bluuebunny/crossref_metadata_2025 huggingface dataset:
Social class, cluster simplification and following context: Sociolinguistic variation in word-final post-obstruent liquid deletion in French
Authors: BOUGHTON ZOË
Published: November 2013

This article is a quantitative study of the variable deletion of post-obstruent /l/ and /R/ in word-final obstruent-liquid clusters (OLC) in French (capable [kapab(l)], cidre [sid(ʁ)]). The analysis of over a thousand tokens extracted from a corpus of interviews gathered in Nancy and Rennes shows that the reduction of word-final OLCs is a stable sociolinguistic marker in northern, standardised metropolitan French. Patterns of stylistic and social stratification in age, gender, and social class and interaction with following phonological context are attested, but OLC reduction does not appear to be an ongoing change. It is argued that the data provide further evidence of variable morpheme-final consonant clusters as a ‘primitive’ feature of vernacular dialects.
Croatian clinical epidemiological study (2008–2011): the use of standardised risk scores in paediatric congenital cardiac surgery for a case complexity selection and gradual progress of cardiosurgical model in developing countries
Authors: Dilber Daniel , Malčić Ivan , Dasović Buljević Andrea , Anić Darko , Belina Dražen , Zovko Ana
Published: November 2013

Objective: By employing the widely used and accepted methodologies of case-mix complexity adjustment in congenital cardiac surgery, we tried to evaluate our performance and use the ABC scores for a case complexity selection that may have different outcomes in various centres. Methods: We analysed outcomes of cardiac surgical procedures – with or without cardiopulmonary bypass – performed in our institution between January, 2008 and December, 2011. Data were collected from the European Association for Cardio-Thoracic Surgery database. Together with prospective collection of these data, the data of all patients sent abroad to foreign cardiosurgical centres were recorded. Results: During the period of study, 634 operations were performed; among them, 60% were performed in Croatia and 40% in foreign cardiosurgical centres. The number of operations performed in Croatia showed a linear increase: 55, 78, 121, and 126 operations performed in the years 2008, 2009, 2010, and 2011, respectively. Early mortality rates were 1.82%, 5.41%, 3.64%, and 3.48% in 2008, 2009, 2010, and 2011, respectively. The increase in the number of operations was followed by a satisfactory low average mortality rate of 3.85%. The mean ABC score complexity for operations performed in Croatia was 5.77. We determined a linear correlation between ABC score and early mortality, especially for the more complex operations. Conclusion: The use of standardised risk scores allows selection of complex cardiac diseases, which may have very different outcomes in various centres. In our case, those with higher ABC scores were correctly identified and referred for treatment abroad. In this way, we allowed gradual progress of the cardiosurgical model in Croatia and maintained an enviably low mortality rate.
Reduced long-term exercise capacity in young adults operated for ventricular septal defect
Authors: Heiberg Johan , Laustsen Sussie , Petersen Annemette K. , Hjortdal Vibeke E.
Published: November 2013

Background

Ventricular septal defects are normally closed in early childhood, and post-surgically the patients are considered as healthy and fit as their peers. However, data are inconsistent. We exercise-tested a cohort of ventricular septal defect-operated patients and a group of matched controls to evaluate long-term physical fitness.

Methods

Cardiopulmonary exercise capacity was tested on an ergometer cycle in 30 patients and 30 healthy age and gender-matched controls. Pulmonary ventilation and gas exchange were simultaneously measured breath-by-breath with Jaeger MasterScreen CPX® (CareFusion, San Diego, United States of America). During the test session, respiratory gas exchange was measured along with heart rate, blood pressure, and electrocardiogram. The endpoints were peak oxygen uptake, maximal workload, and ventilatory anaerobic threshold. The International Physical Activity Questionnaire and the SF-36 were applied for Health-Related Quality-of-Life assessment.

Results

Ventricular septal defect-operated adults had a markedly lower peak oxygen uptake: mean 38.0(±8.2 ml O2/kg/minute) versus 47.9(±6.5 ml O2/kg/minute) in controls, p<0.01. Furthermore, ventilatory anaerobic threshold was impaired in ventricular septal defect patients: mean 25.3(±7.8 ml O2/kg/minute) versus 35.2(±7.7 ml O2/kg/minute) in controls, p<0.01. Maximal workload was reduced: mean 3.3(±0.7 W/kg) versus 4.0(±0.5 W/kg) in the control group, p<0.01. Lastly, ventricular septal defect patients had a significantly lower peak heart rate: mean 182(±8.8 beats/minute) versus 188(±9.0 beats/minute) in controls, p=0.03. Regarding Health-Related Quality of Life, the ventricular septal defect group had significantly lower scores in physical functioning, role physical, and social functioning.

Conclusion

Young adults with a surgically closed ventricular septal defect had a markedly reduced cardiopulmonary exercise capacity and a lower peak heart rate compared with controls.
Association between N-terminal pro-brain natriuretic peptide and quality of life in adult patients with congenital heart disease
Authors: Younge John O. , Eindhoven Jannet A. , Utens Elisabeth W. M. J. , Opić Petra , Cuypers Judith A. A. E. , van den Bosch Annemien E. , Witsenburg Maarten , van Domburg Ron T. , Hunink M. G. Myriam , Roos-Hesselink Jolien W.
Published: November 2013

Aims: Advances in medical treatment have resulted in increased life expectancy in congenital heart disease. Consequently, the focus of management has shifted from reducing mortality to reducing long-term morbidity with the goal of improving quality of life. A predictor of quality of life might be N-terminal pro-brain natriuretic peptide, a well-established marker for heart failure. We aimed to determine the association between N-terminal pro-brain natriuretic peptide and quality of life in patients with congenital heart disease. Methods: We collected blood samples from consecutive patients who were initially operated between 1968 and 1980 (47.8% women; mean age 40.2±5.4 years). The 36-item Short-Form Health Survey was completed to assess subjective health status as a measure of quality of life. Analysis was performed for the entire group and for subgroups defined as simple versus complex congenital heart diseases. Median N-terminal pro-brain natriuretic peptide level was 15.2 pmol/L (overall range 1.3–299.3 pmol/L). N-terminal pro-brain natriuretic peptide levels were associated with the subdomain physical functioning (β=−0.074, p=0.031). This association remained significant after adjustment for age and sex (β=−0.071, p=0.038) and after adjustment for age, sex, body mass index, left ventricular function, and renal function (β=−0.069, p=0.048). In complex congenital heart disease, the association between N-terminal pro-brain natriuretic peptide and physical functioning remained significant in multivariable analysis (β=−0.076, p=0.046). No associations were found in the simple congenital heart disease group or on the other health status subdomains. Conclusion: In adults operated for congenital heart disease, N-terminal pro-brain natriuretic peptide is associated with the subdomain physical, primarily in the complex subgroup.
Economic growth and the transition from non-renewable to renewable energy
Authors: Greiner Alfred , Gruene Lars , Semmler Willi
Published: November 2013

The paper considers the transition of an economy from non-renewable to renewable energy. We set up a canonical growth model with damages in the household's welfare function and two energy sources – non-renewable and renewable energy. To produce renewable energy a capital stock must be built up. A socially optimal solution is considered that takes into account the negative externality from the non-renewable energy. We also study how the optimal solution can be mimicked in a market economy by policies using subsidies and tax rates. To solve the model numerically, we use Nonlinear Model Predictive Control. We study when a transition to renewable energy takes place and whether it occurs before the non-renewable resource is exhausted. In addition, we analyze the impact of the initial values of the non-renewable resource and of the capital stock on the time of paths of the variables.
From Unequal Treaties to Differential Treatment: Is There a Role for Equality in Treaty Relations?
Authors: DE JONGE Alice
Published: November 2013

In 2005, Matthew Craven noted that “[t]he phenomenon of unequal treaties [has] largely evaporated as an issue from the domain of international law”. In Craven's opinion, international lawyers have demonstrated an “unwillingness to engage effectively with the problem of equality”. This paper argues that states have, in fact, addressed issues of inequity in recent treaty negotiations. When states have had to unite around common goals, various methods of according special and differential treatment have been used to address concerns about substantive equality. Drawing upon precedents from environmental law and international trade, this paper proposes the recognition of a principle of equality in treaty relations. It is suggested that the persistence of inequality should provide grounds for seeking the renegotiation of a treaty, and that a general principle in favour of remedying unacceptable levels of inequality should be applied to build flexibility and stability into treaty relationships.
HCV NS3 protease enhances liver fibrosis via binding to and activating TGF-β type I receptor
Authors: Sakata Kotaro , Hara Mitsuko , Terada Takaho , Watanabe Noriyuki , Takaya Daisuke , Yaguchi So-ichi , Matsumoto Takehisa , Matsuura Tomokazu , Shirouzu Mikako , Yokoyama Shigeyuki , Yamaguchi Tokio , Miyazawa Keiji , Aizaki Hideki , Suzuki Tetsuro , Wakita Takaji , Imoto Masaya , Kojima Soichi
Published: November 2013

Viruses sometimes mimic host proteins and hijack the host cell machinery. Hepatitis C virus (HCV) causes liver fibrosis, a process largely mediated by the overexpression of transforming growth factor (TGF)-β and collagen, although the precise underlying mechanism is unknown. Here, we report that HCV non-structural protein 3 (NS3) protease affects the antigenicity and bioactivity of TGF-β2 in (CAGA)9-Luc CCL64 cells and in human hepatic cell lines via binding to TGF-β type I receptor (TβRI). Tumor necrosis factor (TNF)-α facilitates this mechanism by increasing the colocalization of TβRI with NS3 protease on the surface of HCV-infected cells. An anti-NS3 antibody against computationally predicted binding sites for TβRI blocked the TGF-β mimetic activities of NS3 in vitro and attenuated liver fibrosis in HCV-infected chimeric mice. These data suggest that HCV NS3 protease mimics TGF-β2 and functions, at least in part, via directly binding to and activating TβRI, thereby enhancing liver fibrosis.
Rediscovering the genus Lyticum, multiflagellated symbionts of the order Rickettsiales
Authors: Boscaro Vittorio , Schrallhammer Martina , Benken Konstantin A. , Krenek Sascha , Szokoli Franziska , Berendonk Thomas U. , Schweikert Michael , Verni Franco , Sabaneyeva Elena V. , Petroni Giulio
Published: November 2013

Among the bacterial symbionts harbored by the model organism Paramecium, many still lack a recent investigation that includes a molecular characterization. The genus Lyticum consists of two species of large-sized bacteria displaying numerous flagella, despite their inability to move inside their hosts' cytoplasm. We present a multidisciplinary redescription of both species, using the deposited type strains as well as newly collected material. On the basis of 16S rRNA gene sequences, we assigned Lyticum to the order Rickettsiales, that is intensely studied because of its pathogenic representatives and its position as the extant group most closely related to the mitochondrial ancestor. We provide conclusive proofs that at least some Rickettsiales possess actual flagella, a feature that has been recently predicted from genomic data but never confirmed. We give support to the hypothesis that the mitochondrial ancestor could have been flagellated and provide the basis for further studies on these ciliate endosymbionts.
Improved synthesis of 4-/6-substituted 2-carboxy-1H-indole-3-propionic acid derivatives and structure–activity relationships as GPR17 agonists
Authors: Baqi Younis , Alshaibani Samer , Ritter Kirsten , Abdelrahman Aliaa , Spinrath Andreas , Kostenis Evi , Müller Christa E.
Published: November 2013

Several tri- and tetra-substituted indole derivatives were synthesized and evaluated as human GPR17 agonists. Steep structure–activity relationships were observed.
Gram-scale synthesis of high-temperature (900 °C) stable anatase TiO2 nanostructures assembled by tunable building subunits for safer lithium ion batteries
Authors: Charette Kevin , Zhu Jian , Salley Steven O. , Ng K. Y. Simon , Deng Da
Published: November 2013

Unusually thermal stable anatase TiO2 with high-order structures and controlled grain size were produced for highly reversible lithium ion storage.
Carbonaceous hydrogels and aerogels for supercapacitors
Authors: Wu Xi-Lin , Xu An-Wu
Published: November 2013

This feature article gives an overview of the recent advances in the use of carbonaceous hydrogels and aerogels for supercapacitors.
Bisubstrate UDP–peptide conjugates as human O-GlcNAc transferase inhibitors
Authors: Borodkin Vladimir S. , Schimpl Marianne , Gundogdu Mehmet , Rafie Karim , Dorfmueller Helge C. , Robinson David A. , van Aalten Daan M. F.
Published: November 2013

Inhibitors of OGT (O-GlcNAc transferase) are valuable tools to study the cell biology of protein O-GlcNAcylation. We report OGT bisubstrate-linked inhibitors (goblins) in which the acceptor serine in the peptide VTPVSTA is covalently linked to UDP, eliminating the GlcNAc pyranoside ring. Goblin1 co-crystallizes with OGT, revealing an ordered C3 linker and retained substrate-binding modes, and binds the enzyme with micromolar affinity, inhibiting glycosyltransfer on to protein and peptide substrates.
Structure of RDE-4 dsRBDs and mutational studies provide insights into dsRNA recognition in the Caenorhabditis elegans RNAi pathway
Authors: Chiliveri Sai Chaitanya , Deshmukh Mandar V.
Published: November 2013

The association of RDE-4 (RNAi defective 4), a protein containing two dsRBDs (dsRNA-binding domains), with long dsRNA and Dcr-1 (Dicer1 homologue) initiates the siRNA pathway in Caenorhabditis elegans. Unlike its homologues in higher eukaryotes, RDE-4 dsRBDs possess weak (micromolar) affinity for short dsRNA. With increasing length of dsRNA, RDE-4 exhibits enhanced affinity due to co-operativity. The linker and dsRBD2 are indispensable for RDE-4's simultaneous interaction with dsRNA and Dcr-1. In the present study, we have determined the solution structures of RDE-4 constructs that contain both dsRBDs and the linker region. In addition to the canonical dsRBD fold, both dsRBDs of RDE-4 show modified structural features such as truncation in the β1–β2 loop that rationalize RDE-4's relatively weak dsRNA affinity. Structure and binding studies demonstrate that dsRBD2 plays a decisive role in the RDE-4–dsRNA interaction; however, in contrast with previous findings, we found ephemeral interaction of RDE-4 dsRBD1 with dsRNA. More importantly, mutations in two tandem lysine residues (Lys217 and Lys218) in dsRBD2 impair RDE-4's dsRNA-binding ability and could obliterate RNAi initiation in C. elegans. Additionally, we postulate a structural basis for the minimal requirement of linker and dsRBD2 for RDE-4's association with dsRNA and Dcr-1.
Suppression of abdominal aortic aneurysm formation by inhibition of prolyl hydroxylase domain protein through attenuation of inflammation and extracellular matrix disruption
Authors: Watanabe Aya , Ichiki Toshihiro , Sankoda Chikahiro , Takahara Yusuke , Ikeda Jiro , Inoue Eriko , Tokunou Tomotake , Kitamoto Shiro , Sunagawa Kenji
Published: November 2013

In the present study we sought to determine the effect of CoCl2, an inhibitor of PHD (prolyl hydroxylase domain protein), on the development of AAA (abdominal aortic aneurysm). AAA was induced in C57BL/6 mice by periaortic application of CaCl2 (AAA group). NaCl (0.9%)-treated mice were used as a sham control (SHAM group). Mice were treated with 0.05% CoCl2 in the drinking water (AAA/CoCl2 group). At 1 and 6 weeks after the operation, aortic tissue was excised for further examination. After 6 weeks of CaCl2 treatment, aortic diameter and macrophage infiltration into the aortic adventitia were increased in the AAA group compared with the SHAM group. Treatment with CoCl2 reduced the aneurysmal size and macrophage infiltration compared with the AAA group. Aortic expression of inflammatory cytokines and MCP-1 (monocyte chemoattractant protein-1) and the activities of MMP-9 (matrix metalloproteinase-9) and MMP-2 were enhanced in the AAA group and attenuated in the AAA/CoCl2 group. Expression of cytokines and the activities of MMPs were already increased after 1 week of CaCl2 treatment, but were suppressed by CoCl2 treatment in association with reduced NF-κB (nuclear factor κB) phosphorylation. Treatment with CoCl2 in mice prevented the development of CaCl2-induced AAA in association with reduced inflammation and ECM (extracellular matrix) disruption. The results of the present study suggest that PHD plays a critical role in the development of AAA and that there is a therapeutic potential for PHD inhibitors in the prevention of AAA development.
The Relationship of Aphasia Type and Gesture Production in People With Aphasia
Authors: Sekine Kazuki , Rose Miranda L.
Published: November 2013

Purpose

For many individuals with aphasia, gestures form a vital component of message transfer and are the target of speech-language pathology intervention. What remains unclear are the participant variables that predict successful outcomes from gesture treatments. The authors examined the gesture production of a large number of individuals with aphasia—in a consistent discourse sampling condition and with a detailed gesture coding system—to determine patterns of gesture production associated with specific types of aphasia.

Method

The authors analyzed story retell samples from AphasiaBank (TalkBank, n.d.), gathered from 98 individuals with aphasia resulting from stroke and 64 typical controls. Twelve gesture types were coded. Descriptive statistics were used to describe the patterns of gesture production. Possible significant differences in production patterns according to aphasia type were examined using a series of chi-square, Fisher exact, and logistic regression statistics.

Results

A significantly higher proportion of individuals with aphasia gestured as compared to typical controls, and for many individuals with aphasia, this gesture was iconic and was capable of communicative load. Aphasia type impacted significantly on gesture type in specific identified patterns, detailed here.

Conclusion

These type-specific patterns suggest the opportunity for gestures as targets of aphasia therapy.

Supplemental Material

https://doi.org/10.23641/asha.14963538
Treating Speech Subsystems in Childhood Apraxia of Speech With Tactual Input: The PROMPT Approach
Authors: Dale Philip S. , Hayden Deborah A.
Published: November 2013

Purpose

Prompts for Restructuring Oral Muscular Phonetic Targets (PROMPT; Hayden, 2004; Hayden, Eigen, Walker, & Olsen, 2010)—a treatment approach for the improvement of speech sound disorders in children—uses tactile-kinesthetic-proprioceptive (TKP) cues to support and shape movements of the oral articulators. No research to date has systematically examined the efficacy of PROMPT for children with childhood apraxia of speech (CAS).

Method

Four children (ages 3;6 [years;months] to 4;8), all meeting the American Speech-Language-Hearing Association (2007) criteria for CAS, were treated using PROMPT. All children received 8 weeks of 2 × per week treatment, including at least 4 weeks of full PROMPT treatment that included TKP cues. During the first 4 weeks, 2 of the 4 children received treatment that included all PROMPT components except TKP cues. This design permitted both between-subjects and within-subjects comparisons to evaluate the effect of TKP cues. Gains in treatment were measured by standardized tests and by criterion-referenced measures based on the production of untreated probe words, reflecting change in speech movements and auditory perceptual accuracy.

Results

All 4 children made significant gains during treatment, but measures of motor speech control and untreated word probes provided evidence for more gain when TKP cues were included.

Conclusion

PROMPT as a whole appears to be effective for treating children with CAS, and the inclusion of TKP cues appears to facilitate greater effect.
Language Comprehension Profiles of Young Adolescents With Fragile X Syndrome
Authors: Oakes Ashley , Kover Sara T. , Abbeduto Leonard
Published: November 2013

Purpose

In this study, the authors sought to characterize the language phenotype of fragile X syndrome (FXS), focusing on the extent of impairment in receptive syntax, within-syndrome variability in those impairments in relation to gender, and the syndrome specificity of those impairments.

Method

The Test for Reception of Grammar, Version 2 (Bishop, 2003), was used to examine the overall receptive syntactic skills of adolescents with FXS (n= 35; 30 males, 5 females), adolescents with Down syndrome (DS;n= 28; 18 males, 10 females), and younger typically developing (TD) children (n= 23; 14 males, 9 females) matched on nonverbal cognition. Performance on specific grammatical constructions and error types was examined for a subset of matched participants.

Results

Participants with FXS had overall receptive syntax scores that were lower than those of the TD participants but higher than those of the participants with DS; however, there was no difference in performance between the FXS and DS groups when females were excluded. Grammatical constructions that were especially difficult for participants with FXS and those with DS were identified, especially relative clause constructions and reversible constructions requiring attention to word order encoded by syntactic features.

Conclusion

The current findings have implications for understanding the nature of the language learning difficulties of individuals with FXS and for language interventions.
Phonological Processing Skills of Children Adopted Internationally
Authors: Scott Kathleen A. , Pollock Karen , Roberts Jenny A. , Krakow Rena
Published: November 2013

Purpose

In recent years, large numbers of children have been adopted from abroad into the United States. This has prompted an interest in understanding and improving the developmental outcomes for these children. Although a growing number of studies have investigated the early language development of children who have been adopted internationally, few have focused specifically on the phonological processing development of this group of children, even though it is widely acknowledged that phonological processing skills are important in language and literacy acquisition. The purpose of this study was to examine the phonological processing skills of a group of children who had been adopted from China into the United States.

Method

The participants were 45 children who had been adopted from China (
M
age
at adoption = 13.09 months). The children were assessed between the ages of 6;10 (years;months) and 9;4. Their phonological processing skills, spoken language skills, and reading comprehension skills were assessed using norm-referenced measures.

Results

Overall, the majority of children scored at or above the average ranges across measures of phonological awareness, phonological memory, and rapid naming. The children's reading comprehension scores were moderately to highly correlated with their phonological processing scores, but age at the time of adoption was not highly correlated with phonological processing or reading comprehension.

Conclusion

The findings of the current study provide a basis for an optimistic view regarding the later language and literacy development of school-age children who were internationally adopted by the age of 2 years.
1. Patient compliance with screening and treatment protocols for anal dysplasia in a high-risk population
Authors: Alrefai Sameer , Levine Rebecca A.
Published: November 2013

Background
Anal cancer rates are increasing in the US and particularly in patients with HIV. High-resolution anoscopy (HRA) with ablation of precursor lesions is thought to be critical towards reversing this trend but patient compliance is poor. The aim of this study was to identify factors associated with loss to follow-up, so that targeted initiatives might be introduced to improve compliance and maximise cancer prevention. Methods: Data on all patients undergoing HRA at our institution was reviewed. We categorised patients as ‘compliant’ if they underwent continued surveillance or ablation within recommended time intervals or as ‘non-compliant’ if they delayed treatment or were lost to follow-up entirely. Demographic factors and disease-related parameters were compared across both groups. Results: 153 patients underwent HRA, including 114 men (71% MSM) and 123 HIV-positive patients (99.2% on ART). Most patients had LSIL on Pap smear (51%) with 23.5% ASCUS and 7.8% HSIL. 35% of patients had high-grade biopsies. 96 patients were compliant with follow-up (62.7%) and 57 patients were not. There were no significant demographic differences between the two groups. However, the compliant group contained a significantly higher proportion of patients with high-grade lesions compared with the non-compliant group (27.1% vs 15.8%, P = 0.0003). Conclusions: In this preliminary report, there were no demographic variables associated with likelihood of follow-up. However, high-grade pathology was more frequently identified in the compliant group. Whether this was due to more aggressive tracking of these patients remains unclear. Further efforts to identify predictive factors for compliance are essential.
18. Topical 5% 5-flourouracil (t5FU) for treatment of diffuse anal high-grade squamous intraepithelial lesions (aHSIL)
Authors: Jay Naomi , Berry J. Michael , Walhart Tara , Darragh Teresa
Published: November 2013

Background
Treatment of anal high-grade squamous intraepithelial lesions (aHSIL) may prevent anal cancer. Options for treatment of diffuse lesions include staged ablation, often requiring surgery, although in-office treatment is preferable. Topical 5% 5-fluorouracil (t5FU) has been used to treat diffuse female genital HPV-associated disease. We report our experience using t5FU for treatment of diffuse aHSIL considered unsuitable for ablation, to evaluate its tolerability and efficacy. Methods: Patients were given t5FU for treatment of diffuse aHSIL in doses of 0.5 mL self-applied 2× daily for 5 days followed by 9 days off. Patients were assessed on average following 4–8 cycles for complete response (CR), defined as the absence of HSIL on exam, cytology and/or histology, or partial response (PR), defined as a reduction in the amount of disease. Patients with PR then received ablative therapy. Results: 73 patients (55 HIV infected, 18 uninfected) were treated, including 13 women and 60 men. In 69 patients who used t5FU for at least one cycle, CR occurred in 8 (~11%) patients, 53 (~77%) had a partial response indicating reduction of disease, 6 (9%) had no response, and 1 had more widespread disease, 1 chart was not evaluable. Treatment was discontinued after <1 cycle in 4 patients due to side effects. Patients with PR were treated successfully with in-office ablation, except 2 patients referred for surgery. Conclusions: t5FU was well tolerated although side effects occur. Most patients had clinical improvement, suggesting that t5FU may play an important role in aHSIL treatment. Further studies may determine its optimal use.
33. Gradually decreasing anal cancer incidence in the HIV+ population in the Netherlands after a decade of cART
Authors: Richel O. , Van der Zee R. P. , Smit C. , De Vries H. J. C. , Prins J. M.
Published: November 2013

Background
Anal cancer incidence has been increasing in the combined antiretroviral therapy (cART) era in HIV+ patients. In this study we surveyed trends in anal cancer incidence between 1995 and 2012, and analysed a range of potential risk factors. Methods: We retrieved data for all patients diagnosed with anal cancer from the Dutch HIV observational cohort (ATHENA) database. Incidence rates were calculated per 100 000 person-years of follow-up (FU), for the whole period of 18 years, and per 2-year blocks. Potential risk factors were analysed in a uni- and multivariable Cox proportional hazard model. Results: For all HIV+ patients, men who have sex with men (MSM), and heterosexual men and women, respectively, the incidence of anal cancer was 83 (95% CI 70–99), 116 (95% CI 95–140), 44 (95% CI 21–83) and 12 (95% 3–30) per 100 000 person-years of FU. In 2005–2006, a peak in incidence rates was observed of 114 (95% CI 74–169) in the total HIV population and 168 (95% CI 103–259) among HIV+ MSM, followed by a decrease to 72 (95% CI 42–113) and 100 (95% CI 56–164), respectively, in 2011–2012. Low nadir CD4 (<110), alcohol abuse and smoking were significantly associated with anal cancer in MSM, with hazard ratios (HR) of 2.41 (95%CI 1.5–3.89), 2.23 (95% CI 1.28–3.89) and 1.60 (95% CI 1.07–2.41), respectively. Conclusions: Anal cancer remains a serious problem in predominantly HIV+ MSM; however, it seems that incidence rates are levelling off. A low nadir CD4 count, alcohol abuse and smoking are risk factors for the development of anal cancer.
38. Anal cancer screening in HIV primary care: uptake and outcomes
Authors: Salit Irving E. , Blitz Sandra , Collins Evan , Aggarwal Banita , Raboud Janet , Tinmouth Jill , Kovacs Colin , Conway Denis , Hedgcock Malcolm , Merkley Barry , Fletcher David , Calzavara Liviana
Published: November 2013

Background
Anal cytology (Pap tests) plus high-resolution anoscopy (HRA) as required are felt to be the optimal approach to anal cancer screening. We present preliminary results from STANDOUT, a study of acceptability and outcomes of anal cancer screening of HIV+ MSM in primary care practices. Methods: All previously unscreened HIV+ MSM from 9 HIV primary care practices, were invited by email or letter to receive anal cancer screening. Responders had anal cytology done at specially arranged or routine clinic visits. Those with high-grade squamous intraepithelial lesions (HSIL) on anal cytology were offered HRA to assess for anal intraepithelial neoplasia (AIN). Those with AIN 2/3 on biopsy were randomised to receive trichloroacetic acid (TCA) or infrared coagulator (IRC) treatments. Results: 1733 patients were invited and 921 (53%) agreed to have anal cytology done. Among those screened, 3 had unsatisfactory samples; 596 (65%) had normal cytology, 253 (27%) had low-grade squamous intraepithelial lesions (LSIL) and 69 (7.5%) had HSIL. HRA results are available in 64: 41 (64%) had histologic high-grade disease (29 had AIN2 and 12 had AIN3). Those with AIN 2/3 were randomised to receive treatment with TCA (16 patients) or IRC (18 patients). Treatment successes at 3 months were 6 of 15 patients for TCA (40%) and 11 of 16 patients for IRC (69%). Conclusions: In this sample of HIV+ MSM, about half of those invited for anal cancer screening agreed to have it done. Most with HSIL had histological high-grade disease and were treated. IRC was more successful than TCA at ablating high-grade disease.
48. Cidofovir treatment prevents invasion of invasive HPV-16-positive anal keratinocytes
Authors: Wechsler Erin Isaacson , Tugizov Sharof , Palefsky Joel
Published: November 2013

Background
The nucleotide analogue cidofovir has been shown to be effective in treating precancerous HPV-associated lesions located in the respiratory tract, cervix, vulva and anus. Cidofovir has been shown to have a 51% efficacy in the short-term treatment of high-grade perianal squamous intraepithelial lesions in HIV-infected persons. Less is known about the effect of cidofovir in treating more advanced stages of HPV-associated disease such as invasive cancer. Methods: We established an immortalised anal keratinocyte cell line (AKC2) following transfection of the HPV-16 genome into primary anal keratinocytes and long-term culture. AKC2 cells were invasive using in vitro collagen invasion assays. To determine the effect of cidofovir on invasion, AKC2 cells were treated for up to 7 days with different concentrations of cidofovir (10, 25 and 50 µg mL–1) and studied using the collagen invasion assays. Untreated cells served as a control. Results: We detected a decrease in invasion of AKC2 cells (50%, 70% and 90% decrease) with 10, 25 and 50 µg mL–1 cidofovir, respectively. Cellular toxicity was not detected in any of the cidofovir-treated samples. Preliminary data suggest that cidofovir directly or indirectly impairs the formation of actin filaments and cellular filopodia, which are known to play a role in cellular invasion. Conclusions: Cidofovir inhibits invasion of HPV-16-transformed anal keratinocytes potentially through affecting pathways that are involved in actin filament formation. Cidofovir could potentially be useful as an adjuvant treatment for invasive anal cancers, and its mechanism of action in inhibiting cellular invasion requires further study.
Both the
cis
-
trans
equilibrium and isomerization dynamics of a single proline amide modulate β2-microglobulin amyloid assembly
Authors: Torbeev Vladimir Yu. , Hilvert Donald
Published: November 2013

Significance

β2-Microglobulin is an abundant and normally soluble protein. In patients undergoing chronic dialysis, however, it forms insoluble amyloid plaques, leading to medical complications. It has been suggested that the conformational transformation of soluble protein monomers into polymeric amyloids is mediated by isomerization of a single amino acid, namely, proline 32. In this study, we probed the role of this amino acid by chemically synthesizing uniquely tailored protein analogs containing noncanonical amino acids at position 32. Our results show that both the chemical equilibrium and rate of
cis-trans
isomerization of proline 32 are critical for the solubility of β2-microglobulin and its self-assembly into morphologically distinct amyloid fibrils. These insights may aid ongoing efforts to provide remedies against dialysis-related amyloidosis.
Lhx2 regulates a cortex-specific mechanism for barrel formation
Authors: Shetty Ashwin S. , Godbole Geeta , Maheshwari Upasana , Padmanabhan Hari , Chaudhary Rahul , Muralidharan Bhavana , Hou Pei-Shan , Monuki Edwin S. , Kuo Hung-Chih , Rema V. , Tole Shubha
Published: November 2013

Significance

The somatosensory barrels are a unique feature of the rodent cortex. Each barrel represents a functional unit in which clustered innervation from an individual whisker connects with a ring of cortical neurons. This study reports that when a single transcription factor, LIM homeobox 2, is deleted specifically in the cortex, neither the barrel cores nor the cortical barrel walls are able to form, although a rudimentary functional mapping of the somatosensory innervation does occur. Understanding how barrels form will shed light on how functional neurocircuitry is assembled in its final stages, and this insight may be broadly applicable in the nervous system.
Bottom-up limits to Newfoundland capelin (Mallotus villosus) rebuilding: the euphausiid hypothesis
Authors: Obradovich Shannon G. , Carruthers Erin H. , Rose George A.
Published: November 2013

Capelin (Mallotus villosus) is the key forage fish species in the Newfoundland and Labrador Shelf ecosystem. Capelin stocks collapsed in the early 1990s, concurrent with declines in “northern” Atlantic cod, Gadus morhua. Neither has fully recovered yet. Changes in growth, condition, and behaviour accompanied capelin declines on the northern Grand Banks (NGB), and remain two decades later. Feeding, growth, and condition of NGB capelin were all lower when compared with capelin from the eastern Scotian Shelf (ESS), where abundance increased following predator declines. For age 2–5 capelin of both sexes, all but one of five comparable age–sex groups were significantly larger on the ESS (e.g. age 3 females average 169 mm on the ESS and 151 mm on the NGB). Neither temperature nor density-dependence explain these differences. However, dietary differences were prominent. ESS capelin had higher total fullness indices (TFIs) than NGB fish at all sizes [mean TFIESS = 1.43 (± 1.14), mean TFINGB = 0.48 (± 0.70)]. Euphausiids (especially Thysanoessa spp.) were a main dietary component on the ESS but not on the NGB. Stable isotope analyses (δ15N and δ13C) for NGB capelin also indicated few dietary euphausiids. Trophic fractionation of δ 15N was 4.740/00, suggesting NGB capelin were food limited. Capelin recovery on the Newfoundland and Labrador Shelf appears limited by bottom-up forcing, in particular lack of euphausiid prey.
Ultrasound Assessment of the Abdominal Muscles at Rest and During the ASLR Test Among Adolescents With Scoliosis
Authors: Linek Paweł , Saulicz Edward , Kuszewski Michał , Wolny Tomasz
Published: November 2013

Study Design:

Observational study.

Objective:

Are there deviations in the thickness of abdominal muscles at rest in individuals with adolescent idiopathic scoliosis (AIS)? Are there deviations in abdominal muscular activity in people with AIS during the active straight leg raise (ASLR) test?

Summary of Background Data:

Ultrasound imaging can be used to assess the lateral abdominal muscle. Some authors suggest that scoliosis develops through a weakness or improper functioning of the abdominal muscles that cannot provide adequate support to the spinal segments. However, the literature lacks studies on the functioning of the abdominal muscles in individuals with spinal deviations. This study focuses on the evaluation of the thickness of the external oblique (EO), internal oblique (IO), and transversus abdominalis (TrA) muscles of individuals with AIS.

Materials and Methods:

Seventy-one healthy adolescents and 71 patients with AIS, all aged 10–16 years, were studied. The thickness of the muscles at rest was measured at the end of normal exhalation in millimeters. Muscular activity during the ASLR test was measured in the final position, and the standards were normalized with the thickness produced at rest. Muscular activity during the ASLR test was represented as a percentage change in the muscle thickness.

Results:

The AIS group demonstrated a smaller resting thickness of all tested muscles of both sides (P<0.01). All the muscles on the right side of the body showed higher activity in the AIS group during the ASLR test (P<0.01).

Conclusions:

Patients with AIS had thinner EO, IO, and TrA at rest in the supine position. During the ASLR test, the AIS patients displayed higher activity of the EO, IO, and TrA muscles on the right side.
Characterization of a novel Negevirus and a novel Bunyavirus isolated from Culex (Culex) declarator mosquitoes in Trinidad
Authors: Auguste Albert J. , Carrington Christine V. F. , Forrester Naomi L. , Popov Vsevolod L. , Guzman Hilda , Widen Steven G. , Wood Thomas G. , Weaver Scott C. , Tesh Robert B.
Published: November 2013

Pools of mosquitoes were tested for insect-specific viruses using cytopathic effect (CPE) assays on Aedes albopictus (C6/36) cells. Illumina sequencing of RNA from pool TR7094, which produced extensive CPE 2 days post-infection, yielded the complete genome sequences of a previously unknown Bunyavirus, designated Cumuto virus (CUMV), and a second virus designated Wallerfield virus (WALV). WALV shared highest amino acid identity (60.1 %) with Dezidougou virus from Côte d’Ivoire, a positive-sense, single-strand RNA, insect-specific virus belonging to the newly proposed genus Negevirus associated with mosquitoes and phlebotomine sandflies. The S, M and L segments of CUMV were most closely related to those of Gouleako virus, also from Côte d’Ivoire (amino acid identities of 36 %, 38 % and 54 % respectively). Neither virus produced CPE on vertebrate cells, or illness in newborn mice. Isolation and characterization of these viruses increase our knowledge of the geographical distribution, diversity and host range of mosquito-specific bunyaviruses and negeviruses.
Transcriptome characterization by RNA sequencing identifies a major molecular and clinical subdivision in chronic lymphocytic leukemia
Authors: Ferreira Pedro G. , Jares Pedro , Rico Daniel , Gómez-López Gonzalo , Martínez-Trillos Alejandra , Villamor Neus , Ecker Simone , González-Pérez Abel , Knowles David G. , Monlong Jean , Johnson Rory , Quesada Victor , Djebali Sarah , Papasaikas Panagiotis , López-Guerra Mónica , Colomer Dolors , Royo Cristina , Cazorla Maite , Pinyol Magda , Clot Guillem , Aymerich Marta , Rozman Maria , Kulis Marta , Tamborero David , Gouin Anaïs , Blanc Julie , Gut Marta , Gut Ivo , Puente Xose S. , Pisano David G. , Martin-Subero José Ignacio , López-Bigas Nuria , López-Guillermo Armando , Valencia Alfonso , López-Otín Carlos , Campo Elías , Guigó Roderic
Published: November 2013

Chronic lymphocytic leukemia (CLL) has heterogeneous clinical and biological behavior. Whole-genome and -exome sequencing has contributed to the characterization of the mutational spectrum of the disease, but the underlying transcriptional profile is still poorly understood. We have performed deep RNA sequencing in different subpopulations of normal B-lymphocytes and CLL cells from a cohort of 98 patients, and characterized the CLL transcriptional landscape with unprecedented resolution. We detected thousands of transcriptional elements differentially expressed between the CLL and normal B cells, including protein-coding genes, noncoding RNAs, and pseudogenes. Transposable elements are globally derepressed in CLL cells. In addition, two thousand genes—most of which are not differentially expressed—exhibit CLL-specific splicing patterns. Genes involved in metabolic pathways showed higher expression in CLL, while genes related to spliceosome, proteasome, and ribosome were among the most down-regulated in CLL. Clustering of the CLL samples according to RNA-seq derived gene expression levels unveiled two robust molecular subgroups, C1 and C2. C1/C2 subgroups and the mutational status of the immunoglobulin heavy variable (IGHV) region were the only independent variables in predicting time to treatment in a multivariate analysis with main clinico-biological features. This subdivision was validated in an independent cohort of patients monitored through DNA microarrays. Further analysis shows that B-cell receptor (BCR) activation in the microenvironment of the lymph node may be at the origin of the C1/C2 differences.
4-Formyl-2-nitrophenyl 2-chlorobenzoate
Authors: Moreno-Fuquen Rodolfo , Hernandez Geraldine , Ellena Javier , De Simone Carlos A. , Tenorio Juan C.
Published: November 2013

In the title compound, C14H8ClNO5, the benzene rings form a dihedral angle of 19.55 (9)°. The mean plane of the central ester group [r.m.s. deviation = 0.024 Å] forms dihedral angles of 53.28 (13) and 36.93 (16)°, respectively, with the nitro- and chloro-substituted rings. The nitro group forms a dihedral angle of 19.24 (19)° with the benzene ring to which it is attached. In the crystal, molecules are linked by weak C—H...O hydrogen bonds, formingC(7) chains, which run along [100].
Ethyl 3-(10-bromoanthracen-9-yl)-5-methyl-1,2-oxazole-4-carboxylate
Authors: Li Chun , Campbell Michael J. , Weaver Matthew J. , Duncan Nathan S. , Hunting Janet L. , Natale Nicholas R.
Published: November 2013

In the title compound, C21H16BrNO3, the mean planes of the anthracene tricycle and isoxazole ring are inclined to each other at a dihedral angle of 72.12 (7)°. The carboxy group is slightly out of the isoxazole mean plane, with a maximum deviation of 0.070 (5) Å for the carbonyl O atom. In the crystal, pairs of weak C—H...O hydrogen bonds link the molecules into dimers, and weak C—H...N interactions further link these dimers into corrugated layers parallel to thebcplane.
1-(2-Bromomethyl-1-phenylsulfonyl-1H-indol-3-yl)propan-1-one
Authors: Umadevi M. , Saravanan V. , Yamuna R. , Mohanakrishnan A. K. , Chakkaravarthi G.
Published: November 2013

In the title compound, C18H16BrNO3S, the dihedral angle between the phenyl ring and the indole ring system is 89.91 (11)°. The molecular structure features weak C—H...O and C—H...Br hydrogen bonds. In the crystal, molecules are linked by weak C—H...O hydrogen bonds, forming chains along thea-axis direction. The chains are further linked by C—H...π interactions, forming a layer parallel to theabplane.
6-(4-Aminophenyl)-2-methoxy-4-phenylnicotinonitrile
Authors: Suwunwong Thitipone , Chantrapromma Suchada , Quah Ching Kheng , Fun Hoong-Kun
Published: November 2013

In the structure of the title nicotinonitrile derivative, C19H15N3O, the pyridine ring makes dihedral angles of 11.50 (7) and 43.36 (8)° with the 4-aminophenyl and phenyl rings, respectively, and the dihedral angle between the phenyl rings is 36.28°. In the crystal, molecules are linked by N—H...N hydrogen bonds into wave-like sheets parallel to (10-2). These sheets are stacked by π–π interactions between the 4-aminophenyl rings of adjacent sheets, with centroid–centroid distances of 3.7499 (9) Å. C—H...π interactions are also present.
(E)-1-(2-Hydroxy-6-methoxyphenyl)-3-(2,4,6-trimethoxyphenyl)prop-2-en-1-one
Authors: Koh Dongsoo
Published: November 2013

In the title molecule, C19H20O6, the conformation about the C=C bond of the central enone group isE. The dihedral angle formed by the benzene rings is 11.6 (2)°. The hydroxy group is involved in an intramolecular O—H...O hydrogen bond. In the crystal, weak C—H...O hydrogen bonds link the molecules into chains along [010].
Poly[[octaaqua-μ4-(benzene-1,2,4,5-tetracarboxylato)-dicobalt(II)] octahydrate]
Authors: Camara Magatte , Tine Modou , Daiguebonne Carole , Guillou Olivier , Roisnel Thierry
Published: November 2013

The title polymeric coordination compound, {[Co2(C10H2O8)(H2O)8]·8H2O}n, was obtained by slow diffusion of a dilute aqueous solution of CoCl2and the sodium salt of benzene-1,2,4,5-tetracarboxylic acid (H4btec) through an agar–agar gel bridge in a U-shaped tube. The two independent Co2+ions are each situated on an inversion centre and are coordinated in a slightly distorted octahedral geometry by four water O atoms and two carboxylate O atoms from two btec4−ligands (-1> symmetry), forming a layer parallel to (11-1). This layer can be described as a molecular two-dimensional square grid with the benzene rings at the nodes and the CoIIatoms connecting the nodes. O—H...O hydrogen-bonding interactions involving the coordinating water molecules, the carboxylate O atoms and lattice water molecules lead to the formation of a three-dimensional network.
2-Methoxy-3-(trimethylsilyl)phenylboronic acid
Authors: Durka Krzysztof , Luliński Sergiusz , Serwatowski Janusz
Published: November 2013

The molecular structure of the title compound, C10H17BO3Si, features an intramolecular O—H...O hydrogen bond; the boronic group group has anexo–endoconformation. In the crystal, the molecules interact with each other by O—H...O hydrogen bonds, producing centrosymmetric dimers that are linked by weak π–π stacking interactions featuring specific short B...C contacts [e.g. 3.372 (2) Å], forming an infinite columnar structure aligned along thea-axis direction.