bluuebunny/crossref_metadata_2025_split huggingface dataset:
Are Klinefelter boys hypogonadal?
Authors: Rey Rodolfo A , Gottlieb Silvia , Pasqualini Titania , Bastida María G , Grinspon Romina P , Campo Stella M , Bergadá Ignacio 
Published: January 2011

AbstractMale hypogonadism implies decreased function of one or more testicular cell population, i.e. germ, Leydig and/or Sertoli cells. In the normal prepubertal boy, Sertoli cells are very active, as indicated by high anti‐Müllerian hormone (AMH) and inhibin B secretion, whereas the functional activity of Leydig cells is minimal, as evidenced by low testosterone production, and germ cells do not undergo the full spermatogenic process. Klinefelter syndrome is the most frequent cause of hypogonadism in the adult male. In this review, we discuss whether the gonadal failure is already established during infancy and childhood. In Klinefelter syndrome, there is increased germ cells degeneration from mid‐foetal life – resulting in a decreased number at birth – which persists during infancy and childhood and becomes dramatic during puberty. Controversial results exist in the literature regarding Leydig cell function in Klinefelter boys: while some authors have found normal to low testosterone levels in infancy and childhood, others have reported normal to high values. Sertoli cell products AMH and inhibin B are normal in prepubertal boys and only decline during mid‐ to late puberty.Conclusion:  Klinefelter syndrome is a primary hypogonadism affecting all testicular cell populations. Germ cells are affected from foetal life, and a severe depletion occurs at puberty. Leydig cell function may be normal or mildly affected in foetal and early postnatal life. Sertoli cell function is not impaired until mid‐ to late puberty, as reflected by normal AMH and inhibin B in Klinefelter boys.
Rational Design of α‐Helical Antimicrobial Peptides to Target Gram‐negative Pathogens, Acinetobacter baumannii and Pseudomonas aeruginosa: Utilization of Charge, ‘Specificity Determinants,’ Total Hydrophobicity, Hydrophobe Type and Location as Design Parameters to Improve the Therapeutic Ratio
Authors: Jiang Ziqing , Vasil Adriana I. , Gera Lajos , Vasil Michael L. , Hodges Robert S. 
Published: January 2011

The rapidly growing problem of increased resistance to classical antibiotics makes the development of new classes of antimicrobial agents with lower rates of resistance urgent. Amphipathic cationic α‐helical antimicrobial peptides have been proposed as a potential new class of antimicrobial agents. The goal of this study was to take a broad‐spectrum, 26‐residue, antimicrobial peptide in the all‐D conformation, peptide D1 (K13) with excellent biologic properties and address the question of whether a rational design approach could be used to enhance the biologic properties if the focus was on Gram‐negative pathogens only. To test this hypothesis, we used 11 and 6 diverse strains of Acinetobacter baumannii and Pseudomonas aeruginosa, respectively. We optimized the number and location of positively charged residues on the polar face, the number, location, and type of hydrophobe on the non‐polar face and varied the number of ‘specificity determinants’ in the center of the non‐polar face from 1 to 2 to develop four new antimicrobial peptides. We demonstrated not only improvements in antimicrobial activity, but also dramatic reductions in hemolytic activity and unprecedented improvements in therapeutic indices. Compared to our original starting peptide D1 (V13), peptide D16 had a 746‐fold improvement in hemolytic activity (i.e. decrease), maintained antimicrobial activity, and improved the therapeutic indices by 1305‐fold and 895‐fold against A. baumannii and P. aeruginosa, respectively. The resulting therapeutic indices for D16 were 3355 and 895 for A. baumannii and P. aeruginosa, respectively. D16 is an ideal candidate for commercialization as a clinical therapeutic to treat Gram‐negative bacterial infections.
Stroke Epidemiology and One-Month Fatality among an Urban Population in Iran
Authors: Delbari Ahmad , Salman Roghani Reza , Tabatabaei Sayed Shahaboddin , Rahgozar Mehdi , Lokk Johan 
Published: January 2011

Objective Stroke is one of the most common causes of death and disability in Iran. This study evaluated stroke patient profiles with respect to rate, risk factors, and one-month fatality. Material and method A cross-sectional, hospital-based study on all stroke patients older than 45 years admitted to hospitals in the city of Qom throughout 2001. Results Four hundred and sixty patients older than 45 years were admitted as stroke. The annual stroke rate was estimated to 338/100 000 (95% confidence interval, 300–360) inhabitants older than 45 years. The annual rate of stroke was 384/100 000 (95% confidence interval, 381–386) when adjusted to the European population. Stroke subtypes were; ischaemic infarction 75%, intracranial haemorrhage 20·7%, subarachnoid haemorrhage 3%, and undetermined 1·3%. Main risk factors were hypertension in 74·6% and diabetes in 55·7%. Mortality rate was 24·6% within the first month. Conclusion Stroke incidence was higher than in Western countries. Hypertension and diabetes mellitus were considerably more frequent in our studied stroke patients than in other developing countries. Our findings need to be addressed in future health education programmes in Iran identifying patients at risk and focusing on more aggressive prevention programmes to lower stroke incidence.
Homo heuristicus Outnumbered: Comment on Gigerenzer and Brighton (2009)
Authors: Hilbig Benjamin E. , Richter Tobias 
Published: January 2011

Abstract Gigerenzer and Brighton (2009) have argued for a “Homo heuristicus” view of judgment and decision making, claiming that there is evidence for a majority of individuals using fast and frugal heuristics. In this vein, they criticize previous studies that tested the descriptive adequacy of some of these heuristics. In addition, they provide a reanalysis of experimental data on the recognition heuristic that allegedly supports Gigerenzer and Brighton’s view of pervasive reliance on heuristics. However, their arguments and reanalyses are both conceptually and methodologically problematic. We provide counterarguments and a reanalysis of the data considered by Gigerenzer and Brighton. Results clearly replicate previous findings, which are at odds with the claim that simple heuristics provide a general description of inferences for a majority of decision makers.
Identifying Optimum Performance Trade‐Offs Using a Cognitively Bounded Rational Analysis Model of Discretionary Task Interleaving
Authors: Janssen Christian P. , Brumby Duncan P. , Dowell John , Chater Nick , Howes Andrew 
Published: January 2011

AbstractWe report the results of a dual‐task study in which participants performed a tracking and typing task under various experimental conditions. An objective payoff function was used to provide explicit feedback on how participants should trade off performance between the tasks. Results show that participants’ dual‐task interleaving strategy was sensitive to changes in the difficulty of the tracking task and resulted in differences in overall task performance. To test the hypothesis that people select strategies that maximize payoff, a Cognitively Bounded Rational Analysis model was developed. This analysis evaluated a variety of dual‐task interleaving strategies to identify the optimal strategy for maximizing payoff in each condition. The model predicts that the region of optimum performance is different between experimental conditions. The correspondence between human data and the prediction of the optimal strategy is found to be remarkably high across a number of performance measures. This suggests that participants were honing their behavior to maximize payoff. Limitations are discussed.
Risk Attitude in Decision Making: In Search of Trait‐Like Constructs
Authors: Yechiam Eldad , Ert Eyal 
Published: January 2011

AbstractWe evaluate the consistency of different constructs affecting risk attitude in individuals’ decisions across different levels of risk. Specifically, we contrast views suggesting that risk attitude is a single primitive construct with those suggesting it consists of multiple latent components. Additionally, we evaluate such constructs as sensitivity to losses, diminishing sensitivity to increases in payoff, sensitivity to variance, and risk acceptance (the willingness to accept probable outcomes over certainty). In search of trait‐like constructs, the paper reviews experimental results focusing on the consistency of these constructs in different tasks as well as their temporal consistency. Overall, the findings show that the most consistent factor is risk acceptance, and they also demonstrate its potential boundaries. These results are modeled with a simple quantitative index of subjective risk. A survey of decisions under risk further reveals that participants exhibit almost no consistency across different tasks in this setting, highlighting the advantage of experiential tasks for studying individual differences.
The Evolution of a Goal‐Directed Exploration Model: Effects of Information Scent and GoBack Utility on Successful Exploration
Authors: Teo Leonghwee , John Bonnie E. 
Published: January 2011

AbstractWe explore the match of a computational information foraging model to participant data on multi‐page web search tasks and find its correlation on several important metrics to be too low to be used with confidence in the evaluation of user‐interface designs. We examine the points of mismatch to inspire changes to the model in how it calculates information scent scores and how it assesses the utility of backing up from a lower‐level page to a higher‐level page. The outcome is a new model that qualitatively matches participant behavior better than the original model, has utility equations more appealing to “common sense” than the original equations, and significantly improves the correlation between model and participant data on our metrics.
Pulse Diode Laser Irradiation (830 nm) of Lumbosacral Spinal Roots Diminished Hyperreflexia‐Induced by Acetic Acid or Prostaglandin E2 Infusion in Rat Urinary Bladder
Authors: ITO Tomoko , ISHIKAWA Tomomi , MATSUMOTO‐MIYAI Kazumasa , KAWATANI Masahito 
Published: January 2011

Objectives: Low power diode Iaser (830 nm) irradiation is a useful analgesic tool in superficial pain. Pulse laser irradiation allows us to increase the laser power because the non‐irradiation time reduces heating effects and/or direct tissue damage at the irradiation area. This new irradiation device using pulse laser was applied to the dorsal skin to investigate the effects on the micturition reflex in the rat by targeting underlying sacral spinal roots.Methods: Vesical pressure measurement during the continuous infusion of the urinary bladder with saline, acetic acid (AA, 0.1%) or prostaglandin E2 (PGE2, 10−5 M) were performed in un‐anesthetized rats. Multi‐unit recording from bladder afferent nerves preformed under urethane anesthesia. Laser irradiation, either continuously at 1 W or in 10 W‐pulse mode, was delivered at 830 nm from 1.5 cm above the skin at the lumbosacral joint.Results: During continuous saline infusion to the urinary bladder, neither continuous (1 W) nor pulse (10 W) laser irradiation altered the intercontraction interval and nerve firing during distention of the bladder. Pulse laser, but not continuous laser irradiation, increased the intercontraction interval with AA or PGE2 infusion and diminished nerve firing during distention of the bladder with AA or PGE2 infusion.Conclusion: These data indicate that pulse laser could diminish inflammation related nerve firing from the bladder. Since this laser irradiation did not affect the normal bladder distention elicited nerve firing, it appears capable of reducing urgency sensation without loss of the basic micturition reflex.
Therapeutic effects of hyperoxic ventilation during shock
Authors: BITTERMAN HAIM 
Published: January 2011

SUMMARYDecreased availability of oxygen to metabolizing cells is a major feature of circulatory shock that leads to tissue damage and multiple organ dysfunctions. A wish to alleviate tissue hypoxia underlies the common clinical use of hyperoxic ventilation in shock. Yet, this straightforward approach is met by skepticism that is based on the potential pro‐inflammatory effects of hyperoxia and the acknowledged roles of reactive oxygen species and oxidative stress in tissue injury. A steadily growing body of experimental data indicates that hyperoxia exerts an extensive profile of physiologic and pharmacologic effects that improve tissue oxygenation, exert anti‐inflammatory and antibacterial effects, augment tissue repair mechanisms, and may also decrease oxidative stress during shock. The currently available preclinical information on the benefits of early use of safe regimens of hyperoxic ventilation alone or in combination with other commonly employed modalities sets the stage for renewal of careful clinical evaluation of oxygen therapy in resuscitation of circulatory shock.
Streptococcus anginosusl‐cysteine desulfhydrase gene expression is associated with abscess formation in BALB/c mice
Authors: Takahashi Y. , Yoshida A. , Nagata E. , Hoshino T. , Oho T. , Awano S. , Takehara T. , Ansai T. 
Published: January 2011

Summary Streptococcus anginosus, an anginosus group bacterium, is frequently isolated from odontogenic abscesses, and is the oral bacterium that is primarily responsible for producing hydrogen sulfide from l‐cysteine through the action of its l‐cysteine desulfhydrase (βC‐S lyase) enzyme. However, the relationship between its production of hydrogen sulfide and abscess formation has not been investigated. To elucidate the etiological role of hydrogen sulfide in abscess formation, we initially measured, using specific primers, expression of the lcd gene, which encodes βC‐S lyase, in the pus of abscesses that formed in BALB/c mice following subcutaneous injection of S. anginosus into the dorsa. Expression of lcd was >15‐fold higher when l‐cysteine was present than when it was absent. A mouse virulence assay revealed that the mean diameter of abscesses caused by S. anginosus FW73 plus l‐cysteine was greater than that of abscesses caused by S. anginosus FW73 in the absence of l‐cysteine. These findings demonstrate that the lcd gene of S. anginosus is upregulated in mouse abscesses and that hydrogen sulfide, the product of a reaction catalyzed by βC‐S lyase, plays an etiological role in odontogenic abscess formation.
Abstract A12: Differential micro-RNA expression in a multistage 5-fluorouracil resistant colon cancer model
Authors: Mader Robert M. , Wieser Matthias , Berger Walter , Kalipciyan Maria , Hackl Matthias , Steger Guenther G. , Grillari Johannes 
Published: January 2011

Abstract
Purpose: Among small non-coding RNAs, micro-RNAs have demonstrated a variety of essential functions under both physiological and pathological conditions such as cell cycle progression, oncogenic transformation and apoptosis. Thus, we hypothesized that micro-RNAs may play a major role in cellular stress adaptation.
Methods: To attain this aim, we evaluated a multi-stage colon cancer system with increasing degrees of resistance to the antimetabolite 5-fluorouracil by i) differential expression profiling (micro-RNA arrays) and ii) subsequent validation of the candidate RNAs by quantitative PCR.
Results: Among 15 differential expressed micro-RNAs in our model system, 9 were confirmed by qPCR and selected for further investigations. Noteworthy, for every level of drug resistance (low, intermediate, and high) specific micro-RNAs were identified indicating an individual response to escalating cytotoxic stress at the molecular level. With regard to micro-RNA functions, our findings point at an involvement - if not a regulatory function - of the recognized micro-RNAs in the following processes (data from the literature): doxorubicin resistance (miR-130a), survival signaling, DNA-oriented stress, and oncogenic properties (all miR-19), epithelial-mesenchymal transition (miR-141 and miR-200), as well as invasion and metastasis (miR-10b). Some of these features are currently under investigation by transfection of the corresponding micro-RNA precursors or antagomirs in the chemoresistant model in order to assess the contribution of the identified micro-RNAs to the resistance phenotype.
Conclusions: Previous work from our team has demonstrated the orchestrated response of cancer cells to xenobiotics at the molecular level by global gene expression profiling. The investigated subclones, derived from the metastatic colon cancer cell line CCL 227, were characterized by stage dependent mRNA regulations affecting vital cellular functions such as cytoskeleton, cell-cell communication, signal transduction, cell cycle control and apoptosis. Remarkably, different degrees of chemoresistance addressed different cellular mechanisms, thus providing to the cancer cell the necessary flexibility to adapt to different levels of stress. Likewise, micro-RNAs seem to follow a similar behavior with different micro-RNA patterns reflecting the development of resistance to 5-fluorouracil. As micro-RNAs are very likely to play a decisive role in the cellular response to therapeutic stress, their regulation might offer novel starting points to understand and to oppose drug resistance. This work has been supported by the “Initiative Krebsforschung”, Austria.
Citation Information: Clin Cancer Res 2010;16(7 Suppl):A12
Abstract A13: Selective role of iNOS reveals its negative regulatory influence on the expression of TNFR1, NF-κB and other cell survival signaling events during a P19-induced apoptosis in HL-60 cells
Authors: Malik Fayaz 
Published: January 2011

Abstract
P19, a semi-synthetic analog of sesquiterpene lactone ‘Parthenin’, is a promising template to develop into novel anti-cancer leads. P19 induced robust cell death in human leukemia cell lines compared to normal cells when observed after 48h treatment with IC50 of 3.5 μM in HL-60 cells to that of 35 μM in human normal gingival fibroblast cells. Mechanistic studies into HL-60 cells death after 6 h exposure to 10 μM P19 were investigated. It killed cells by apoptosis consequent to robust generation of NO through enhanced expression of iNOS. N-acetyl-L-cysteine (NAC) and s-methyl isothiourea (sMIT) suppressed apoptosis equipotently by inhibiting endogenous NO formation. P19 disrupted mitochondrial functions by altering Bax/Bcl2 ratio, cytosolic Bid loss, Drp1 over expression, Bax and cytochrome c translocation leading predominantly to caspase-9 activation. P19 also translocated AIF from mitochondria to the nucleus which may further potentiate caspases-independent cell death, because pan caspase inhibitor offered incomplete protection. On the contrary, activation of caspase-8 was augmented with concomitant selective enhanced expression of apical death receptor DR4 rather than TNFR1 and FASR. Activation of pre-executioner caspases positively regulated the activation of caspase-3 leading to PARP-1 cleavage and therefore, DNA fragmentation. Down-regulation of activator TNFR1 and transactivator PARP-1 of NF-κB with attendant decreased expression of both the subunits p50 and p65 of NF-κB argue against the plausible involvement of NF-κB as a transcription factor in the induction of iNOS. Further, P19 potently inhibited pro-survival proteins pSTAT-3 and survivin that are overtly expressed in cancer cells. The multimodal proapoptotic features of P19 raises its potential usefulness as a promising anti-cancer therapeutic.
Citation Information: Clin Cancer Res 2010;16(7 Suppl):A13
Abstract A16: Overexpression of activin A is associated with poor prognosis in patients with oral squamous cell carcinoma and promotes the proliferation, motility and invasion of oral cancer cells.
Authors: Chang Kai-Ping , Tsai Chi-Neu 
Published: January 2011

Abstract
Objective: Both activin A, a member of transforming growth factor superfamily, and its inhibitor follistatin have been shown to be overexpressed in various cancers. We examined the expression of activin A and follistatin in tissue and blood samples from patients with oral squamous cell carcinoma.
Methods: The study population comprises 92 patients with oral squamous cell carcinoma. activin A and follistatin levels in tissues and sera were examined by qRT-PCR, immunohistochemistry and ELISA, respectively. Effects of activin A on oral cancer cells were investigated by trans-well migration/invasion assays and RNA interference.
Results: Overexpression of immunohistochemically detected activin A was correlated with positive N stage, poor histological differentiation, and perineural invasion (P = 0.029, 0.002, and 0.014, respectively). Statistical significant correlations between activin A and FST were observed in both mRNA and immunohistochemical expression (Pearson's correlation r = 0.507, P = 0.008 and r = 0.354 and P = 0.0005, respectively). In survival analyses, patients with oral squamous cell carcinoma whose tumors overexpressed activin A had a worse prognosis for overall survival and disease-free survival (P = 0.009 and 0.007). However, expression of follistatin in tumor was not correlated with overall survival or disease-free survival. Serum activin A and follistatin levels in 111 untreated patients were neither significantly different from those of 91 control samples nor associated with any clinicopathological manifestations. In vitro suppression of activin A expression in OC3 cells using specific interfering RNA attenuated cell proliferation, migration, and invasiveness.
Conclusion: These findings suggest that activin A overexpression in oral squamous cell carcinomas is associated with patients survival and may contribute to tumor progression and metastasis.
Citation Information: Clin Cancer Res 2010;16(7 Suppl):A16
Abstract A19: Targeting follicle stimulating hormone receptor in postmenopausal epithelial ovarian cancer
Authors: Bose Chinmay K. , Mukhopadhyay Ashis 
Published: January 2011

Abstract
Objectives: Recent studies have established expression of gonadotrphin receptor especially more important Follicle Stimulating hormone Receptor (FSHR) in ovarian surface epithelium (OSE), its benign and early malignant tumours. There is no explanation as yet for such unusual finding. Hence, an extensive search of concerned literatures is made to find out the probable cause of this aberrant expression.
Materials and Methods: A systematic review of reports from MEDLINE/PUBMED was performed from May ′02 to June ′05 on mechanism of FSHR expression in OSE and ovarian cancer. Many reports were collected from journal and additional reports were perused from the reference lists of retrieved articles.
Results: The neurotrophins (NT) including nerve growth factor (NGF) are a family of related growth factors that are of major importance in the regulation of neuronal survival and differentiation. In the ovary, they can help in follicular maturation and ovulation by inducing the FSH receptor (FSHR). NTs can be implicated as the cause of this aberrant expression of FSHR in OSE. This is because unlike other factors responsible for FSHR expression NT has central action and can lower serum FSH, as is found in such ovarian cancer.
Conclusion: NGF deregulates expression of FSHR in OSE and secretion of FSH from the pituitary. This phenomenon may hold the key to the hitherto unexplained carcinogenic process of sporadic epithelial ovarian cancer.
Citation Information: Clin Cancer Res 2010;16(7 Suppl):A19