bluuebunny/crossref_metadata_2025_split huggingface dataset:
Improving Pediatric Dosing Through Pediatric Initiatives: What We Have Learned
Authors: Rodriguez William , Selen Arzu , Avant Debbie , Chaurasia Chandra , Crescenzi Terrie , Gieser Gerlie , Di Giacinto Jennifer , Huang Shiew-Mei , Lee Peter , Mathis Lisa , Murphy Dianne , Murphy Shirley , Roberts Rosemary , Sachs Hari Cheryl , Suarez Sandra , Tandon Veneeta , Uppoor Ramana S. 
Published: February 2008

OBJECTIVE. The goal was to review the impact of pediatric drug studies, as measured by the improvement in pediatric dosing and other pertinent information captured in the drug labeling.
METHODS. We reviewed the pediatric studies for 108 products submitted (July 1998 through October 2005) in response to a Food and Drug Administration written request for pediatric studies, and the subsequent labeling changes. We analyzed the dosing modifications and focused on drug clearance as an important parameter influencing pediatric dosing.
RESULTS. The first 108 drugs with new or revised pediatric labeling changes had dosing changes or pharmacokinetic information (n = 23), new safety information (n = 34), information concerning lack of efficacy (n = 19), new pediatric formulations (n = 12), and extended age limits (n = 77). A product might have had ≥1 labeling change. We selected specific examples (n = 16) that illustrate significant differences in pediatric pharmacokinetics.
CONCLUSIONS. Critical changes in drug labeling for pediatric patients illustrate that unique pediatric dosing often is necessary, reflecting growth and maturational stages of pediatric patients. These changes provide evidence that pediatric dosing should not be determined by simply applying weight-based calculations to the adult dose. Drug clearance is highly variable in the pediatric population and is not readily predictable on the basis of adult information.
Increased Concordance of Severe Respiratory Syncytial Virus Infection in Identical Twins
Authors: Thomsen Simon Francis , Stensballe Lone Graff , Skytthe Axel , Kyvik Kirsten Ohm , Backer Vibeke , Bisgaard Hans 
Published: February 2008

OBJECTIVE. We estimated differences in the severity of respiratory syncytial virus infection attributable to genetic and environmental factors.
METHODS. Record linkage data on hospitalizations attributable to respiratory syncytial virus infection were gathered on all twins (12346 pairs) born in Denmark between 1994 and 2003. Latent-factor models of genetic and environmental effects were fitted to the observed data by using maximal likelihood methods.
RESULTS. Identical twins resembled each other significantly more than did fraternal twins for respiratory syncytial virus hospitalization (concordance rate: 0.66 vs 0.53), which suggests genetic influences on disease severity. Genetic factors accounted for 16%, family environment for 73%, and nonshared environment for 11% of the individual susceptibility to develop severe respiratory syncytial virus infection.
CONCLUSIONS. The severity of respiratory syncytial virus infection is determined partly by genetic factors. This result should stimulate the search for genetic markers of disease severity.
Cord Blood and Breast Milk Iron Status in Maternal Anemia
Authors: Kumar Ashok , Rai Arun Kumar , Basu Sriparna , Dash Debabrata , Singh Jamuna Saran 
Published: February 2008

OBJECTIVES. The purpose of this work was to assess the effect of severe maternal iron-deficiency anemia and nutritional status on cord blood and breast milk iron status.
METHODS. We conducted a prospective observational study over a 6-month period in a teaching hospital in central India. The study population consisted of 55 anemic (hemoglobin: &lt;110 g/L) and 20 healthy nonanemic (hemoglobin: ≥110 g/L) pregnant women who delivered singleton live births at term gestation. We measured hemoglobin, iron, and ferritin levels in paired maternal and cord blood and iron levels in early (day 3 ± 1) and late (day 15 ± 3) transitional milk. Maternal anthropometry, including weight, height, midarm circumference, triceps skinfold thickness, and placental weight, were recorded. The main outcome measure of the study was to find out the relationship of maternal hemoglobin, iron, ferritin, and anthropometry with hemoglobin, iron, and ferritin in cord blood and iron levels in breast milk.
RESULTS. Concentrations of hemoglobin, iron, and ferritin were significantly lower in the cord blood of anemic mothers and showed linear relationships with maternal hemoglobin and ferritin levels. Breast milk iron content was significantly reduced in severely anemic mothers but not in those with mild-to-moderate anemia. Breast milk iron level correlated with maternal hemoglobin and iron levels but not with ferritin levels. Maternal anthropometry had significant correlations with indices of iron nutriture in maternal and cord blood but showed no relationship with breast milk iron content. Placental weight was comparable between anemic and nonanemic mothers.
CONCLUSIONS. Maternal anemia, particularly the severe type, adversely affects cord blood and breast milk iron status. Maternal nutritional status exerts a significant influence on fetal iron status but has little influence on breast milk iron content.
Characterization of Bipotential Epidermal Progenitors Derived from Human Sebaceous Gland: Contrasting Roles of c-Myc and β-Catenin
Authors: Lo Celso Cristina , Berta Melanie A. , Braun Kristin M. , Frye Michaela , Lyle Stephen , Zouboulis Christos C. , Watt Fiona M. 
Published: February 2008

Abstract
The current belief is that the epidermal sebaceous gland (SG) is maintained by unipotent stem cells that are replenished by multipotent stem cells in the hair follicle (HF) bulge. However, sebocytes can be induced by c-Myc (Myc) activation in interfollicular epidermis (IFE), suggesting the existence of bipotential stem cells. We found that every SZ95 immortalized human sebocyte that underwent clonal growth in culture generated progeny that differentiated into both sebocytes and cells expressing involucrin and cornifin, markers of IFE and HF inner root sheath differentiation. The ability to generate involucrin positive cells was also observed in a new human sebocyte line, Seb-E6E7. SZ95 xenografts differentiated into SG and IFE but not HF. SZ95 cells that expressed involucrin had reduced Myc levels; however, this did not correlate with increased expression of the Myc repressor Blimp1, and Blimp1 expression did not distinguish cells undergoing SG, IFE, or HF differentiation in vivo. Overexpression of Myc stimulated sebocyte differentiation, whereas overexpression of β-catenin stimulated involucrin and cornifin expression. In transgenic mice simultaneous activation of Myc and β-catenin revealed mutual antagonism: Myc blocked ectopic HF formation and β-catenin reduced SG differentiation. Overexpression of the Myc target gene Indian hedgehog did not promote sebocyte differentiation in culture and cyclopamine treatment, while reducing proliferation, did not block Myc induced sebocyte differentiation in vivo. Our studies provide evidence for a bipotential epidermal stem cell population in an in vitro model of human epidermal lineage selection and highlight the importance of Myc as a regulator of sebocyte differentiation.
Disclosure of potential conflicts of interest is found at the end of this article.
Functional Network Reconstruction Reveals Somatic Stemness Genetic Maps and Dedifferentiation-Like Transcriptome Reprogramming Induced by GATA2
Authors: Huang Tse-Shun , Hsieh Jui-Yu , Wu Yu-Hsuan , Jen Chih-Hung , Tsuang Yang-Hwei , Chiou Shih-Hwa , Partanen Jukka , Anderson Heidi , Jaatinen Taina , Yu Yau-Hua , Wang Hsei-Wei 
Published: February 2008

Abstract
Somatic stem cell transplantation holds great promise in regenerative medicine. The best-characterized adult stem cells are mesenchymal stem cells (MSCs), neural stem cells (NSCs), and CD133+ hematopoietic stem cells (HSCs). The applications of HSCs are hampered since these cells are difficult to maintain in an undifferentiated state in vitro. Understanding genes responsible for stem cell properties and their interactions will help on this issue. The construction of stem cell genetic networks will also help to develop rational strategies to revert somatic cells back to a stem-like state. We performed a systemic study on human CD133+ HSCs, NSCs, MSCs, and embryonic stem cells and two different progenies of CD133+ HSCs, microvascular endothelial cells (MVECs) and peripheral blood mononuclear cells. Genes abundant in each or in all three somatic stem cells were identified. We also observed complex genetic networks functioning in postnatal stem cells, in which several genes, such as PTPN11 and DHFR, acted as hubs to maintain the stability and connectivity of the whole genetic network. Eighty-seven HSC genes, including ANGPT1 and GATA2, were independently identified by comparing CD34+CD33−CD38− hematopoietic stem cells with CD34+ precursors and various matured progenies. Introducing GATA2 into MVECs resulted in dedifferentiation-like transcriptome reprogramming, with HSC genes (such as ANGPT1) being up and endothelial genes (such as EPHB2) being down. This study provides a foundation for a more detailed understanding of human somatic stem cells. Expressing the newly discovered stem cell genes in matured cells might lead to a global reversion of somatic transcriptome to a stem-like status.
Disclosure of potential conflicts of interest is found at the end of this article.
Horizontal Basal Cells Are Multipotent Progenitors in Normal and Injured Adult Olfactory Epithelium
Authors: Iwai Naomi , Zhou Zhijian , Roop Dennis R. , Behringer Richard R. 
Published: February 2008

Abstract
The mammalian olfactory neuroepithelium provides a unique system for understanding the regulation of neurogenesis by adult neural stem cells. Recently, mouse horizontal basal cells (HBCs) were identified as stem cells that regenerate olfactory receptor neurons (ORNs) and non-neuronal cell types only after extensive injury of the olfactory epithelium (OE). Here we report a broader spectrum of action for these cells. We show that even during normal neuronal turnover, HBCs actively generate neuronal and non-neuronal cells throughout adulthood. This occurs in a temporally controlled manner: an initial wave of HBC-derived neurogenesis was observed soon after birth, and a second wave of neurogenesis was observed at 4 months of age. Moreover, upon selective depletion of mature ORNs by olfactory bulbectomy, HBCs give rise to more neurons. Our findings demonstrate a crucial role for HBCs as multipotent progenitors in the adult OE, acting during normal neuronal turnover as well as in acute regeneration upon injury.
Disclosure of potential conflicts of interest is found at the end of this article.
Misclassification Bias and the Estimated Effect of Parental Involvement Laws on Adolescents' Reproductive Outcomes
Authors: Colman Silvie , Joyce Ted , Kaestner Robert 
Published: February 2008

Objectives. We evaluated the presence of misclassification bias in the estimated effect of parental involvement laws on minors’ reproductive outcomes when subjection to such laws was measured by age at the time of pregnancy resolution. Methods. Using data from abortion and birth certificates, we evaluated the effect of Texas's parental notification law on the abortion, birth, and pregnancy rates of adolescents aged 17 years compared with those aged 18 years on the basis of age at the time of pregnancy resolution and age at conception. Results. On the basis of age at the time of the abortion or birth, the law was associated with a fall of 26%, 7%, and 11% in the abortion, birth, and pregnancy rates, respectively, of 17- relative to 18-year-olds. Based on age at the time of conception, the abortion rate fell 15%, the birth rate rose 2%, and the pregnancy rate remained unchanged. Conclusions. Previous studies of parental involvement laws should be interpreted with caution because their methodological limitations have resulted in an overestimation of the fall in abortions and underestimation of the rise in births, possibly leading to the erroneous conclusion that pregnancies decline in response to such laws.
Effects of the Solvent Evaporation Technique on the Degree of Conversion of One-Bottle Adhesive Systems
Authors: Giannini M. , Arrais C. A. G. , Vermelho P. M. , Reis R. S. , Santos L. P. S. , Leite E. R. 
Published: February 2008

Clinical Relevance
Since methods of solvent evaporation can change the degree of conversion for some adhesives, practitioners should be aware of the type and composition of bonding agents used.
Shear Bond Strength of Self-etch Adhesives to Enamel with Additional Phosphoric Acid Etching
Authors: Lührs A-K. , Guhr S. , Schilke R. , Borchers L. , Geurtsen W. , Günay H. 
Published: February 2008

Clinical Relevance
When using self-etch adhesives to bond composite materials to enamel, there is concern about the ability to achieve bond strengths comparable to approved etch-and-rinse systems. An additional phosphoric acid etching can improve the shear bond strength of self-etch adhesives to enamel.
Effect of Cyclic Loading on the Bond Strength of Class II Restorations with Different Composite Materials
Authors: Cavalcanti A. N. , Mitsui F. H. O. , Silva F. , Peris A. R. , Bedran-Russo A. , Marchi G. M. 
Published: February 2008

Clinical Relevance
New resin composite technologies, such as nano-filled-based systems, have been developed. The assessment of such materials in a simulated laboratory chewing condition may assist with the selection of composites in a clinical situation.
Could late rebleeding overturn the superiority of cranial aneurysm coil embolization over clip ligation seen in the International Subarachnoid Aneurysm Trial?
Authors: Mitchell Patrick , Kerr Richard , Mendelow A. David , Molyneux Andy 
Published: February 2008

Object
The present purpose is to define the sensitivity of the superiority of coil embolization observed in the International Subarachnoid Aneurysm Trial (ISAT) according to the rate of late rebleeding over a reasonable range, and to find the range of rebleeding rates for which it may be overturned. In the ISAT, coil embolization appears to be safer than clip ligation at 1 year, and clip occlusion has better long-term efficacy at preventing rebleeding. This leaves open the question of which is better in the longer term.

Methods
The authors calculate the life expectancy of patients following a subarachnoid hemorrhage (SAH) and compare the life expectancy of those who underwent coil embolization with those who underwent clip ligation in the ISAT cohort.

Results
The 1-year poor outcome rate following treatment climbs rapidly with advancing age. A consequence is that the absolute difference between the poor outcome rates after coil embolization and clip occlusion is lower in those < 50 years of age (3.3%) than it is for those > 50 years of age (10.1%). This difference may be enough to give clip application the advantage in the < 40-year-old group despite the small size of the difference in 1-year rebleeding rates thus far observed (0.152%).

Conclusions
When treating ruptured cerebral aneurysms, the advantage of coil embolization over clip ligation cannot be assumed for patients < 40 years old. In this age range the difference in the safety of the 2 procedures is small, and the better long-term protection from SAH afforded by clip placement may give this treatment an advantage in life expectancy for patients < 40 years of age.
Intracranial aneurysms treated with Guglielmi detachable coils: long-term imaging follow-up with contrast-enhanced magnetic resonance angiography
Authors: Gauvrit Jean-Yves , Caron Sabine , Taschner Christian A. , Lejeune Jean-Paul , Pruvo Jean-Pierre , Leclerc Xavier 
Published: February 2008

Object
The aim of this study was to assess the long-term results of intracranial aneurysms treated with Guglielmi detachable coils (GDCs) with the aid of contrast-enhanced magnetic resonance (MR) angiography.

Methods
Between January 1998 and August 2001, 92 patients with 92 aneurysms treated by endovascular coiling with GDCs underwent contrast-enhanced MR angiography. These patients underwent long-term follow-up (range 32–78 months, mean 42.1 ± 11.9 months [standard deviation]) after endovascular treatment. All images were compared with digital subtraction angiograms and contrast-enhanced MR angiograms that had been obtained during the short-term follow-up (range 5–25 months, mean 13 ± 5.1 months after treatment). The MR angiograms were analyzed independently by 2 senior radiologists. Findings were assigned to 1 of 3 categories: complete obliteration (Class 1), residual neck (Class 2), or residual aneurysm (Class 3).

Results
Of 92 contrast-enhanced MR angiograms obtained at the long-term follow-up, complete obliteration of the aneurysm was noted in 57 patients (Class 1), a residual neck was seen in 22 (Class 2), and a residual aneurysm was observed in 13 (Class 3). One patient experienced aneurysm rehemorrhaging during the follow-up period. The comparison of short- and long-term follow-up angiograms demonstrated a change in aneurysm classification in 7 patients (7.6%), including 4 that progressed from Class 1 to Class 2 and 3 from Class 2 to Class 3. However, 4 (14.2%) of the 28 long-term recurrences were not detected on the short-term control images.

Conclusions
Long-term follow-up with contrast-enhanced MR angiography after selective embolization of intracranial aneurysms can identify late aneurysm recanalization that is undetected at short-term follow-up.
High-dose intraarterial verapamil in the treatment of cerebral vasospasm after aneurysmal subarachnoid hemorrhage
Authors: Keuskamp Janine , Murali Raj , Chao Kuo H. 
Published: February 2008

Object
Because oral calcium channel blockers appear to reduce the severity of cerebral vasospasm after aneurysmal subarachnoid hemorrhage (SAH), interest in their application intraarterially has emerged for cases in which noninvasive means of alleviating vasospasm are unsuccessful. Studies to date have been limited to the administration of low intraarterial doses because of concerns about hemodynamic stability and changes in intracranial pressure. These doses, although effective in cases of milder vasospasm, were inadequate in severe cases. The authors present a series of 10 patients with cerebral vasospasm who underwent 12 procedures in which they received ≥ 20 mg of intraarterial verapamil per procedure.

Methods
A retrospective review was undertaken of all patients who underwent endovascular treatment for cerebral vasospasm due to aneurysmal SAH by the senior author between February 2005 and October 2006. Ten patients were identified who had undergone a total of 12 procedures during which ≥20 mg of intraarterial verapamil had been administered. From angiography reports, anesthesia records, and nursing records, we obtained pre- and postverapamil mean arterial blood pressures (MABPs), heart rates, intracranial pressures (ICPs) (when available), and visible changes in the degree of vasospasm.

Results
No statistically significant changes in MABP, heart rate, or ICP were observed after administration of ≥ 20 mg of intraarterial verapamil, and the degree of improvement in vasospasm was statistically significant based on our grading system. No correlation was found between the change in hemodynamic parameters and the total dose of verapamil.

Conclusions
This study indicates that high-dose intraarterial verapamil may be used to treat cerebral vasospasm without compromising hemodynamic stability or increasing ICP.
Functional assessment of C-5 ventral rootlets by intraoperative electrical stimulation of the supraclavicular segment of the long thoracic nerve during brachial plexus surgery
Authors: Flores Leandro Pretto 
Published: February 2008

Object
Anatomical and functional assessment of the intradural segment of the spinal nerves is imperative in brachial plexus surgery, as the repair of postganglionic elements in the setting of a confirmed nerve root avulsion is of no benefit. None of the current techniques to detect these avulsions can provide full information that ensures the functional status of the preganglionic segment of the roots. The objective of this study was to evaluate intraoperative electrical stimulation of the supraclavicular segment of the long thoracic nerve (LTN) as a method to differentiate C-5 nerve root extraforaminal rupture from its intradural avulsion.

Methods
The author performed a prospective analysis of data obtained in 14 patients presenting with the loss of C-5 nerve root function secondary to traumatic brachial plexus injury. The patients were divided into 2 groups: 8 patients in whom the intradural segment of C-5 nerve root was preserved (5 cases of closed traction injuries in whom the computed tomography [CT] myelograms confirmed the integrity of C-5 root and 3 cases of open sharp injuries) and a control group of 6 patients in whom CT myelography demonstrated avulsion of the root.

Results
The results of the intraoperative electrical stimulation of the LTN and the surgical outcome of each patient were recorded. The LTN electrical stimulation elicited serratus anterior muscle contraction in cases in which C-5 root was not avulsed, and there were no responses in patients whose radiological evaluation had demonstrated nerve root avulsion. In those patients in whom LTN stimulation proved to be positive, the C-5 root was used as a graftable stump to the suprascapular nerve and/or to the posterior division of the superior trunk. In these cases, favorable results were observed regarding arm abduction in all cases—Medical Research Council Grades M3 (37%) and M4 (62%). In the control group, the C-5 root was not used as a donor stump and a multiple nerve transfer technique was adopted as the preferred surgical option.

Conclusions
Intraoperative electrical stimulation of the supraclavicular segment of the LTN is a useful complementary method to test the functional status of the C-5 ventral rootlets. If the test is positive (that is, a response is present) it is indicative of extraforaminal rupture of the root, and if negative, it is suggestive of its avulsion.