bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical Biologic Pathophysiologies of Women's Sexual Dysfunction
Authors: Nappi Rossella , Salonia Andrea , Traish Abdulmaged M. , Van Lunsen Rik H.W. , Vardi Yoram , Kodiglu Ates , Goldstein Irwin 
Published: January 2005

ABSTRACTIntroductionData concerning the biologic pathophysiology of desire, arousal, and orgasm in women are limited.AimTo gain knowledge of biologic paThophysiology of female sexual function.MethodsTo provide state-of-the-art knowledge concerning female sexual dysfunction, representing the opinions of seven experts from five countries developed in a consensus process over a 2-year period.Main Outcome MeasureAn International Consultation in alliance with key urological and sexual medicine societies convened over 200 multidisciplinary specialists from 60 countries into 17 consultation committees. The aims, goals and intentions of each committee were defined. Expert opinion was based on grading of evidence-based medical literature, extensive internal committee dialogue, open presentation, and debate.ResultsThree critical physiologic requirements, including intact sex steroids, autonomic/somatic nerves, and arterial inflow/perfusion pressure to women's genital organs play fundamental roles in maintaining women's sexual function. Despite this, there are nominal data supporting a direct pathophysiologic involvement of abnormal sex steroid values, and/or damage/injury to neurologic and/or blood flow integrity in women with problems in sexual desire, arousal, and/or orgasm. This summary details the available literature concerning hormonal, neurologic, and vascular organic pathophysiologies of women's sexual dysfunctions.ConclusionsAdditional research on clinical pathophysiologies in women's sexual dysfunction is needed. This chapter encompasses data presented at the 2nd International Consultation on Sexual Medicine in Paris, France, June 28–July 1, 2003.
Scale for Quality of Sexual Function (QSF) as an Outcome Measure for Both Genders?
Authors: Heinemann Lothar A.J. , Potthoff Peter , Heinemann Klaas , Pauls Alfred , Ahlers Christoph J. , Saad Farid 
Published: January 2005

ABSTRACT

Background
For years, there has been interest in sexual dysfunction and its impact on quality of life but usually focused on one gender. Therapeutic options that became available raised the interest to evaluate effects on the other partner but there is no standardized instrument applicable for both genders. This paper reports first data regarding the development of a new general “Quality of Sexual Function” (QSF) scale.

Methods
The raw scale was based on our own gender-specific scales and the pertinent literature. The scale was applied in over 700 persons of a cross-sectional survey in Germany. Factorial analyses were performed to describe the internal structure (domains) of the scale and for item reduction. Internal consistency reliability and some aspects of validity were analyzed with the same community sample preliminary reference values determined.

Results
The scale consists of 32 specific items and eight general questions. Four dimensions were identified: “psycho-somatic quality of life,”“sexual activity,”“sexual (dys)function—self-reflection,” and “sexual (dys)function—partner's view.” The internal consistency reliability coefficients of the total scale and the subscales were good as were the total–domain correlations. Content validity was promising.

Conclusion
This self-administrable 40-item QSF scale can measure and compare quality of sexual function for both genders. The scale was well accepted by the respondents. It is easy to answer and the evaluation is simple. Only a few results of reliability and validity have been established in this early stage of the development of the new instrument. Further research is needed to complete many missing aspects of reliability and the construct validity, particular its sensitivity to treatment effects.
Vardenafil Improves Satisfaction Rates, Depressive Symptomatology, and Self-Confidence in a Broad Population of Men with Erectile Dysfunction
Authors: Hatzichristou Dimitrios , Cuzin Beatrice , Martin-Morales Antonio , Buvat Jacques , Porst Hartmut , Laferriere Nicole , Bandel Tiemol Jerg , Montorsi Francesco 
Published: January 2005

ABSTRACT

Introduction
Vardenafil is a potent and selective phosphodiesterase 5 (PDE5) inhibitor developed for the treatment of erectile dysfunction (ED). Fixed-dose and flexible-dose studies have previously established the efficacy and tolerability of vardenafil.

Aim
To assess, besides the usual measures of efficacy, the quality of erection, satisfaction with the sexual experience, symptoms of depression, and overall confidence.

Methods
This 12-week double-blind, placebo-controlled flexible-dose study assessed patients from the general ED population. Patients underwent a 4-week treatment-free period before randomization to vardenafil or matching placebo. Initial dosage was vardenafil 10 mg for 4 weeks. At 4 weeks, patients could switch to 5 or 20 mg (or corresponding placebo), or remain on 10 mg for an additional 4 weeks; dose switching was also optional for the last 4 weeks. This paper describes per-patient success in satisfaction with hardness of erection, satisfaction with overall sexual experience, effect on overall self-confidence, and an assessment of symptoms of depression using the Center for Epidemiologic Studies Depression Scale.

Results
Mean per-patient satisfaction rates with erection hardness increased after vardenafil treatment to 43%, 59%, and 63% at weeks 4, 8, and 12, respectively, compared to placebo with 10%, 21%, and 23% (all P &lt; 0.005 vs. placebo). Vardenafil also improved mean per-patient overall satisfaction 50–65% over the 4–12 week study period compared with 17–28% for placebo (P &lt; 0.005). Symptoms of depression were statistically significantly reduced compared to placebo (P = 0.02); the effect was observed particularly in patients who were depressed at baseline (P = 0.01). Significantly more patients in the vardenafil treatment group reported improved self-confidence than those who received placebo (P &lt; 0.005).

Conclusions
A flexible-dose regimen of vardenafil improved satisfaction rates, symptoms of depression, and self-confidence, providing patients with an effective ED therapy that contributes to overall improvements in sexual function and confidence.
A Broken Intracavernous Needle: Successful Ultrasound-Guided Removal
Authors: Shamloul Rany , Kamel Ihab 
Published: January 2005

ABSTRACT

Introduction
Common complications of intracavernous injection therapy include pain, hematoma formation, syncope, prolonged erections, and penile fibrosis. Rare reported complications include postinjection cavernositis, intracorporeal needle breakage.

Aim
We report a case of postinjection intracavernous needle breakage with successful ultrasound-guided retrieval.

Methods
A 32-year-old patient complaining of a 6-month penile pain following intracavernous papaverine injection presented to our department. Clinical examination and penile ultrasound revealed a broken intracavernous needle at the left mid-dorsum aspect of the penis with surrounding fibrosis. A decision was made to remove the broken needle.

Results
The needle was dislodged effortlessly under local anesthesia.

Conclusion
A deeply seated intracavernous broken needle should be immediately retrieved. Patients must be carefully instructed on the proper injection technique with emphasis on the delicacy of the needle and the possibility of needle breakage during injection.
Intracavernous Sodium Nitroprusside (SNP) Versus Papaverine/Phentolamine in Erectile Dysfunction: A Comparative Study of Short-Term Efficacy and Side-Effects
Authors: Shamloul Rany , Atteya Ahmed , Elnashaar Abdelrahman , Gadallah Amr , Zohdy Wael , Abdelsalam Wael 
Published: January 2005

ABSTRACT

Objective
The aim of our work is to evaluate the efficacy of intracavernous sodium nitroprusside (SNP) in management of erectile dysfunction (ED) in a clinical comparative study with papaverine/phentolamine in ED patients.

Methods
The study included 40 patients with ED divided into two groups. Group I include 20 patients receiving intracavernous (30 mg papaverine + 1 mg phentolamine) followed 1 week later by intracavernous 300 µg SNP. Group II included 20 patients receiving the same regimen of group I but with intracavernous SNP first followed by papaverine/phentolamine 1 week later. All patients were assessed clinically for their response and any developing complications.

Results
The numbers of good and poor responders were not statistically significant (P &gt; 0.05) among the two groups. The mean erectile duration of SNP was similar to bimix (P &gt; 0.05). No side-effects whether local or systemic occurred with SNP while priapism and local penile pain were recorded with bimix solution.

Conclusions
Intracavernous pharmacotherapy is still a reliable method both for diagnosis and for treatment of ED. While preliminary results of our study show a potential of SNP to be an effective and safe intracavernous agent, long-term self-injection clinical trials are needed before large-scale usage is recommended.
Ex vivo culture of Fancc-/- stem/progenitor cells predisposes cells to undergo apoptosis, and surviving stem/progenitor cells display cytogenetic abnormalities and an increased risk of malignancy
Authors: Li Xiaxin , Le Beau Michelle M. , Ciccone Samantha , Yang Feng-Chun , Freie Brian , Chen Shi , Yuan Jin , Hong Ping , Orazi Attilio , Haneline Laura S. , Clapp D. Wade 
Published: January 2005

AbstractCurrent strategies for genetic therapy using Moloney retroviruses require ex vivo manipulation of hematopoietic cells to facilitate stable integration of the transgene. While many studies have evaluated the impact of ex vivo culture on normal murine and human stem/progenitor cells, the cellular consequences of ex vivo manipulation of stem cells with intrinsic defects in genome stability are incompletely understood. Here we show that ex vivo culture of Fancc-/- bone marrow cells results in a time-dependent increase in apoptosis of primitive Fancc-/- progenitor cells in conditions that promote the proliferation of wild-type stem/progenitor cells. Further, recipients reconstituted with the surviving Fancc-/- cells have a high incidence of cytogenetic abnormalities and myeloid malignancies that are associated with an acquired resistance to tumor necrosis factor α (TNF-α). Collectively, these data indicate that the intrinsic defects in the genomic stability of Fancc-/- stem/progenitor cells provide a selective pressure for cells that are resistant to apoptosis and have a propensity for the evolution to clonal hematopoiesis and malignancy. These studies could have implications for the design of genetic therapies for treatment of Fanconi anemia and potentially other genetic diseases with intrinsic defects in genome stability.
B-cell kinetics in humans: rapid turnover of peripheral blood memory cells
Authors: Macallan Derek C. , Wallace Diana L. , Zhang Yan , Ghattas Hala , Asquith Becca , de Lara Catherine , Worth Andrew , Panayiotakopoulos George , Griffin George E. , Tough David F. , Beverley Peter C. L. 
Published: January 2005

AbstractInformation about the kinetic behavior and lifespan of lymphocytes is crucial to understanding the mechanisms that regulate processes such as immunologic memory. We have used in vivo labeling of dividing cells with 6,6-2H2-glucose, combined with cell sorting and gas-chromatography-mass spectrometry for deuterium enrichment, in order to analyze the kinetics of human total, naive, or memory B lymphocytes, separated from peripheral blood using monoclonal antibodies. We show that total blood B cells of young adults divide at an average rate of 1.9% (±1.0%) per day and at a similar though slightly slower rate, 1.5% (±1.3%) per day, in the elderly. Separation of naive and memory B cells according to expression of CD27 indicates that naive peripheral blood B cells divide slowly (0.46% per day), while memory cells proliferate more rapidly (2.66% per day). These data are compatible with the view that B-cell memory may be maintained by clones of proliferating B cells.
Effects of PM10 in human peripheral blood monocytes and J774 macrophages
Authors: Brown DM , Donaldson K , Stone V 
Published: January 2005

AbstractThe effects of PM10, one of the components of particulate air pollution, was investigated using human monocytes and a mouse macrophage cell line (J774). The study aimed to investigate the role of these nanoparticles on the release of the pro-inflammatory cytokine TNF-α and IL-1α gene expression. We also investigated the role of intracellular calcium signalling events and oxidative stress in control of these cytokines and the effect of the particles on the functioning of the cell cytoskeleton. We showed that there was an increase in intracellular calcium concentration in J774 cells on treatment with PM10 particles which could be significantly reduced with concomitant treatment with the calcium antagonists verapamil, the intracellular calcium chelator BAPTA-AM but not with the antioxidant nacystelyn or the calmodulin inhibitor W-7. In human monocytes, PM10 stimulated an increase in intracellular calcium which was reduced by verapamil, BAPTA-AM and nacystelyn. TNF-α release was increased with particle treatment in human monocytes and reduced by only verapamil and BAPTA-AM. IL-1α gene expression was increased with particle treatment and reduced by all of the inhibitors. There was increased F-actin staining in J774 cells after treatment with PM10 particles, which was significantly reduced to control levels with all the antagonists tested. The present study has shown that PM10 particles may exert their pro-inflammatory effects by modulating intracellular calcium signalling in macrophages leading to expression of pro-inflammatory cytokines. Impaired motility and phagocytic ability as shown by changes in the F-actin cytoskeleton is likely to play a key role in particle clearance from the lung.
The "Transport Specificity Ratio": a structure-function tool to search the protein fold for loci that control transition state stability in membrane transport catalysis
Authors: King Steven C 
Published: January 2005

Abstract
Background
In establishing structure-function relationships for membrane transport proteins, the interpretation of phenotypic changes can be problematic, owing to uncertainties in protein expression levels, sub-cellular localization, and protein-folding fidelity. A dual-label competitive transport assay called "Transport Specificity Ratio" (TSR) analysis has been developed that is simple to perform, and circumvents the "expression problem," providing a reliable TSR phenotype (a constant) for comparison to other transporters.

Results
Using the Escherichia coli GABA (4-aminobutyrate) permease (GabP) as a model carrier, it is demonstrated that the TSR phenotype is largely independent of assay conditions, exhibiting: (i) indifference to the particular substrate concentrations used, (ii) indifference to extreme changes (40-fold) in transporter expression level, and within broad limits (iii) indifference to assay duration. The theoretical underpinnings of TSR analysis predict all of the above observations, supporting that TSR has (i) applicability in the analysis of membrane transport, and (ii) particular utility in the face of incomplete information on protein expression levels and initial reaction rate intervals (e.g., in high-throughput screening situations). The TSR was used to identify gab permease (GabP) variants that exhibit relative changes in catalytic specificity (kcat/Km) for [14C]GABA (4-aminobutyrate) versus [3H]NA (nipecotic acid).

Conclusions
The TSR phenotype is an easily measured constant that reflects innate molecular properties of the transition state, and provides a reliable index of the difference in catalytic specificity that a carrier exhibits toward a particular pair of substrates. A change in the TSR phenotype, called a Δ(TSR), represents a specificity shift attributable to underlying changes in the intrinsic substrate binding energy (ΔGb) that translocation catalysts rely upon to decrease activation energy ("Equation missing"). TSR analysis is therefore a structure-function tool that enables parsimonious scanning for positions in the protein fold that couple to the transition state, creating stability and thereby serving as functional determinants of catalytic power (efficiency, or specificity).
GOtcha: a new method for prediction of protein function assessed by the annotation of seven genomes
Authors: Martin David MA , Berriman Matthew , Barton Geoffrey J 
Published: January 2005

Abstract
Background
The function of a novel gene product is typically predicted by transitive assignment of annotation from similar sequences. We describe a novel method, GOtcha, for predicting gene product function by annotation with Gene Ontology (GO) terms. GOtcha predicts GO term associations with term-specific probability (P-score) measures of confidence. Term-specific probabilities are a novel feature of GOtcha and allow the identification of conflicts or uncertainty in annotation.

Results
The GOtcha method was applied to the recently sequenced genome for Plasmodium falciparum and six other genomes. GOtcha was compared quantitatively for retrieval of assigned GO terms against direct transitive assignment from the highest scoring annotated BLAST search hit (TOPBLAST). GOtcha exploits information deep into the 'twilight zone' of similarity search matches, making use of much information that is otherwise discarded by more simplistic approaches.
At a P-score cutoff of 50%, GOtcha provided 60% better recovery of annotation terms and 20% higher selectivity than annotation with TOPBLAST at an E-value cutoff of 10-4.

Conclusions
The GOtcha method is a useful tool for genome annotators. It has identified both errors and omissions in the original Plasmodium falciparum annotation and is being adopted by many other genome sequencing projects.
A functional hierarchical organization of the protein sequence space
Authors: Kaplan Noam , Friedlich Moriah , Fromer Menachem , Linial Michal 
Published: January 2005

Abstract
Background
It is a major challenge of computational biology to provide a comprehensive functional classification of all known proteins. Most existing methods seek recurrent patterns in known proteins based on manually-validated alignments of known protein families. Such methods can achieve high sensitivity, but are limited by the necessary manual labor. This makes our current view of the protein world incomplete and biased. This paper concerns ProtoNet, a automatic unsupervised global clustering system that generates a hierarchical tree of over 1,000,000 proteins, based solely on sequence similarity.

Results
In this paper we show that ProtoNet correctly captures functional and structural aspects of the protein world. Furthermore, a novel feature is an automatic procedure that reduces the tree to 12% its original size. This procedure utilizes only parameters intrinsic to the clustering process. Despite the substantial reduction in size, the system's predictive power concerning biological functions is hardly affected. We then carry out an automatic comparison with existing functional protein annotations. Consequently, 78% of the clusters in the compressed tree (5,300 clusters) get assigned a biological function with a high confidence. The clustering and compression processes are unsupervised, and robust.

Conclusions
We present an automatically generated unbiased method that provides a hierarchical classification of all currently known proteins.
Hierarchical structure and modules in the Escherichia coli transcriptional regulatory network revealed by a new top-down approach
Authors: Ma Hong-Wu , Buer Jan , Zeng An-Ping 
Published: January 2005

Abstract
Background
Cellular functions are coordinately carried out by groups of genes forming functional modules. Identifying such modules in the transcriptional regulatory network (TRN) of organisms is important for understanding the structure and function of these fundamental cellular networks and essential for the emerging modular biology. So far, the global connectivity structure of TRN has not been well studied and consequently not applied for the identification of functional modules. Moreover, network motifs such as feed forward loop are recently proposed to be basic building blocks of TRN. However, their relationship to functional modules is not clear.

Results
In this work we proposed a top-down approach to identify modules in the TRN of E. coli. By studying the global connectivity structure of the regulatory network, we first revealed a five-layer hierarchical structure in which all the regulatory relationships are downward. Based on this regulatory hierarchy, we developed a new method to decompose the regulatory network into functional modules and to identify global regulators governing multiple modules. As a result, 10 global regulators and 39 modules were identified and shown to have well defined functions. We then investigated the distribution and composition of the two basic network motifs (feed forward loop and bi-fan motif) in the hierarchical structure of TRN. We found that most of these network motifs include global regulators, indicating that these motifs are not basic building blocks of modules since modules should not contain global regulators.

Conclusion
The transcriptional regulatory network of E. coli possesses a multi-layer hierarchical modular structure without feedback regulation at transcription level. This hierarchical structure builds the basis for a new and simple decomposition method which is suitable for the identification of functional modules and global regulators in the transcriptional regulatory network of E. coli. Analysis of the distribution of feed forward loops and bi-fan motifs in the hierarchical structure suggests that these network motifs are not elementary building blocks of functional modules in the transcriptional regulatory network of E. coli.
Clustering under the line graph transformation: application to reaction network
Authors: Nacher Jose C , Ueda Nobuhisa , Yamada Takuji , Kanehisa Minoru , Akutsu Tatsuya 
Published: January 2005

Abstract
Background
Many real networks can be understood as two complementary networks with two kind of nodes. This is the case of metabolic networks where the first network has chemical compounds as nodes and the second one has nodes as reactions. In general, the second network may be related to the first one by a technique called line graph transformation (i.e., edges in an initial network are transformed into nodes). Recently, the main topological properties of the metabolic networks have been properly described by means of a hierarchical model. While the chemical compound network has been classified as hierarchical network, a detailed study of the chemical reaction network had not been carried out.

Results
We have applied the line graph transformation to a hierarchical network and the degree-dependent clustering coefficient C(k) is calculated for the transformed network. C(k) indicates the probability that two nearest neighbours of a vertex of degree k are connected to each other. While C(k) follows the scaling law C(k) ~ k-1.1 for the initial hierarchical network, C(k) scales weakly as k0.08 for the transformed network. This theoretical prediction was compared with the experimental data of chemical reactions from the KEGG database finding a good agreement.

Conclusions
The weak scaling found for the transformed network indicates that the reaction network can be identified as a degree-independent clustering network. By using this result, the hierarchical classification of the reaction network is discussed.