bluuebunny/crossref_metadata_2025_split huggingface dataset:
A dimerized urea-based inhibitor of the prostate-specific membrane antigen for 68Ga-PET imaging of prostate cancer
Authors: Schäfer Martin , Bauder-Wüst Ulrike , Leotta Karin , Zoller Frederic , Mier Walter , Haberkorn Uwe , Eisenhut Michael , Eder Matthias 
Published: June 2012

Abstract

Background
Alternative positron-emission tomography (PET) probes like labeled inhibitors of the prostate-specific membrane antigen (PSMA) are of emerging clinical impact as they show the ability to image small lesions of recurrent prostate cancer. Here, the dimerization of the pharmacophore Glu‐ureido‐Lys via the 68Ga chelator N,N′-bis[2-hydroxy-5-(carboxyethyl)benzyl]ethylenediamine-N,N′-diacetic acid (HBED-CC) was investigated to further improve the binding characteristics and pharmacokinetics.

Methods
The peptidomimetic structures were synthesized by solid-phase chemistry, and the resulting products were coupled with the respective 2,3,5,6-tetrafluorophenol esters of HBED-CC to form the monomeric reference and the dimeric Glu‐ureido‐Lys derivative. The binding properties were analyzed in competitive binding, internalization, and cell surface retention experiments. PET images and biodistribution data were obtained 1 h after injection in BALB/c nu/nu mice bearing LNCaP tumor xenografts.

Results
Cell binding data revealed significant better binding properties of the dimer (IC50 = 3.9 ± 1.8 nM; IC50 (monomer) = 12.1 ± 2.1 nM). The inhibition potency investigated by the enzyme-based NAALADase assay confirmed these results. Specific internalization in LNCaP cells was demonstrated for both, the monomer and dimer. As shown by efflux measurements, the dimeric compound was more effectively retained on the cell surface, resulting in advanced in vivo properties (T/BMonomer = 9.2; T/BDimer = 26.5).

Conclusions
The dimeric [68Ga]7 is a promising imaging agent for PSMA-expressing tumors as it shows higher tumor uptake while observing more favorable background clearance. As compared to the respective monomer, the higher affinity and prolonged tumor retention additionally represent promising features and warrant further evaluation regarding 68Ga-PET imaging of PSMA expression.
Electrocardiographic changes in therapeutic hypothermia
Authors: Rolfast Corina L , Lust Erik J , de Cock Carel C 
Published: June 2012

Abstract
Introduction
During therapeutic hypothermia (TH), electrocardiographic (ECG) abnormalities such as Osborn waves and/or ST-segment elevation have been described. However, the incidence and prognostic value of these ECG changes are uncertain given the small-scale studies that have been carried out to date. The aim of this study is to further evaluate the electrocardiographic changes during TH.

Methods
During a period of 3 years, 81 patients (age 63 ± 14 years) were included retrospectively. All patients underwent TH after being resuscitated. ECG registrations before, during and after TH were collected and analyzed. Patients were divided into two groups based on the presence or absence of transmural ischemia ST elevation on the first representative ECG upon arrival at the hospital (ST-segment elevation myocardial infarction (STEMI) and non-STEMI).

Results
A total of 243 ECGs were analyzed. During TH 24 patients (30%) had Osborn waves, which disappeared in 22 patients (92%) after regaining normal body temperature. The presence of Osborn waves was not associated with age, gender, average pH, electrolytes, or lactate levels and was not associated with excess in-hospital mortality. In 10 patients (12%, six non-STEMI patients) new STEMI was observed during TH, which disappeared after TH discontinuation. The STEMI group (44 patients) had significantly more Osborn waves during TH than the non-STEMI group (38.6% vs. 15.2%, odds ratio = 3.508; 95% confidence interval = 1.281 to 9.610).

Conclusions
Hypothermia-induced Osborn waves are relatively common and are not associated with an unfavorable short-term outcome. TH is associated with ECG changes that may mimic STEMI.
Structure of major depressive disorder in adolescents and adults in the US general population
Authors: Lamers Femke , Burstein Marcy , He Jian-ping , Avenevoli Shelli , Angst Jules , Merikangas Kathleen R. 
Published: June 2012

BackgroundAlthough techniques such as latent class analysis have been used to derive empirically based subtypes of depression in adult samples, there is limited information on subtypes of depression in youth.AimsTo identify empirically based subtypes of depression in a nationally representative sample of US adolescents, and to test the comparability of subtypes of depression in adolescents with those derived from a nationally representative sample of adults.MethodRespondents included 912 adolescents and 805 adults with a 12-month major depressive disorder, selected from the National Comorbidity Survey Adolescent Supplement and the National Comorbidity Survey Replication samples respectively. Latent class analysis was used to identify subtypes of depression across samples. Sociodemographic and clinical correlates of derived subtypes were also examined to establish their validity.ResultsThree subtypes of depression were identified among adolescents, whereas four subtypes were identified among adults. Two of these subtypes displayed similar diagnostic profiles across adolescent and adult samples (P=0.43); these subtypes were labelled ‘severe typical’ (adults 45%, adolescents 35%) and ‘atypical’ (adults 16%, adolescents 26%). The latter subtype was characterised by increased appetite and weight gain.ConclusionsThe structure of depression observed in adolescents is highly similar to the structure observed in adults. Longitudinal research is necessary to evaluate the stability of these subtypes of depression across development.
Sexual dysfunction in people with prodromal or first-episode
psychosis
Authors: Marques Tiago Reis , Smith Shubulade , Bonaccorso Stefania , Gaughran Fiona , Kolliakou Anna , Dazzan Paola , Mondelli Valeria , Taylor Heather , DiForti Marta , McGuire Philip K. , Murray Robin M. , Howes Oliver D. 
Published: June 2012

BackgroundSexual dysfunction is common in psychotic disorder but it is not clear
whether it is intrinsic to the development of the illness or secondary to
other factors.AimsTo compare sexual function in people at ultra-high risk (UHR) of a
psychotic disorder, patients with first-episode psychosis predominantly
taking antipsychotic drugs and healthy volunteers.MethodSexual function was assessed in a UHR group (n = 31), a
group with first-episode psychosis (n = 37) and a
matched control group of healthy volunteers (n = 56)
using the Sexual Function Questionnaire.ResultsThere was a significant effect of group on sexual function
(P<0.001). Sexual dysfunction was evident in 50%
of the UHR group, 65% of first-episode patients and 21% of controls.
Within the UHR group, sexual dysfunction was more marked in those who
subsequently developed psychosis than in those who did not. Across all
groups the severity of sexual dysfunction was correlated with the
severity of psychotic symptoms (P<0.001). Within the
first-episode group there was no significant difference in sexual
dysfunction between patients taking prolactin-raising v.
prolactin-sparing antipsychotics.ConclusionsSexual dysfunction is present prior to onset of psychosis, suggesting it
is intrinsic to the development of illness unlikely to be related to the
prolactin-raising properties of antipsychotic medication.
Phenotypic diversity in patients with lipodystrophy associated with LMNA mutations
Authors: Mory Patricia B , Crispim Felipe , Freire Maria Beatriz S , Salles João Eduardo N , Valério Cynthia M , Godoy-Matos Amelio F , Dib Sérgio A , Moisés Regina S 
Published: June 2012

ObjectiveMutations inLMNAhave been linked to diverse disorders called laminopathies, which display heterogeneous phenotypes and include diseases affecting muscles, axonal neurons, progeroid syndromes, and lipodystrophies. Among the lipodystrophies,LMNAmutations have been reported most frequently in patients with familial partial lipodystrophy (FPLD) of the Dunnigan variety; however, phenotypic heterogeneity in the pattern of body fat loss has been observed. In this study, we searched forLMNAmutations in patients with various forms of lipodystrophy.Design and methodsWe studied 21 unrelated individuals with lipodystrophy. Subjects underwent a complete clinical evaluation and were classified as typical FPLD (n=12), atypical partial lipodystrophy (n=7), or generalized lipodystrophy (n=2). Molecular analysis ofLMNAgene, analysis of body fat by dual-energy X-ray absorptiometry, and biochemical measurements were performed.ResultsAll patients with typical FPLD were found to carryLMNAmutations: seven patients harbored the heterozygous p.R482W (c.1444C>T), two patients harbored the p.R482Q (c.1445G>A), and two individuals harbored the novel heterozygous variant p.N466D (c.1396A>G), all in exon 8. Also, a homozygous p.R584H (c.1751 G>A) mutation in exon 11 was found. Among patients with atypical partial lipodystrophy, two of them were found to haveLMNAmutations: a novel heterozygous p.R582C variation (c.1744 C>T) in exon 11 and a heterozygous substitution p.R349W (c.1045C>T) in exon 6. Among patients with generalized lipodystrophy, only one harboredLMNAmutation, a heterozygous p.T10I (c.29C>T) in exon 1.ConclusionsWe have identifiedLMNAmutations in phenotypically diverse lipodystrophies. Also, our study broadens the spectrum ofLMNAmutations in lipodystrophy.
Nanosecond and picosecond laser structuring of electrode materials for lithium-ion batteries
Authors: Kohler Robert , Proell Johannes , Besser Heino , Torge Maika , Scholz Steffen , Dobrev Todor , Ulrich Sven , Pfleging Wilhelm 
Published: June 2012

ABSTRACTA comparative study for picosecond and nanosecond laser structuring was performed in order to identify structure geometries and dimensions that efficiently reduce the significant volume changes during electrochemical cycling of SnO2, a promising anode material. Line structures with widths of 20 μm could significantly improve cycling stability of 3 μm thick magnetron sputtered SnO2 thin films. A reduction of structure size led to further improvement of capacity retention. Free-standing conical micro-structures exhibited the best cycling behavior.
Relationships between Levels of Urinary Podocalyxin, Number of Urinary Podocytes, and Histologic Injury in Adult Patients with IgA Nephropathy
Authors: Asao Rin , Asanuma Katsuhiko , Kodama Fumiko , Akiba-Takagi Miyuki , Nagai-Hosoe Yoshiko , Seki Takuto , Takeda Yukihiko , Ohsawa Isao , Mano Satoshi , Matsuoka Kiyoshi , Kurosawa Hiroyuki , Ogasawara Shinya , Hirayama Yoshiaki , Sekine Sakari , Horikoshi Satoshi , Hara Masanori , Tomino Yasuhiko 
Published: June 2012

Summary

Background and objectives
Podocalyxin (PCX) is present on the apical cell membrane of podocytes and is shed in urine from injured podocytes. Urinary podocalyxin (u-PCX) is associated with severity of active glomerular injury in patients with glomerular diseases. This study examined the relationship between number of urinary podocytes, levels of u-PCX, and glomerular injury in adults with IgA nephropathy (IgAN).

Design, setting, participants, & measurements
Urine samples voided in the morning on the day of biopsy were obtained from 51 patients with IgAN (18 men and 33 women; mean age, 31 years). All renal biopsy specimens were analyzed histologically. Pathologic variables of IgAN were analyzed per Shigematsu classification, the Oxford classification of IgAN, and the Clinical Guidelines of IgAN in Japan. Levels of u-PCX were measured by sandwich ELISA.

Results
Histologic analysis based on Shigematsu classification revealed a significant correlation between levels of u-PCX and severity of acute extracapillary abnormalities (r=0.72; P<0.001), but levels of urinary protein excretion did not correlate with acute glomerular abnormalities. Levels of urinary protein excretion in patients with segmental sclerosis (n=19) were higher than in patients without (n=22) (0.49 [interquartile range (IQR), 0.20–0.88] g/g creatinine versus 0.20 [IQR, 0.10–0.33] g/g creatinine; P<0.01). The number of urinary podocytes in patients with segmental sclerosis was higher than in patients without (1.05 [IQR, 0.41–1.67] per mg creatinine versus 0.28 [IQR, 0.10–0.66] per mg creatinine; P<0.01).

Conclusions
Levels of u-PCX and the number of urinary podocytes are associated with histologic abnormalities in adults with IgAN.
Probing the Mechanisms of Intradialytic Hypertension
Authors: Inrig Jula K. , Van Buren Peter , Kim Catherine , Vongpatanasin Wanpen , Povsic Thomas J. , Toto Robert 
Published: June 2012

Summary

Background and objectives
Intradialytic hypertension may be caused by an impaired endothelial cell response to hemodialysis. Carvedilol has been shown to improve endothelial cell function in vivo and to block endothelin-1 release in vitro. This study hypothesized that carvedilol would improve endothelial cell function and reduce the occurrence of intradialytic hypertension.

Design, setting, participants, & measurements
A prospective 12-week pilot study of carvedilol titrated to 50 mg twice daily was performed among 25 hemodialysis participants with intradialytic hypertension. Each patient served as his or her own control. Paired tests were used to analyze changes in BP and endothelial cell function—assessed by flow-mediated vasodilation, endothelial progenitor cells (aldehyde dehydrogenase bright activity and CD34+CD133+), asymmetric dimethylarginine, and endothelin-1—from baseline to study end.

Results
Flow-mediated vasodilation was significantly improved with carvedilol (from 1.03% to 1.40%, P=0.02). There was no significant change in endothelial progenitor cells, endothelin-1, or asymmetric dimethylarginine. Although prehemodialysis systolic BP was unchanged (144–146 mmHg, P=0.5), posthemodialysis systolic BP, 44-hour ambulatory systolic BP, and the frequency of intradialytic hypertension decreased with carvedilol (159–142 mmHg, P<0.001; 155–148 mmHg, P=0.05; and 77% [4.6 of 6] to 28% [1.7 of 6], P<0.001, respectively).

Conclusions
Among hemodialysis participants with intradialytic hypertension, targeting endothelial cell dysfunction with carvedilol was associated with modest improvements in endothelial function, improved intradialytic and interdialytic BP, and reduced frequency of intradialytic hypertension. Randomized controlled trials are required to confirm these findings.
Management Forecast Accuracy and CEO Turnover
Authors: Lee Sam (Sunghan) , Matsunaga Steven R. , Park Chul W. 
Published: June 2012

ABSTRACT
We investigate whether management forecast accuracy provides a signal regarding CEOs' ability to anticipate and respond to future events by examining the relation between management forecast errors and CEO turnover. We find that the probability of CEO turnover is positively related to the magnitude of absolute forecast errors when firm performance is poor and that this positive relation holds for both positive and negative forecast errors. In addition, we find that the positive relation between CEO turnover and the absolute forecast errors is concentrated in the sample of less entrenched CEOs. Our findings indicate that boards of directors use management forecast accuracy as a signal of CEOs' managerial ability and that managers bear a cost for issuing inaccurate forecasts.
Independent Effect of Ethnicity on Glycemia in South Asians and White Europeans
Authors: Mostafa Samiul A. , Davies Melanie J. , Webb David R. , Srinivasan Balasubramanian Thiagarajan , Gray Laura J. , Khunti Kamlesh 
Published: June 2012

OBJECTIVE
HbA1c levels are higher in most ethnic groups compared with white Europeans (WEs) independent of glycemic control. This comparison has not been performed between South Asians (SAs) and WEs. We analyzed the independent effect of ethnicity on HbA1c and fasting and 2-h plasma glucose (FPG and 2hrPG, respectively) between these groups.

RESEARCH DESIGN AND METHODS
Analysis of the ADDITION-Leicester study, in which 4,688 WEs and 1,352 SAs underwent oral glucose tolerance testing, HbA1c, and other risk factor measurements.

RESULTS
Significant associations with HbA1c included ethnicity, FPG, 2hrPG, and homeostasis model assessment of β-cell function (P &lt; 0.001); age and sex (P &lt; 0.01); and fasting insulin and potassium (P &lt; 0.05). After adjusting for these and other risk factors, SAs demonstrated higher HbA1c (6.22 and 6.02%, mean difference 0.20%, 0.10–0.30, P &lt; 0.001), FPG (5.15 and 5.30 mmol/L, mean difference 0.15 mmol/L, 0.09–0.21, P &lt; 0.001), and 2hrPG (5.82 and 6.57 mmol/L, mean difference 0.75 mmol/L, 0.59–0.92, P &lt; 0.001) compared with WEs, respectively.

CONCLUSIONS
HbA1c, FPG, and 2hrPG levels were higher in SAs independent of factors affecting glycemic control.
Determinants of Insulin Resistance in Infants at Age 1 Year
Authors: Borgoño Carla A. , Hamilton Jill K. , Ye Chang , Hanley Anthony J. , Connelly Philip W. , Sermer Mathew , Zinman Bernard , Retnakaran Ravi 
Published: June 2012

OBJECTIVE
The offspring of women with gestational diabetes mellitus (GDM) display a propensity for the early accrual of cardiometabolic risk factors, including insulin resistance, in childhood and adolescence. Thus, we sought to identify early life determinants of insulin resistance in infants of women with and without GDM.

RESEARCH DESIGN AND METHODS
In total, 104 full-term, singleton infants born to women with (n = 36) and without (n = 68) GDM were evaluated at age 1 year, with insulin resistance assessed by homeostasis model (HOMA-IR).

RESULTS
HOMA-IR at 1 year did not differ between infants born to mothers with and without GDM (P = 0.74). The sole independent predictor of infant HOMA-IR in the non-GDM group was birth weight (t = 3.33, P = 0.002). In contrast, weight gain in the 1st year was the only independent predictor of HOMA-IR in infants of women with GDM (t = 2.19, P = 0.039).

CONCLUSIONS
In the 1st year of life, weight gain in infants born to women with GDM is associated with insulin resistance, unlike in their peers.
Stress Management as an Adjunct to Physical Therapy for Chronic Neck Pain
Authors: Bruflat Angela K. , Balter Jaclyn E. , McGuire Denise , Fethke Nathan B. , Maluf Katrina S. 
Published: June 2012

Background and Purpose
Chronic neck pain is prevalent in the workplace. Research suggests that psychosocial stress may contribute to the development of neck pain by causing excessive or prolonged muscle activity in some individuals. The purpose of this case report is to describe the rationale, development, and implementation of stress management as an adjunct to standard physical therapist management of chronic neck pain in a female office worker who responded to psychosocial stress with elevated muscle activity prior to treatment.

Case Description
A 44-year-old female office employee with an 8-year history of chronic neck pain participated in this case report. The patient was selected from a group of research participants who demonstrated elevated electromyographic (EMG) activity of the trapezius muscle in response to simulated occupational stressors. The multidisciplinary intervention consisted of 8 physical therapy sessions, supplemented by 8 stress management sessions that included EMG biofeedback and psychotherapy to facilitate muscle relaxation.

Outcomes
Neck disability decreased by 50%, trait anxiety decreased by 21%, and the duration of trapezius muscle rest in the workplace increased by 56% immediately after the 8-week intervention. These improvements were maintained 6 months after treatment, and the patient reported a complete absence of neck disability at the 2-year follow-up assessment.

Discussion
A sustained reduction in neck disability was observed for a patient with chronic neck pain after participating in a multidisciplinary intervention that combined physical therapy and stress management approaches to facilitate muscle relaxation in the workplace. Future clinical trials are needed to assess whether stress management is a useful adjunct therapy for patients with chronic neck pain who show elevated muscle activity in response to psychosocial stress.
Cervical implantation of intrathecal baclofen pump catheter in children with severe scoliosis
Authors: Ughratdar Ismail , Muquit Samiul , Ingale Harshal , Moussa Ahmad , Ammar Amr , Vloeberghs Michael 
Published: June 2012

Object
Intrathecal baclofen (ITB) pump catheter placement is traditionally performed through entry into the spinal sac at the lumbar spine. A minority of children with cerebral palsy have severe concomitant neuromuscular scoliosis. In these children, whether surgically treated or not, access to the intradural space via the lumbar spine may prove technically challenging. The authors report on a series of children in whom, for various reasons, an ITB catheter was implanted using a posterior cervical spine approach.

Methods
The records of 20 children in whom a baclofen catheter had been placed were retrospectively reviewed to assess the demographic details, indications, and outcome of this procedure.

Results
This approach was successful in all but one of the children in whom the procedure was abandoned given the presence of significant extradural scar tissue. Of the 20 children, 7 had previously undergone lumbar ITB catheter implantation, although the catheter was subsequently, iatrogenically transected during scoliosis surgery. Nine children had had corrective scoliosis surgery, and the fusion mass obviated access to the lumbar spinal sac. Four children had untreated scoliosis and corrective surgery was being contemplated. Complications included infection requiring explantation (2 patients), catheter migration (1 patient), intolerance to ITB (1 patient), and failure of implantation (1 patient). All patients who tolerated the ITB experienced improvement in spasticity. No complications were associated with the spinal level of catheter insertion.

Conclusions
Implantation of an ITB catheter via a cervical approach is safe and feasible and should be considered in children with severe corrected or uncorrected scoliosis, and thus avoiding the lumbar spinal sac.
Radiosurgery for melanoma brain metastases in the ipilimumab era and the possibility of longer survival
Authors: Knisely Jonathan P. S. , Yu James B. , Flanigan Jaclyn , Sznol Mario , Kluger Harriet M. , Chiang Veronica L. S. 
Published: June 2012

Object
A prospectively collected cohort of 77 patients who underwent definitive radiosurgery between 2002 and 2010 for melanoma brain metastases was retrospectively reviewed to assess the impact of ipilimumab use and other clinical variables on survival.

Methods
The authors conducted an institutional review board–approved chart review to assess patient age at the time of brain metastasis diagnosis, sex, primary disease location, initial radiosurgery date, number of metastases treated, performance status, systemic therapy and ipilimumab history, whole-brain radiation therapy (WBRT) use, follow-up duration, and survival at the last follow-up. The Diagnosis-Specific Graded Prognostic Assessment (DSGPA) score was calculated for each patient based on performance status and the number of brain metastases treated.

Results
Thirty-five percent of the patients received ipilimumab. The median survival in this group was 21.3 months, as compared with 4.9 months in patients who did not receive ipilimumab. The 2-year survival rate was 47.2% in the ipilimumab group compared with 19.7% in the nonipilimumab group. The DS-GPA score was the most significant predictor of overall survival, and ipilimumab therapy was also independently associated with an improvement in the hazard for death (p = 0.03).

Conclusions
The survival of patients with melanoma brain metastases managed with ipilimumab and definitive radiosurgery can exceed the commonly anticipated 4–6 months. Using ipilimumab in a supportive treatment paradigm of radiosurgery for brain oligometastases was associated with an increased median survival from 4.9 to 21.3 months, with a 2-year survival rate of 19.7% versus 47.2%. This association between ipilimumab and prolonged survival remains significant even after adjustment for performance status without an increased need for salvage WBRT.