bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stem Cells Genetically Modified With the Developmental Gene MT1-MMP Improve Regeneration of the Supraspinatus Tendon-to-Bone Insertion Site
Authors: Gulotta Lawrence V. , Kovacevic David , Montgomery Scott , Ehteshami John R. , Packer Jonathon D. , Rodeo Scott A. 
Published: April 2010

Background: Rotator cuffs heal through a scar tissue interface after repair, which makes them prone to failure. Membrane type 1 matrix metalloproteinase (MT1-MMP) is upregulated during embryogenesis in areas that develop into tendon-bone insertion sites. Hypothesis: Bone marrow-derived stem cells in the presence of the developmental signal from MT1-MMP will drive the healing process toward regeneration and away from scar formation. Study Design: Controlled laboratory study. Methods: Sixty Lewis rats underwent unilateral detachment and repair of the supraspinatus tendon. Thirty animals received mesenchymal stem cells (MSCs) in a fibrin glue carrier, and 30 received adenoviral MT1-MMP (Ad-MT1-MMP)–transduced MSCs. Animals were sacrificed at 2 weeks and 4 weeks and evaluated for the presence of fibrocartilage and collagen fiber organization at the insertion. Biomechanical testing was performed to determine the structural and material properties of the repaired tissue. Statistical analysis was performed with a Wilcoxon rank-sum test with significance set at P = .05. Results: There were no differences between the Ad-MT1-MMP and MSC groups in any outcome variable at 2 weeks. At 4 weeks, the Ad-MT1-MMP group had more fibrocartilage ( P = .05), higher ultimate load to failure ( P = .01), higher ultimate stress to failure ( P = .005), and higher stiffness values ( P = .02) as compared with the MSC group. Conclusion: Mesenchymal stem cells genetically modified to overexpress the developmental gene MT1-MMP can augment rotator cuff healing at 4 weeks by the presence of more fibrocartilage at the insertion and improved biomechanical strength. Clinical Relevance: Biologic augmentation of repaired rotator cuffs with MT1-MMP–transduced MSCs may reduce the incidence of retears. However, further studies are needed to determine if this remains safe and effective in larger models.
Effect of 2 Soccer Matches in a Week on Physical Performance and Injury Rate
Authors: Dupont Gregory , Nedelec Mathieu , McCall Alan , McCormack Derek , Berthoin Serge , Wisløff Ulrik 
Published: April 2010

Background: Recovery duration may be too short during the congested fixtures of professional soccer players with regard to maintaining physical performance and a low injury rate. Purpose: To analyze the effects of 2 matches per week on physical performance and injury rate in male elite soccer players. Study Design: Cohort study; Level of evidence, 3. Methods: Match results, match-related physical performance, and injuries were monitored during 2 seasons (2007–2008 and 2008–2009) for 32 professional soccer players in a top-level team participating in the UEFA (Union of European Football Associations) Champions League. Total distance, high-intensity distance, sprint distance, and number of sprints were collected for 52 home matches. Injuries and player participation in matches and training were recorded throughout the full season. Results: Physical performance, as characterized by total distance covered, high-intensity distance, sprint distance, and number of sprints, was not significantly affected by the number of matches per week (1 versus 2), whereas the injury rate was significantly higher when players played 2 matches per week versus 1 match per week (25.6 versus 4.1 injuries per 1000 hours of exposure; P < .001). Conclusion: The recovery time between 2 matches, 72 to 96 hours, appears sufficient to maintain the level of physical performance tested but is not long enough to maintain a low injury rate. The present data highlight the need for player rotation and for improved recovery strategies to maintain a low injury rate among athletes during periods with congested match fixtures.
Correlation of Torque and Elbow Injury in Professional Baseball Pitchers
Authors: Anz Adam W. , Bushnell Brandon D. , Griffin Leah Passmore , Noonan Thomas J. , Torry Michael R. , Hawkins Richard J. 
Published: April 2010

Background: During the pitching motion, velocity is generated by the upper extremity kinetic chain on internal rotation of the shoulder and trunk translational/rotational motion. This generation of power places significant forces and torques on the elbow and shoulder. Elbow valgus torque and shoulder rotational torque are theoretically linked to elbow injury. Hypothesis: Pitchers experiencing higher levels of elbow valgus torque and shoulder external rotation torque throughout the pitching motion are more likely to suffer elbow injury than pitchers with lower levels of torque. Study Design: Cohort study; Level of evidence, 3. Methods: With an established biomechanical analysis model, 23 professional baseball pitchers were videotaped during spring training games and followed prospectively for the next 3 seasons for elbow injury. A mixed statistical model using differences of least squares means and analysis of variance was used to analyze the association between elbow injury and torque levels throughout the pitching motion as well as at each major event within the pitching motion. Results: There were overall statistical trends relating elbow injury with both higher elbow valgus torque ( P = .0547) and higher shoulder external rotation torque ( P = .0548) throughout the entire pitching motion. More importantly, there was an individual significant correlation of elbow injury with both higher elbow valgus torque ( P = .0130) and higher shoulder external rotation torque ( P = .0018) at the late cocking phase (pitching event of maximum external rotation of the shoulder). Conclusion: This study provides information that supports existing theories about how and why certain injuries occur during the throwing motion in baseball. The late cocking phase appears to be the critical point in the pitching motion, where higher levels of torque at the shoulder and elbow can result in increased risk of injury. Manipulation of pitching mechanics to alter these torque levels or using these measures to identify pitchers at risk may help decrease injury rates.
Endoscopic Compartment Release for Chronic Exertional Compartment Syndrome
Authors: Wittstein Jocelyn , Moorman Claude T. , Levin L. Scott 
Published: April 2010

Background: Chronic exertional compartment syndrome is an entity that typically fails nonoperative management and requires operative treatment with fasciotomies for return to activity. Fasciotomies performed through single or multiple incisions may fail to totally release the fascia of the afflicted compartment(s) and may result in injury to neurovascular structures that cannot be visualized. Purpose: The authors report results of endoscopic compartment release with the assistance of a balloon dissector in the treatment of chronic exertional compartment syndrome. Study Design: Case series; Level of evidence, 4. Methods: The clinical outcomes of 14 cases of chronic exertional compartment syndrome in 9 patients treated with endoscopic release were assessed with a retrospective chart review and the results of mailed questionnaires. Results: Fourteen legs in 9 patients (4 male and 5 female; average age, 24 years) were treated with endoscopic compartment release for chronic exertional compartment syndrome. Eight of 9 patients were able to resume preoperative activities, including collegiate athletics in 5 cases and recreational sport in 3 cases. No neurovascular injuries occurred. Complications were isolated to postoperative hematomas that resolved in 2 patients. Seven patients completed questionnaires an average of 3.75 years after surgery. There were no recurrences of symptoms. Conclusion: Endoscopic compartment release is a cosmetic, safe, and effective means of treating chronic exertional compartment syndrome.
Can Osteochondral Grafting Be Augmented With Microfracture in an Extended-Size Lesion of Articular Cartilage?
Authors: Lane John G. , Healey Robert M. , Chen Albert C. , Sah Robert L. , Amiel David 
Published: April 2010

Background: Both microfracture and osteochondral autografting procedures have been useful in treating osteochondral lesions. Hypothesis: Combining microfracture and osteochondral autografting procedures can extend the size of lesions that can be treated with either technique. Study Design: Descriptive laboratory study. Methods: Eight adult goats underwent osteochondral autograft transfer of a 4.5-mm femoral trochlea plug into an 8-mm full-thickness chondral defect. Microfracture was performed in the gap region surrounding the autograft. The animals were allowed normal activity until the end of the experiment at 6 months. At harvest, the knees were assessed grossly, and then evaluation was performed by histology, histomorphometry, biochemistry, and biomechanics. Results: The osteochondral plugs healed well, with integration of the bone and preservation of the chondral cap. The chondral gap between the host site articular cartilage and the transferred plug had decreased from 3 mm at implant to less than 0.1 mm. Histologic analysis demonstrated regions of variable cartilage repair, with integration of the cartilage layer at some sites but incomplete healing at others. Histomorphometry demonstrated filling of the chondral gap to 75% to 85% of the normal volume. Biochemical analysis revealed greater than 90% type II collagen at most sites, with some areas containing 80% type II collagen. Biomechanical indentation testing indicated that the repaired area had variable thickness and stiffness, with a trend of increased stiffness in the bulk graft and decreased softness at the proximal microfracture interface site. Conclusion: The performance of a combined microfracture and osteochondral autograft transfer procedure to resurface a large chondral defect appears promising. Clinical Relevance: This combined technique shows promise for treatment of large chondral defects with a single operative procedure with autogenous tissue that is safe and potentially would have a shorter period of rehabilitation, similar to that of osteochondral transfers and microfracture, in a cost-effective setting.
Vaccination with synthetic analog peptides derived from WT1 oncoprotein induces T-cell responses in patients with complete remission from acute myeloid leukemia
Authors: Maslak Peter G. , Dao Tao , Krug Lee M. , Chanel Suzanne , Korontsvit Tatyana , Zakhaleva Victoria , Zhang Ronghua , Wolchok Jedd D. , Yuan Jianda , Pinilla-Ibarz Javier , Berman Ellin , Weiss Mark , Jurcic Joseph , Frattini Mark G. , Scheinberg David A. 
Published: April 2010

Abstract
A pilot study was undertaken to assess the safety, activity, and immunogenicity of a polyvalent Wilms tumor gene 1 (WT1) peptide vaccine in patients with acute myeloid leukemia in complete remission but with molecular evidence of WT1 transcript. Patients received 6 vaccinations with 4 WT1 peptides (200 μg each) plus immune adjuvants over 12 weeks. Immune responses were evaluated by delayed-type hypersensitivity, CD4+ T-cell proliferation, CD3+ T-cell interferon-γ release, and WT1 peptide tetramer staining. Of the 9 evaluable patients, 7 completed 6 vaccinations and WT1-specific T-cell responses were noted in 7 of 8 patients. Three patients who were HLA-A0201-positive showed significant increase in interferon-γ–secreting cells and frequency of WT1 tetramer-positive CD8+ T cells. Three patients developed a delayed hypersensitivity reaction after vaccination. Definite related toxicities were minimal. With a mean follow-up of 30 plus or minus 8 months after diagnosis, median disease-free survival has not been reached. These preliminary data suggest that this polyvalent WT1 peptide vaccine can be administered safely to patients with a resulting immune response. Further studies are needed to establish the role of vaccination as viable postremission therapy for acute myeloid leukemia. This study was registered at www.clinicaltrials.gov as #NCT00398138.
Rebalanced hemostasis in patients with liver disease: evidence and clinical consequences
Authors: Lisman Ton , Porte Robert J. 
Published: April 2010

AbstractPatients with liver disease frequently acquire a complex disorder of hemostasis secondary to their disease. Routine laboratory tests such as the prothrombin time and the platelet count are frequently abnormal and point to a hypocoagulable state. With more sophisticated laboratory tests it has been shown that patients with liver disease may be in hemostatic balance as a result of concomitant changes in both pro- and antihemostatic pathways. Clinically, this rebalanced hemostatic system is reflected by the large proportion of patients with liver disease who can undergo major surgery without any requirement for blood product transfusion. However, the hemostatic balance in the patient with liver disease is relatively unstable as evidenced by the occurrence of both bleeding and thrombotic complications in a significant proportion of patients. Although it is still common practice to prophylactically correct hemostatic abnormalities in patients with liver disease before invasive procedures by administration of blood products guided by the prothrombin time and platelet count, we believe that this policy is not evidence-based. In this article, we will provide arguments against the traditional concept that patients with liver failure have a hemostasis-related bleeding tendency. Consequences of these new insights for hemostatic management will be discussed.
Damaged DNA-binding protein 2 (DDB2) protects against UV irradiation in human cells and Drosophila
Authors: Sun Nian-Kang , Sun Chun-Ling , Lin Chia-Hua , Pai Li-Mai , Chao Chuck CK 
Published: April 2010

Abstract

Background
We observed previously that cisplatin-resistant HeLa cells were cross-resistant to UV light due to accumulation of DDB2, a protein implicated in DNA repair. More recently, we found that cFLIP, which represents an anti-apoptotic protein whose level is induced by DDB2, was implicated in preventing apoptosis induced by death-receptor signaling. In the present study, we investigated whether DDB2 has a protective role against UV irradiation and whether cFLIP is also involved in this process.

Methods
We explored the role of DDB2 in mediating UV resistance in both human cells and Drosophila. To do so, DDB2 was overexpressed by using a full-length open reading frame cDNA. Conversely, DDB2 and cFLIP were suppressed by using antisense oligonucleotides. Cell survival was measured using a colony forming assay. Apoptosis was monitored by examination of nuclear morphology, as well as by flow cytometry and Western blot analyses. A transcription reporter assay was also used to assess transcription of cFLIP.

Results
We first observed that the cFLIP protein was upregulated in UV-resistant HeLa cells. In addition, the cFLIP protein could be induced by stable expression of DDB2 in these cells. Notably, the anti-apoptotic effect of DDB2 against UV irradiation was largely attenuated by knockdown of cFLIP with antisense oligonucleotides in HeLa cells. Moreover, overexpression of DDB2 did not protect against UV in VA13 and XP-A cell lines which both lack cFLIP. Interestingly, ectopic expression of human DDB2 in Drosophila dramatically inhibited UV-induced fly death compared to control GFP expression. On the other hand, expression of DDB2 failed to rescue a different type of apoptosis induced by the genes Reaper or eiger.

Conclusion
Our results show that DDB2 protects against UV stress in a cFLIP-dependent manner. In addition, the protective role of DDB2 against UV irradiation was found to be conserved in divergent living organisms such as human and Drosophila. In addition, UV irradiation may activate a cFLIP-regulated apoptotic pathway in certain cells.
A knowledge-guided strategy for improving the accuracy of scoring functions in binding affinity prediction
Authors: Cheng Tiejun , Liu Zhihai , Wang Renxiao 
Published: April 2010

Abstract

Background
Current scoring functions are not very successful in protein-ligand binding affinity prediction albeit their popularity in structure-based drug designs. Here, we propose a general knowledge-guided scoring (KGS) strategy to tackle this problem. Our KGS strategy computes the binding constant of a given protein-ligand complex based on the known binding constant of an appropriate reference complex. A good training set that includes a sufficient number of protein-ligand complexes with known binding data needs to be supplied for finding the reference complex. The reference complex is required to share a similar pattern of key protein-ligand interactions to that of the complex of interest. Thus, some uncertain factors in protein-ligand binding may cancel out, resulting in a more accurate prediction of absolute binding constants.

Results
In our study, an automatic algorithm was developed for summarizing key protein-ligand interactions as a pharmacophore model and identifying the reference complex with a maximal similarity to the query complex. Our KGS strategy was evaluated in combination with two scoring functions (X-Score and PLP) on three test sets, containing 112 HIV protease complexes, 44 carbonic anhydrase complexes, and 73 trypsin complexes, respectively. Our results obtained on crystal structures as well as computer-generated docking poses indicated that application of the KGS strategy produced more accurate predictions especially when X-Score or PLP alone did not perform well.

Conclusions
Compared to other targeted scoring functions, our KGS strategy does not require any re-parameterization or modification on current scoring methods, and its application is not tied to certain systems. The effectiveness of our KGS strategy is in theory proportional to the ever-increasing knowledge of experimental protein-ligand binding data. Our KGS strategy may serve as a more practical remedy for current scoring functions to improve their accuracy in binding affinity prediction.
Starr: Simple Tiling ARRay analysis of Affymetrix ChIP-chip data
Authors: Zacher Benedikt , Kuan Pei Fen , Tresch Achim 
Published: April 2010

AbstractBackgroundChromatin immunoprecipitation combined with DNA microarrays (ChIP-chip) is an assay used for investigating DNA-protein-binding or post-translational chromatin/histone modifications. As with all high-throughput technologies, it requires thorough bioinformatic processing of the data for which there is no standard yet. The primary goal is to reliably identify and localize genomic regions that bind a specific protein. Further investigation compares binding profiles of functionally related proteins, or binding profiles of the same proteins in different genetic backgrounds or experimental conditions. Ultimately, the goal is to gain a mechanistic understanding of the effects of DNA binding events on gene expression.ResultsWe present a free, open-sourceR/Bioconductor packageStarrthat facilitates comparative analysis of ChIP-chip data across experiments and across different microarray platforms. The package provides functions for data import, quality assessment, data visualization and exploration.Starrincludes high-level analysis tools such as the alignment of ChIP signals along annotated features, correlation analysis of ChIP signals with complementary genomic data, peak-finding and comparative display of multiple clusters of binding profiles. It uses standard Bioconductor classes for maximum compatibility with other software. Moreover,Starrautomatically updates microarray probe annotation files by a highly efficient remapping of microarray probe sequences to an arbitrary genome.ConclusionStarris anRpackage that covers the complete ChIP-chip workflow from data processing to binding pattern detection. It focuses on the high-level data analysis, e.g., it provides methods for the integration and combined statistical analysis of binding profiles and complementary functional genomics data.Starrenables systematic assessment of binding behaviour for groups of genes that are alingned along arbitrary genomic features.
HAb18G/CD147 cell-cell contacts confer resistance of a HEK293 subpopulation to anoikis in an E-cadherin-dependent manner
Authors: Ma Xiao-Kui , Wang Li , Li Yu , Yang Xiang-Ming , Zhao Pu , HaoTang  , Zhu Ping , Li Ling , Chen Zhi-Nan 
Published: April 2010

Abstract

Background
Acquisition of resistance to "anoikis" facilitates the survival of cells under independent matrix-deficient conditions, such as cells in tumor progression and the production of suspension culture cells for biomedical engineering. There is evidence suggesting that CD147, an adhesion molecule associated with survival of cells in tumor metastasis and cell-cell contacts, plays an important role in resistance to anoikis. However, information regarding the functions of CD147 in mediating cell-cell contacts and anoikis-resistance remains limited and even self-contradictory.

Results
An anoikis-resistant clone (HEK293ar), derived from anoikis-sensitive parental Human Embryonic Kidney 293 cells, survived anoikis by the formation of cell-cell contacts. The expression of HAb18G/CD147 (a member of the CD147 family) was upregulated and the protein was located at cell-cell junctions. Upregulation of HAb18G/CD147 in suspended HEK293ar cells suppressed anoikis by mediating the formation of cell-cell adhesions. Anoikis resistance in HEK293ar cells also required E-cadherin-mediated cell-cell contacts. Knock-down of HAb18G/CD147 and E-cadherin inhibited cell-cell contacts formation and increased anoikis sensitivity respectively. When HAb18G/CD147 was downregulated, E-cadherin expression in HEK293ar cells was significantly suppressed; however, knockdown of E-cadherin by E-cadherin siRNA or blocking of E-cadherin binding activity with a specific antibody and EDTA had no significant effect on HAb18G/CD147 expression. Finally, pretreatment with LY294002, a phosphoinositide 3-kinase (PI3K/AKT) inhibitor, disrupted cell-cell contacts and decreased cell number, but this was not the case in cells treated with the extracellular signal-regulated kinase (ERK) inhibitor PD98059.

Conclusions
Our results provide new evidence that HAb18G/CD147-mediated cell-cell contact confers anoikis resistance in an E-cadherin-dependent manner; and cell-cell contact mediated resistance to anoikis implicates PI3K pathway in a highly relevant cell model (HEK293ar). Understanding of the role of HAb18G/CD147 cell-cell contacts in anoikis resistance may help in understanding the survival of cells in anchorage-independent growth, such as cells in tumor metastasis and suspension culture produced for biomedical engineering. Our results also contribute to a better understanding of the biology of HEK293 cell spheroids, a major workhorse for producing human therapeutic agents and viral vaccines.