinforce the need for a large randomized trial in this population.