bluuebunny/crossref_metadata_2025 huggingface dataset:
Anxiety Disorder Comorbidity in Bipolar Disorder, Schizophrenia and Schizoaffective Disorder
Authors: Young Sarah , Pfaff Danielle , Lewandowski Kathryn Eve , Ravichandran Caitlin , Cohen Bruce M. , Öngür Dost
Published: November 2012

Background: Reported rates of comorbid anxiety disorders in psychotic and mood disorders vary widely among studies. Sampling and Methods: We used the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, to examine rates of comorbid anxiety disorders in patients with schizoaffective disorder (SZA; n = 153), bipolar I disorder (BP; n = 304) and schizophrenia (SZ; n = 174). Results: The rates of anxiety disorders in participants with SZA (30.1%), BP (22.4%) and SZ (16.7%) differed significantly [χ2(2) = 8.368, p = 0.015]. Among anxiety disorders, this effect was most pronounced for panic disorder (PD). PD rates were significantly higher in participants with SZA (15.7%) as compared to participants with BP (6.9%) and SZ [6.9%; χ2(2) = 10.879, p = 0.004]. Logistic regression models controlling for demographic and clinical characteristics confirmed that primary diagnosis (SZA, BP or SZ) was a significant predictor of PD comorbidity and approached significance in predicting the comorbidity of any anxiety disorder. Conclusions: Our findings suggest that patients with SZA have high rates of anxiety disorders. Clinicians treating patients with SZA should evaluate for anxiety disorder comorbidity, especially as anxiety symptoms may not be reported at first presentation.
Clinical Aspects and Molecular Genetics of Persistent Müllerian Duct Syndrome Associated with Transverse Testicular Ectopia: Report of Three Cases
Authors: Ju Xiaobing , Li ZhongXing , Zhang Chao , Qin Chao , Shao Pengfei , Li Jie , Li Pu , Cao Qiang , Zhang Wei , Wang Zengjun , Yin Changjun
Published: November 2012

Persistent müllerian duct syndrome (PMDS) is a rare form of male pseudohermaphroditism, characterized by the presence of a uterus and fallopian tubes owing to failure of müllerian duct regression in genotypically normal males. The association between a persistent müllerian duct and transverse testicular ectopia (TTE) is even more uncommon. PMDS with TTE is a very rare pathological association, often discovered during repair for inguinal hernia or cryptorchidism. We report 3 cases of Chinese patients with PMDS associated with TTE. Hysterectomy was performed, with resection of the underdeveloped fallopian tubes. Both gonads were placed into subdartos pouches in each scrotum by the transseptal approach. PMDS with TTE is a rarely encountered form of male pseudohermaphroditism usually unexpectedly found at surgery for cryptorchidism or inguinal hernia. Surgical treatment should avoid damage of fertile testes and vasa deferens.
Dynamic Tissue Perfusion Measurement: A New Tool for Characterizing Renal Perfusion in Renal Cell Carcinoma Patients
Authors: Rosenbaum Clemens , Wach Sven , Kunath Frank , Wullich Bernd , Scholbach Thomas , Engehausen Dirk G.
Published: November 2012

Introduction: Renal cell carcinoma (RCC) is characterized by intense angiogenesis with hyperexpression of proangiogenic factors. This study explored the potential of dynamic tissue perfusion measurement (DTPM) to detect differences in tissue perfusion between kidneys with RCC and corresponding healthy kidneys. Patients and Methods: 30 patients with unilateral, histologically confirmed RCC underwent DTPM by color Doppler ultrasound. Before scheduled surgery, Doppler ultrasound data were acquired from four transverse areas of the affected kidney and the contralateral healthy kidney. Doppler ultrasound data were recorded over a 10-second period and characteristic tissue perfusion parameters were determined. Results: The kidneys with RCC displayed characteristic changes in perfusion parameters. A significant increase in signal intensity and a significant decrease in flow resistance were noted. A combination of several DTPM parameters was used to distinguish correctly between kidneys bearing RCC or healthy kidneys with up to 75% accuracy. There was no association between the perfusion parameters and the pathological characteristics of the respective tumors. Conclusions: DTPM is a promising tool for the evaluation of whole-organ tissue perfusion. This study demonstrates the feasibility of performing DTPM measurements in kidneys bearing RCC lesions. In tumors that are characterized by extensive neovascularization, this method has the potential to be a valuable diagnostic tool.
The Impact of Tunneled Pleural Catheters on the Quality of Life of Patients with Malignant Pleural Effusions
Authors: Sabur Natasha F. , Chee Alex , Stather David R. , MacEachern Paul , Amjadi Kayvan , Hergott Christopher A. , Dumoulin Elaine , Gonzalez Anne V. , Tremblay Alain
Published: November 2012

Background: Tunneled pleural catheters (TPC) are used in the management of malignant pleural effusions (MPE), but the impact of this palliative procedure on patient quality of life (QoL) has not been well described. Objectives: To ascertain the impact of TPCs on symptoms and QoL of patients with recurrent MPE. Methods: Patients with recurrent MPE completed the EORTC QLQ-C30 and LC13 QoL questionnaires at baseline, 2 and 14 weeks; FACIT-TS-G© treatment satisfaction surveys were completed at 14 weeks. Results: A total of 82 patients were recruited. Thirty-seven patients (37/82, 45%) died prior to their 14-week follow-up appointment. Significant improvements in dyspnea at 2 weeks were demonstrated with both dyspnea scores (LC13 baseline score 64.1, 2-week score 43.7, mean change –20.4, n = 56, p < 0.001; C30 baseline score 78.9, 2-week score 46.6, mean change –32.4, n = 68, p < 0.001), as well as with the MRC score (baseline median score 4, 2-week score 3, n = 70, p < 0.001). Global health status/QoL was also significantly improved at 2 weeks (baseline score 34.1, 2-week score 46.3, mean change 12.3, n = 68, p < 0.001). Improvements in cough, fatigue and all functional scales were noted at 2 weeks. The improvements in dyspnea and global health status/QoL were maintained to 14 weeks in surviving subjects and there was further improvement in the MRC score at 14 weeks. Patients who completed the FACIT-TS-G survey demonstrated overall satisfaction with TPC treatment. Conclusions: TPCs are associated with a significant improvement in global health status, QoL and dyspnea at the 2-week time point in patients with recurrent MPE.
Genetic Variation in the Scavenger Receptor MARCO and Its Association with Chronic Obstructive Pulmonary Disease and Lung Infection in 10,604 Individuals
Authors: Thomsen Mette , Nordestgaard Børge G. , Kobzik Lester , Dahl Morten
Published: November 2012

Background: MARCO (macrophage receptor with collagenous structure) is a dominant receptor for unopsonized particles and bacteria in the lungs. Reduced function of this receptor due to genetic variation may be associated with susceptibility to chronic obstructive pulmonary disease (COPD) and lung infection. Objectives: To identify novel genetic variants in MARCO that are associated with reduced lung function, or increased risk of COPD or lung infection. Methods: We first screened 760 individuals with extreme lung phenotypes in a large general population study to identify novel variants in the MARCO gene. We next genotyped the entire cohort consisting of 10,604 individuals to assess the clinical relevance of these variants. Results: We identified 4 novel (R124H, K201N, P303L and G340W) and 5 previously described (H101Q, F282S, G319V, K387Q and E511D) non-synonymous variants. When screening the entire cohort for these variants, we found low minor allele frequencies ranging from 0.005 to 5%. None of the individual MARCO genotypes were associated with reduced lung function, or risk of COPD or lung infection. H101Q heterozygotes had an increased odds ratio for sepsis of 2.2 (95% CI: 1.1–4.4) compared to non-carriers, but none of the other MARCO genotypes were associated with the risk of sepsis. Conclusions: We identified 9 non-synonymous variants in the MARCO gene and showed that these variants are not major risk factors for COPD or lung infection in the Danish population. H101Q heterozygotes had increased sepsis risk, but further research is required to confirm this finding. This study is the first to examine genetic variants in MARCO and the risk of COPD and infections in humans.
Effects of Deep Brain Stimulation in the Caudal Zona Incerta on Verbal Fluency
Authors: Fytagoridis Anders , Sjöberg Rickard L. , Åström Mattias , Fredricks Anna , Nyberg Lars , Blomstedt Patric
Published: November 2012

Background: Deep brain stimulation (DBS) of the caudal zona incerta (cZi) is a relatively unexplored and promising treatment in patients with severe essential tremor (ET). Preliminary data further indicate that the ability to produce language may be slightly affected by the treatment. Objective: To evaluate the effects on verbal fluency following cZi DBS in patients with ET. Method: Seventeen consecutive patients who had undergone DBS of the cZi for ET were tested regarding verbal fluency before surgery, 3 days after surgery and after 1 year. Ten patients were also evaluated by comparing performance on versus off stimulation after 1 year. Results: The total verbal fluency score decreased slightly, but significantly, from 22.7 (SD = 10.9) before surgery to 18.1 (SD = 7.5) 3 days after surgery (p = 0.036). After 1 year the score was nonsignificantly decreased to 20.1 (SD = 9.7, p = 0.2678). There was no detectable difference between stimulation on and off after 1 year. Conclusion: There was a tendency of an immediate and mostly transient postoperative decline in verbal fluency following cZi DBS for ET. In some of the patients this reduction was, however, more pronounced and also sustained over time.
Vitamin D Status and Parathyroid Hormone Levels in Patients with Obstructive Sleep Apnea
Authors: Barceló Antonia , Esquinas Cristina , Piérola Javier , De la Peña Mónica , Sánchez-de-la-Torre Manuel , Montserrat Josep María , Marín José María , Duran Joaquín , Arqué Meritxell , Bauça Josep Miquel , Barbé Ferrán
Published: November 2012

Background: Vitamin D insufficiency and high levels of parathyroid hormone (PTH) appear to be emerging risk factors for metabolic syndrome (MS), diabetes and cardiovascular disease, conditions that occur frequently in patients with obstructive sleep apnea syndrome (OSAS). Objectives: This study examined whether serum concentrations of 25-hydroxyvitamin D [25(OH)D] and PTH were associated with the presence of MS, diabetes and hypertension among an OSAS population. Methods: A total of 826 patients (635 men and 191 women) with newly diagnosed OSAS were studied. The occurrence of the MS was analyzed according to the National Cholesterol Education Program Adult Treatment Panel III clinical criteria. Serum levels of 25(OH)D, PTH, glucose, triglycerides, cholesterol, HDL cholesterol, creatinine and uric acid were determined. Results: In 55.3% of the men and in 63.2% of the women, the serum 25(OH)D level was less than 30 ng/ml (insufficient status). After adjusting for age, sex and seasonality, there was a significant trend of decreasing odds for diabetes [odds ratio (OR) 0.55, 95% confidence interval (CI) 0.33-0.94, ptrend = 0.038] and MS (OR 0.34, 95% CI 0.21-0.56, ptrend < 0.001) with increasing vitamin D levels. Higher PTH levels were associated with a higher prevalence of obesity (OR 2.05, 95% CI 1.06-3.09, ptrend < 0.001) and hypertension (OR 1.83, 95% CI 1.01-3.05, ptrend = 0.049). Conclusions: These data suggest an inverse association of 25(OH)D with diabetes and MS and a positive association of PTH with obesity and hypertension among patients with OSAS. Based on our observational study, the causative nature of the associations cannot be established. These findings require further examination in prospective studies including clinical trials.
Virtual Ligand-Based Screening Reveals Purmorphamine Analogs with the Capacity to Induce the Osteogenic Differentiation of Human Mesenchymal Stem Cells
Authors: Granéli Cecilia , Karlsson Camilla , Lindahl Anders , Thomsen Peter
Published: November 2012

Human mesenchymal stem cells (hMSCs) have extensive proliferative capacity, are able to self-renew and have the potential to differentiate into cells of the connective tissue lineages. These properties make them a putative cell type for tissue engineering applications, as well as a possible in vivo target for the pharmaceutical modulation of the differentiation processes. The aim of this study was to find one or more small-molecule substances that would enhance the osteogenic differentiation of hMSCs in vitro. The strategy used here was ligand-based virtual screening for substances similar to the previously suggested osteoinductive purmorphamine followed by an in vitro screening of the selected analogs in hMSCs isolated from bone marrow. We investigated the osteoinductive capacity of several purmorphamine analogs by determining the protein and gene expression of markers for osteogenic differentiation as well as the extracellular matrix (ECM) mineralization of these cells. Treatment with two candidate substances or purmorphamine resulted in increased levels of alkaline phosphatase (ALP) activity compared to the control. Other purmorphamine analogs demonstrated higher calcium deposition in the ECM after 5 weeks of osteogenic differentiation, compared to both purmorphamine and the control condition. The resulting substances, which had positive effects on the osteogenic differentiation, are promising as possible modes of treatment for bone-related diseases or defects that target and enhance the osteogenic differentiation of MSCs, in vitro or in vivo. Furthermore, the concept of combining the virtual ligand-based screening method with in vitro screening, using human adult stem cells as a possible strategy for drug discovery, is demonstrated.
Increased Pulsatility Index Is Associated with Intracranial Arterial Calcification
Authors: Park Kwang-Yeol , Chung Pil-Wook , Kim Yong Bum , Moon Heui-Soo , Suh Bum-Chun , Yoon Won Tae
Published: November 2012

Background/Aims: An increase in the pulsatility index (PI) has been suggested to reflect distal vascular resistance. The purpose of the present study was to investigate the association between intracranial arterial calcification and intracranial PIs. Methods: Consecutive patients with acute ischemic stroke or transient ischemic attack were included. The PIs of both middle cerebral arteries (MCAs) were measured by transcranial Doppler ultrasonography. Intracranial carotid artery calcification (ICAC) was assessed on computed tomography angiography, and then compared with the mean PI of both MCAs. Patients with internal carotid artery steno-occlusion were excluded from this study. Results: A total of 156 patients were finally enrolled. The prevalence of diabetes increased as the PI value increased (p for trends; p = 0.025). PI was correlated with ICAC score (r = 0.413, p < 0.001) and age (r = 0.507, p < 0.001). Multiple linear regression analysis indicated that aging and ICAC were independent determinants of the PI of MCA after adjusting for sex, systolic blood pressure, smoking, and the presence of diabetes. Conclusions: This study shows that an increase in PI was correlated with the severity of ICAC, which suggests calcification-related vascular resistance might have a role in the elevation of PI.
Neurotrophin-4 Is More Potent than Brain-Derived Neurotrophic Factor in Promoting, Attracting and Suppressing Geniculate Ganglion Neurite Outgrowth
Authors: Runge Elizabeth M. , Hoshino Natalia , Biehl Matthew J. , Ton Son , Rochlin M. William
Published: November 2012

The geniculate ganglion, which provides innervation to taste buds in the anterior tongue and palate, is unique among sensory ganglia in that its neurons depend on both neurotrophin-4 (NT4) and brain-derived neurotrophic factor (BDNF) for survival. Whereas BDNF is additionally implicated in taste axon guidance at targeting stages, much less is known about the guidance role of NT4 during targeting, or about either neurotrophin during initial pathfinding. NT4 and BDNF have distinct expression patterns in vivo, raising the possibility of distinct roles. We characterized the influence of NT4 and BDNF on geniculate neurites in collagen I gels at early embryonic through postnatal stages. During early pathfinding to the tongue (embryonic days 12–13; E12–13), NT4 and BDNF promote significantly longer outgrowth than during intralingual targeting (E15–18). NT4 is more potent than BDNF at stimulating neurite outgrowth and both factors exhibit concentration optima, i.e. intermediate concentrations (0.25 ng/ml NT4 or 25 ng/ml BDNF) promote maximal neurite extension and high concentrations (10 ng/ml NT4 or 200 ng/ml BDNF) suppress it. Only partial suppression was seen at E12 (when axons first emerge from the ganglion in vivo) and postnatally, but nearly complete suppression occurred from E13 to E18. We show that cell death is not responsible for suppression. Although blocking the p75 receptor reduces outgrowth at the optimum concentrations of NT4 and BDNF, it did not reduce suppression of outgrowth. We also report that NT4, like BDNF, can act as a chemoattractant for geniculate neurites, and that the tropic influence is strongest during intralingual targeting (E15–18). NT4 does not appear to act as an attractant in vivo, but it may prevent premature invasion of the epithelium by suppressing axon growth.
White Matter Hyperintensities in Mild Lewy Body Dementia
Authors: Oppedal K. , Aarsland D. , Firbank M.J. , Sonnesyn H. , Tysnes O.B. , O’Brien J.T. , Beyer M.K.
Published: November 2012

Background: The objective of this study was to explore the load of white matter hyperintensities (WMH) in patients with Lewy body dementia (LBD) and compare to Alzheimer’s disease (AD) and normal controls (NC). Methods: Diagnosis of LBD and AD was made according to consensus criteria and cognitive tests were administered. MRI scans for 77 (61 AD and 16 LBD) patients and 37 healthy elderly control subjects were available for analysis. We segmented WMH from FLAIR images using an automatic thresholding technique and calculated the volume of WMH in several regions of the brain, using non-parametric tests to compare groups. Multivariate regression was applied. Results: There were no significant differences in WMH between AD and LBD. We found a significant correlation between total and frontal WMH and Mini-Mental State Examination (MMSE) and verbal fluency scores in the AD group, but not in the LBD group. Conclusion: The WMH load in LBD was similar to that of AD. A correlation between WMH load and cognition was found in the AD group, but not in the LBD group, suggesting that vascular disease contributes to cognitive impairment in AD but not LBD.
Risk Score for Predicting Recurrence in Patients with Ischemic Stroke: The Fukuoka Stroke Risk Score for Japanese
Authors: Kamouchi Masahiro , Kumagai Naoko , Okada Yasushi , Origasa Hideki , Yamaguchi Takenori , Kitazono Takanari ,   for the FSR Investigators
Published: November 2012

Background: Currently, there are only a few risk scores to predict long-term recurrence of ischemic stroke and no risk score has been developed for the Asian population. The aim of the present study was to develop a new risk score to predict 1-year recurrence in Japanese patients with ischemic stroke and compare it with the other ones. Methods: Data used in this analysis were extracted from the Fukuoka stroke registry (FSR) database, including 3,067 Japanese patients who experienced ischemic stroke. FSR is a multicenter, hospital-based, prospective registry of Japanese patients with acute stroke. Associations between potential clinical variables that could be involved in the increase of risk and recurrence of ischemic stroke within 1 year after initial stroke onset were evaluated using univariate and multivariate analyses. To calculate risk scores, weighted points proportionally based on standardized coefficient values were assigned to variables that were identified to be significant risks for recurrence by multivariate analysis. The Hosmer-Lemeshow goodness-of-fit test was used to test agreement between a predicted outcome using a model and an actual observed outcome. Kaplan-Meier analysis was used to estimate average cumulative recurrence rates within three risk groups. Intergroup comparisons in recurrence rate among the risk groups were performed using a log-rank test. Results: Univariate and multivariate analyses identified nine significant predictors for 1-year recurrence, to which we assigned the following points: age (65–74 years, 1 point; ≥75 years, 2 points), hypertension (1 point), diabetes mellitus (1 point), smoker (1 point), atrial fibrillation (1 point), cardiac diseases (1 point), chronic kidney disease (1 point), nonlacunar stroke (1 point), and previous ischemic stroke (2 points). The Hosmer-Lemeshow goodness-of-fit test demonstrated good agreement between the observed and predicted recurrence rate (χ2 = 2.30, p = 0.97). The ROC curve for the risk score models showed acceptable discriminant power with a C-statistic of 0.636 (95% confidence interval: 0.573–0.698). Trends toward increased risk of recurrence with higher scores were observed. The 1-year recurrence rates were 2.93, 5.83 and 7.96% in low- (≤3 points), intermediate (4–5 points), and high-risk groups (≥6 points), respectively. Kaplan-Meier curves with log-rank test showed a significant difference in recurrence among the three risk groups (p < 0.0001). Conclusions: A new risk score was developed and successfully validated. Our results suggest that this simple risk score enables clinicians to assess 1-year recurrence risk in Japanese patients with ischemic stroke.
Terrestrial Foraging by Cacajao melanocephalus ouakary (Primates) in Amazonian Brazil: Is Choice of Seed Patch Size and Position Related to Predation Risk?
Authors: Barnett Adrian A. , Almeida Thais , Spironello Wilson R. , Silva Welma Sousa , MacLarnon Ann , Ross Caroline
Published: November 2012

We analyse the behaviour ofCacajao melanocephalus ouakaryfeeding at patches of germinating seedlings in dried-out flooded forest. Seedlings ofEschweilera tenuifolia(Lecythidaceae) were the most commonly eaten (88.9%). Some seed patches were revisited over several days, while others were consistently ignored. We tested 3 predictions relating uacari terrestrial foraging behaviour to: (1) arboreal escape route proximity, (2) seed patch size choice and (3) temporal patterns of repeat exploitation. Comparison of fed-at and ignored patches revealed significant preferences for larger patches, and for those close to arboreal refuges but distant from dense ground-based vegetation. Support for these predictions is interpreted as evidence for predation risk-sensitive foraging.
Testicular Fusion in a Patient with Crossed Testicular Ectopia: A Rare Entity
Authors: Yanaral Fatih , Yildirim Mehmet Erol
Published: November 2012

Crossed testicular ectopia (CTE) is a well-described, rare congenital abnormality of testicular descent, in which both testes migrate through one inguinal canal. The objective of this work is to present a case of fused two testicles in a hemiscrotum as a rare entity of CTE. We describe a rare case of CTE in a 19-year-old boy presenting to the Department with left testis placed in the right hemiscrotum with right inguinal hernia. Ultrasound and magnetic resonance imaging revealed fused testes with their own vasa deferentia in the left hemiscrotum. Azoospermia was detected in semen analysis. The patient was referred to microTESE and ICSI procedure for his infertility problem. CTE should be kept in mind in patients with an inguinal hernia and contralateral nonpalpable testis.
Feasibility and Safety of Endoscopic Submucosal Dissection of Esophageal or Gastric Carcinomas under General Anesthesia
Authors: Rong Qiu-Hua , Zhao Guo-Li , Xie Jia-Ping , Wang Le-Xin
Published: November 2012

Objective: To investigate the feasibility and safety of endoscopic submucosal dissection (ESD) of esophageal or gastric carcinomas under general anesthesia. Subjects and Methods: ESD removal of esophageal or gastric carcinomas was performed in 59 patients under midazolam sedation (control group), and in 46 patients under general anesthesia (GA group). The procedural times, perioperative complications and patient's satisfaction with the procedures were recorded. Results: There was no statistically significant difference in age (65 ±12 vs. 58 ±11), male gender (43.5 vs. 49.2%), types or location or the size of the carcinomas (30 ± 6 vs. 28 ± 7 mm) between the control and GA groups (p > 0.05). The mean procedural time in the GA group was shorter than in the control group (42.5 ± 5.5 vs. 79.0 ± 13.2 min, p = 0.01). The combined gastric perforation and postprocedural bleeding rate in the GA group was lower than in the control group, but the difference did not reach statistical significance (p = 0.06). In the GA group, all patients rated the procedural experience as satisfactory, while in the control group, 38 (64.5%) rated the experience as satisfactory (p = 0.001). Conclusion: ESD under general anesthesia was associated with a shorter procedure time and a high rate of patient's satisfaction with the procedures.
The Clinical Significance of PCDH10 Promoter Methylation in Patients with Bladder Transitional Cell Carcinoma
Authors: Lin Ying-Li , Li Zhi-Gang , Guan Tong-Yu
Published: November 2012

Objective: To investigate the clinical significance of PCDH10 (protocadherin 10) promoter methylation in patients with bladder transitional cell carcinoma (TCC). Materials and Methods: 107 samples of bladder TCC and 38 normal bladder epithelial tissues were investigated using methylation-specific PCR, and the relationships between PCDH10 methylation and clinicopathologic features as well as patients' outcome were analyzed. Results: PCDH10 methylation was detected in 63 (58.9%) bladder TCC samples, but no methylation of PCDH10 was found in controls. Moreover, PCDH10 methylation was significantly associated with larger tumor size (p = 0.0074), non-papillary shape (p = 0.0268), tumor relapse (p = 0.0029), high grade (p = 0.0397), advanced stage (p = 0.0004) and poor prognosis (p = 0.0009). In addition, multivariate analysis indicated that PCDH10 methylation is independently associated with poor outcome and may be used as a useful independent prognostic factor (p = 0.0255). Conclusions: PCDH10 methylation is closely associated with malignancy of bladder TCC and may be used as an independent predictor for patients with bladder TCC.
TLR7 Contributes to the Rapid Progression but Not to the Overall Fatal Outcome of Secondary Pneumococcal Disease following Influenza A Virus Infection
Authors: Stegemann-Koniszewski Sabine , Gereke Marcus , Orrskog Sofia , Lienenklaus Stefan , Pasche Bastian , Bader Sophie R. , Gruber Achim D. , Akira Shizuo , Weiss Siegfried , Henriques-Normark Birgitta , Bruder Dunja , Gunzer Matthias
Published: November 2012

Increased risk for bacterial superinfections substantially contributes to the mortality caused by influenza A virus (IAV) epidemics. While the mechanistic basis for this lethal synergism is still insufficiently understood, immune modulation through the viral infection has been shown to be involved. Since the pattern-recognition receptor (PRR) toll-like receptor 7 (TLR7) is a major sensor for the viral genome, we studied how IAV recognition by TLR7 influences the development of secondary pneumococcal infection. In a mouse model of IAV, TLR7-deficient hosts induced a potent antiviral response and showed unchanged survival. In secondary pneumococcal infection during acute influenza, TLR7ko mice showed a fatal outcome similar to wild-type (WT) hosts, despite significantly delayed disease progression. Also, when bacterial superinfection occurred after virus clearance, WT and TLR7-deficient hosts showed similar mortality, even though we found the phagocytic activity of alveolar macrophages isolated from IAV-pre-infected hosts to be enhanced in TLR7ko over WT mice. Thus, we show that a virus-sensing PRR modulates the progression of secondary pneumococcal infection following IAV. However, the fatal overall outcome in WT as well as TLR7ko hosts suggests that processes distinct from TLR7-triggering override the contribution of this single PRR.
Diabetic Embryopathy: A Developmental Perspective from Fertilization to Adulthood
Authors: Castori M.
Published: November 2012

Maternal diabetes mellitus is one of the strongest human teratogens. Despite recent advances in the fields of clinical embryology, experimental teratology and preventive medicine, diabetes-related perturbations of the maternofetal unit maintain a considerable impact on the Healthcare System. Classic consequences of prenatal exposure to hyperglycemia encompass (early) spontaneous abortions, perinatal death and malformations. The spectrum of related malformations comprises some recurrent blastogenic monotopic patterns, i.e. holoprosencephaly, caudal dysgenesis and oculoauriculovertebral spectrum, as well as pleiotropic syndromes, i.e. femoral hypoplasia-unusual face syndrome. Despite this, most malformed fetuses display multiple blastogenic defects of the VACTERL type, whose (apparently) casual combination preclude recognizing recurrent patterns, but accurately testifies to their developmental stage at onset. With the application of developmental biology in modern medicine, the effects of diabetes on the unborn patient are expanded to include the predisposition to develop insulin resistance in adulthood. The mechanisms underlying the transgenerational correlation between maternal diabetes and proneness to adult disorders in the offspring remain unclear, and the epigenetic plasticity may represent the missing link. In this scenario, a development-driven summary of the multifaced consequences of maternal diabetes on fertility and child health may add a practical resource to the repertoire of available information on early stages of embryogenesis.
VATER/VACTERL Association: Evidence for the Role of Genetic Factors
Authors: Reutter H. , Ludwig M.
Published: November 2012

The VATER/VACTERL association is typically defined by the presence of at least 3 of the following congenital malformations: Vertebral anomalies, Anal atresia, Cardiac malformations, Tracheo-Esophageal fistula, Renal anomalies, and Limb abnormalities. The involvement of genetic factors in the development of this rare association is suggested by reports of familial occurrence, the increased prevalence of component features among first-degree relatives of affected individuals, high concordance rates among monozygotic twins, chromosomal (micro-)aberrations or single gene mutations in individuals with the VATER/VACTERL phenotype, as well as murine knock-out models. Despite substantial efforts over the past decade, the genetic etiology of the VATER/VACTERL association in most instances remains elusive. The application of new genomic technologies such as high-resolution copy number variation studies or next-generation exome sequencing might lead to the identification of some of these causes.
Association Between 2 Angiographic Subtypes of Renal Artery Fibromuscular Dysplasia and Clinical Characteristics
Authors: Savard Sébastien , Steichen Olivier , Azarine Arshid , Azizi Michel , Jeunemaitre Xavier , Plouin Pierre-François
Published: November 2012

Background—

Initially based on histology, the diagnosis of renal artery fibromuscular dysplasia (FMD) is now based mostly on angiographic appearance because arterial tissue samples are rarely available. This retrospective cross-sectional study aimed to assess the clinical relevance of a binary angiographic classification of FMD lesions (unifocal or multifocal) based on computed tomographic or magnetic resonance angiography.

Methods and Results—

Adult patients diagnosed with FMD in a single tertiary care center for hypertension management were identified by screening of electronic files. FMD lesions were reviewed and classified according to computed tomography or magnetic resonance angiography as multifocal if there were at least 2 stenoses in the same arterial segment; otherwise, they were classified as unifocal. Of 337 patients with established renal artery FMD, 276 (82%) were classified as multifocal. Patients with unifocal and multifocal lesions differed significantly in median age at diagnosis of FMD (30 and 49 years) and hypertension (26 and 40 years), sex distribution (female:male ratio, 2:1 and 5:1), initial blood pressure (157/97 and 146/88 mm Hg), current smoking (50% and 26%), prevalence of unilateral renal artery lesions (79% and 38%), presence of kidney asymmetry (33% and 10%), renal revascularization procedures (90% and 35%), and hypertension cure rates in patients who underwent revascularization (54% and 26%).

Conclusions—

A binary angiographic classification into unifocal or multifocal renal artery FMD is straightforward and discriminates 2 groups of patients with different clinical phenotypes.
Cytochrome P450 Subfamily 2J Polypeptide 2 Expression and Circulating Epoxyeicosatrienoic Metabolites in Preeclampsia
Authors: Herse Florian , LaMarca Babbette , Hubel Carl A. , Kaartokallio Tea , Lokki A. Inkeri , Ekholm Eeva , Laivuori Hannele , Gauster Martin , Huppertz Berthold , Sugulle Meryam , Ryan Michael J. , Novotny Sarah , Brewer Justin , Park Joon-Keun , Kacik Michael , Hoyer Joachim , Verlohren Stefan , Wallukat Gerd , Rothe Michael , Luft Friedrich C. , Muller Dominik N. , Schunck Wolf-Hagen , Staff Anne C. , Dechend Ralf
Published: November 2012

Background—

Preeclampsia is a multisystem disorder of pregnancy, originating in the placenta. Cytochrome P450 (CYP)-dependent eicosanoids regulate vascular function, inflammation, and angiogenesis, which are mechanistically important in preeclampsia.

Methods and Results—

We performed microarray screening of placenta and decidua (maternal placenta) from 25 preeclamptic women and 23 control subjects. The CYP subfamily 2J polypeptide 2 (CYP2J2) was upregulated in preeclamptic placenta and decidua. Reverse-transcription polymerase chain reaction confirmed the upregulation, and immunohistochemistry localized CYP2J2 in trophoblastic villi and deciduas at 12 weeks and term. The CYP2J2 metabolites, 5,6-epoxyeicosatrienoic acid (EET), 14,15-EET, and the corresponding dihydroxyeicosatrienoic acids, were elevated in preeclamptic women compared with controls in the latter two thirds of pregnancy and after delivery. Stimulating a trophoblast-derived cell line with the preeclampsia-associated cytokine tumor necrosis factor-α enhanced CYP2J2 gene and protein expression. In 2 independent rat models of preeclampsia, reduced uterine-perfusion rat and the transgenic angiotensin II rat, we observed elevated EET, dihydroxyeicosatrienoic acid, and preeclamptic features that were ameliorated by the CYP epoxygenase inhibitor N-(methylsulfonyl)-2-(2-propynyloxy)-benzenehexanamide (MsPPOH). Uterine arterial rings of these rats also dilated in response to MsPPOH. Furthermore, 5,6-EET could be metabolized to a thromboxane analog. In a bioassay, 5,6-EET increased the beating rate of neonatal cardiomyocytes. Blocking thromboxane synthesis reversed that finding and also normalized large-conductance calcium-activated potassium channel activity.

Conclusions—

Our data implicate CYP2J2 in the pathogenesis of preeclampsia and as a potential candidate for the disturbed uteroplacental remodeling, leading to hypertension and endothelial dysfunction.
Relational Features in Fine-Grained Opinion Analysis
Authors: Johansson Richard , Moschitti Alessandro
Published: November 2012

Fine-grained opinion analysis methods often make use of linguistic features but typically do not take the interaction between opinions into account. This article describes a set of experiments that demonstrate that relational features, mainly derived from dependency-syntactic and semantic role structures, can significantly improve the performance of automatic systems for a number of fine-grained opinion analysis tasks: marking up opinion expressions, finding opinion holders, and determining the polarities of opinion expressions. These features make it possible to model the way opinions expressed in natural-language discourse interact in a sentence over arbitrary distances. The use of relations requires us to consider multiple opinions simultaneously, which makes the search for the optimal analysis intractable. However, a reranker can be used as a sufficiently accurate and efficient approximation.

A number of feature sets and machine learning approaches for the rerankers are evaluated. For the task of opinion expression extraction, the best model shows a 10-point absolute improvement in soft recall on the MPQA corpus over a conventional sequence labeler based on local contextual features, while precision decreases only slightly. Significant improvements are also seen for the extended tasks where holders and polarities are considered: 10 and 7 points in recall, respectively. In addition, the systems outperform previously published results for unlabeled (6 F-measure points) and polarity-labeled (10–15 points) opinion expression extraction. Finally, as an extrinsic evaluation, the extracted MPQA-style opinion expressions are used in practical opinion mining tasks. In all scenarios considered, the machine learning features derived from the opinion expressions lead to statistically significant improvements.
Selectional Preferences for Semantic Role Classification
Authors: Zapirain Beñat , Agirre Eneko , Màrquez Lluís , Surdeanu Mihai
Published: November 2012

This paper focuses on a well-known open issue in Semantic Role Classification (SRC) research: the limited influence and sparseness of lexical features. We mitigate this problem using models that integrate automatically learned selectional preferences (SP). We explore a range of models based on WordNet and distributional-similarity SPs. Furthermore, we demonstrate that the SRC task is better modeled by SP models centered on both verbs and prepositions, rather than verbs alone. Our experiments with SP-based models in isolation indicate that they outperform a lexical baseline with 20 F1 points in domain and almost 40 F1 points out of domain. Furthermore, we show that a state-of-the-art SRC system extended with features based on selectional preferences performs significantly better, both in domain (17% error reduction) and out of domain (13% error reduction). Finally, we show that in an end-to-end semantic role labeling system we obtain small but statistically significant improvements, even though our modified SRC model affects only approximately 4% of the argument candidates. Our post hoc error analysis indicates that the SP-based features help mostly in situations where syntactic information is either incorrect or insufficient to disambiguate the correct role.
OntoLearn Reloaded: A Graph-Based Algorithm for Taxonomy Induction
Authors: Velardi Paola , Faralli Stefano , Navigli Roberto
Published: November 2012

In 2004 we published in this journal an article describing OntoLearn, one of the first systems to automatically induce a taxonomy from documents and Web sites. Since then, OntoLearn has continued to be an active area of research in our group and has become a reference work within the community. In this paper we describe our next-generation taxonomy learning methodology, which we name OntoLearn Reloaded. Unlike many taxonomy learning approaches in the literature, our novel algorithm learns both concepts and relations entirely from scratch via the automated extraction of terms, definitions, and hypernyms. This results in a very dense, cyclic and potentially disconnected hypernym graph. The algorithm then induces a taxonomy from this graph via optimal branching and a novel weighting policy. Our experiments show that we obtain high-quality results, both when building brand-new taxonomies and when reconstructing sub-hierarchies of existing taxonomies.
Crime and Punishment in Ottoman Times: Corruption and Fines
Authors: Coşgel Metin M. , Ergene Boǧaç , Etkes Haggay , Miceli Thomas J.
Published: November 2012

Ruling for more than six centuries over lands that spanned three continents, the Ottomans developed a system of law enforcement that initially relied on fines collected by local agents. In the sixteenth century, much of the revenue from these fines went to the local officials in charge of identifying suspects and punishing criminals. To prevent corruption, the personnel responsible for adjudicating criminals were not also responsible for punishing them; public officials were periodically rotated between regions; and law-enforcement agents' compensation derived from criminal fines as well as local taxes. After the seventeenth century, high levels of inflation, imperial decentralization in the provinces, and the institution of long-term tax farming altered the government's relationship with local law-enforcement agents, thereby reducing the effectiveness of mechanisms that previously helped to control corruption. These developments impelled the Ottomans to decrease their reliance on fines for punishment in later periods.
An Assessment of Six Dissimilarity Metrics for Climate Analogs
Authors: Grenier Patrick , Parent Annie-Claude , Huard David , Anctil François , Chaumont Diane
Published: November 2012

Spatial analog techniques consist in identifying locations whose historical climate is similar to the anticipated future climate at a reference location. In the process of identifying analogs, one key step is the quantification of the dissimilarity between two climates separated in time and space, which involves the choice of a metric. In this study, six a priori suitable metrics are described (the standardized Euclidean distance, the Kolmogorov–Smirnov statistic, the nearest-neighbor distance, the Zech–Aslan energy statistic, the Friedman–Rafsky runs statistic, and the Kullback–Leibler divergence) and criteria are proposed and investigated in an attempt to identify the best metric for selecting spatial analogs. The case study involves the use of numerical simulations performed with the Canadian Regional Climate Model (CRCM, version 4.2.3), from which three annual indicators (total precipitation, heating degree-days, and cooling degree-days) are calculated over 30-yr periods (1971–2000 and 2041–70). It is found that the six metrics identify comparable analog regions at a relatively large scale but that best analogs may differ substantially. For best analogs, it is shown that the uncertainty stemming from the metric choice does not generally exceed that stemming from the simulation or model choice. On the basis of the set of criteria considered in this study, the Zech–Aslan energy statistic stands out as the most recommended metric for analog studies, whereas the Friedman–Rafsky runs statistic is the least recommended.
West African Monsoon Intraseasonal Variability: A Precipitable Water Perspective
Authors: Poan D. Emmanuel , Roehrig Romain , Couvreux Fleur , Lafore Jean-Philippe
Published: November 2012

West African monsoon intraseasonal variability has important implications for food security and drought early warnings. In the present study, intraseasonal variability over the Sahel is assessed from the perspective of precipitable water, as provided by model reanalyses and GPS measurements. In the eastern Sahel, precipitable water variability is dominated by time scales longer than 10 days, whereas synoptic scales dominate in the western Sahel, especially because of African easterly waves (AEWs).

The present work then focuses on the moisture footprint of AEWs along the northern side of the African easterly jet, as detected and analyzed directly from the main synoptic disturbances associated with precipitable water. Composite wet and dry precipitable water anomalies within AEWs propagate westward with a 5–6-day period. Their robustness, consistency, and spatial footprint, as well as their significant modulation of the convective activity, imply potential skill for short- to medium-range forecasts of wet and dry events over the Sahel. A composite moisture budget points out the key processes involved in the evolution of moisture anomalies. Advection processes are shown to be dominant during their life cycle. A linear adiabatic analysis of the propagation and growth of AEW precipitable water anomalies captures the main observed properties well, even though a key role of diabatic processes such as rain evaporation is needed to fully understand the life cycle of such precipitable water anomalies, especially their growth over the continent.
Mourning Beyond Melancholia: Freud's Psychoanalysis of Loss
Authors: Clewell Tammy
Published: November 2012

Freud's mourning theory has been criticized for assuming a model of subjectivity based on a strongly bounded form of individuation. This model informs “Mourning and Melancholia” (1917), in which Freud argued that mourning comes to a decisive end when the subject severs its emotional attachment to the lost one and reinvests the free libido in a new object. Yet Freud revised his mourning theory in writings concerned with the Great War and in The Ego and the Id (1923), where he redefined the identification process previously associated with melancholia as an integral component of mourning. By viewing the character of the ego as an elegiac formation, that is, as “a precipitate of abandoned object-cathexes,” Freud's later work registers the endlessness of normal grieving; however, it also imports into mourning the violent characteristics of melancholia, the internal acts of moralized aggression waged in an effort to dissolve the internal trace of the other and establish an autonomous identity. Because it is not immediately clear how Freud's text offers a theory of mourning beyond melancholy violence, his account of the elegiac ego is shown here to ultimately undermine the wish for an identity unencumbered by the claims of the lost other and the past, and to suggest the affirmative and ethical aspects of mourning.
Writing About Patients: II. Patients' Reading About Themselves and Their Analysts' Perceptions of Its Effect
Authors: Kantrowitz Judy L.
Published: November 2012

Thirty American analysts who have published articles that include clinical material were interviewed about their methods for ensuring patient confidentiality. Eight of these analysts had patients who had read about themselves or heard their cases presented, though their analyst had not requested permission to use this material. Eighteen patients had been asked and gave their consent to have their material used. Twelve of these patients were shown the material written about them. The analysts' thoughts and reactions to their experiences of obtaining consent and having their patients read material about themselves, and of disguising material without asking consent and then having it inadvertently discovered and read by their patients, are discussed. Their views of the effect on their patients of reading written material about themselves are elaborated with case illustrations.
Revisiting Rapprochement in the Light of Contemporary Developmental Theories
Authors: Bergman Anni , Harpaz-Rotem Ilan
Published: November 2012

Margaret Mahler's thinking, revolutionary for its time, led to the observational study of mother-infant pairs, followed almost day by day as the preverbal infant developed into a toddler whose increasing cognitive capacities made new demands on the mother's presence and emotional availability. The rapprochement crisis, as formulated based on these observations, is reexamined in the light of contemporary theory, and the concept of co-construction is used to show how mother and toddler repair misunderstandings and inevitable conflicts. With the growth of new verbal capacities during rapprochement, the toddler moves from early, sensorimotor interactions to interactions governed by language, in the process gaining new understanding of his or her emotional life.