bluuebunny/crossref_metadata_2025 huggingface dataset:
Clear Cell Cancer of the Uterine Corpus: The Association of Clinicopathologic Parameters and Treatment on Disease Progression
Authors: Varughese Joyce , Hui Pei , Lu Lingeng , Yu Herbert , Schwartz Peter E.
Published: December 2011

This paper presents a single-institution experience regarding the clinicopathologic features and treatment strategies used in uterine clear cell cancer (UCC), a rare, aggressive histologic subtype of uterine cancer with poor prognosis and discusses parameters associated with progression-free survival (PFS) and overall survival (OS). A retrospective chart review was performed on all patients () diagnosed with UCC and treated between 1994 and 2009 at a single academic institution. Data on demographics, FIGO stage, treatment regimens, and recurrences were collected. Patients with early-stage UCC had an excellent survival regardless of adjuvant therapy. Advanced-stage patients had a worse survival. Vaginal apex brachytherapy was associated with an increased OS () but not PFS (). The use of platinum-based chemotherapy in combination with vaginal apex brachytherapy did not significantly improve survival. Innovative therapies still need to be identified for this uncommon uterine cancer.
Electrophoretic Mobility of Cardiac Myosin Heavy Chain Isoforms Revisited: Application of MALDI TOF/TOF Analysis
Authors: Arnostova Petra , Jedelsky Petr L. , Soukup Tomáš , Zurmanova Jitka
Published: December 2011

The expression of two cardiac myosin heavy chain (MyHC) isoforms in response to the thyroid status was studied in left ventricles (LVs) of Lewis rats. Major MyHC isoform in euthyroid and hyperthyroid LVs had a higher mobility on SDS‐PAGE, whereas hypothyroid LVs predominantly contained a MyHC isoform with a lower mobility corresponding to that of the control soleus muscle. By comparing the MyHC profiles obtained under altered thyroid states together with the control soleus, we concluded that MyHCα was represented by the lower band with higher mobility and MyHCβ by the upper band. The identity of these two bands in SDS‐PAGE gels was confirmed by western blot and mass spectrometry. Thus, in contrast to the literature data, we found that the MyHCα possessed a higher mobility rate than the MyHCβ isoform. Our data highlighted the importance of the careful identification of the MyHCα and MyHCβ isoforms analyzed by the SDS‐PAGE.
Complex Dynamics of Discrete SEIS Models with Simple Demography
Authors: Cao Hui , Zhou Yicang , Song Baojun
Published: December 2011

We investigate bifurcations and dynamical behaviors of discrete SEIS models with exogenous reinfections and a variety of treatment strategies. Bifurcations identified from the models include period doubling, backward, forward‐backward, and multiple backward bifurcations. Multiple attractors, such as bistability and tristability, are observed. We also estimate the ultimate boundary of the infected regardless of initial status. Our rigorously mathematical analysis together with numerical simulations show that epidemiological factors alone can generate complex dynamics, though demographic factors only support simple equilibrium dynamics. Our model analysis supports and urges to treat a fixed percentage of exposed individuals.
Surgical Excision of Benign Papillomas Diagnosed with Core Biopsy: A Community Hospital Approach
Authors: Rozentsvayg Eka , Carver Kristen , Borkar Sunita , Mathew Melvy , Enis Sean , Friedman Paul
Published: December 2011

Our goal was to assess the value of surgical excision of benign papillomas of the breast diagnosed on percutaneous core biopsy by determining the frequency of upgrade to malignancies and high risk lesions on a final surgical pathology. We reviewed 67 patients who had biopsies yielding benign papilloma and underwent subsequent surgical excision. Surgical pathology of the excised lesions was compared with initial core biopsy pathology results. 54 patients had concordant benign core and excisional pathology. Cancer (ductal carcinoma in situ and invasive ductal carcinoma) was diagnosed in five (7%) patients. Surgery revealed high-risk lesions in 8 (12%) patients, including atypical ductal hyperplasia, atypical lobular hyperplasia, and lobular carcinoma in situ. Cancer and high risk lesions accounted for 13 (19%) upstaging events from benign papilloma diagnosis. Our data suggests that surgical excision is warranted with core pathology of benign papilloma.
The Roles of Tumor-Derived Exosomes in Cancer Pathogenesis
Authors: Yang Chenjie , Robbins Paul D.
Published: December 2011

Exosomes are endosome-derived, 30–100 nm small membrane vesicles released by most cell types including tumor cells. They are enriched in a selective repertoire of proteins and nucleic acids from parental cells and are thought to be actively involved in conferring intercellular signals. Tumor-derived exosomes have been viewed as a source of tumor antigens that can be used to induce antitumor immune responses. However, tumor-derived exosomes also have been found to possess immunosuppressive properties and are able to facilitate tumor growth, metastasis, and the development of drug resistance. These different effects of tumor-derived exosomes contribute to the pathogenesis of cancer. This review will discuss the roles of tumor-derived exosomes in cancer pathogenesis, therapy, and diagnostics.
Psychosis and Silent Celiac Disease in a Down Syndrome Adolescent: A Case Report
Authors: Morant Amparo
Published: December 2011

Celiac disease is an autoimmune systemic disorder. It presents gastrointestinal and nongastrointestinal manifestations as well as associated conditions. We report a 16-year-old Down syndrome girl who presented psychosis symptomatology, and she was diagnosed as having silent celiac disease. Olanzapine treatment and gluten-free diet were satisfactory. It is necessary to consider celiac disease in Down syndrome patients with psychiatric symptoms, mainly psychotic symptomatology.
Can Dynamic Contrast-Enhanced Magnetic Resonance Imaging Combined with Texture Analysis Differentiate Malignant Glioneuronal Tumors from Other Glioblastoma?
Authors: Eliat Pierre-Antoine , Olivié Damien , Saïkali Stephan , Carsin Béatrice , Saint-Jalmes Hervé , de Certaines Jacques D.
Published: December 2011

An interesting approach has been proposed to differentiate malignant glioneuronal tumors (MGNTs) as a subclass of the WHO grade III and IV malignant gliomas. MGNT histologically resemble any WHO grade III or IV glioma but have a different biological behavior, presenting a survival twice longer as WHO glioblastomas and a lower occurrence of metastases. However, neurofilament protein immunostaining was required for identification of MGNT. Using two complementary methods, dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and texture analysis (MRI-TA) from the same acquisition process, the challenge is toin vivoidentify MGNT and demonstrate that MRI postprocessing could contribute to a better typing and grading of glioblastoma. Results are obtained on a preliminary group of 19 patients a posteriori selected for a blind investigation of DCE T1-weighted and TA at 1.5 T. The optimal classification (0/11 misclassified MGNT) is obtained by combining the two methods, DCE-MRI and MRI-TA.
The Hedgehog Pathway Conditions the Bone Microenvironment for Osteolytic Metastasis of Breast Cancer
Authors: Das Shamik , Samant Rajeev S. , Shevde Lalita A.
Published: December 2011

The microenvironment at the site of tumor metastasis plays a key role in determining the fate of the metastasizing tumor cells. This ultimately has a direct impact on the progression of cancer. Bone is the preferred site of metastasis of breast cancer. Painful, debilitating osteolytic lesions are formed as a result of crosstalk between breast cancer cells and cells in the bone, predominantly the osteoblasts and osteoclasts. In this paper, we have discussed the temporal and spatial role of hedgehog (Hh) signaling in influencing the fate of metastatic breast cancer cells in bone. By virtue of its secreted ligands, the Hh pathway is capable of homotypic and heterotypic signaling and consequently altering the microenvironment in the bone. We also have put into perspective the therapeutic implications of using Hh inhibitors to prevent and/or treat bone metastases of breast cancer.
CDKN2A/BAlterations Impair Prognosis in AdultBCR-ABL1–Positive Acute Lymphoblastic Leukemia Patients
Authors: Iacobucci Ilaria , Ferrari Anna , Lonetti Annalisa , Papayannidis Cristina , Paoloni Francesca , Trino Stefania , Storlazzi Clelia Tiziana , Ottaviani Emanuela , Cattina Federica , Impera Luciana , Abbenante Maria Chiara , Vignetti Marco , Vitale Antonella , Potenza Leonardo , Paolini Stefania , Soverini Simona , Pane Fabrizio , Luppi Mario , Foà Robin , Baccarani Michele , Martinelli Giovanni
Published: December 2011

Purpose: The 9p21 locus, encoding three important tumor suppressors (p16/CDKN2A, p14/ARF, and p15/CDKN2B), is a major target of inactivation in the pathogenesis of many human tumors.

Patients and Methods: To explore, at high resolution, the frequency and size of alterations affecting this locus in adult BCR-ABL1–positive acute lymphoblastic leukemia (ALL) and to investigate their prognostic value, 112 patients (101 de novo and 11 relapsed cases) were analyzed by genome-wide single-nucleotide polymorphism arrays and gene candidate deep exon sequencing. Paired diagnosis–relapse samples were further available and analyzed for 19 (19%) cases.

Results: CDKN2A/ARF and CDKN2B genomic alterations were identified in 29% and 25% of newly diagnosed patients, respectively. Deletions were monoallelic in 72% of cases, and in 43% of them, the minimal overlapping region of the lost area spanned only the CDKN2A/B gene locus. An analysis conducted at relapse showed an increase in the detection rate of CDKN2A/ARF loss (47%) compared with the time of diagnosis (P = 0.06). Point mutations within the 9p21 locus were found at very low levels, with only a nonsynonymous substitution in the exon 2 of CDKN2A. Of note, deletions of CDKN2A/B were significantly associated with poor outcomes in terms of overall survival (P = 0.0206), disease free-survival (P = 0.0010), and cumulative incidence of relapse (P = 0.0014).

Conclusions: Inactivation of the 9p21 locus by genomic deletion is a frequent event in BCR-ABL1–positive ALL. Deletions are frequently acquired during leukemia progression and are a poor prognostic marker of long-term outcomes. Clin Cancer Res; 17(23); 7413–23. ©2011 AACR.
Evaluation of the Antitumor Effects and Mechanisms of PF00299804, a Pan-HER Inhibitor, Alone or in Combination with Chemotherapy or Targeted Agents in Gastric Cancer
Authors: Nam Hyun-Jin , Ching Keith A. , Kan Julie , Kim Hwang-Phill , Han Sae-Won , Im Seock-Ah , Kim Tae-You , Christensen James G. , Oh Do-Youn , Bang Yung-Jue
Published: December 2011

Recently, HER2-directed treatment, such as trastuzumab, has shown clinical benefit in HER2-amplified gastric cancer. On the basis of recent studies about epidermal growth factor receptor (EGFR) or HER2-targeting agents (including gefitinib, lapatinib, and trastuzumab) in gastric cancer, the potent effects of pan-HER inhibitors targeting the HER family are anticipated. In this study, we evaluated the activity and mechanisms of PF00299804, an irreversible pan-HER inhibitor, in gastric cancer in vitro and in vivo models. PF00299804 showed significant growth-inhibitory effects in HER2-amplified gastric cancer cells (SNU216, N87), and it had lower 50% inhibitory concentration values compared with other EGFR tyrosine kinase inhibitors, including gefitinib, lapatinib, BIBW-2992, and CI-1033. PF00299804 induced apoptosis and G1 arrest and inhibited phosphorylation of receptors in the HER family and downstream signaling pathways including STAT3, AKT, and extracellular signal–regulated kinases (ERK) in HER2-amplified gastric cancer cells. PF00299804 also blocked EGFR/HER2, HER2/HER3, and HER3/HER4 heterodimer formation as well as the association of HER3 with p85α in SNU216 cells. The combination of PF00299804 with clinically relevant chemotherapeutic agents or molecular-targeted agents including trastuzumab (an anti-HER2 monoclonal antibody), CP751871 (an IGF1R inhibitor), PD0325901 (an ERK1/2 inhibitor), and PF04691502 (a PI3K/mTOR inhibitor) produced synergistic effects. These findings indicate that PF00299804 can be used as a targeted therapy for the treatment of HER2-amplified gastric cancer through inhibition of HER family heterodimer formation and may augment antitumor efficacy of chemotherapeutic and/or molecular-targeted agents. Mol Cancer Ther; 11(2); 439–51. ©2011 AACR.
Remote Influence of the Tropical Atlantic on the Variability and Trend in North West Australia Summer Rainfall
Authors: Lin Zhongda , Li Yun
Published: December 2011

Rainfall in North West Australia (NWA) has been increasing over the past decades, occurring mainly in the austral summer season (December–March). A range of factors such as decreased land albedo in Australia and increasing anthropogenic aerosols in the Northern Hemisphere, identified using simulations from climate models, have been implicated in this wetting trend. However, the impact of land albedo and aerosols on Australian rainfall remains unclear. In addition, previous studies showed that dominant sea surface temperature (SST) signals in the Pacific–Indian Ocean including El Niño–Southern Oscillation (ENSO), ENSO Modoki, and the Indian Ocean dipole mode have no significant impact on the NWA rainfall trend. The present study proposes another viewpoint on the remote influence of tropical Atlantic atmospheric vertical motion on the observed rainfall variability and trend in NWA.

It is found that, with the atmospheric ascent instigated by the warming of SST over the tropical Atlantic, a Rossby wave train is emanating southeastward from off the west coast of subtropical South America to the midlatitudes of the South Atlantic Ocean. It then travels eastward embedded in the westerly jet waveguide over the South Atlantic and South Indian Oceans. The eastward-propagated Rossby wave induces an anticyclonic anomaly in the upper troposphere over Australia, which is at the exit of the westerly jet waveguide. This leads to an in situ upper-tropospheric divergence, ascending motion and a lower-tropospheric convergence, and the associated increase in rainfall in NWA. Thus, the increasing trend in atmospheric upward motion induced by the warming trend of SST in the tropical Atlantic may partially explain the observed rainfall trend in NWA.
Variance Function Regression in Hierarchical Age-Period-Cohort Models
Authors: Zheng Hui , Yang Yang , Land Kenneth C.
Published: December 2011

Two long-standing research problems of interest to sociologists are sources of variations in social inequalities and differential contributions of the temporal dimensions of age, time period, and cohort to variations in social phenomena. Recently, scholars have introduced a model called Variance Function Regression for the study of the former problem, and a model called Hierarchical Age-Period-Cohort regression has been developed for the study of the latter. This article presents an integration of these two models as a means to study the evolution of social inequalities along distinct temporal dimensions. We apply the integrated model to survey data on subjective health status. We find substantial age, period, and cohort effects, as well as gender differences, not only for the conditional mean of self-rated health (i.e., between-group disparities), but also for the variance in this mean (i.e., within-group disparities)—and it is detection of age, period, and cohort variations in the latter disparities that application of the integrated model permits. Net of effects of age and individual-level covariates, in recent decades, cohort differences in conditional means of self-rated health have been less important than period differences that cut across all cohorts. By contrast, cohort differences of variances in these conditional means have dominated period differences. In particular, post-baby boom birth cohorts show significant and increasing levels of within-group disparities. These findings illustrate how the integrated model provides a powerful framework through which to identify and study the evolution of variations in social inequalities across age, period, and cohort temporal dimensions. Accordingly, this model should be broadly applicable to the study of social inequality in many different substantive contexts.
Billboards, Youth, Unemployment and Superstition in Mamfe-Akuapem, Ghana
Authors: Ayesu Ebenezer
Published: December 2011

On a sunny day in May 1983 a section of the youth of Mamfe-Akuapem in south-eastern Ghana – reeking heavily of alcohol and marijuana, armed with machetes and pick-axes and angrily singing war songs, drumming and dancing – went to the residence of Nana Ama Ansaa Sasraku III, their queen mother. Their mission was very simple. They were to inform her of their plans to demolish the billboard which welcomed motorists and visitors on their arrival in the town. According to them, the billboard was inhabited by an evil spirit responsible for the general incidence of unemployment and the absence of development in the town.
Together in the middle: Back-channel negotiation in the Irish peace process
Authors: Dochartaigh Niall Ó
Published: November 2011

This article examines the development of cooperative relationships in back-channel communication and their impact on intraparty negotiation. It draws on extensive newly available evidence on back-channel communication in the Irish peace process to expand the range of detailed case studies on a topic which is shrouded in secrecy and resistant to academic inquiry. The article analyses the operation of a secret back channel that linked the Irish Republican Army to the British government over a period of 20 years, drawing on unique material from the private papers of the intermediary, Brendan Duddy, and a range of other primary sources. The article finds that interaction through this back channel increased predictability and laid a foundation of extremely limited trust by providing information and increasing mutual understanding. Strong cooperative relationships developed at the intersection between the two sides, based to a great extent on strong interpersonal relationships and continuity in personnel. This in turn produced direct pressure for changes in the position of parties as negotiators acted as advocates of movement in intraparty negotiations. The article finds that this back channel was characterized by a short chain, the direct involvement of principals and the establishment of a single primary channel of communication and that these features combined with secrecy to generate the distinctive cooperative dynamics identified in this article. It concludes that the potential for the development of cooperative relationships is particularly strong in back-channel negotiation for two reasons; first, the joint project of secrecy creates an ongoing shared task that builds trust and mutual understanding regardless of progress in the negotiations. Secondly, as a shared project based on the explicit aim of bypassing spoilers, the process creates structural pressures for cooperation to manage internal opponents on both sides, pressures intensified by the secrecy of the process.
‘You can't play politics with people's jobs and people's services’: Localism and the politics of local government finance
Authors: Wilks-Heeg Stuart
Published: November 2011

Despite growing cross-party support for the principles of localism, the coalition's radical devolution agenda looks set to provoke a level of tension in central–local relations not seen since the 1980s. This article argues that the central cause of this friction, the front-loading of cuts in the local government financial settlement for 2011–2013, must be understood as the centrepiece of theConservatives’ agenda for local government reform. It is argued that, as with the introduction of the poll tax after 1987, the Conservatives have adopted a high-risk political strategy that will require the government to persuade voters that cuts in services arise from the failings of local councils. Evidence from opinion polls in the first half of 2011 suggests that the public is yet to be convinced that the blame lies with local government, but that they remain open to persuasion. However, a regionalized analysis of projected public sector job loss and voting patterns at the 2011 English local elections suggests that voters look set to blame central government in the areas where the cuts will hit hardest. If future local elections repeat this pattern, the limitations of the political strategy behind the localism agenda will become highly apparent.
Development, Structure, and Keratin Expression in C57BL/6J Mouse Eccrine Glands
Authors: Taylor D. K. , Bubier J. A. , Silva K. A. , Sundberg J. P.
Published: December 2011

Eccrine sweat glands in the mouse are found only on the footpads and, when mature, resemble human eccrine glands. Eccrine gland anlagen were first apparent at 16.5 days postconception (DPC) in mouse embryos as small accumulations of cells in the mesenchymal tissue beneath the developing epidermis resembling hair follicle placodes. These cells extended into the dermis where significant cell organization, duct development, and evidence of the acrosyringium were observed in 6- to 7-postpartum day (PPD) mice. Mouse-specific keratin 1 (K1) and 10 (K10) expression was confined to the strata spinosum and granulosum. In 16.5 and 18.5 DPC embryos, K14 and K17 were both expressed in the stratum basale and diffusely in the gland anlagen. K5 expression closely mimicked K17 throughout gland development. K6 expression was not observed in the developing glands of the embryo but was apparent in the luminal cell layer of the duct by 6 to 7 PPD. By 21 PPD, the gland apertures appeared as depressions in the surface surrounded by cornified squames, and the footpad surface lacked the organized ridge and crease system seen in human fingers. These data serve as a valuable reference for investigators who use genetically engineered mice for skin research.
Functional Treatment After Surgical Repair for Acute Lateral Ligament Disruption of the Ankle in Athletes
Authors: Takao Masato , Miyamoto Wataru , Matsui Kentaro , Sasahara Jun , Matsushita Takashi
Published: December 2011

Background: There have been several reports showing 20% to 40% failure after nonoperative functional treatment for acute lateral ligament disruption of the ankle.

Hypothesis: Functional treatment after primary surgical repair has the advantage of decreasing the failure rate in comparison with functional treatment alone.

Study Design: Cohort study; Level of evidence, 3.

Methods: A total of 132 feet of 132 patients were included in this study. Of these, 78 patients were treated with functional treatment alone (group F), and the remaining 54 patients were treated with functional treatment after primary surgical repair (group RF). The clinical results were evaluated using the Japanese Society for Surgery of the Foot Ankle-Hindfoot scale (JSSF) score, measuring the talar tilt angle and the anterior displacement of the talus in stress radiography, and noting the elapsed time between the injury and the return to the full athletic activity with no external supports.

Results: The mean JSSF scores at 2 years after injury were 95.6 ± 5.0 points in group F and 97.5 ± 2.6 points in group RF ( P = .0669). The differences of the talar tilt angles compared with the contralateral side and displacement of the talus on stress radiography at 2 years after injury were 1.1° ± 1.5° and 3.6 ± 1.6 mm in group F, and 0.8° ± 0.9° and 3.2 ± 0.8 mm in group RF, respectively ( P = .4093, .1883). In group F, 8 cases showed fair to poor results, with JSSF scores below 80 points and instability at 2 years after injury. In group RF, 9 cases (9.4%) showed dorsum foot pain along the superficial peroneal nerve, which disappeared within a month. The time elapsed between the injury and the patient’s return to full athletic activity without any external supports was 16.0 ± 5.6 weeks in group F and 10.1 ± 1.8 weeks in group RF ( P < .0001).

Conclusion: Nonoperative functional treatment alone and functional treatment after primary surgical repair showed similar overall results after acute lateral ankle sprain, but functional treatment alone had an approximately 10% failure rate and a slower return to full athletic activity. The authors recommend that treatment be tailored to suit each individual athlete.
Epidemiology of Isolated Meniscal Injury and Its Effect on Performance in Athletes From the National Basketball Association
Authors: Yeh Peter C. , Starkey Chad , Lombardo Stephen , Vitti Gary , Kharrazi F. Daniel
Published: December 2011

Background: The current incidence and outcomes of meniscal injury have not been quantified in professional athletes.

Purpose: To describe the incidence, risk, amount of time lost, and effect on performance for isolated meniscal injury in athletes from the National Basketball Association (NBA). Demographic factors predicting the risk of meniscal tears and the effect of injury in return to play were also investigated.

Study Design: Descriptive epidemiology study.

Methods: A centralized database was queried to identify meniscal injuries occurring in the NBA over 21 seasons. The frequency of injury, time lost, game exposures, and incidence, rate, and risk were calculated. The preinjury and postinjury player efficiency rating (PER) was used to identify changes in player performance.

Results: We identified 129 isolated meniscal tears in NBA athletes during a 21-season span. From this number, 77 (59.7%) involved the lateral meniscus and 52 (40.3%) the medial meniscus. Injuries occurred more frequently in games. The lateral meniscus had a statistically significant higher injury rate. Both left and right knees were equally affected. The number of days missed for lateral meniscal tears and medial meniscal tears was 43.8 ± 35.7 days and 40.9 ± 29.7 days, respectively, and was not statistically different. There was a significant inverse relationship between age and rate of lateral meniscal tears, with lateral meniscal tears more likely to occur up to age 30 years; beyond that medial meniscal tears were more common. Players with a body mass index (BMI) greater than 25 had a significantly increased risk of meniscal tears compared with players with a BMI less than 25, specifically with an increased risk of lateral meniscal tears. Twenty-five players (19.4%) did not return to play. For those who did, upon returning to competition, there was no statistical change in PER from their preinjury status, and the mean number of seasons completed was 4.1 ± 3.7 seasons.

Conclusion: The lateral meniscus is more frequently torn than the medial meniscus, but there was no difference in the amount of playing time lost. Both right and left knees were equally affected. There was an inverse relationship between age and the rate of lateral meniscal tears. Risk of tears was increased in players having a BMI greater than 25. Injury did not negatively affect playing performance.
Assessing a Measure of Femininity Ideology for Low-Income, Latina Adolescent Girls
Authors: Williford Anne
Published: December 2011

The purpose of the study presented here was to examine whether a measure of femininity ideology, normed on largely white, middle-class samples of adolescent girls, could be verified among a sample of low-income Latina adolescents. The results revealed that the previously identified factor structure could not be confirmed for this sample, which brings the scales’ validity for use with low-income, Latina samples into question. These findings suggest that minority girls may interpret femininity ideologies differently than do white, middle-class girls and underscore the importance of examining the validity of measurement tools for use with diverse populations. They emphasize that improving measurement for diverse populations is needed to develop culturally responsive and relevant intervention strategies.
Thermoplastic–lignocellulose composites enhanced by chemically treated Alcell lignin as compatibilizer
Authors: Tay GS , Shannon-Ong SH , Goh SW , Rozman HD
Published: December 2011

In this study, chemically treated Alcell lignin was used as a compatibilizer in the preparation of polypropylene–oil palm empty fruit bunch (PP-EFB) composites. Basically, this study was divided into two stages. In the first stage, glycidyl methacrylate (GMA) and allyl glycidyl ether (AGE) were used to treat Alcell lignin in different ratios (1:1, 1:2 and 1:3) based on equivalent weight. Then, the treated lignin was used as a compatibilizer at different percentages (1%, 3% and 5%, based on the weight of EFB filler) in the preparation of lignocellulosic–thermoplastic composites. The size of the EFB filler used for this study was 53–180 µm and the ratio of PP to EFB filler was fixed at 40%:60% (based on weight). The results showed that the incorporation of GMA- and AGE-treated lignin had enhanced the mechanical properties and increased the hydrophobicity of lignocellulosic–thermoplastic composites. By comparison, those with the GMA-treated lignin exhibited better enhancement in mechanical properties as compared to those with AGE-treated lignin.
‘Psychogenic Psychoses’ by August Wimmer (1936): Part 2
Authors: Schioldann Johan
Published: November 2011

This is a continuation of Classic Text No. 87, published in History of Psychiatry 22(3): 334–367, and is the second part of the translation from Wimmer’s book Speciel klinisk Psykiatri for Studerende og Læger [Special Clinical Psychiatry for Students and Doctors] published in Copenhagen in 1936.
Beyond Clara Schumann
Authors: Artesani Laura
Published: December 2011

To provide a comprehensive and balanced curriculum, the accomplishments of women composers and performers must be included in general music classes. This article addresses obstacles that have challenged women musicians and provides an outline for a unit that highlights seven American women who have achieved significant “firsts” in the world of music.
Changing times, changing perspectives: Reconciling ‘transition’ and ‘cultural’ perspectives on youth and young adulthood
Authors: Furlong Andy , Woodman Dan , Wyn Johanna
Published: November 2011

This article explores the changing relationship between the ‘transitions’ and ‘cultural’ perspectives in youth studies. Changes in the relationship between the two approaches are currently being driven by shifting theoretical paradigms that place a greater weight on reflexive life management, thereby making it more difficult to maintain a theoretical distinction between structural and cultural analysis. Indeed, we argue that relationships between the two approaches are showing signs of convergence, partly as a consequence of the emergence of new ways of managing life contexts which frequently involve the blending of contexts, the search for new meanings and a changing sense of self in time. We trace the trends in the relationship between the ‘transitions’ and ‘cultural’ perspectives against the backdrop of changing opportunity structures. Focusing on contemporary contexts, we explore some of the ways in which recent socio-economic changes challenge traditional ways of interpreting subjectivities. We conclude by exploring the ways in which the sociology of youth can move forward using a social generation approach.
The Impact of Patient and Provider Factors on Depression Screening of American Indian and Alaska Native People in Primary Care
Authors: Dillard Denise A. , Muller Clemma J. , Smith Julia J. , Hiratsuka Vanessa Y. , Manson Spero M.
Published: December 2011

Introduction: The US Preventive Services Task Force recommends routine depression screening in primary care, yet regular screening does not occur in most health systems serving Alaska Native and American Indian people. The authors examined factors associated with administration of depression screening among Alaska Native and American Indian people in a large urban clinic. Methods: Medical records of 18 625 Alaska Native and American Indian adults were examined 1 year after implementation of a depression screening initiative. Multilevel logistic regression models examined associations between patient and provider factors and administration of the Patient Health Questionnaire–9. Results: Forty-seven percent of patients were screened. Women were more likely than men to be screened (50% vs 43%, P < .001). Increased screening odds were associated with older age, increased service use, and chronic disease ( P < .001) but not with substance abuse disorders or prior antidepressant dispensation. Women previously diagnosed with depression had higher odds of screening ( P = .002). Men seen by male providers had higher odds of screening than did men seen by female providers ( P = .040). Screening rates peaked among providers with 2 to 5 years of employment with the clinic. Limitations: Cross-sectional analysis of medical record data was of unknown reliability; there were limited sociodemographic data. Conclusions: Even with significant organizational support for annual depression screening, primary care providers systematically missed men and patients with infrequent primary care visits. Outreach to male patients and additional supports for primary care providers, especially in the first years of practice, may improve screening and treatment for depression among Alaska Native and American Indian people.
Molecular mechanisms of inflammation and tissue injury after major trauma-is complement the "bad guy"?
Authors: Neher Miriam D , Weckbach Sebastian , Flierl Michael A , Huber-Lang Markus S , Stahel Philip F
Published: December 2011

Trauma represents the leading cause of death among young people in industrialized countries. Recent clinical and experimental studies have brought increasing evidence for activation of the innate immune system in contributing to the pathogenesis of trauma-induced sequelae and adverse outcome. As the "first line of defense", the complement system represents a potent effector arm of innate immunity, and has been implicated in mediating the early posttraumatic inflammatory response. Despite its generic beneficial functions, including pathogen elimination and immediate response to danger signals, complement activation may exert detrimental effects after trauma, in terms of mounting an "innocent bystander" attack on host tissue. Posttraumatic ischemia/reperfusion injuries represent the classic entity of complement-mediated tissue damage, adding to the "antigenic load" by exacerbation of local and systemic inflammation and release of toxic mediators. These pathophysiological sequelae have been shown to sustain the systemic inflammatory response syndrome after major trauma, and can ultimately contribute to remote organ injury and death. Numerous experimental models have been designed in recent years with the aim of mimicking the inflammatory reaction after trauma and to allow the testing of new pharmacological approaches, including the emergent concept of site-targeted complement inhibition. The present review provides an overview on the current understanding of the cellular and molecular mechanisms of complement activation after major trauma, with an emphasis of emerging therapeutic concepts which may provide the rationale for a "bench-to-bedside" approach in the design of future pharmacological strategies.
Novel base triples in RNA structures revealed by graph theoretical searching methods
Authors: Firdaus-Raih Mohd , Harrison Anne-Marie , Willett Peter , Artymiuk Peter J
Published: December 2011

Background

Highly hydrogen bonded base interactions play a major part in stabilizing the tertiary structures of complex RNA molecules, such as transfer-RNAs, ribozymes and ribosomal RNAs.

Results

We describe the graph theoretical identification and searching of highly hydrogen bonded base triples, where each base is involved in at least two hydrogen bonds with the other bases. Our approach correlates theoretically predicted base triples with literature-based compilations and other actual occurrences in crystal structures. The use of ‘fuzzy’ search tolerances has enabled us to discover a number of triple interaction types that have not been previously recorded nor predicted theoretically.

Conclusions

Comparative analyses of different ribosomal RNA structures reveal several conserved base triple motifs in 50S rRNA structures, indicating an important role in structural stabilization and ultimately RNA function.
Non-nucleosidic inhibition of Herpes simplex virus DNA polymerase: mechanistic insights into the anti-herpetic mode of action of herbal drug withaferin A
Authors: Grover Abhinav , Agrawal Vibhuti , Shandilya Ashutosh , Bisaria Virendra S , Sundar Durai
Published: December 2011

Background

Herpes Simplex Virus 1 and 2 causes several infections in humans including cold sores and encephalitis. Previous antiviral studies on herpes viruses have focussed on developing nucleoside analogues that can inhibit viral polymerase and terminate the replicating viral DNA. However, these drugs bear an intrinsic non-specificity as they can also inhibit cellular polymerase apart from the viral one. The present study is an attempt to elucidate the action mechanism of naturally occurring withaferin A in inhibiting viral DNA polymerase, thus providing an evidence for its development as a novel anti-herpetic drug.

Results

Withaferin A was found to bind very similarly to that of the previously reported 4-oxo-DHQ inhibitor. Withaferin A was observed binding to the residues Gln 617, Gln 618, Asn 815 and Tyr 818, all of which are crucial to the proper functioning of the polymerase. A comparison of the conformation obtained from docking and the molecular dynamics simulations shows that substantial changes in the binding conformations have occurred. These results indicate that the initial receptor-ligand interaction observed after docking can be limited due to the receptor rigid docking algorithm and that the conformations and interactions observed after simulation runs are more energetically favoured.

Conclusions

We have performed docking and molecular dynamics simulation studies to elucidate the binding mechanism of prospective herbal drug withaferin A onto the structure of DNA polymerase of Herpes simplex virus. Our docking simulations results give high binding affinity of the ligand to the receptor. Long de novo MD simulations for 10 ns performed allowed us to evaluate the dynamic behaviour of the system studied and corroborate the docking results, as well as identify key residues in the enzyme-inhibitor interactions. The present MD simulations support the hypothesis that withaferin A is a potential ligand to target/inhibit DNA polymerase of the Herpes simplex virus. Results of these studies will also guide the design of selective inhibitors of DNA POL with high specificity and potent activity in order to strengthen the therapeutic arsenal available today against the dangerous biological warfare agent represented by Herpes Simplex Virus.
Directional gene expression and antisense transcripts in sexual and asexual stages of Plasmodium falciparum
Authors: López-Barragán María J , Lemieux Jacob , Quiñones Mariam , Williamson Kim C , Molina-Cruz Alvaro , Cui Kairong , Barillas-Mury Carolina , Zhao Keji , Su Xin-zhuan
Published: December 2011

Background

It has been shown that nearly a quarter of the initial predicted gene models in the Plasmodium falciparum genome contain errors. Although there have been efforts to obtain complete cDNA sequences to correct the errors, the coverage of cDNA sequences on the predicted genes is still incomplete, and many gene models for those expressed in sexual or mosquito stages have not been validated. Antisense transcripts have widely been reported in P. falciparum; however, the extent and pattern of antisense transcripts in different developmental stages remain largely unknown.

Results

We have sequenced seven bidirectional libraries from ring, early and late trophozoite, schizont, gametocyte II, gametocyte V, and ookinete, and four strand-specific libraries from late trophozoite, schizont, gametocyte II, and gametocyte V of the 3D7 parasites. Alignment of the cDNA sequences to the 3D7 reference genome revealed stage-specific antisense transcripts and novel intron-exon splicing junctions. Sequencing of strand-specific cDNA libraries suggested that more genes are expressed in one direction in gametocyte than in schizont. Alternatively spliced genes, antisense transcripts, and stage-specific expressed genes were also characterized.

Conclusions

It is necessary to continue to sequence cDNA from different developmental stages, particularly those of non-erythrocytic stages. The presence of antisense transcripts in some gametocyte and ookinete genes suggests that these antisense RNA may play an important role in gene expression regulation and parasite development. Future gene expression studies should make use of directional cDNA libraries. Antisense transcripts may partly explain the observed discrepancy between levels of mRNA and protein expression.
Liverome: a curated database of liver cancer-related gene signatures with self-contained context information
Authors: Lee Langho , Wang Kai , Li Gang , Xie Zhi , Wang Yuli , Xu Jiangchun , Sun Shaoxian , Pocalyko David , Bhak Jong , Kim Chulhong , Lee Kee-Ho , Jang Ye Jin , Yeom Young Il , Yoo Hyang-Sook , Hwang Seungwoo
Published: December 2011

Background

Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide. A number of molecular profiling studies have investigated the changes in gene and protein expression that are associated with various clinicopathological characteristics of HCC and generated a wealth of scattered information, usually in the form of gene signature tables. A database of the published HCC gene signatures would be useful to liver cancer researchers seeking to retrieve existing differential expression information on a candidate gene and to make comparisons between signatures for prioritization of common genes. A challenge in constructing such database is that a direct import of the signatures as appeared in articles would lead to a loss or ambiguity of their context information that is essential for a correct biological interpretation of a gene’s expression change. This challenge arises because designation of compared sample groups is most often abbreviated, ad hoc, or even missing from published signature tables. Without manual curation, the context information becomes lost, leading to uninformative database contents. Although several databases of gene signatures are available, none of them contains informative form of signatures nor shows comprehensive coverage on liver cancer. Thus we constructed Liverome, a curated database of liver cancer-related gene signatures with self-contained context information.

Description

Liverome’s data coverage is more than three times larger than any other signature database, consisting of 143 signatures taken from 98 HCC studies, mostly microarray and proteome, and involving 6,927 genes. The signatures were post-processed into an informative and uniform representation and annotated with an itemized summary so that all context information is unambiguously self-contained within the database. The signatures were further informatively named and meaningfully organized according to ten functional categories for guided browsing. Its web interface enables a straightforward retrieval of known differential expression information on a query gene and a comparison of signatures to prioritize common genes. The utility of Liverome-collected data is shown by case studies in which useful biological insights on HCC are produced.

Conclusion

Liverome database provides a comprehensive collection of well-curated HCC gene signatures and straightforward interfaces for gene search and signature comparison as well. Liverome is available at http://liverome.kobic.re.kr.
INDUS - a composition-based approach for rapid and accurate taxonomic classification of metagenomic sequences
Authors: Mohammed Monzoorul Haque , Ghosh Tarini Shankar , Reddy Rachamalla Maheedhar , Reddy Chennareddy Venkata Siva Kumar , Singh Nitin Kumar , Mande Sharmila S
Published: December 2011

Background

Taxonomic classification of metagenomic sequences is the first step in metagenomic analysis. Existing taxonomic classification approaches are of two types, similarity-based and composition-based. Similarity-based approaches, though accurate and specific, are extremely slow. Since, metagenomic projects generate millions of sequences, adopting similarity-based approaches becomes virtually infeasible for research groups having modest computational resources. In this study, we present INDUS - a composition-based approach that incorporates the following novel features. First, INDUS discards the 'one genome-one composition' model adopted by existing compositional approaches. Second, INDUS uses 'compositional distance' information for identifying appropriate assignment levels. Third, INDUS incorporates steps that attempt to reduce biases due to database representation.

Results

INDUS is able to rapidly classify sequences in both simulated and real metagenomic sequence data sets with classification efficiency significantly higher than existing composition-based approaches. Although the classification efficiency of INDUS is observed to be comparable to those by similarity-based approaches, the binning time (as compared to alignment based approaches) is 23-33 times lower.

Conclusion

Given it's rapid execution time, and high levels of classification efficiency, INDUS is expected to be of immense interest to researchers working in metagenomics and microbial ecology.

Availability

A web-server for the INDUS algorithm is available at http://metagenomics.atc.tcs.com/INDUS/
Phase I-II study of everolimus and low-dose oral cyclophosphamide in patients with metastatic renal cell cancer
Authors: Huijts Charlotte M , Santegoets Saskia J , van den Eertwegh Alfons J , Pijpers Laura S , Haanen John B , de Gruijl Tanja D , Verheul Henk M , van der Vliet Hans J
Published: December 2011

Background

For patients with metastatic renal cell cancer (mRCC) who progressed on vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitor therapy, the orally administered mammalian target of rapamycin (mTOR) inhibitor everolimus has been shown to prolong progression free survival. Intriguingly, inhibition of mTOR also promotes expansion of immunosuppressive regulatory T cells (Tregs) that can inhibit anti-tumor immune responses in a clinically relevant way in various tumor types including RCC. This study intends to investigate whether the antitumor efficacy of everolimus can be increased by preventing the detrimental everolimus induced expansion of Tregs using a metronomic schedule of cyclophosphamide.

Methods/design

This phase I-II trial is a national multi-center study of different doses and schedules of low-dose oral cyclophosphamide in combination with a fixed dose of everolimus in patients with mRCC not amenable to or progressive after a VEGF-receptor tyrosine kinase inhibitor containing treatment regimen. In the phase I part of the study the optimal Treg-depleting dose and schedule of metronomic oral cyclophosphamide when given in combination with everolimus will be determined. In the phase II part of the study we will evaluate whether the percentage of patients progression free at 4 months of everolimus treatment can be increased from 50% to 70% by adding metronomic cyclophosphamide (in the dose and schedule determined in the phase I part). In addition to efficacy, we will perform extensive immune monitoring with a focus on the number, phenotype and function of Tregs, evaluate the safety and feasibility of the combination of everolimus and cyclophosphamide, perform monitoring of selected angiogenesis parameters and analyze everolimus and cyclophosphamide drug levels.

Discussion

This phase I-II study is designed to determine whether metronomic cyclophosphamide can be used to counter the mTOR inhibitor everolimus induced Treg expansion in patients with metastatic renal cell carcinoma and increase the antitumor efficacy of everolimus.

Trial Registration

ClinicalTrials.gov Identifier NCT01462214, EudraCT number 2010-024515-13, Netherlands Trial Register number NTR3085.