bluuebunny/crossref_metadata_2025_split huggingface dataset:
Posterior Hip Pain in an Athletic Population: Differential Diagnosis and Treatment Options
Authors: Frank Rachel M. , Slabaugh Mark A. , Grumet Robert C. , Virkus Walter W. , Bush-Joseph Charles A. , Nho Shane J. 
Published: April 2010

Context: Posterior hip pain is a relatively uncommon but increasingly recognized complaint in the orthopaedic community. Patient complaints and presentations are often vague or nonspecific, making diagnosis and subsequent treatment decisions difficult. The purposes of this article are to review the anatomy and pathophysiology related to posterior hip pain in the athletic patient population. Evidence Acquisition: Data were collected through a thorough review of the literature via a MEDLINE search of all relevant articles between 1980 and 2010. Results: Many patients who complain of posterior hip pain actually have pain referred from another part of the body—notably, the lumbar spine or sacroiliac joint. Treatment options for posterior hip pain are typically nonoperative; however, surgery is warranted in some cases. Conclusions: Recent advancements in the understanding of hip anatomy, pathophysiology, and treatment options have enabled physicians to better diagnosis athletic hip injuries and select patients for appropriate treatment.
A Minimally Disruptive Surgical Technique for the Treatment of Osteitis Pubis in Athletes
Authors: Hechtman Keith S. , Zvijac John E. , Popkin Charles A. , Zych Gregory A. , Bemden Angie Botto-van 
Published: April 2010

Background: Multiple surgical procedures exist for the treatment of osteitis pubis: curettage of the symphysis joint, wedge resection, complete resection of the joint, placement of extraperitoneal retropubic synthetic mesh, and arthrodesis of the joint. However, a paucity of literature has reported long-term successful outcomes with the aforementioned approaches. Patients treated operatively have reported recalcitrant pain resulting from iatrogenic instability. The article presents the results of a conservative operative technique that avoids disruption of adjacent ligaments. Hypothesis: Preserving the adjacent ligamentous structures will allow competitive athletes to return to competition and activities of daily living free of iatrogenic pelvic instability and pain. Study Design: Case series. Methods: Four competitive athletes (2 professional and 2 collegiate football players) diagnosed with osteitis pubis were treated conservatively for a minimum of 6 months. Patients underwent surgical intervention upon failure to respond to nonoperative management. The degenerative tissue was resected, allowing only bleeding cancellous bone to remain while preserving the adjacent ligaments. An arthroscope was used to assist in curettage, allowing the debridement to be performed through a small incision in the anterior capsule. Results: The symptoms of all 4 patients resolved, and they returned to competitive athletics. This ligament-sparing technique provided a solid, stable repair and pain relief. Conclusion: This surgical technique preserves the adjacent ligamentous structures and allows competitive athletes to return to competition and activities of daily living free of pain and void of pelvic instability. Clinical Relevance: This technique is a surgical treatment option for athletes with osteitis pubis who fail conservative treatment.
Groin Injuries in Sports Medicine
Authors: Tyler Timothy F. , Silvers Holly J. , Gerhardt Michael B. , Nicholas Stephen J. 
Published: April 2010

Context: An in-season groin injury may be debilitating for the athlete. Proper diagnosis and identification of the pathology are paramount in providing appropriate intervention. Furthermore, an adductor strain that is treated improperly can become chronic and career threatening. Any one of the 6 muscles of the adductor muscle group can be involved. The degree of injury can range from a minor strain (grade 1), where minimal playing time is lost, to a severe strain (grade 3), in which there is complete loss of muscle function. Persistent groin pain and muscle imbalance may lead to athletic pubalgia. Evidence Acquisition: Relevant studies were identified through a literature search of MEDLINE and the Cochrane database from 1990 to 2009, as well as a manual review of reference lists of identified sources. Results: Ice hockey and soccer players seem particularly susceptible to adductor muscle strains. In professional ice hockey and soccer players throughout the world, approximately 10% to 11% of all injuries are groin strains. These injuries have been linked to hip muscle weakness, a previous injury to that area, preseason practice sessions, and level of experience. This injury may be prevented if these risk factors are addressed before each season. Conclusion: Despite the identification of risk factors and strengthening intervention for athletes, adductor strains continue to occur throughout sport. If groin pain persists, the possibility of athletic pubalgia needs to be explored, because of weakening or tears in the abdominal wall muscles. A diagnosis is confirmed by exclusion of other pathology.
Virally infected and matured human dendritic cells activate natural killer cells via cooperative activity of plasma membrane-bound TNF and IL-15
Authors: Vujanovic Lazar , Szymkowski David E. , Alber Sean , Watkins Simon C. , Vujanovic Nikola L. , Butterfield Lisa H. 
Published: April 2010

AbstractRecombinant adenovirus-engineered dendritic cells (Ad.DCs) are potent immunologic adjuvants of antiviral and anticancer vaccines. The effectiveness of Ad.DC-based vaccines may depend on the ability of Ad.DCs to crosstalk with natural killer (NK) cells and to activate, polarize, and bridge innate and adaptive immunity. We investigated, for the first time, whether and how human Ad.DCs activate NK cells, and compared the Ad.DC function with that of immature DCs and matured DCs (mDCs). We found that adenovirus transduction and lipopolysaccharide/interferon-γ-induced maturation increased expression of transmembrane tumor necrosis factor (TNF) and trans-presented (trans) interleukin-15 (IL-15) on DCs, leading to enhanced NK cell activation without enhancing DC susceptibility to NK cell-mediated killing. This crosstalk enhanced NK cell CD69 expression, interferon-γ secretion, proliferation, and antitumor activities, with Ad.DCs being significantly more effective than immature DCs, but less effective than mDCs. The Ad.DC and mDC crosstalk with NK cells was largely prevented by physical separation of DCs and NK cells, and neutralization of total TNF and IL-15, but not by selective sequestration of soluble TNF. These findings demonstrate that both Ad.DCs and mDCs can efficiently promote innate immune functions by activation of NK cells through the cooperative activities of tmTNF and trans-IL-15 mediated by cell-to-cell contact.
Treatment with Imiquimod enhances antitumor immunity induced by therapeutic HPV DNA vaccination
Authors: Chuang Chi-Mu , Monie Archana , Hung Chien-Fu , Wu T-C 
Published: April 2010

AbstractBackgroundThere is an urgent need to develop new innovative therapies for the control of advanced cancer. The combination of antigen-specific immunotherapy with the employment of immunomodulatory agents has emerged as a potentially plausible approach for the control of advanced cancer.MethodsIn the current study, we explored the combination of the DNA vaccine encoding calreticulin (CRT) linked to human papillomavirus type 16 (HPV-16) E7 antigen (CRT/E7) with the TLR7 agonist imiquimod for their ability to generate E7-specific immune responses and antitumor effects in tumor-bearing mice.ResultsWe observed that treatment with CRT/E7 DNA in combination with imiquimod leads to an enhancement in the E7-specific CD8+ T cell immune responses and a decrease in the number of myeloid-derived suppressor cells in the tumor microenvironment of tumor-bearing mice. Furthermore, treatment with CRT/E7 DNA in combination with imiquimod leads to significantly improved antitumor effects and prolonged survival in treated mice. In addition, treatment with imiquimod led to increased number of NK1.1+ cells and F4/80+ cells in the tumor microenvironment. Macrophages and NK1.1+ cells were found to play an important role in the antitumor effects mediated by treatment with CRT/E7 DNA in combination with imiquimod.ConclusionsThus, our data suggests that the combination of therapeutic HPV DNA vaccination with topical treatment with the TLR7 agonist imiquimod enhances the antitumor immunity induced by DNA vaccination. The current study has significant implications for future clinical translation.
Bomapin is a redox-sensitive nuclear serpin that affects responsiveness of myeloid progenitor cells to growth environment
Authors: Przygodzka Patrycja , Ramstedt Björn , Tengel Tobias , Larsson Göran , Wilczynska Malgorzata 
Published: April 2010

Abstract

Background
Haematopoiesis is a process of formation of mature blood cells from hematopoietic progenitors in bone marrow. Haematopoietic progenitors are stimulated by growth factors and cytokines to proliferate and differentiate, and they die via apoptosis when these factors are depleted. An aberrant response to growth environment may lead to haematological disorders. Bomapin (serpinb10) is a hematopoietic- and myeloid leukaemia-specific protease inhibitor with unknown function.

Results
We found that the majority of naturally expressed bomapin was located in the nucleus. Both the natural and recombinant bomapin had a disulfide bond which linked the only two bomapin cysteines: one located in the CD-loop and the other near the C-terminus. Computer modelling showed that the cysteines are distant in the reduced bomapin, but can easily be disulfide-linked without distortion of the overall bomapin structure. Low-level ectopic expression of bomapin in bomapin-deficient K562 cells resulted in about 90% increased cell proliferation under normal growth conditions. On the other hand, antisense-downregulation of natural bomapin in U937 cells resulted in a decreased cell proliferation. Bomapin C395S mutant, representing the reduced form of the serpin, had no effect on cell proliferation, suggesting that the disulfide bond-linked conformation of bomapin is biologically important. The bomapin-dependent effect was specific for myeloid cells, since ectopic expression of the serpin in HT1080 cells did not change cell proliferation. In contrast to the survival-promoting activity of bomapin in cells cultured under optimal growth conditions, bomapin enhanced cell apoptosis following growth factor withdrawal.

Conclusions
We propose that bomapin is a redox-sensitive nuclear serpin that augments proliferation or apoptosis of leukaemia cells, depending on growth factors availability.
Human intronic enhancers control distinct sub-domains of Gli3 expression during mouse CNS and limb development
Authors: Abbasi Amir A , Paparidis Zissis , Malik Sajid , Bangs Fiona , Schmidt Ansgar , Koch Sabine , Lopez-Rios Javier , Grzeschik Karl-Heinz 
Published: April 2010

Abstract
Background
The zinc-finger transcription factor GLI3 is an important mediator of Sonic hedgehog signaling and crucial for patterning of many aspects of the vertebrate body plan. In vertebrates, the mechanism of SHH signal transduction and its action on target genes by means of activating or repressing forms of GLI3 have been studied most extensively during limb development and the specification of the central nervous system. From these studies it has emerged, that Gli3 expression must be subject to a tight spatiotemporal regulation. However, the genetic mechanisms and the cis-acting elements controlling the expression of Gli3 remained largely unknown.

Results
Here, we demonstrate in chicken and mouse transgenic embryos that human GLI3-intronic conserved non-coding sequence elements (CNEs) autonomously control individual aspects of Gli3 expression. Their combined action shows many aspects of a Gli3-specific pattern of transcriptional activity. In the mouse limb bud, different CNEs enhance Gli3-specific expression in evolutionary ancient stylopod and zeugopod versus modern skeletal structures of the autopod. Limb bud specificity is also found in chicken but had not been detected in zebrafish embryos. Three of these elements govern central nervous system specific gene expression during mouse embryogenesis, each targeting a subset of endogenous Gli3 transcription sites. Even though fish, birds, and mammals share an ancient repertoire of gene regulatory elements within Gli3, the functions of individual enhancers from this catalog have diverged significantly. During evolution, ancient broad-range regulatory elements within Gli3 attained higher specificity, critical for patterning of more specialized structures, by abolishing the potential for redundant expression control.

Conclusion
These results not only demonstrate the high level of complexity in the genetic mechanisms controlling Gli3 expression, but also reveal the evolutionary significance of cis-acting regulatory networks of early developmental regulators in vertebrates.
Screening mutations in myosin binding protein C3 gene in a cohort of patients with Hypertrophic Cardiomyopathy
Authors: Rodríguez-García María Isabel , Monserrat Lorenzo , Ortiz Martín , Fernández Xusto , Cazón Laura , Núñez Lucía , Barriales-Villa Roberto , Maneiro Emilia , Veira Elena , Castro-Beiras Alfonso , Hermida-Prieto Manuel 
Published: April 2010

Abstract

Background

MyBPC3 mutations are amongst the most frequent causes of hypertrophic cardiomyopathy, however, its prevalence varies between populations. They have been associated with mild and late onset disease expression. Our objectives were to establish the prevalence of MyBPC3 mutations and determine their associated clinical characteristics in our patients.

Methods
Screening by Single Strand Conformation Polymorphisms (SSCP) and sequencing of the fragments with abnormal motility of the MyBPC3 gene in 130 unrelated consecutive HCM index cases. Genotype-Phenotype correlation studies were done in positive families.

Results
16 mutations were found in 20 index cases (15%): 5 novel [D75N, V471E, Q327fs, IVS6+5G>A (homozygous), and IVS11-9G>A] and 11 previously described [A216T, R495W, R502Q (2 families), E542Q (3 families), T957S, R1022P (2 families), E1179K, K504del, K600fs, P955fs and IVS29+5G>A]. Maximum wall thickness and age at time of diagnosis were similar to patients with MYH7 mutations [25(7) vs. 27(8), p = 0.16], [46(16) vs. 44(19), p = 0.9].

Conclusions
Mutations in MyBPC3 are present in 15% of our hypertrophic cardiomyopathy families. Severe hypertrophy and early expression are compatible with the presence of MyBPC3 mutations. The genetic diagnosis not only allows avoiding clinical follow up of non carriers but it opens new possibilities that includes: to take preventive clinical decisions in mutation carriers than have not developed the disease yet, the establishment of genotype-phenotype relationship, and to establish a genetic diagnosis routine in patients with familial HCM.
Clinical significance of Phosphatidyl Inositol Synthase overexpression in oral cancer
Authors: Kaur Jatinder , Sawhney Meenakshi , DattaGupta Siddartha , Shukla Nootan K , Srivastava Anurag , Ralhan Ranju 
Published: April 2010

Abstract

Background
We reported increased levels of Phosphatidyl Inositol synthase (PI synthase), (enzyme that catalyses phosphatidyl inositol (PI) synthesis-implicated in intracellular signaling and regulation of cell growth) in smokeless tobacco (ST) exposed oral cell cultures by differential display. This study determined the clinical significance of PI synthase overexpression in oral squamous cell carcinoma (OSCC) and premalignant lesions (leukoplakia), and identified the downstream signaling proteins in PI synthase pathway that are perturbed by smokeless tobacco (ST) exposure.

Methods
Tissue microarray (TMA) Immunohistochemistry, Western blotting, Confocal laser scan microscopy, RT-PCR were performed to define the expression of PI synthase in clinical samples and in oral cell culture systems.

Results
Significant increase in PI synthase immunoreactivity was observed in premalignant lesions and OSCCs as compared to oral normal tissues (p = 0.000). Further, PI synthase expression was significantly associated with de-differentiation of OSCCs, (p = 0.005) and tobacco consumption (p = 0.03, OR = 9.0). Exposure of oral cell systems to smokeless tobacco (ST) in vitro confirmed increase in PI synthase, Phosphatidylinositol 3-kinase (PI3K) and cyclin D1 levels.

Conclusion
Collectively, increased PI synthase expression was found to be an early event in oral cancer and a target for smokeless tobacco.
Meta-analysis of archived DNA microarrays identifies genes regulated by hypoxia and involved in a metastatic phenotype in cancer cells
Authors: Pierre Michael , DeHertogh Benoît , Gaigneaux Anthoula , DeMeulder Bertrand , Berger Fabrice , Bareke Eric , Michiels Carine , Depiereux Eric 
Published: April 2010

AbstractBackgroundMetastasis is a major cancer-related cause of death. Recent studies have described metastasis pathways. However, the exact contribution of each pathway remains unclear. Another key feature of a tumor is the presence of hypoxic areas caused by a lack of oxygen at the center of the tumor. Hypoxia leads to the expression of pro-metastatic genes as well as the repression of anti-metastatic genes. As many Affymetrix datasets about metastasis and hypoxia are publicly available and not fully exploited, this study proposes to re-analyze these datasets to extract new information about the metastatic phenotype induced by hypoxia in different cancer cell lines.MethodsAffymetrix datasets about metastasis and/or hypoxia were downloaded from GEO and ArrayExpress. AffyProbeMiner and GCRMA packages were used for pre-processing and the Window Welchttest was used for processing. Three approaches of meta-analysis were eventually used for the selection of genes of interest.ResultsThree complementary approaches were used, that eventually selected 183 genes of interest. Out of these 183 genes, 99, among which the well knownJUNB,FOSandTP63, have already been described in the literature to be involved in cancer. Moreover, 39 genes of those, such asSERPINE1andMMP7, are known to regulate metastasis. Twenty-one genes includingVEGFAandID2have also been described to be involved in the response to hypoxia. Lastly, DAVID classified those 183 genes in 24 different pathways, among which 8 are directly related to cancer while 5 others are related to proliferation and cell motility. A negative control composed of 183 random genes failed to provide such results. Interestingly, 6 pathways retrieved by DAVID with the 183 genes of interest concern pathogen recognition and phagocytosis.ConclusionThe proposed methodology was able to find genes actually known to be involved in cancer, metastasis and hypoxia and, thus, we propose that the other genes selected based on the same methodology are of prime interest in the metastatic phenotype induced by hypoxia.
Higher expression levels of SOCS 1,3,4,7 are associated with earlier tumour stage and better clinical outcome in human breast cancer
Authors: Sasi Walid , Jiang Wen G , Sharma Anup , Mokbel Kefah 
Published: April 2010

Abstract

Background
Suppressors of cytokine signaling (SOCS) are important negative feedback regulators of the JAK/STAT signaling pathway, and have been recently investigated for their role in the development of different cancers. In this study, we examined the expression of SOCS1-7 genes in normal and breast cancer tissue and correlated this with several clinico-pathological and prognostic factors.

Methods
SOCS1-7 mRNA extraction and reverse transcription were performed on fresh frozen breast cancer tissue samples (n = 127) and normal background breast tissue (n = 31). Transcript levels of expression were determined using real-time PCR and analyzed against TNM stage, tumour grade and clinical outcome over a 10 year follow-up period.

Results
SOCS1,4,5,6 and 7 expression decreased with increased TNM stage (TNM1 vs. TNM3 p = 0.039, TNM1 vs. TNM4 p = 0.016, TNM2 vs. TNM4 p = 0.025, TNM1 vs. TNM3 p = 0.012, and TNM1 vs. TNM3 p = 0.044 respectively). SOCS2 and 3 expression decreased with increased Nottingham Prognostic Index (NPI) (NPI1 vs. NPI3 p = 0.033, and NPI2 vs. NPI3 p = 0.041 respectively). SOCS7 expression decreased with higher tumour grade (Grade 3 vs. Grade 2 p = 0.037). After a median follow up period of 10 years, we found higher levels of SOCS1,2 and 7 expression among those patients who remained disease-free compared to those who developed local recurrence (p = 0.0073, p = 0.021, and p = 0.039 respectively). Similarly, we found higher levels of SOCS 2,4, and 7 expression in those who remained disease-free compared to those who developed distant recurrence (p = 0.022, p = 0.024, and p = 0.033 respectively). Patients who remained disease-free had higher levels of SOCS1 and 2 expression compared to those who died from breast cancer (p = 0.02 and p = 0.033 respectively). The disease free survival (DFS) and overall survival (OS) curves showed that higher levels of SOCS1, 3 and 7 were significant predictors of higher DFS (p = 0.015, p = 0.024 and 0.03 respectively) and OS (p = 0.005, p = 0.013 and p = 0.035 respectively). Higher levels of SOCS 4 were significant in predicting better OS (p = 0.007) but not DFS. Immunohistochemical staining of representative samples showed a correlation between SOCS1, 3, 7 protein staining and the SOCS1, 3, 7 mRNA expression.

Conclusion
Higher mRNA expression levels of SOCS1, 3, 4 and 7 are significantly associated with earlier tumour stage and better clinical outcome in human breast cancer.
Blechnum Orientale Linn - a fern with potential as antioxidant, anticancer and antibacterial agent
Authors: Lai How Y , Lim Yau Y , Kim Kah H 
Published: April 2010

Abstract

Background

Blechnum orientale Linn. (Blechnaceae) is used ethnomedicinally for the treatment of various skin diseases, stomach pain, urinary bladder complaints and sterilization of women. The aim of the study was to evaluate antioxidant, anticancer and antibacterial activity of five solvent fractions obtained from the methanol extract of the leaves of Blechnum orientale Linn.

Methods
Five solvent fractions were obtained from the methanol extract of B. orientale through successive partitioning with petroleum ether, chloroform, ethyl acetate, butanol and water. Total phenolic content was assessed using Folin-Ciocalteu's method. The antioxidant activity was determined by measuring the scavenging activity of DPPH radicals. Cytotoxic activity was tested against four cancer cell lines and a non-malignant cell using MTT assay. Antibacterial activity was assessed using the disc diffusion and broth microdilution assays. Standard phytochemical screening tests for saponins, tannins, terpenoids, flavonoids and alkaloids were also conducted.

Results
The ethyl acetate, butanol and water fractions possessed strong radical scavenging activity (IC50 8.6-13.0 μg/ml) and cytotoxic activity towards human colon cancer cell HT-29 (IC50 27.5-42.8 μg/ml). The three extracts were also effective against all Gram-positive bacteria tested: Bacillus cereus, Micrococcus luteus, methicillin-susceptible Staphylococcus aureus (MSSA), methicillin-resistant Staphylococcus aureus (MRSA) and Stapylococcus epidermidis(minimum inhibitory concentration MIC 15.6-250 μg/ml; minimum bactericidal concentration MBC 15.6-250 μg/ml). Phytochemical analysis revealed the presence of flavonoids, terpenoids and tannins. Ethyl acetate and butanol fractions showed highest total phenolic content (675-804 mg gallic acid equivalent/g).

Conclusions
The results indicate that this fern is a potential candidate to be used as an antioxidant agent, for colon cancer therapy and for treatment of MRSA infections and other MSSA/Gram-positive bacterial infectious diseases.