bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gender Differences in Life Stressors Associated with Child and Adolescent Suicides in Singapore from 1995 to 2003
Authors: Ang Rebecca P. , Chia B. H. , Fung Daniel S.S. 
Published: January 2007

Aims: This study explored gender differences in life stressors of children and adolescents who died by suicide. Three main classes of life stressors have been identified by previous research to be significant risk factors for suicide in children and adolescents: interpersonal/relationship problems, family problems, and academic/school problems. Methods: The sample consisted of 156 (89 males and 67 females) completed child and adolescent suicides in Singapore from 1995 to 2003. The age of these individuals ranged from 10 to 19 years with a mean age of 16.49 (SD = 2.59). Results: Significantly more females were found to have had interpersonal/relationship problems as recent life stressors compared with males. No gender differences were found for the other two life stressors, family problems and academic/school problems. In addition, among the three life stressors studied, only interpersonal/relationship problems emerged as a significant predictor of female child and adolescent suicide. Conclusions: Consistent with previous research literature, these findings contribute to a growing literature documenting the relatively larger impact of relational life stressors on child and adolescent female suicidality. Implications for suicide intervention and prevention, especially among young females, were discussed.
Nonredundant roles for Stat5a/b in directly regulating Foxp3
Authors: Yao Zhengju , Kanno Yuka , Kerenyi Marc , Stephens Geoffrey , Durant Lydia , Watford Wendy T. , Laurence Arian , Robinson Gertraud W. , Shevach Ethan M. , Moriggl Richard , Hennighausen Lothar , Wu Changyou , O'Shea John J. 
Published: January 2007

AbstractStats (signal transducers and activators of transcription) regulate multiple aspects of T-cell fate. T regulatory (Treg) cells are a critical subset that limits immune responses, but the relative importance of Stat5a/b versus Stat3 for Treg cell development has been contentious. We observed that peripheral CD25+CD4+ T cells were reduced in Stat5ΔN mice; however, the levels of Foxp3, a transcription factor that is critical for Treg cells, were normal in splenic CD4+ T cells even though they were reduced in the thymus. In contrast, complete deletion of Stat5a/b (Stat5−/−) resulted in dramatic reduction in CD25- or Foxp3-expressing CD4+ T cells. An intrinsic requirement was demonstrated by reduction of Stat5a/b in CD4-expressing cells and by stem cell transplantation using Stat5−/− fetal liver cells. Stat5a/b were also required for optimal induction of Foxp3 in vitro and bound directly to the Foxp3 gene. Reduction of Stat3 in T cells did not reduce the numbers of Treg cells in the thymus or spleen; however, Stat3 was required for IL-6–dependent down-regulation of Foxp3. Therefore, we conclude that Stat5a/b have an essential, nonredundant role in regulating Treg cells, and that Stat3 and Stat5a/b appear to have opposing roles in the regulation of Foxp3.
Overestimating resistance in field testing of malaria parasites: simple methods for estimating high EC50 values using a Bayesian approach
Authors: Stepniewska Kasia , Chotivanich Kesinee , Brockman Alan , Day Nicholas PJ , White Nicholas J 
Published: January 2007

AbstractConventional methods of assessing in-vitro antimalarial drug-concentration effect relationships in field testing of fresh isolates assess each parasite isolate individually. This leads to systematic overestimation of EC50values for the most resistant isolates, and thus overestimation of the degree of resistance. In antimalarial drug-susceptibility studies conducted on the north-western border of Thailand the overestimation of EC50for the most resistant isolate ranged from 15% for artesunate to 43% for mefloquine. If isolates cannot be stored for re-testing, more accurate estimations of the degree of resistance can be obtained using a Bayesian approach to data analysis which is described here.
Direct non-cell autonomous Pax6 activity regulates eye development in the zebrafish
Authors: Lesaffre Brigitte , Joliot Alain , Prochiantz Alain , Volovitch Michel 
Published: January 2007

Abstract
Background
Modifications in Pax6 homeogene expression produce strong eye phenotypes. This suggested to us that eye development might be an appropriate model to verify if homeoprotein intercellular passage has important functions in early development. Similar to other homeoproteins, Pax6 has two domains that enable secretion and internalization by live cells and, thus, intercellular passage. In principle, a straightforward way to test the hypothesis would be to mutate one of the two sequences to produce a 'cell autonomous only' Pax6. However, this was not possible because these sequences are in the homeodomain and their modification would affect Pax6 transcriptional properties. We have thus developed an approach aimed at blocking Pax6 only in the extracellular milieu of developing zebrafish embryos.

Results
A first strategy was to inject a one-cell embryo with a mRNA encoding a secreted single-chain anti-Pax6 antibody. A second, complementary, strategy was to inject a Pax6 antibody in the blastula extracellular milieu. In both cases, 'dissymmetric eyes', 'one eye only' and 'no eye' phenotypes were produced. In most cases, lens phenotypes paralleled retina malformations. Although eye phenotypes were analyzed 30 hours post-fertilization, there was a strong correlation between early eye field asymmetry, early asymmetry in Pax6 expression and later-occurring eye malformations. Several controls were introduced, demonstrating that the effect is specific to Pax6 and cannot be explained by intracellular antibody activities.

Conclusion
This study supports the hypothesis that the Pax6 transcription factor is also a signaling molecule with direct non-cell autonomous activity.
Protein Metabolism in Acromegaly: Differential Effects of Short- and Long-Term Treatment
Authors: Gibney James , Wolthers Troels , Burt Morton G. , Leung Kin-Chuen , Umpleby A. Margot , Ho Ken K. Y. 
Published: January 2007

Abstract
Context: GH acutely increases body protein by stimulating protein synthesis and reducing protein oxidation.
Objective: The objective of the study was to determine whether these changes in protein metabolism are sustained in long-term GH excess and reversed by correction.
Design: We conducted a cross-sectional study in 16 acromegalic and 18 normal subjects and a longitudinal study in which acromegalic subjects were studied before and after short-term (n = 8) or long-term (n = 10) treatment.
Setting: The study was conducted at a clinical research center.
Main Outcome Measures: Whole-body rates of leucine appearance (leucine Ra; an index of protein breakdown), leucine oxidation, and nonoxidative leucine disposal (NOLD; an index of protein synthesis) estimated using infusion of 1-[13C] leucine were measured.
Results: Leucine Ra and NOLD were greater (P &lt; 0.01) in acromegalic compared with normal subjects, whereas leucine oxidation did not differ. Leucine oxidation increased significantly (P &lt; 0.05) after short-term treatment but returned to baseline after long-term treatment. Both leucine Ra and NOLD decreased significantly (P &lt; 0.05) after short- and long-term treatment. Adjustment for body composition did not affect results.
Conclusions: In acromegalic subjects, protein breakdown and synthesis are increased, whereas protein oxidation does not differ from normal subjects. Protein oxidation increases transiently, whereas protein breakdown and synthesis are stably reduced after treatment. Because protein oxidation represents irreversible loss, we conclude that the normal state of protein oxidation found in acromegaly and after long-term treatment represents metabolic adaptation, which maintains protein mass at a steady state after stable changes in GH status.
Malignant Paragangliomas Associated with Mutations in the Succinate Dehydrogenase D Gene
Authors: Havekes B. , Corssmit E. P. M. , Jansen J. C. , van der Mey A. G. L. , Vriends A. H. J. T. , Romijn J. A. 
Published: January 2007

Abstract
Introduction: Malignant paragangliomas have been well described in carriers of mutations of the succinate dehydrogenase B (SDHB) gene, but have rarely been associated with mutations in the succinate dehydrogenase D (SDHD) gene.
Aim: The aim of the study was to report the different clinical expression patterns of malignant paragangliomas in five patients with SDHD (D92Y) mutations observed in approximately 200 SDHD (D92Y) mutation carriers followed in our institution.
Results: Metastasis and/or local tumor invasion was documented 0 (n = 2), 1, 18, and 30 yr after the initial diagnosis of paraganglioma. Malignancy was proven by paraganglioma bone metastases (n = 2), intrathoracic paraganglioma with lymph node metastases, locally invasive head-and-neck paraganglioma with destruction of the petrosal bone, and locally invasive paraganglioma of the bladder with lymph node metastases. Four of the five patients developed catecholamine excess during follow-up due to intraadrenal paraganglioma (pheochromocytoma) (n = 1), extra adrenal paraganglioma (n = 2), and presumed subclinical disease (n = 1).
Conclusion: SDHD mutations (D92Y) are associated with malignant paragangliomas and catecholamine excess with remarkable interindividual variations despite the same mutation. We estimate that the prevalence of malignancy in carriers of D92Y mutations is at least 2.5%.
Update on the Epidemiology of Paget's Disease of Bone
Authors: Cooper Cyrus , Harvey Nicholas C , Dennison Elaine M , van Staa Tjeerd P 
Published: January 2007

Abstract
Paget's disease of bone (PDB) is characterized by rapid bone remodeling and the formation of bone that is structurally abnormal. Recent studies have confirmed that both genetic and environmental factors are important in its etiology. Epidemiological studies in Europe and North America have revealed that PDB shows an increasing frequency of occurrence with age and is more prevalent among men than women. There is marked geographic variation in the prevalence of PDB throughout western nations, with the highest rates reported during the 1970s in Britain. Recent studies of the secular trends in PDB suggest declining rates in both prevalence and severity at diagnosis. Thus, the overall age/sex standardized prevalence rate in Britain during the period 1993–1995 was found to be 2.5% among men and 1.6% among women ≥55 years of age. Prevalence rates had fallen by ∼50% in several of the centers studied, suggesting an environmental contribution to the etiology of this disorder. Similar findings have been reported from other European countries and New Zealand. Recent study of the incidence and clinical manifestations of PDB have emerged from large cohort studies in primary care record linkage resources, such as the General Practice Research Database. Over the period 1988–1999, the incidence rate of clinically diagnosed PDB was found to be 5 per 10,000 person-years among men and 3 per 10,000 person-years among women 75 years of age. The disorder was associated with an increased risk of back pain (RR, 2.1; 95% CI, 1.9–2.3); osteoarthritis (RR, 1.7; 95% CI, 1.5–1.9); and fracture (RR, 1.2; 95% CI, 1.0–1.5). Using life table methodology, the estimated proportion of patients dying within 5 years of follow-up was 32.7% among the cohort with PDB compared with 28.0% among control patients (p &lt; 0.05).
Osteosarcoma in Paget's Disease of Bone
Authors: Hansen Marc F , Seton Margaret , Merchant Anand 
Published: January 2007

Abstract
Paget's disease of bone (PDB) is a focal disorder of bone metabolism first described by Sir James Paget in 1876. It is presumed benign in nature and mediated by abnormal osteoclast function. The incidence of osteosarcomas complicating PDB is estimated at &lt;1%. These cancers occur mostly in persons with long-standing, polyostotic disease and affect patients in their seventh decade or when osteosarcoma is remarkably rare in the general population. Epidemiological studies suggest that this late peak of osteosarcomas is absent in regions where Paget's is infrequently reported. Whereas PDB has a predilection for the axial skeleton, skull, femurs, and tibias, pagetic osteosarcoma tend to spare the spine, and are reported more commonly in the pelvis, femur, humerus, and skull. A molecular basis for the association of osteosarcoma with Paget's disease is unclear. These osteosarcomas are osteogenic in origin, consistently arise in sites of pagetic bone, and may present as metachronous, multifocal lesions. On histopathology, the lesions are usually osteoblastic, and the tumor phenotype is sometimes characterized as an exaggerated, chaotic form of the accelerated bone remodeling that characterizes PDB. New insights from the biology of adolescent osteosarcomas, VCP and SQSTM1 mutations now defined in patients with Paget's disease, and emerging evidence that stromal lesions are present in patients with Paget's disease are changing the way we think about the pathogenesis of PDB and the rare complication of pagetic osteosarcomas.
Nonmalignant Complications of Paget's Disease
Authors: Bone Henry G 
Published: January 2007

Abstract
Paget's disease of bone is a focal or multifocal disorder characterized by intense disorderly remodeling activity at sites of involvement, producing dramatic alterations of local bone architecture. These functional and structural alterations, interacting with the specific characteristics of the site of involvement, account for most of the complications of the disease. This presentation will focus on selected nonneoplastic complications of particular current interest.
Medical Management of Paget's Disease of Bone: Indications for Treatment and Review of Current Therapies
Authors: Siris Ethel S , Lyles Kenneth W , Singer Frederick R , Meunier Pierce J 
Published: January 2007

Abstract
Treatment with a potent bisphosphonate is indicated in patients with Paget's disease who have symptoms likely to respond to reduced bone turnover at pagetic sites. In asymptomatic patients with active disease at sites susceptible to local progression and late complications, treatment is also recommended. Biochemical remission is achievable in a majority of patients with pamidronate, alendronate, risedronate, or zoledronic acid. Indications for medical treatment of active Paget's disease of bone include symptoms referable to sites of the disease such as bone pain, joint pain, and neurological complications; elective surgery at an active pagetic site to reduce intraoperative blood loss from highly vascular bone; management of rare instances of immobilization hypercalcemia with polyostotic disease; and presence of disease activity in asymptomatic patients at sites at risk for future complications to limit progression and possibly lower that risk. The treatment of choice is a potent nitrogen-containing bisphosphonate, including oral alendronate or risedronate or intravenous pamidronate or zoledronic acid. Etidronate and tiludronate are less potent and are second-line choices. Recent data with zoledronic acid indicate that a single infusion of 5 mg is associated with normalization of serum alkaline phosphatase in 89% of patients and a prolonged biochemical remission, making it the most effective therapy available to date. Side effect profiles with alendronate and risedronate include esophageal irritation in a minority of patients. Intravenous pamidronate and zoledronic acid may induce an acute phase reaction with fever and flu-like symptoms with the first dose, primarily in patients who are treatment naïve to nitrogen-containing bisphosphonates. Calcium and vitamin D repletion are mandatory with these potent anti-osteoclast therapies to avoid hypocalcemia. Acquired resistance to etidronate and pamidronate has been reported in some patients, leading to lesser reductions in bone turnover and shorter periods of remission, but substitution with a different bisphosphonate provides a more robust response. It is not known whether resistance to other bisphosphonates in Paget's disease occurs.
Gsα Mutations in Fibrous Dysplasia and McCune-Albright Syndrome
Authors: Weinstein Lee S 
Published: January 2007

Abstract
Fibrous dysplasia (FD) is a focal bone lesion composed of immature mesenchymal osteoblastic precursor cells. Some FD patients also have hyperpigmented skin lesions (café-au-lait spots), gonadotropin-independent sexual precocity, and/or other endocrine and nonendocrine manifestations (McCune-Albright syndrome [MAS]). MAS results from somatic mutations occurring during early development, resulting in a widespread mosaic of normal and mutant-bearing cells, which predicts that the clinical presentation of each patient is determined by the extent and distribution of abnormal cells. These mutations encode constitutively active forms of Gsα, the ubiquitously expressed G protein α-subunit that couples hormone receptors to intracellular cAMP generation. These mutations lead to substitution of amino acid residues that are critical for the intrinsic GTPase activity that is normally required to deactivate the G protein. This leads to prolonged activation of Gsα and its downstream effectors even with minimal receptor activation. This explains why MAS patients have stimulation of multiple peripheral endocrine glands in the absence of circulating stimulatory pituitary hormones and increased skin pigment, which is normally induced by melanocyte-stimulating hormone through Gsα/cAMP. Similar mutations are also present in 40% of pituitary tumors in acromegaly patients and less commonly in other endocrine tumors. FD results from increased cAMP in bone marrow stromal cells, leading to increased proliferation and abnormal differentiation. Parental origin of the mutated allele may also affect the clinical presentation, because Gsα is imprinted and expressed only from the maternal allele in some tissues (e.g., pituitary somatotrophs).
Breast Cancer–Associated Gene 3 (BCA3) Is a Novel Rac1-Interacting Protein
Authors: Yu Kuan-ping , Itokawa Takashi , Zhu Mei-ling , Syam Sujata , Seth Arun , Insogna Karl 
Published: January 2007

Abstract
BCA3 was identified in a yeast two-hybrid screen as a novel Rac1-interacting partner in osteoclasts. BCA3 binds directly to Rac and, in vivo, binds GTP-Rac but not GDP-Rac. Perinuclear co-localization of BCA3 and Rac1 is observed in CSF-1–treated osteoclasts. Overexpression of BCA3 attenuates CSF-1–induced cell spreading. We conclude that BCA3 regulates CSF-1–dependent Rac activation.
Introduction: Rac1, a ubiquitously expressed GTPase, is a mediator of colony-stimulating factor 1 (CSF-1)–dependent actin remodeling in osteoclasts. Because the role of Rac in osteoclasts has not been fully defined, we undertook a yeast two-hybrid screen to identify Rac-interacting partners in these cells.
Materials and Methods: A yeast two-hybrid screen was undertaken using a cDNA library prepared from osteoclast-like cells as prey and either native Rac1 or constitutively active Rac1 (Q61L) as bait. Radiolabeled breast cancer–associated gene 3 (BCA3) protein constructs were generated in vitro using rabbit reticulate lysates and used in vitro binding assays with Rac1. In vivo binding was assessed using myc-tagged Rac1(Q61L) and HA-tagged BCA3. PBD pull-down assays were used to determine if GTP-loaded Rac1 preferentially bound BCA3. Co-localization of Rac1 and BCA3 in osteoclasts was assessed using confocal immunofluorescence. The functional significance of the BCA3–Rac1 interaction was assessed by examining the effect of overexpressing BCA3 in RAW 264.7 cells on the subsequent spreading response to CSF-1.
Results: One of three positive clones from the wildtype Rac1 screen and all three positive clones from the Rac1(Q61L) screen encoded the same protein, BCA3. BCA3 expression in osteoclasts was confirmed by RT-PCR and immunocytochemistry. BCA3 bound directly to Rac1 in vitro. Deletional analysis indicated that amino acids 76–125 in BCA3 are important for its ability to bind Rac. In vivo association of the two proteins was shown by co-immunoprecipitation of BCA3 and Rac1. Only GTP-bound-Rac but not GDP-bound Rac could interact with BCA3 in vivo. Confocal immunocytochemistry showed perinuclear co-localization of BCA3 and Rac1 in CSF-1–treated neonatal rat osteoclasts but not in resting osteoclasts. Overexpression of BCA3 markedly attenuated the spreading response to CSF-1 in RAW 264.7 cells.
Conclusions: These data establish that BCA3 is a novel Rac1-interacting protein and suggest that it may influence the ability of Rac1 to remodel the actin cytoskeleton.
Management of Recurrent Testicular Germ Cell Tumors
Authors: Sonpavde Guru , Hutson Thomas E. , Roth Bruce J. 
Published: January 2007

Learning Objectives
After completing this course, the reader will be able to: Discuss the different salvage conventional and high-dose chemotherapy regimens for germ cell tumors.List the prognostic factors for recurrent germ cell tumors.Explain the role of surgical salvage therapy for recurrent germ cell tumors.
CME Access and take the CME test online and receive 1 AMA PRA Category 1 Credit™ at CME.TheOncologist.com
Health and Economic Value of Eliminating Socioeconomic Disparities in US Youth Physical Activity
Authors: Powell-Wiley Tiffany M. , Martinez Marie F. , Heneghan Jessie , Weatherwax Colleen , Osei Baah Foster , Velmurugan Kavya , Chin Kevin L. , Ayers Colby , Cintron Manuel A. , Ortiz-Whittingham Lola R. , Sandler Dana , Sharda Sonal , Whitley Meredith , Bartsch Sarah M. , O’Shea Kelly J. , Tsintsifas Alexandra , Dibbs Alexis , Scannell Sheryl A. , Lee Bruce Y. 
Published: March 2024

ImportanceThere are considerable socioeconomic status (SES) disparities in youth physical activity (PA) levels. For example, studies show that lower-SES youth are less active, have lower participation in organized sports and physical education classes, and have more limited access to PA equipment.ObjectiveTo determine the potential public health and economic effects of eliminating disparities in PA levels among US youth SES groups.Design and SettingAn agent-based model representing all 6- to 17-year-old children in the US was used to simulate the epidemiological, clinical, and economic effects of disparities in PA levels among different SES groups and the effect of reducing these disparities.Main Outcomes and MeasuresAnthropometric measures (eg, body mass index) and the presence and severity of risk factors associated with weight (stroke, coronary heart disease, type 2 diabetes, or cancer), as well as direct and indirect cost savings.ResultsThis model, representing all 50 million US children and adolescents 6 to 17 years old, found that if the US eliminates the disparity in youth PA levels across SES groups, absolute overweight and obesity prevalence would decrease by 0.826% (95% CI, 0.821%-0.832%), resulting in approximately 383 000 (95% CI, 368 000-399 000) fewer cases of overweight and obesity and 101 000 (95% CI, 98 000-105 000) fewer cases of weight-related diseases (stroke and coronary heart disease events, type 2 diabetes, or cancer). This would result in more than $15.60 (95% CI, $15.01-$16.10) billion in cost savings over the youth cohort’s lifetime. There are meaningful benefits even when reducing the disparity by just 25%, which would result in $1.85 (95% CI, $1.70-$2.00) billion in direct medical costs averted and $2.48 (95% CI, $2.04-$2.92) billion in productivity losses averted. For every 1% in disparity reduction, total productivity losses would decrease by about $83.8 million, and total direct medical costs would decrease by about $68.7 million.Conclusions and RelevanceThis study quantified the potential savings from eliminating or reducing PA disparities, which can help policymakers, health care systems, schools, funders, sports organizations, and other businesses better prioritize investments toward addressing these disparities.