bluuebunny/crossref_metadata_2025_split huggingface dataset:
Familial secondary erythrocytosis due to increased oxygen affinity is caused by destabilization of the T state of hemoglobin Brigham (α2β2Pro100Leu)
Authors: Mollan Todd L. , Abraham Bindu , Strader Michael Brad , Jia Yiping , Lozier Jay N. , Olson John S. , Alayash Abdu I. 
Published: July 2012

AbstractHemoglobin Brigham (β Pro100 to Leu) was first reported in a patient with familial erythrocytosis. Erythrocytes of an affected individual from the same family contain both HbA and Hb Brigham and exhibit elevated O2 affinity compared with normal cells (P50 = 23 mm Hg vs. 31 mmHg at pH 7.4 at 37°C). O2 affinities measured for hemolysates were sensitive to changes in pH or chloride concentrations, indicating little change in the Bohr and Chloride effects. Hb Brigham was separated from normal HbA by nondenaturing cation exchange liquid chromatography, and the amino acid substitution was verified by mass spectrometry. The properties of Hb Brigham isolated from the patient's blood were then compared with those of recombinant Hb Brigham expressed in Escherichia coli. Kinetic experiments suggest that the rate constants for ligand binding and release in the high (R) and low (T) affinity quaternary states of Hb Brigham are similar to those of native hemoglobin. However, the Brigham mutation decreases the T to R equilibrium constant (L) which accelerates the switch to the R state during ligand binding to deoxy‐Hb, increasing the rate of association by approximately twofold, and decelerates the switch during ligand dissociation from HbO2, decreasing the rate approximately twofold. These kinetic data help explain the high O2 affinity characteristics of Hb Brigham and provide further evidence for the importance of the contribution of Pro100 to intersubunit contacts and stabilization of the T quaternary structure.
Prostate health index (phi) and prostate cancer antigen 3 (PCA3) significantly improve diagnostic accuracy in patients undergoing prostate biopsy
Authors: Perdonà Sisto , Bruzzese Dario , Ferro Matteo , Autorino Riccardo , Marino Ada , Mazzarella Claudia , Perruolo Giuseppe , Longo Michele , Spinelli Rosa , Di Lorenzo Giuseppe , Oliva Andrea , De Sio Marco , Damiano Rocco , Altieri Vincenzo , Terracciano Daniela 
Published: July 2012

AbstractBACKGROUNDProstate health index (phi) and prostate cancer antigen 3 (PCA3) have been recently proposed as novel biomarkers for prostate cancer (PCa). We assessed the diagnostic performance of these biomarkers, alone or in combination, in men undergoing first prostate biopsy for suspicion of PCa.METHODSOne hundred sixty male subjects were enrolled in this prospective observational study. PSA molecular forms, phi index (Beckman coulter immunoassay), PCA3 score (Progensa PCA3 assay), and other established biomarkers (tPSA, fPSA, and %fPSA) were assessed before patients underwent a 18‐core first prostate biopsy. The discriminating ability between PCa‐negative and PCa‐positive biopsies of Beckman coulter phi and PCA3 score and other used biomarkers were determined.RESULTSOne hundred sixty patients met inclusion criteria. %p2PSA (p2PSA/fPSA × 100), phi and PCA3 were significantly higher in patients with PCa compared to PCa‐negative group (median values: 1.92 vs. 1.55, 49.97 vs. 36.84, and 50 vs. 32, respectively, P ≤ 0.001). ROC curve analysis showed that %p2PSA, phi, and PCA3 are good indicator of malignancy (AUCs = 0.68, 0.71, and 0.66, respectively). A multivariable logistic regression model consisting of both the phi index and PCA3 score allowed to reach an overall diagnostic accuracy of 0.77. Decision curve analysis revealed that this “combined” marker achieved the highest net benefit over the examined range of the threshold probability.CONCLUSIONSphi and PCA3 showed no significant difference in the ability to predict PCa diagnosis in men undergoing first prostate biopsy. However, diagnostic performance is significantly improved by combining phi and PCA3. Prostate 73: 227–235, 2013. © 2012 Wiley Periodicals, Inc.
Urine TMPRSS2:ERG fusion transcript integrated with PCA3 score, genotyping, and biological features are correlated to the results of prostatic biopsies in men at risk of prostate cancer
Authors: Cornu Jean‐Nicolas , Cancel‐Tassin Géraldine , Egrot Christophe , Gaffory Cécile , Haab François , Cussenot Olivier 
Published: July 2012

AbstractBACKGROUNDDetection of fusion gene TMPRSS2:ERG transcripts in urine have been recently described in order to refine urine‐based detection of prostate cancer (PCa), but data its clinical impact remain scarce. We aimed at investigating the correlation of TMPRSS2:ERG, prostate cancer antigen 3 (PCA3), prostate specific antigen (PSA) density, genetic variants, and androgenic status with outcome and pathological findings at prostatic biopsy.METHODSBetween 2007 and 2011, 291 patients at risk of PCa because of PSA > 3.0 ng/ml (55%) or candidate to active surveillance protocol justifying restaging biopsy management (45%) were recruited. TMPRSS2:ERG was detected by urine assay (Progensa™). PCA3‐score, PSA level, bioavailable testosterone level, prostate volume, rs1447295 and rs6983267 genotypes were prospectively assessed. Univariate and multivariate analysis by logistic regression model (logit) were conducted to study the correlation of TMPRSS2:ERG status, PCA3, and PSA density with biopsy results, and Gleason score.RESULTSOf 291 patients, 173 had PCa and 118 had negative biopsy. PCA3 score, PSA density and TMPRSS2:ERG‐score were correlated with presence of PCa (P < 0.0001, P = 0.046, and P < 0.0001, respectively). This correlation remained strong on multivariable analysis model (area under curve 0.743). PCA3 score and PSA density were significantly associated with presence of Grade 4 through multivariable analysis. PCA3 score was also correlated to the percentage of positive cores at biopsy (P = 0.008).CONCLUSIONSIntegration of levels TMPRSS2:ERG transcripts in urine, with PCA3‐score, androgenic status, genetic status and traditional clinical variables could significantly increase detection of high risk localized PCa. Prostate 73: 242–249, 2013. © 2012 Wiley Periodicals, Inc.
Use of β‐blockers is associated with prostate cancer‐specific survival in prostate cancer patients on androgen deprivation therapy
Authors: Grytli Helene Hartvedt , Fagerland Morten Wang , Fosså Sophie D. , Taskén Kristin Austlid , Håheim Lise Lund 
Published: July 2012

AbstractBACKGROUNDExperimental evidence suggests a role for the β2‐adrenergic receptor pathway in prostate cancer (PCa). We have investigated the association of β‐blocker use with PCa incidence and survival in a Norwegian cohort.METHODSData from the Oslo II study in 2000 (n = 6515) were linked with information from the Cancer Registry of Norway and Statistics Norway. PCa risk and overall‐ and PCa‐specific mortality were analyzed using uni‐ and multi‐variable Cox‐ and competing risk regression models.RESULTSAt baseline, 776 men (11.9%) reported using a β‐blocker. 212 men (3.3%) were diagnosed with PCa before the survey, leaving 6,303 eligible for incidence analysis. During a median follow‐up of 122 months, 448 (7.1%) men were diagnosed with PCa. β‐blocker use was not associated with PCa risk [hazard ratio (HR): 1.05, 95% CI: 0.79–1.40]. For all patients (n = 655; including med diagnosed before the survey), β‐blocker use was not associated with PCa‐specific mortality (HR: 0.55, 95% CI 0.24–1.26, P = 0.16). However, in the subgroup of men planned to receive androgen deprivation therapy (ADT), as reported to the Cancer Registry (n = 263), β‐blocker use was associated with reduced PCa‐specific mortality (HR: 0.14, 95% CI 0.02–0.85, P = 0.032). No effect on overall mortality was seen (HR, all patients: 0.88, 95% CI 0.56–1.38, P = 0.57). β‐blocker use did not appear to affect PSA level, Gleason score, or T‐stage at diagnosis; however, these variables were missing for many cases.CONCLUSIONSOur findings demonstrate a possible benefit of β‐blocker use for men treated with ADT, suggesting the need for investigation in larger cohorts. Prostate 73: 250–260, 2013. © 2012 Wiley Periodicals, Inc.
The activity of the androgen receptor variant AR‐V7 is regulated by FOXO1 in a PTEN‐PI3K‐AKT‐dependent way
Authors: Mediwala Sanjay N. , Sun Huiying , Szafran Adam T. , Hartig Sean M. , Sonpavde Guru , Hayes Teresa G. , Thiagarajan Perumal , Mancini Michael A. , Marcelli Marco 
Published: July 2012

AbstractBACKGROUNDThe androgen receptor (AR) AR‐V7 splice isoform is a constitutively active outlaw transcription factor. Transition of prostate cancer (PC) to the castration‐resistant phenotype correlates with AR‐V7 accumulation, suggesting that PC progression in patients refractory to conventional therapy is due to the activity of this AR isoform. The mechanism of AR‐V7 constitutive activation is not known.METHODSWe analyzed potential signaling pathways associated with AR‐V7 constitutive activation in PTEN (−) PC‐3 and LNCaP cells. We used transient and stable transfection, reporter gene assay, RNAi technology together with a number of kinase inhibitors to determine if AR‐V7 activation is linked to a kinase‐dependent signaling pathway.RESULTSIn these cell lines, AR‐V7 transcriptional activity was inhibited by LY294002, Wortmanin, and AKT inhibitor II. Analysis of the contributing mechanisms demonstrated the involvement of the Phosphatidylinositol 3‐kinase (PI3K)‐AKT‐FOXO1 signaling pathway, and a significant reduction of AR‐V7 constitutive activity under conditions of PTEN reactivation.CONCLUSIONSOur study identifies a pathway regulating AR‐V7 constitutive activity and potential therapeutic targets for the treatment of castration‐resistant PC. Prostate 73: 267–277, 2013. © 2012 Wiley Periodicals, Inc.
Corneal Goblet Cells and Their Niche: Implications for Corneal Stem Cell Deficiency
Authors: Pajoohesh-Ganji Ahdeah , Pal-Ghosh Sonali , Tadvalkar Gauri , Stepp Mary Ann 
Published: July 2012

Abstract
Goblet cells are terminally differentiated cells secreting mucins and antibacterial peptides that play an important role in maintaining the health of the cornea. In corneal stem cell deficiency, the progenitor cells giving rise to goblet cells on the cornea are presumed to arise from differentiation of cells that migrate onto the cornea from the neighboring conjunctiva. This occurs in response to the inability of corneal epithelial progenitor cells at the limbus to maintain an intact corneal epithelium. This study characterizes clusters of cells we refer to as compound niches at the limbal:corneal border in the unwounded mouse. Compound niches are identified by high expression of simple epithelial keratin 8 (K8) and 19 (K19). They contain variable numbers of cells in one of several differentiation states: slow-cycling corneal progenitor cells, proliferating cells, nonproliferating cells, and postmitotic differentiated K12+Muc5ac+ goblet cells. Expression of K12 differentiates these goblet cells from those in the conjunctival epithelium and suggests that corneal epithelial progenitor cells give rise to both corneal epithelial and goblet cells. After wounds that remove corneal epithelial cells near the limbus, compound niches migrate from the limbal:corneal border onto the cornea where K8+ cells proliferate and goblet cells increase in number. By contrast, no migration of goblet cells from the bulbar conjunctiva onto the cornea is observed. This study is the first description of compound niches and corneal goblet cells and demonstration of a role for these cells in the pathology typically associated with corneal stem cell deficiency.
Deficient DNA Damage Response and Cell Cycle Checkpoints Lead to Accumulation of Point Mutations in Human Embryonic Stem Cells
Authors: Hyka-Nouspikel Nevila , Desmarais Joëlle , Gokhale Paul J. , Jones Mark , Meuth Mark , Andrews Peter W. , Nouspikel Thierry 
Published: July 2012

Abstract
Human embryonic stem cells (hESCs) tend to lose genomic integrity during long periods of culture in vitro and to acquire a cancer-like phenotype. In this study, we aim at understanding the contribution of point mutations to the adaptation process and at providing a mechanistic explanation for their accumulation. We observed that, due to the absence of p21/Waf1/Cip1, cultured hESCs lack proper cell cycle checkpoints and are vulnerable to the kind of DNA damage usually repaired by the highly versatile nucleotide excision repair (NER) pathway. In response to UV-induced DNA damage, the majority of hESCs succumb to apoptosis; however, a subpopulation continues to proliferate, carrying damaged DNA and accumulating point mutations with a typical UV-induced signature. The UV-resistant cells retain their proliferative capacity and potential for pluripotent differentiation and are markedly less apoptotic to subsequent UV exposure. These findings demonstrate that, due to deficient DNA damage response, the modest NER activity in hESCs is insufficient to prevent increased mutagenesis. This provides for the appearance of genetically aberrant hESCs, paving the way for further major genetic changes.
Study of anisotropic black branes in asymptotically anti-de Sitter
Authors: Iizuka Norihiro , Maeda Kengo 
Published: July 2012

AbstractWe investigate the four dimensional gravitational theories which admit homogeneous but anisotropic black brane solutions in asymptotically AdS space-time. The gravitational theories we consider are 1) Einstein-Maxwell-dilaton theory, and 2) EinsteinMaxwell-dilaton-axion theory with SL(2, R) symmetry. We obtain the solutions both analytically and numerically. Analytical solutions are obtained by perturbation from the isotropic solutions. Our solutions approach singular behavior at the horizon in the extremal limit but in non-extremal case, they are smooth everywhere. We also discuss how the third law of thermodynamics holds in our set-up.
Leading‐edge populations do not show low genetic diversity or high differentiation in a wind‐pollinated tree
Authors: Shi Miao‐Miao , Chen Xiao‐Yong 
Published: July 2012

AbstractClimate changes can shift species’ ranges. Knowledge on genetic variation of the leading‐edge populations provides critical information to understand responses and adaptation of plants to projected climate warming. To date, the research into genetic variation of leading‐edge populations has been limited, particularly in the role of wind‐mediated pollen flow in maintaining high genetic variation. Castanopsis sclerophylla (Fagaceae) is a wind‐pollinated and gravity‐dispersed tree. In the present study, we used seven polymorphic microsatellites to genotype 482 samples from five leading‐edge and 12 non‐edge populations. Significant effects of recent population bottleneck events were found in three of the five leading‐edge populations, indicating that the leading‐edge populations might have been recolonized after the Last Glacial Maximum. Genetic diversity was higher, though not significantly, in leading‐edge than in non‐edge populations. Relationship between genetic diversity and latitude indicated an increasing trend of genetic diversity towards leading‐edge populations. No significant difference in genetic differentiation was found between leading‐edge and non‐edge populations. The inconsistence with the general predictions by leading‐edge colonization model could be explained by high gene flow via pollen grains. Pollen‐mediated gene flow could maintain high genetic diversity within and low differentiation among leading‐edge populations. In response to climate warming, high genetic variation may provide leading‐edge populations raw materials for evolutionary adaptation to future environmental conditions.
Genetic Counseling, Activism and ‘Genotype‐First’ Diagnosis of Developmental Disorders
Authors: Navon Daniel 
Published: July 2012

AbstractThis paper presents a sociological examination of the role of genetic counselors as advocates, not only for patients and their families, but also for genetic conditions themselves. In becoming activists for new disorders, genetic counselors are helping to create new categories that will shape expectations and treatment regimens for both existing patients and those who are yet to be diagnosed. By virtue of their expertise and their position at the intersection of several key professions and constituencies, genetic counselors are likely to play a central role in the way the genetic testing technologies, and especially ‘genotype‐first’ diagnosis, impacts the way we understand and categorize developmental difference. I outline some of the promises and dangers that this kind of activism holds for people with developmental disabilities, and particularly the challenge presented by systemic ascertainment bias in the face of genotype‐phenotype uncertainty. I argue that new testing techniques like microarray analysis that do not need to be targeted on the basis of clinical presentation throw these challenges into sharp relief, and that the genetic counseling community should consider how to marry advocacy for new genetic conditions with an emphasis on the indeterminate developmental potential of every child.
Missed opportunities for prevention of mother‐to‐child transmission of HIV‐1 in the NISDI Perinatal and LILAC cohorts
Authors: Read Jennifer S. , Cohen Rachel A. , Hance Laura Freimanis , Machado Elizabeth S. , Mussi‐Pinhata Marisa M. , Ceriotto Mariana , Santos Breno , Succi Regina , Pilotto Jose H. , Alarcon Jorge O. , Kreitchmann Regis 
Published: July 2012

AbstractObjectiveTo evaluate cases of mother‐to‐child transmission of HIV‐1 at multiple sites in Latin America and the Caribbean in terms of missed opportunities for prevention.MethodsPregnant women infected with HIV‐1 were eligible for inclusion if they were enrolled in either the NISDI Perinatal or LILAC protocols by October 20, 2009, and had delivered a live infant with known HIV‐1 infection status after March 1, 2006.ResultsOf 711 eligible mothers, 10 delivered infants infected with HIV‐1. The transmission rate was 1.4% (95% CI, 0.7–2.6). Timing of transmission was in utero or intrapartum (n = 5), intrapartum (n = 2), intrapartum or early postnatal (n = 1), and unknown (n = 2). Possible missed opportunities for prevention included poor control of maternal viral load during pregnancy; late initiation of antiretrovirals during pregnancy; lack of cesarean delivery before labor and before rupture of membranes; late diagnosis of HIV‐1 infection; lack of intrapartum antiretrovirals; and incomplete avoidance of breastfeeding.ConclusionEarly knowledge of HIV‐1 infection status (ideally before or in early pregnancy) would aid timely initiation of antiretroviral treatment and strategies designed to prevent mother‐to‐child transmission. Use of antiretrovirals must be appropriately monitored in terms of adherence and drug resistance. If feasible, breastfeeding should be completely avoided. Presented in part at the XIX International AIDS Conference (Washington, DC; July 22–27, 2012); abstract WEPE163.
Ventricular asystole due to atrial oversensing by a VVI pacemaker: VVT mode as a simple solution
Authors: Tanaka Kazushi , Fujimura Osamu 
Published: July 2012

AbstractWe report a rare case of atrial oversensing by a VVI pacemaker that caused ventricular asystole. Changing the programming to VVT mode not only eliminated the problem but also provided atrioventricular synchrony and rate responsiveness.
Parachute mitral valve accompanied by bicuspid aortic valve on three‐dimensional transesophageal echocardiography
Authors: Feng Tian‐Ying , Li Zhi‐An , He Yi‐Hua , Han Jian‐Cheng , Luan Shu‐Rong , Wang Lin‐Lin 
Published: July 2012

AbstractWe report the findings of three‐dimensional (3D) transesophageal echocardiography (TEE) in a patient with a parachute mitral valve (MV) accompanied by aortic valve (AV) malformation. The results indicated an enhanced echo in MV anterior leaves, incrassate, and shortened subvalvular chordae tendineae, and posteromedial papillary muscle that had echo reinforcement, calcification, retroposition, and a significant decrease compared with anterolateral papillary muscle. In addition, the anterolateral papillary muscle was huge, with the bilateral papillary muscles fused partly, and the posterior subvalvular chordae tendineae incrassate, shortened, and attached parachute‐like to the anterolateral papillary muscle. The MV appeared dome‐shaped for the open limit in diastole with an MV area of 1.6 cm. Moreover, the left ventricle increased in size and the bicuspid AV was malformed. Continuous wave Doppler angiograph showed that the flow rate increased to 398 cm/seconds at the AV orifice area. A 3D form of the MV structure was observed from the left ventricle using 3D‐TEE inspection. The anterolateral papillary muscle was fused with its posteromedial homologue. The chordae tendineae was attached to the anterolateral papillary with the parachute‐like structure, indicating dome movement.
Modified basket plate for inferior patellar pole avulsion fractures—A report of three cases
Authors: Huang Hui‐Cheng , Su Jiing‐Yuan , Cheng Yuh‐Min 
Published: July 2012

AbstractIn patients who have sustained an avulsion fracture of the inferior patellar pole, the extensor mechanism is disrupted and should be repaired. The normal height of the patella can be maintained by preserving the patellar pole, but fractures of the inferior pole of the patella are not easy to reduce and fix firmly. In contrast with partial patellectomy, which requires postoperative immobilization, internal fixation with a basket plate allows for immediate mobilization and early weight‐bearing. Owing to the unavailability of the basket plate in Taiwan, we have modified the plate with the titanium mesh as a possible alternative. We present three cases of this modified basket plate, which took place between 2008 and 2010. This technique avoided long‐term immobilization of the knee with good clinical results.
Re-evaluating the origins of late Pleistocene fire areas on Santa Rosa Island, California, USA
Authors: Rick Torben C. , Wah John S. , Erlandson Jon M. 
Published: July 2012

AbstractAt the close of the Pleistocene, fire regimes in North America changed significantly in response to climate change, megafaunal extinctions, anthropogenic burning and possibly, even an extraterrestrial impact. On California's Channel Islands, researchers have long debated the nature of late Pleistocene “fire areas,” discrete red zones in sedimentary deposits, interpreted by some as prehistoric mammoth-roasting pits created by humans. Further research found no evidence that these red zones were cultural in origin, and two hypotheses were advanced to explain their origin: natural fires and groundwater processes. Radiocarbon dating, X-ray diffraction analysis, and identification of charcoal from six red zones on Santa Rosa Island suggest that the studied features date between ~ 27,500 and 11,400 cal yr BP and resulted from burning or heating, not from groundwater processes. Our results show that fire was a component of late Pleistocene Channel Island ecology prior to and after human colonization of the islands, with no clear evidence for increased fire frequency coincident with Paleoindian settlement, extinction of pygmy mammoths, or a proposed Younger Dryas impact event.