bluuebunny/crossref_metadata_2025_split huggingface dataset:
Emergence of biopharmaceutical innovators in China, India, Brazil, and South Africa as global competitors and collaborators
Authors: Rezaie Rahim , McGahan Anita M , Frew Sarah E , Daar Abdallah S , Singer Peter A 
Published: June 2012

Abstract
Biopharmaceutical innovation has had a profound health and economic impact globally. Developed countries have traditionally been the source of most innovations as well as the destination for the resulting economic and health benefits. As a result, most prior research on this sector has focused on developed countries. This paper seeks to fill the gap in research on emerging markets by analyzing factors that influence innovative activity in the indigenous biopharmaceutical sectors of China, India, Brazil, and South Africa. Using qualitative research methodologies, this paper a) shows how biopharmaceutical innovation is taking place within the entrepreneurial sectors of these emerging markets, b) identifies common challenges that indigenous entrepreneurs face, c) highlights the key role played by the state, and d) reveals that the transition to innovation by companies in the emerging markets is characterized by increased global integration. It suggests that biopharmaceutical innovators in emerging markets are capitalizing on opportunities to participate in the drug development value chain and thus developing capabilities and relationships for competing globally both with and against established companies headquartered in developed countries.
The adapter protein ADAP is required for selected dendritic cell functions
Authors: Togni Mauro , Engelmann Swen , Reinhold Dirk , Schraven Burkhart , Reinhold Annegret 
Published: June 2012

Abstract

Background
The cytosolic adaptor protein ADAP (adhesion and degranulation promoting adapter protein) is expressed by T cells, natural killer cells, myeloid cells and platelets. ADAP is involved in T-cell-receptor-mediated inside-out signaling, which leads to integrin activation, adhesion and reorganization of the actin cytoskeleton. However, little is known about the role of ADAP in myeloid cells. In the present study, we analyzed the function of ADAP in bone-marrow-derived dendritic cells (BMDCs) from ADAP-deficient mice.

Results
ADAP-deficient BMDCs showed almost normal levels of antigen uptake, adhesion, maturation, migration from the periphery to the draining lymph nodes, antigen-specific T-cell activation, and production of the proinflammatory cytokines IL-6 and TNF-∝. Furthermore, we provide evidence that the activation of signaling pathways after lipopolysaccharide (LPS) stimulation are not affected by the loss of ADAP. In contrast, ADAP-deficient BMDCs showed defects in CD11c-mediated cellular responses, with significantly diminished production of IL-6, TNF-∝ and IL-10. Actin polymerization was enhanced after CD11c integrin stimulation.

Conclusions
In summary, we propose that the adapter molecule ADAP is critical for selected CD11c integrin-mediated functions of dendritic cells.
An improved ITU-R rain attenuation prediction model over terrestrial microwave links in tropical region
Authors: Islam Rafiqul MD , Abdulrahman Yusuf A , Rahman Tharek A 
Published: June 2012

AbstractAn improved approach of predicting rain attenuation cumulative distribution (CD) over terrestrial microwave links operating in tropical regions is presented in this article. The proposed method offers a better extrapolation approach for determining the values of rain attenuation at different exceedance probability from the measured attenuation at 0.01% of the time. The experimental data consist of measured rainfall rates and rain attenuation over six geographically spread DIGI MINI-LINKs operating at 15 GHz in Malaysia. A new set of numerical coefficients was derived for improved rain attenuation CD predictions in the Malaysian tropical climate. In order to test the applicability of the proposed extrapolation method, a validation was performed using rain rate and rain attenuation measurements from five Brazilian and seven Nigerian tropical locations. When tested against measurements, the proposed method seems to provide a significant improvement over the current extrapolation method adopted by ITU-R Recommendations P.530-14, for the prediction of rain attenuation CD over tropical regions.
Predictive value of IgE/IgG4 antibody ratio in children with egg allergy
Authors: Okamoto Shindou , Taniuchi Shoichiro , Sudo Kyoko , Hatano Yasuko , Nakano Keiji , Shimo Tomohiko , Kaneko Kazunari 
Published: June 2012

Abstract

Background
The aim of this study was to investigate the role of specific IgG4 antibodies to hen’s egg white and determine their utility as a marker for the outcome of oral challenge test in children sensitized to hen’s egg

Methods
The hen’s egg oral food challenge test was performed in 105 sensitized children without atopic dermatitis, and the titers of egg white-specific immunoglobulin G4 (IgG4) and immunoglobulin E (IgE) antibodies were measured. To set the cut-off values of IgG4, IgE, and the IgE/IgG4 ratio for predicting positive results in oral challenges, receiver operating characteristic curves were plotted and the area under the curves (AUC) were calculated.

Results
Sixty-four of 105 oral challenges with whole eggs were assessed as positive. The AUC for IgE, IgG4, and IgE/IgG4 for the prediction of positive results were 0.609, 0.724, and 0.847, respectively. Thus, the IgE/IgG4 ratio generated significantly higher specificity, sensitivity, positive predictive value (%), and negative predictive value (%) than the individual IgE and IgG4. The negative predictive value of the IgE/IgG4 ratio was 90% at a value of 1.

Conclusions
We have demonstrated that the egg white-specific serum IgE/IgG4 ratio is important for predicting reactivity to egg during food challenges.
Immunodominant fragments of myelin basic protein initiate T cell-dependent pain
Authors: Liu Huaqing , Shiryaev Sergey A , Chernov Andrei V , Kim Youngsoon , Shubayev Igor , Remacle Albert G , Baranovskaya Svetlana , Golubkov Vladislav S , Strongin Alex Y , Shubayev Veronica I 
Published: June 2012

Abstract

Background
The myelin sheath provides electrical insulation of mechanosensory Aβ-afferent fibers. Myelin-degrading matrix metalloproteinases (MMPs) damage the myelin sheath. The resulting electrical instability of Aβ-fibers is believed to activate the nociceptive circuitry in Aβ-fibers and initiate pain from innocuous tactile stimulation (mechanical allodynia). The precise molecular mechanisms, responsible for the development of this neuropathic pain state after nerve injury (for example, chronic constriction injury, CCI), are not well understood.

Methods and results
Using mass spectrometry of the whole sciatic nerve proteome followed by bioinformatics analyses, we determined that the pathways, which are classified as the Infectious Disease and T-helper cell signaling, are readily activated in the nerves post-CCI. Inhibition of MMP-9/MMP-2 suppressed CCI-induced mechanical allodynia and concomitant TNF-α and IL-17A expression in nerves. MMP-9 proteolysis of myelin basic protein (MBP) generated the MBP84-104 and MBP68-86 digest peptides, which are prominent immunogenic epitopes. In agreement, the endogenous MBP69-86 epitope co-localized with MHCII and MMP-9 in Schwann cells and along the nodes of Ranvier. Administration of either the MBP84-104 or MBP68-86 peptides into the naïve nerve rapidly produced robust mechanical allodynia with a concomitant increase in T cells and MHCII-reactive cell populations at the injection site. As shown by the genome-wide expression profiling, a single intraneural MBP84-104 injection stimulated the inflammatory, immune cell trafficking, and antigen presentation pathways in the injected naïve nerves and the associated spinal cords. Both MBP84-104-induced mechanical allodynia and characteristic pathway activation were remarkably less prominent in the T cell-deficient athymic nude rats.

Conclusions
These data implicate MBP as a novel mediator of pain. Furthermore, the action of MMPs expressed within 1 day post-injury is critical to the generation of tactile allodynia, neuroinflammation, and the immunodominant MBP digest peptides in nerve. These MBP peptides initiate mechanical allodynia in both a T cell-dependent and -independent manner. In the course of Wallerian degeneration, the repeated exposure of the cryptic MBP epitopes, which are normally sheltered from immunosurveillance, may induce the MBP-specific T cell clones and a self-sustaining immune reaction, which may together contribute to the transition of acute pain into a chronic neuropathic pain state.
Anti-Hyperalgesic Effects of Calcitonin on Neuropathic Pain Interacting with its Peripheral Receptors
Authors: Ito Akitoshi , Takeda Mineko , Yoshimura Takeshi , Komatsu Takayuki , Ohno Takeshi , Kuriyama Hiroshi , Matsuda Akio , Yoshimura Megumu 
Published: June 2012

Background: The polypeptide hormone calcitonin is clinically well known for its ability to relieve neuropathic pain such as spinal canal stenosis, diabetic neuropathy and complex regional pain syndrome. Mechanisms for its analgesic effect, however, remain unclear. Here we investigated the mechanism of anti-hyperalgesic action of calcitonin in a neuropathic pain model in rats. Results: Subcutaneous injection of elcatonin, a synthetic derivative of eel calcitonin, relieved hyperalgesia induced by chronic constriction injury (CCI). Real-time reverse transcriptase-polymerase chain reaction analysis revealed that the CCI provoked the upregulation of tetrodotoxin (TTX)-sensitive Nav.1.3 mRNA and downregulation of TTX-resistant Nav1.8 and Nav1.9 mRNA on the ipsilateral dorsal root ganglion (DRG), which would consequently increase the excitability of peripheral nerves. These changes were reversed by elcatonin. In addition, the gene expression of the calcitonin receptor and binding site of 125I-calcitonin was increased at the constricted peripheral nerve tissue but not at the DRG. The anti-hyperalgesic effect and normalization of sodium channel mRNA by elcatonin was parallel to the change of the calcitonin receptor expression. Elcatonin, however, did not affect the sensitivity of nociception or gene expression of sodium channel, while it suppressed calcitonin receptor mRNA under normal conditions. Conclusions: These results suggest that the anti-hyperalgesic action of calcitonin on CCI rats could be attributable to the normalization of the sodium channel expression, which might be exerted by an unknown signal produced at the peripheral nerve tissue but not by DRG neurons through the activation of the calcitonin receptor. Calcitonin signals were silent in the normal condition and nerve injury may be one of triggers for conversion of a silent to an active signal.
Genetic alterations in a primary medullary thyroid carcinoma and its lymph node metastasis in a patient with 15 years follow-up
Authors: González-Yebra Beatriz , Peralta Raúl , González Ana Lilia , Ayala-Garcia Marco Antonio , de Zarate María E Medrano Ortiz , Salcedo Mauricio 
Published: June 2012

Abstract

Background
Association between DNA alterations and clinical parameters as recurrence, survival or prognosis has been found in a variety of tumors. A clear association between Medullary Thyroid Carcinoma (MTC) and RET oncogene mutation has been accepted. Specifically M918T RET mutation represents the main genetic event in most cases of sporadic MTC (SMTC) and limited chromosomal alterations analyses have been performed.

Methods
In the present work, a comparative genomic hybridization (CGH) study was performed using DNA from a primary tumor in a M918T RET mutation-positive SMTC patient and from its lymph node metastasis to investigate additional genetic alterations. We studied a patient with 15 years of follow-up and persistence of disease, confirmed by periodical elevated serum calcitonin (CT) levels.

Results
Only 3 chromosomal imbalances were identified in the primary tumor, gain of 18p, and loss of 6p and 16p region, whereas 25 chromosomal imbalances were identified in the metastasis (9 gains and 16 losses).

Conclusion
The chromosomal changes 6p-, 16p-, 18p + could determine in part the oncogenic phenotype in the primary M918T RET positive tumor and probably related to persistence of high serum CT levels in this patient. The additional chromosomal changes observed could be related to the metastasis phenotype. We suggest that some genes mapped at 6p, 16p and 18p chromosomal regions, could act as genes associated to cancer and could be related to persistent SMTC and good prognosis.

Virtual slides
The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1720753793691097
Relation between smoking history and gene expression profiles in lung adenocarcinomas
Authors: Staaf Johan , Jönsson Göran , Jönsson Mats , Karlsson Anna , Isaksson Sofi , Salomonsson Annette , Pettersson Helen M , Soller Maria , Ewers Sven-Börje , Johansson Leif , Jönsson Per , Planck Maria 
Published: June 2012

Abstract

Background
Lung cancer is the worldwide leading cause of death from cancer. Tobacco usage is the major pathogenic factor, but all lung cancers are not attributable to smoking. Specifically, lung cancer in never-smokers has been suggested to represent a distinct disease entity compared to lung cancer arising in smokers due to differences in etiology, natural history and response to specific treatment regimes. However, the genetic aberrations that differ between smokers and never-smokers’ lung carcinomas remain to a large extent unclear.

Methods
Unsupervised gene expression analysis of 39 primary lung adenocarcinomas was performed using Illumina HT-12 microarrays. Results from unsupervised analysis were validated in six external adenocarcinoma data sets (n=687), and six data sets comprising normal airway epithelial or normal lung tissue specimens (n=467). Supervised gene expression analysis between smokers and never-smokers were performed in seven adenocarcinoma data sets, and results validated in the six normal data sets.

Results
Initial unsupervised analysis of 39 adenocarcinomas identified two subgroups of which one harbored all never-smokers. A generated gene expression signature could subsequently identify never-smokers with 79-100% sensitivity in external adenocarcinoma data sets and with 76-88% sensitivity in the normal materials. A notable fraction of current/former smokers were grouped with never-smokers. Intriguingly, supervised analysis of never-smokers versus smokers in seven adenocarcinoma data sets generated similar results. Overlap in classification between the two approaches was high, indicating that both approaches identify a common set of samples from current/former smokers as potential never-smokers. The gene signature from unsupervised analysis included several genes implicated in lung tumorigenesis, immune-response associated pathways, genes previously associated with smoking, as well as marker genes for alveolar type II pneumocytes, while the best classifier from supervised analysis comprised genes strongly associated with proliferation, but also genes previously associated with smoking.

Conclusions
Based on gene expression profiling, we demonstrate that never-smokers can be identified with high sensitivity in both tumor material and normal airway epithelial specimens. Our results indicate that tumors arising in never-smokers, together with a subset of tumors from smokers, represent a distinct entity of lung adenocarcinomas. Taken together, these analyses provide further insight into the transcriptional patterns occurring in lung adenocarcinoma stratified by smoking history.
Demographic and clinical correlates of sexual dysfunction among Nigerian male outpatients on conventional antipsychotic medications
Authors: Oyekanmi Aina Kikelomo , Adelufosi Adegoke Oloruntoba , Abayomi Olukayode , Adebowale Timothy Olaolu 
Published: June 2012

Abstract

Background
In psychotic disorders, early intervention with antipsychotic medications increases the likelihood of favourable long-term course. However, the pharmacologic management especially with conventional antipsychotic medications is complicated by a high rate of adverse effects including sexual dysfunction. This study aims to determine the demographic and clinical factors associated with sexual dysfunction among male psychiatric outpatients on conventional antipsychotic medications in South-western Nigeria.

Methods
Two hundred and seventy five consecutive male outpatients with psychotic disorders on conventional antipsychotic medications were interviewed. Data was collected on demographic characteristics, illness-related and medication-related variables. Illness severity was assessed with the Brief psychiatric rating scale. The International Index of Erectile Function questionnaire was used to assess for sexual dysfunctions.

Results
A total of 111 (40.4%) respondents had one or more forms of sexual dysfunction. Sexual desire dysfunction was present in 47 (17.1%) of respondents, erectile dysfunction in 95 (34.5%), orgasmic dysfunctions in 51 (18.5%), intercourse dissatisfaction in 72 (26.2%) and overall dissatisfaction in 64 (23.3%). Sexual dysfunction was significantly associated with employment status, age, marital status, haloperidol use, medication dosage, and presence of psychopathology. Unemployment was the only significant independent correlate of sexual dysfunction, with unemployed respondents twice more likely to have sexual dysfunction compared with those employed (Wald = 3.865, Odds Ratio = 2.033, 95% confidence interval = 1.002 - 4.124, p = 0.049).

Conclusions
The high prevalence of sexual dysfunction found in this study suggests a need among clinicians for increased awareness and recognition of the sexual side effects in patients taking conventional antipsychotic medications. This knowledge should guide conventional antipsychotic medication prescription in the at-risk population to improve treatment adherence.
Natural infection of Didelphis aurita (Mammalia: Marsupialia) with Leishmania infantum in Brazil
Authors: Carreira João Carlos Araujo , da Silva Alba Valéria Machado , de Pita Pereira Daniela , Brazil Reginaldo Peçanha 
Published: June 2012

Abstract

Background
The opossum Didelphis have been considered as natural hosts of Leishmania parasites in the New World, suggesting an important role in the epidemiology of Visceral Leishmaniasis (VL). Among six extant species that belong to the genus Didelphis, only two (D. marsupialis and D. albiventris), have been mentioned as natural hosts of Leishmania infantum in Brazil and Colombia. In the present paper, it is reported for the first time, the observation of intracellular parasites (amastigotes) in tissues of Didelphis aurita naturally infected with Leishmania infantum in Brazil. We also discuss some aspects associated to the relationship between L. infantum and the geographical distribution of some species of the genus Didelphis.

Methods
The opossums studied were caught by wire traps (Tomahawk) in Barra de Guaratiba, a peri-urban area in Rio de Janeiro. The opossums were killed with an overdose of Thiopental sodium.At necropsy, macroscopic alterations were examined and samples from liver, spleen, lymph nodes, ear, abdominal skin, scent glands and bone marrow were collected for parasitological and molecular diagnoses.

Results
Forty-eight opossums were captured in an AVL endemic region, 30 being caught in a mangrove area and eighteen animals in a forest area near to some residential-yards. Among the thirty opossums trapped in the mangrove area, all of them were negative by both imprint and sera samples assayed on Dipstick Tests, that is a test based on a combination of protein-A colloidal gold conjugate and rk39 Leishmania antigen to detect anti-Leishmania antibody in serum or plasma. At the macroscopic examination one out of eighteen opossums, caught close to the forest, presented alterations compatible with spleen hypertrophy and three were positive by Dipstick Tests (16.6%) and presented amastigotes in the spleen and in one of them, the parasites were also observed in a submandibular lymph node. Leishmania infantum infections were confirmed through dot blot hybridization using a L. infantum-specific biotinylated probe.

Conclusions
In the present paper we present the first report of amastigotes in the tissues of Didelphis aurita (Mammalia: Marsupialia) naturally infected with Leishmania infantum. We also attempt to claim the particular role of some opossum species as hosts of Leishmania infantum, contributing at least in part on the description of potential sylvatic reservoirs.
Host feeding patterns and preference of Anopheles minimus (Diptera: Culicidae) in a malaria endemic area of western Thailand: baseline site description
Authors: Tisgratog Rungarun , Tananchai Chatchai , Juntarajumnong Waraporn , Tuntakom Siripun , Bangs Michael J , Corbel Vincent , Chareonviriyaphap Theeraphap 
Published: June 2012

Abstract

Background
Host feeding patterns of Anopheles minimus in relation to ambient environmental conditions were observed during a 2-year period at Tum Sua Village, located in Mae Sot District, Tak Province, in western Thailand, where An. minimus is found in abundance and regarded as the most predominant malaria vector species. Detailed information on mosquito behavior is important for understanding the epidemiology of disease transmission and developing more effective and efficient vector control methods.

Methods
Adult mosquitoes were collected every 2 months for two consecutive nights from 1800 to 0600 hrs. Three collection methods were used; indoor human-landing collections (HLC), outdoor HLC, and outdoor cattle-bait collections (CBC).

Results
A total of 7,663 female Anopheles mosquitoes were collected of which 5,392 were identified as members of 3 different species complexes, the most prevalent being Anopheles minimus complex (50.36%), followed by Anopheles maculatus complex (19.68%) and Anopheles dirus complex (0.33%). An. minimus s.s. comprised virtually all (> 99.8 percent) of Minimus Complex species captured. Blood feeding behavior of An. minimus was more pronounced during the second half of the evening, showing a slight preference to blood feed outdoors (~60%) versus inside structures. Significantly (P < 0.0001) more An. minimus were collected from human-baited methods compared with a tethered cow, indicating a more anthropophilic feeding behavior. Although a significant difference in total number of mosquitoes from the HLC was recorded between the first and second year, the mean biting frequency over the course of the evening hours remained similar.

Conclusions
The Human landing activity of An. minimus in Tum Sua Village showed a stronger preference/attraction for humans compared to a cow-baited collection method. This study supports the incrimination of An. minimus as the primary malaria vector in the area. A better understanding of mosquito behavior related to host preference, and the temporal and spatial blood feeding activity will help facilitate the design of vector control strategies and effectiveness of vector control management programs in Thailand.