bluuebunny/crossref_metadata_2025_split huggingface dataset:
Principles underlying chromatophore addition during maturation in the European cuttlefish, Sepia officinalis
Authors: Yacob Jarred , Lewis Alexandra Cosima , Gosling Allyson , Hilaire Debra H. J. St , Tesar Lindsay , McRae Michelle , Tublitz Nathan J. 
Published: September 2011

SUMMARY
The goal of this work was to identify some of the principles underlying chromatophore growth and development in the European cuttlefish, Sepia officinalis. One set of experiments used a regeneration model to follow the re-growth of black chromatophores for 30 days following excision of a small piece of fin tissue. A separate set of experiments tracked and analyzed the addition of new fin chromatophores during a month of normal, undisturbed growth. We also followed the development of individual chromatophores from their initial appearance to full maturation to determine whether their color type was fixed. Based on the results of these studies, we propose five guiding principles for chromatophore growth and maturation. (1) The three chromatophore cell types – black, reddish-brown and yellow – are present at different spatial frequencies in the cuttlefish fin. (2) During normal growth, new chromatophores are inserted at a higher spatial frequency than existing (control) chromatophores of the same color type. (3) In regenerating tissue, new black chromatophores are initially added at low spatial frequencies. As regeneration continues, new black chromatophores appear at increasing spatial frequencies until they are inserted at a spatial frequency higher than that observed in control tissue, similar to the way in which chromatophores were observed to be added in normally growing tissue. (4) All chromatophores first appear as pale orange cells and slowly darken into their respective color types without passing through intermediate color stages. (5) New black chromatophores undergo a doubling in size as they mature, while reddish-brown and yellow chromatophores do not grow at all after they are inserted in the dermis.
Pleated turtle escapes the box – shape changes in Dermochelys coriacea
Authors: Davenport John , Plot Virginie , Georges Jean-Yves , Doyle Thomas K. , James Michael C. 
Published: September 2011

SUMMARY
Typical chelonians have a rigid carapace and plastron that form a box-like structure that constrains several aspects of their physiology and ecology. The leatherback sea turtle, Dermochelys coriacea, has a flexible bony carapace strengthened by seven longitudinal ridges, whereas the plastron is reduced to an elliptical outer bony structure, so that the ventrum has no bony support. Measurements of the shell were made on adult female leatherbacks studied on the feeding grounds of waters off Nova Scotia (NS) and on breeding beaches of French Guiana (FG) to examine whether foraging and/or breeding turtles alter carapace size and/or shape. NS turtles exhibited greater mass and girth for a given curved carapace length (CCL) than FG turtles. Girth:CCL ratios rose during the feeding season, indicating increased girth. Measurements were made of the direct (straight) and surface (curved) distances between the medial longitudinal ridge and first right-hand longitudinal ridge (at 50% CCL). In NS turtles, the ratio of straight to curved inter-ridge distances was significantly higher than in FG turtles, indicating distension of the upper surfaces of the NS turtles between the ridges. FG females laid 11 clutches in the breeding season; although CCL and curved carapace width remained stable, girth declined between each nesting episode, indicating loss of mass. Straight to curved inter-ridge distance ratios did not change significantly during the breeding season, indicating loss of dorsal blubber before the onset of breeding. The results demonstrate substantial alterations in size and shape of female D. coriacea over periods of weeks to months in response to alterations in nutritional and reproductive status.
Silicon-mediated Direct Conversion of Acyl Chlorides to Carbamoyl Azides or/and Tetrazolinones under Mild Conditions
Authors: Salama Tarek A , Elmorsy Saad S , Khalil Abdel-Galil M , Ismail Mohamed A 
Published: September 2011

Abstract
A simple and mild one-pot procedure for the synthesis of carbamoyl azides from acyl chlorides utilizing a combination of tetrachlorosilane and sodium azide in acetonitrile at ambient temperature is reported. Under gentle heating, 1-aryltetrazolin-5-ones were also obtained in one-pot process presumably via a [3 + 2] cycloaddition step.
Sunitinib-Induced Hyperammonemic Encephalopathy in Gastrointestinal Stromal Tumors
Authors: Lee Na-Ri , Yhim Ho-Young , Yim Chang-Yeol , Kwak Jae-Yong , Song Eun-Kee 
Published: September 2011

Objective: To report 2 cases of hyperammonemic encephalopathy induced by sunitinib in patients with metastatic gastrointestinal stromal tumor (GIST). Case Summary: A 58-year-old man with imatinib-resistant metastatic GIST presented to the emergency department with confusion that developed 17 days after the initiation of sunitinib 50 mg/day. His serum ammonia level was markedly elevated (210 μg/dL). Sunitinib was discontinued, and an enema with lactulose was administered every hour. His neurologic status normalized within 24 hours and his serum ammonia level decreased to 64 μg/dL A 68-year-old woman with imatinib-resistant metastatic GIST was admitted into the emergency department with confusion and irritability that developed 10 days after the start of sunitinib therapy. Her serum ammonia level was markedly elevated (389 μg/dL). Sunitinib was discontinued, and an enema with lactulose was administered every hour. Within 24 hours, her mental status was improved and her serum ammonia level was decreased to 116 μg/dL. Sunitinib was reintroduced, and the same symptoms occurred after day 7 of administration. Sunitinib was not prescribed afterward and the woman did not experience any further encephalopathy symptoms. Discussion: Sunitinib is a small molecule that inhibits multiple receptor tyrosine kinases such as stem cell factor receptor, vascular endothelial growth factor, and platelet-derived growth factor. It is used as second-line therapy for patients with imatinib-resistant GIST. Hyperammonemic encephalopathy is an uncommon fatal complication of chemotherapy. According to the Naranjo probability scale, sunitinib was a probable cause of hyperammonemic encephalopathy in the patients described here. Although the mechanism of hyperammonemia is unclear, hyperammonemic encephalopathy might be caused by a vascular disorder related to the antiangiogenic properties of sunitinib, and it has ethnic differences associated with genetic polymorphisms. Conclusions: Sunitinib may Induce hyperammonemic encephalopathy in some patients. Although further studies are warranted, clinicians should be aware of this severe adverse event when using sunitinib for treatment of GIST.
Molecular Alterations during Progression of Prostate Cancer to Androgen Independence
Authors: Saraon Punit , Jarvi Keith , Diamandis Eleftherios P 
Published: September 2011

BACKGROUND
Prostate cancer is the most commonly diagnosed cancer among men in North America and is a leading cause of death. Standard treatments include androgen deprivation therapy, which leads to improved clinical outcomes. However, over time, most tumors become androgen independent and no longer respond to hormonal therapies. Several mechanisms have been implicated in the progression of prostate cancer to androgen independence.

CONTENT
Most tumors that have become androgen independent still rely on androgen receptor (AR) signaling. Mechanisms that enhance AR signaling in androgen-depleted conditions include: AR gene amplification, AR mutations, changes in the balance of AR cofactors, increases in steroidogenic precursors, and activation via “outlaw” pathways. Along with AR signaling, various other AR-independent “bypass” pathways have been shown to operate aberrantly during androgen independence. Changes in the epigenetic signatures and microRNA concentrations have also been implicated in the development of androgen-independent prostate cancer.

SUMMARY
Understanding of the molecular mechanisms that lead to the development of androgen-independent prostate cancer will allow for improved therapeutic strategies that target key pathways and molecules that are essential for these cells to survive.
Serum sex steroids measured in middle-aged European and African–Caribbean men by gas chromatography–mass spectrometry
Authors: Giton Frank , Fiet Jean , Cornu Jean-Nicolas , Cussenot Olivier , Bélanger Alain , Urien Saîk , Oliva Alejandro , Blanchet Pascal , Multigner Luc 
Published: September 2011

BackgroundDifferences in circulating steroid hormone levels have been hypothesized to explain ethnic differences in steroid-related diseases. The aim of this study was to determine the serum levels of a wide panel of steroid hormones, both androgens and estrogens, in healthy middle-aged African–Caribbean and European men.Design and methodsSerum steroid hormone levels were determined in men participating in a systematic public health study funded by the French National Health Insurance system. Blood was collected in the morning from 304 healthy African–Caribbean and European men aged between 40 and 69 years. Serum steroids were measured by mass spectrometry–gas chromatography, except for DHEAS and sex hormone-binding globulin, which were determined by RIA. Data were analyzed in 10-year age intervals by analysis of covariance, with adjustment for age, body mass index, waist-to-hip ratio, tobacco and alcohol consumption, and season of sampling.ResultsCompared with Europeans, African–Caribbean men presented significantly higher serum levels of measured bioavailable testosterone, 4-androstenedione (4-dione), and estrone (E1) regardless of the age group, of 5-androstenediol (5-diol) in those aged 40–49 and 50–59 years, and of testosterone (TT) and dihydrotestosterone in those aged 40–49 years. In contrast, European men aged 40–69 years showed significantly higher serum levels of DHEA and DHEAS.ConclusionsSignificant differences in serum steroid hormone levels were observed in middle-aged African–Caribbean and European men. Whether such differences could contribute to ethnic differences in disease risk in adult men remains to be investigated. Some steroids, such as bioavailable TT, 4-dione, 5-diol, and E1, deserve particular attention.
Occupational Violence at Lebanese Emergency Departments: Prevalence, Characteristics and Associated Factors
Authors: Alameddine Mohamad , Kazzi Amin , El‐Jardali Fadi , Dimassi Hani , Maalouf Salwa 
Published: September 2011

Occupational Violence at Lebanese Emergency Departments: Prevalence, Characteristics and Associated Factors: Mohamad Alameddine, et al. Health Management and Policy, Faculty of Health Sciences, American University of Beirut, Lebanon—BackgroundEmergency departments (EDs) workers are at increased risk of exposure to occupational violence. The prevalence of occupational violence is potentially higher and consequences are more serious in areas with poor security conditions.ObjectivesWe investigated the prevalence, characteristics and factors associated with the exposure of ED workers to violence at Lebanese hospitals.MethodsAll ED employees at six tertiary hospitals in Lebanon were surveyed using a cross‐sectional design. The survey instrument included four sections collecting demographic/professional information and measuring exposure to violence, degree of job satisfaction and degree of professional burnout. The questionnaire was distributed to all ED employees at participating hospitals and was completed by 256 ED workers (70.3% response rate). Multinomial and binary logistic regressions were used to investigate factors significantly associated with verbal and physical violence.ResultsOver the past 12 mo, four in ive ED employees were verbally abused and one in four was physically assaulted. Exposure to verbal abuse was associated with serious outcomes including significantly higher levels of occupational burnout and an increased likelihood to quit current job. Exposure to physical violence was associated with increased likelihood‐to‐quit, nurse status and “public hospital” employment.ConclusionViolence largely prevails at Lebanese EDs. Most vulnerable are nurses and employees of public hospitals who are disproportionally exposed to violence. ED stakeholders must work collaboratively to investigate the root causes of violence and devise and implement effective antiviolence policies and measures. Such measures will be necessary to protect the well‐being and decrease the turnover of ED workers.
Mapping Geographic Areas of High and Low Drug Adherence in Patients Prescribed Continuing Treatment for Acute Coronary Syndrome After Discharge
Authors: Hoang Cuong , Kolenic Giselle , Kline‐Rogers Eva , Eagle Kim A. , Erickson Steven R. 
Published: September 2011

Study Objective. To determine the feasibility of using geographic information system (GIS) technology to identify geographic areas of high and low adherence to cardiovascular drug therapy for treatment of acute coronary syndrome (ACS) in patients discharged from a university‐affiliated hospital.Design. Retrospective analysis.Data Source. A registry of patients admitted to and discharged from a large university‐affiliated medical center for the treatment of ACS.Patients. A total of 1081 adults distributed over 300 census tracts who were discharged between April 1999 and December 2004 with a diagnosis of an ACS event of unstable angina or acute myocardial infarction.Measurements and Main Results. Data were collected on patient demographics, home addresses, and adherence to four classes of drugs—statins, angiotensin‐converting enzyme inhibitors, β‐blockers, and aspirin—at 6–12 months after discharge for the ACS index event. A GIS program was used to map patient addresses and adherence data to geographic coordinates. Hot Spot Analysis was used to determine the existence of any spatial clustering patterns in adherence rates. The analysis was performed at the census tract level by using the percentage of nonadherent patients within a census tract to represent adherence for the people living within that tract, standardized by the number of residents in a census tract aged 40 years or older. Hot Spot Analysis identified unique geographic areas of high, neutral, and low adherence in the southeast area. Highly adherent census tracts were primarily located in and around the city where the university hospital and clinics are located. Areas of low adherence were located to the west, southwest, and southeast of the city. All other census tracts were considered neutral in adherence rates.Conclusion. Mapping geographic areas of drug adherence is feasible with use of GIS technology, with spatial mapping able to detect areas of varying levels of adherence. Future research should examine local‐level factors associated with low adherence, which can be used to derive tailored, locally relevant interventions to improve long‐term drug adherence.
Steady‐State Pharmacokinetics of Intravenous Levetiracetam in Neurocritical Care Patients
Authors: Spencer Dustin D. , Jacobi Judith , Juenke JoEtta M. , Fleck James D. , Kays Michael B. 
Published: September 2011

Study Objectives. To characterize the steady‐state pharmacokinetics of intravenous levetiracetam in neurocritical care patients requiring seizure prophylaxis after a neurologic injury and to determine which dosing regimens achieve serum concentrations within the recommended therapeutic range of 6–20 μg/ml.Design. Prospective, open‐label, steady‐state pharmacokinetic study.Setting. Neurocritical care unit in a tertiary care medical center.Patients. Twelve adults (five men, seven women) admitted to the neurocritical care unit who required prophylactic anticonvulsant therapy after subarachnoid hemorrhage, subdural hematoma, or traumatic brain injury.Intervention. Patients received an intravenous infusion of levetiracetam 500 mg over 15 minutes every 12 hours.Measurements and Main Results. Serial blood samples were collected from all patients after a minimum of four doses of therapy. Serum levetiracetam concentrations were determined by ultraperformance liquid chromatography with tandem mass spectrometry detection, and pharmacokinetic data were analyzed by compartmental and noncompartmental methods. Monte Carlo simulations were performed for multiple levetiracetam dosing regimens to determine the probability of achieving a target trough concentration of 6 μg/ml or greater, 20 μg/ml or greater, and 6–20 μg/ml. The mean ± SD levetiracetam maximum serum concentration was 28.0 ± 8.0 μg/ml, minimum serum concentration 3.1 ± 1.8 μg/ml, half‐life 5.2 ± 1.2 hours, systemic clearance 5.6 ± 1.8 L/hour, and volume of distribution at steady state 36.8 ± 6.3 L. Increasing the doses of levetiracetam increased the probability of achieving a target trough concentration of 6 μg/ml or greater but also increased the probability of achieving trough concentrations greater than 20 μg/ml. Levetiracetam doses of 1000 mg every 8 hours and 1500–2000 mg every 12 hours provided the highest probability of achieving a target trough concentration between 6 and 20 μg/ml.Conclusion. Compared with previously published results in healthy volunteers and adults in status epilepticus, levetiracetam systemic clearance was faster and the terminal elimination half‐life was shorter in neurocritical care patients. Higher doses or more frequent dosing may be needed to achieve target trough concentrations of 6–20 μg/ml.
Specific Control of Pancreatic Endocrine β- and δ-Cell Mass by Class IIa Histone Deacetylases HDAC4, HDAC5, and HDAC9
Authors: Lenoir Olivia , Flosseau Kathleen , Ma Feng Xia , Blondeau Bertrand , Mai Antonello , Bassel-Duby Rhonda , Ravassard Philippe , Olson Eric N. , Haumaitre Cécile , Scharfmann Raphaël 
Published: September 2011

OBJECTIVEClass IIa histone deacetylases (HDACs) belong to a large family of enzymes involved in protein deacetylation and play a role in regulating gene expression and cell differentiation. Previously, we showed that HDAC inhibitors modify the timing and determination of pancreatic cell fate. The aim of this study was to determine the role of class IIa HDACs in pancreas development.RESEARCH DESIGN AND METHODSWe took a genetic approach and analyzed the pancreatic phenotype of mice lacking HDAC4, -5, and -9. We also developed a novel method of lentiviral infection of pancreatic explants and performed gain-of-function experiments.RESULTSWe show that class IIa HDAC4, -5, and -9 have an unexpected restricted expression in the endocrine β- and δ-cells of the pancreas. Analyses of the pancreas of class IIa HDAC mutant mice revealed an increased pool of insulin-producing β-cells in Hdac5−/− and Hdac9−/− mice and an increased pool of somatostatin-producing δ-cells in Hdac4−/− and Hdac5−/− mice. Conversely, HDAC4 and HDAC5 overexpression showed a decreased pool of insulin-producing β-cells and somatostatin-producing δ-cells. Finally, treatment of pancreatic explants with the selective class IIa HDAC inhibitor MC1568 enhances expression of Pax4, a key factor required for proper β-and δ-cell differentiation and amplifies endocrine β- and δ-cells.CONCLUSIONSWe conclude that HDAC4, -5, and -9 are key regulators to control the pancreatic β/δ-cell lineage. These results highlight the epigenetic mechanisms underlying the regulation of endocrine cell development and suggest new strategies for β-cell differentiation-based therapies.
Evaluation of Nonfasting Tests to Screen for Childhood and Adolescent Dysglycemia
Authors: Lee Joyce M. , Gebremariam Achamyeleh , Wu En-Ling , LaRose Jennifer , Gurney James G. 
Published: September 2011

OBJECTIVE
To assess performance of nonfasting tests to screen children for dysglycemia (prediabetes or diabetes).

RESEARCH DESIGN AND METHODS
This was a cross-sectional study of 254 overweight or obese (BMI ≥85th percentile) children aged 10–17 years. Subjects came for two visits to a clinical research unit. For visit one, they arrived fasting and a 2-h glucose tolerance test and HbA1c and fructosamine testing were performed. For visit two, they arrived nonfasting and had a random plasma glucose, a 1-h 50-g nonfasting glucose challenge test (1-h GCT), and urine dipstick performed. The primary end point was dysglycemia (fasting plasma glucose ≥100 mg/dL or a 2-h postglucose ≥140 mg/dL). Test performance was assessed using receiver operating characteristic (ROC) curves and calculations of area under the ROC curve.

RESULTS
Approximately one-half of children were female, 59% were white, and 30% were black. There were 99 (39%) cases of prediabetes and 3 (1.2%) cases of diabetes. Urine dipstick, HbA1c (area under the curve [AUC] 0.54 [95% CI 0.47–0.61]), and fructosamine (AUC 0.55 [0.47–0.63]) displayed poor discrimination for identifying children with dysglycemia. Both random glucose (AUC 0.66 [0.60–0.73]) and 1-h GCT (AUC 0.68 [0.61–0.74]) had better levels of test discrimination than HbA1c or fructosamine.

CONCLUSIONS
HbA1c had poor discrimination, which could lead to missed cases of dysglycemia in children. Random glucose or 1-h GCT may potentially be incorporated into clinical practice as initial screening tests for prediabetes or diabetes and for determining which children should undergo further definitive testing.
Elevated Liver Function Enzymes Are Related to the Development of Prediabetes and Type 2 Diabetes in Younger Adults
Authors: Nguyen Quoc Manh , Srinivasan Sathanur R. , Xu Ji-Hua , Chen Wei , Hassig Susan , Rice Janet , Berenson Gerald S. 
Published: September 2011

OBJECTIVE
Elevations in alanine aminotransferase (ALT) and γ-glutamyl transferase (GGT), surrogate markers of liver dysfunction and nonalcoholic fatty liver, are considered as part of metabolic syndrome and related type 2 diabetes. However, information is limited regarding the long-term predictability of ALT and GGT in the development of prediabetes and type 2 diabetes.

RESEARCH DESIGN AND METHODS
In this retrospective cohort study, normoglycemic (n = 874), prediabetic (n = 101), and diabetic (n = 80) adults aged 26–50 years (average age 41.3 years) were followed over an average period of 16 years since their young adulthood (aged 18–38 years, average age 25.1 years), with measurements of cardiometabolic risk factor variables including ALT and GGT.

RESULTS
The follow-up prevalence rate of adult diabetes status by quartiles of baseline ALT and GGT levels showed an adverse trend for both prediabetes (P &lt; 0.05) and diabetes (P &lt; 0.01). In a longitudinal multivariate logistic regression analysis that included anthropometric, hemodynamic, and metabolic variables, as well as alcohol consumption and smoking, individuals with elevated baseline ALT and GGT levels (per 1-SD increment) were 1.16 and 1.20 times, respectively, more likely to develop diabetes (P = 0.05 for ALT and P &lt; 0.01 for GGT); no such associations were noted for prediabetes. Regarding the predictive value of ALT and GGT, the area under the receiver operating curve analysis yielded C values ranging from 0.70 to 0.82, with values significantly higher for diabetes compared with prediabetes.

CONCLUSIONS
These findings in younger adults suggest potential clinical utility of including ALT and GGT as biomarkers in diabetes risk assessment formulations.