bluuebunny/crossref_metadata_2025_split huggingface dataset:
Performance Enhancement in the Terminal Phases of Rehabilitation
Authors: Lorenz Daniel S. , Reiman Michael P. 
Published: July 2011

Context: There is a dearth of literature on the performance enhancement in the recovering athlete in the terminal phases of rehabilitation. There are established training methods that target strength, power, speed, endurance, and metabolic capacity that all lead to performance enhancement. Evidence Acquisition: A PubMed search from 1980 to 2010 was undertaken for articles in English. Additional references were accrued from reference lists of research articles. Results: Multiple options are available to improve strength, power, speed, endurance, and metabolic capacity during rehabilitation. Conclusion: Sports clinicians have several components to address in the rehabilitation of a recovering athlete in addition to performance enhancement. Sports clinicians should focus their efforts on increasing power, a product of maximum force and speed of performance.
Lack of Awareness of Fluid Needs Among Participants at a Midwest Marathon
Authors: Brown Sara , Chiampas George , Jaworski Carrie , Passe Dennis 
Published: July 2011

Background: Marathon running has become popular, particularly among inexperienced runners. Hypothesis: Many marathoners are inexperienced and lack concern for potential complications of marathon running. Study Design: Cross-sectional survey. Methods: In sum, 419 runners completed a survey on a variety of topics regarding training for a marathon and hydration strategies. Results: Overall, 211 females (38.3 ± 9.1 years old) and 208 males (41.6 ± 11.0 years old) participated. They trained for 6.8 ± 4.3 months and had run for 9.8 ± 9.1 years; 33.5% had no marathon experience and 16.9% had run 1 marathon. Of the injuries reported, 77.6% and 72.9% were minor musculoskeletal injuries during the current and previous running seasons, respectively. Of the 278 runners who had run a marathon, 54 (19.0%) had been treated in the medical tent, 31.5% of whom for dehydration. Furthermore, 54.9% and 64.3% of the survey participants were “not at all” concerned with musculoskeletal injury and hyponatremia, respectively. Also, 88.7% did not know their sweat rate; 67.8% did not weigh themselves; and 81.3% had no other method of hydration assessment. No significant correlations were found between concern for hyponatremia and age, sex, or experience. Conclusions: Most participants were inexperienced, lacked concern for injury or hyponatremia, and were not using methods of hydration assessment.
Physical Activity After Total Joint Arthroplasty
Authors: Vogel Laura A. , Carotenuto Giuseppe , Basti John J. , Levine William N. 
Published: July 2011

Context: Total joint arthroplasty (TJA) is a common surgical option to treat painful degenerative joint disease. However, there is currently no consensus on the appropriate intensity of physical activity after TJA or how physical activity level affects the rate of revision surgery. Materials and Methods: A systematic review of the literature regarding physical or athletic activity after TJA was performed to determine current clinical opinion and recommendations regarding appropriate activity levels after TJA, as well as variables affecting successful surgery and improved outcomes. Results: Many studies in the literature regarding athletic activity after TJA focus on total hip arthroplasty and total knee arthroplasty. The literature reports contradictory results regarding rates of physical activity after TJA as well as the relationship between physical activity and rates of revision surgery. The current trend in expert opinion shows more liberal recommendations for patients to engage in athletic activity after TJA. Conclusions: Individual characteristics, lifestyle, and patient preferences must be taken into account when one considers appropriate recommendations for athletic activity after TJA. Current trends in clinical opinion favor a higher level of athletic activity after TJA, but clinicians should caution patients not to participate in contact sports or sports that create high joint loads in the replaced joint.
CD63 is an essential cofactor to leukocyte recruitment by endothelial P-selectin
Authors: Doyle Emily L. , Ridger Victoria , Ferraro Francesco , Turmaine Mark , Saftig Paul , Cutler Daniel F. 
Published: July 2011

AbstractThe activation of endothelial cells is critical to initiating an inflammatory response. Activation induces the fusion of Weibel-Palade Bodies (WPB) with the plasma membrane, thus transferring P-selectin and VWF to the cell surface, where they act in the recruitment of leukocytes and platelets, respectively. CD63 has long been an established component of WPB, but the functional significance of its presence within an organelle that acts in inflammation and hemostasis was unknown. We find that ablating CD63 expression leads to a loss of P-selectin–dependent function: CD63-deficient HUVECs fail to recruit leukocytes, CD63-deficient mice exhibit a significant reduction in both leukocyte rolling and recruitment and we show a failure of leukocyte extravasation in a peritonitis model. Loss of CD63 has a similar phenotype to loss of P-selectin itself, thus CD63 is an essential cofactor to P-selectin.
Deletion of Tet2 in mice leads to dysregulated hematopoietic stem cells and subsequent development of myeloid malignancies
Authors: Li Zhe , Cai Xiaoqiang , Cai Chen-Leng , Wang Jiapeng , Zhang Wenyong , Petersen Bruce E. , Yang Feng-Chun , Xu Mingjiang 
Published: July 2011

Abstract
TET2 is mutated/deleted with high frequencies in multiple forms of myeloid malignancies including MDS, CMML, MPN, and AML. However, little is known regarding the biological function of TET2 and its role in the pathogenesis of myeloid malignancies. To study the function of TET2 in vivo, we generated a Tet2 knock out mouse model. Deletion of Tet2 in mice led to dramatic reduction in the 5-hydroxymethylcytosine levels and concomitant increase in the 5-methylcytosine levels in the genomic DNA of BM cells. The Tet2−/− mice contained an increased Lin−Sca-1+c-Kit+ (LSK) cell pool before the development of myeloid malignancies. A competitive reconstitution assay revealed that Tet2−/− LSK cells had an increased hematopoietic repopulating capacity with an altered cell differentiation skewing toward monocytic/granulocytic lineages. Approximately 1/3 of Tet2−/− and 8% of Tet2+/− mice died within 1 year of age because of the development of myeloid malignancies resembling characteristics of CMML, MPD-like myeloid leukemia, and MDS. Furthermore, transplantation of Tet2−/−, but not wild-type (WT) or Tet2+/− BM cells, led to increased WBC counts, monocytosis, and splenomegaly in WT recipient mice. These data indicate that Tet2-deficient mice recapitulate patients with myeloid malignancies, implying that Tet2 functions as a tumor suppressor to maintain hematopoietic cell homeostasis.
Human mesenchymal stem cells derived from induced pluripotent stem cells down-regulate NK-cell cytolytic machinery
Authors: Giuliani Massimo , Oudrhiri Noufissa , Noman Zaeem M. , Vernochet Amelia , Chouaib Salem , Azzarone Bruno , Durrbach Antoine , Bennaceur-Griscelli Annelise 
Published: July 2011

AbstractA major issue in immunosuppressive biotherapy is the use of mesenchymal stem cells (MSCs) that harbor regulatory capacity. However, currently used bone marrow-derived MSCs (BM-MSCs) are short-lived and cannot assure long lasting immunoregulatory function both in vitro and in vivo. Consequently, we have generated MSCs from human induced pluripotent stem (IPS-MSCs) cells that share similar properties with embryonic stem cells (ES-MSCs). Herein, we compared the immunoregulatory properties of ES/IPS-MSCs with those of BM-MSCs and showed, for the first time, that IPS-derived MSCs display remarkable inhibition of NK-cell proliferation and cytolytic function in a similar way to ES-MSCs. Both MSCs disrupt NK-cell cytolytic machinery in the same fashion that BM-MSCs, by down-regulating the expression of different activation markers and ERK1/2 signaling, leading to an impairment to form immunologic synapses with target cells and, therefore, secretion of cytotoxic granules. In addition, they are more resistant than adult BM-MSCs to preactivated NK cells. IPS-MSCs could represent an attractive alternative source of immunoregulatory cells, and their capacity to impair NK-cell cytotoxicity constitutes a complex mechanism to prevent allograft rejection.
SuperSAGE evidence for CD14++CD16+ monocytes as a third monocyte subset
Authors: Zawada Adam M. , Rogacev Kyrill S. , Rotter Björn , Winter Peter , Marell Rolf-R. , Fliser Danilo , Heine Gunnar H. 
Published: July 2011

Abstract
Monocytes are a heterogeneous cell population with subset-specific functions and phenotypes. The differential expression of CD14 and CD16 distinguishes classical CD14++CD16−, intermediate CD14++CD16+, and nonclassical CD14+CD16++ monocytes. Current knowledge on human monocyte heterogeneity is still incomplete: while it is increasingly acknowledged that CD14++CD16+ monocytes are of outstanding significance in 2 global health issues, namely HIV-1 infection and atherosclerosis, CD14++CD16+ monocytes remain the most poorly characterized subset so far. We therefore developed a method to purify the 3 monocyte subsets from human blood and analyzed their transcriptomes using SuperSAGE in combination with high-throughput sequencing. Analysis of 5 487 603 tags revealed unique identifiers of CD14++CD16+ monocytes, delineating these cells from the 2 other monocyte subsets. Gene Ontology (GO) enrichment analysis suggests diverse immunologic functions, linking CD14++CD16+ monocytes to Ag processing and presentation (eg, CD74, HLA-DR, IFI30, CTSB), to inflammation and monocyte activation (eg, TGFB1, AIF1, PTPN6), and to angiogenesis (eg, TIE2, CD105). In conclusion, we provide genetic evidence for a distinct role of CD14++CD16+ monocytes in human immunity. After CD14++CD16+ monocytes have earlier been discussed as a potential therapeutic target in inflammatory diseases, we are hopeful that our data will spur further research in the field of monocyte heterogeneity.
Incidence of therapy-related myeloid neoplasia after initial therapy for chronic lymphocytic leukemia with fludarabine-cyclophosphamide versus fludarabine: long-term follow-up of US Intergroup Study E2997
Authors: Smith Mitchell R. , Neuberg Donna , Flinn Ian W. , Grever Michael R. , Lazarus Hillard M. , Rowe Jacob M. , Dewald Gordon , Bennett John M. , Paietta Elisabeth M. , Byrd John C. , Hussein Mohamad A. , Appelbaum Frederick R. , Larson Richard A. , Litzow Mark R. , Tallman Martin S. 
Published: July 2011

Abstract
Chemotherapy-related myeloid neoplasia (t-MN) is a significant late toxicity concern after cancer therapy. In the randomized intergroup phase 3 E2997 trial, initial therapy of chronic lymphocytic leukemia with fludarabine plus cyclophosphamide (FC) compared with fludarabine alone yielded higher complete and overall response rates and longer progression-free, but not overall, survival. Here, we report t-MN incidence in 278 patients enrolled in E2997 with a median 6.4-year follow-up. Thirteen cases (4.7%) of t-MN occurred at a median of 5 years from initial therapy for chronic lymphocytic leukemia, 9 after FC and 4 after fludarabine alone. By cumulative incidence methodology, rates of t-MN at 7 years were 8.2% after FC and 4.6% after fludarabine alone (P = .09). Seven of the 9 cases of t-MN after FC occurred without additional therapy. Abnormalities involving chromosomes 5 or 7 were found in 10 cases, which suggests alkylator involvement. These data suggest that FC may induce more t-MN than fludarabine alone.
The achievement of an early complete cytogenetic response is a major determinant for outcome in patients with early chronic phase chronic myeloid leukemia treated with tyrosine kinase inhibitors
Authors: Jabbour Elias , Kantarjian Hagop , O'Brien Susan , Shan Jenny , Quintas-Cardama Alfonso , Faderl Stefan , Garcia-Manero Guillermo , Ravandi Farhad , Rios Mary Beth , Cortes Jorge 
Published: July 2011

Abstract
We analyzed the association between achievement of early complete cytogenetic response (CCyR) and event-free survival (EFS) and overall survival (OS) in patients with newly diagnosed chronic myeloid leukemia in chronic phase treated with imatinib 400 mg (n = 73), or imatinib 800 mg daily (n = 208), or second- generation tyrosine kinase inhibitors (n = 154). The overall CCyR rates were 87%, 91%, and 96%, respectively (P = .06); and major molecular response (MMR) rates were 77%, 87%, and 89%, respectively (P = .05). Their 3-year EFS rates were 85%, 92%, and 97% (P = .01), and OS rates were 93%, 97%, and 100% (P = .18), respectively. By landmark analysis, patients with 3-, 6-, and 12-month CCyR had significantly better outcome: 3-year EFS rates of 98%, 97%, and 98% and OS rates of 99%, 99%, and 99%, respectively, compared with 83%, 72%, and 67% and 95%, 90%, and 94%, in patients who did not achieve a CCyR. Among patients achieving CCyR at 12 months, the depth of molecular response was not associated with differences in OS or EFS. In conclusion, second tyrosine kinase inhibitors induced higher rates of CCyR and MMR than imatinib. The achievement of early CCyR remains a major determinant of chronic myeloid leukemia outcome regardless of whether MMR is achieved or not.
The phosphoinositide 3′-kinase delta inhibitor, CAL-101, inhibits B-cell receptor signaling and chemokine networks in chronic lymphocytic leukemia
Authors: Hoellenriegel Julia , Meadows Sarah A. , Sivina Mariela , Wierda William G. , Kantarjian Hagop , Keating Michael J. , Giese Neill , O'Brien Susan , Yu Albert , Miller Langdon L. , Lannutti Brian J. , Burger Jan A. 
Published: July 2011

AbstractIn lymphocytes, the phosphoinositide 3′-kinase (PI3K) isoform p110δ (PI3Kδ) transmits signals from surface receptors, including the B-cell receptor (BCR). CAL-101, a selective inhibitor of PI3Kδ, displays clinical activity in CLL, causing rapid lymph node shrinkage and a transient lymphocytosis. Inhibition of pro-survival pathways, the presumed mechanism of CAL-101, does not explain this characteristic pattern of activity. Therefore, we tested CAL-101 in assays that model CLL-microenvironment interactions in vitro. We found that CAL-101 inhibits CLL cell chemotaxis toward CXCL12 and CXCL13 and migration beneath stromal cells (pseudoemperipolesis). CAL-101 also down-regulates secretion of chemokines in stromal cocultures and after BCR triggering. CAL-101 reduces survival signals derived from the BCR or from nurse-like cells, and inhibits BCR- and chemokine-receptor–induced AKT and MAP kinase (ERK) activation. In stromal cocultures, CAL-101 sensitizes CLL cells toward bendamustine, fludarabine, and dexamethasone. These results are corroborated by clinical data showing marked reductions in circulating CCL3, CCL4, and CXCL13 levels, and a surge in lymphocytosis during CAL-101 treatment. Thus, CAL-101 displays a dual mechanism of action, directly decreasing cell survival while reducing interactions that retain CLL cells in protective tissue microenvironments. These data provide an explanation for the clinical activity of CAL-101, and a roadmap for future therapeutic development.
Defective ribosome assembly in Shwachman-Diamond syndrome
Authors: Wong Chi C. , Traynor David , Basse Nicolas , Kay Robert R. , Warren Alan J. 
Published: July 2011

AbstractShwachman-Diamond syndrome (SDS), a recessive leukemia predisposition disorder characterized by bone marrow failure, exocrine pancreatic insufficiency, skeletal abnormalities and poor growth, is caused by mutations in the highly conserved SBDS gene. Here, we test the hypothesis that defective ribosome biogenesis underlies the pathogenesis of SDS. We create conditional mutants in the essential SBDS ortholog of the ancient eukaryote Dictyostelium discoideum using temperature-sensitive, self-splicing inteins, showing that mutant cells fail to grow at the restrictive temperature because ribosomal subunit joining is markedly impaired. Remarkably, wild type human SBDS complements the growth and ribosome assembly defects in mutant Dictyostelium cells, but disease-associated human SBDS variants are defective. SBDS directly interacts with the GTPase elongation factor-like 1 (EFL1) on nascent 60S subunits in vivo and together they catalyze eviction of the ribosome antiassociation factor eukaryotic initiation factor 6 (eIF6), a prerequisite for the translational activation of ribosomes. Importantly, lymphoblasts from SDS patients harbor a striking defect in ribosomal subunit joining whose magnitude is inversely proportional to the level of SBDS protein. These findings in Dictyostelium and SDS patient cells provide compelling support for the hypothesis that SDS is a ribosomopathy caused by corruption of an essential cytoplasmic step in 60S subunit maturation.
Influence of degree of specific allergic sensitivity on severity of rhinitis and asthma in Chinese allergic patients
Authors: Li Jing , Huang Ying , Lin Xiaoping , Zhao Deyu , Tan Guolin , Wu Jinzhun , Zhao Changqing , Zhao Jing , Spangfort Michael D , Zhong Nanshan ,   China Alliance of Research on Respiratory Allergic Disease (CARRAD)
Published: July 2011

Abstract

Background
The association between sensitizations and severity of allergic diseases is controversial.

Objective
This study was to investigate the association between severity of asthma and rhinitis and degree of specific allergic sensitization in allergic patients in China.

Method
A cross-sectional survey was performed in 6304 patients with asthma and/or rhinitis from 4 regions of China. Patients completed a standardized questionnaire documenting their respiratory and allergic symptoms, their impact on sleep, daily activities, school and work. They also underwent skin prick tests with 13 common aeroallergens. Among the recruited subjects, 2268 provided blood samples for serum measurement of specific IgE (sIgE) against 16 common aeroallergens.

Results
Significantly higher percentage of patients with moderate-severe intermittent rhinitis were sensitized to outdoor allergens while percentage of patients sensitized to indoor allergens was increased with increasing severity of asthma. Moderate-severe intermittent rhinitis was associated with the skin wheal size and the level of sIgE to Artemisia vulgaris and Ambrosia artemisifolia (p < 0.001). Moderate-severe asthma was associated with increasing wheal size and sIgE response to Dermatophagoides (D.) pteronyssinus and D. farinae (p < 0.001). Moderate-severe rhinitis and asthma were also associated with increase in number of positive skin prick test and sIgE.

Conclusions

Artemisia vulgaris and Ambrosia artemisifolia sensitizations are associated with the severity of intermittent rhinitis and D. pteronyssinus and D. farinae sensitizations are associated with increasing severity of asthma in China. Increase in number of allergens the patients are sensitized to may also increase the severity of rhinitis and asthma.
Nano-electrospray tandem mass spectrometric analysis of the acetylation state of histones H3 and H4 in stationary phase in Saccharomyces cerevisiae
Authors: Ngubo Mzwanele , Kemp Gabré , Patterton Hugh G 
Published: July 2011

Abstract

Background
The involvement of histone acetylation in facilitating gene expression is well-established, particularly in the case of histones H3 and H4. It was previously shown in Saccharomyces cerevisiae that gene expression was significantly down-regulated and chromatin more condensed in stationary phase compared to exponential phase. We were therefore interested in establishing the acetylation state of histone H3 and H4 in stationary and in exponential phase, since the regulation of this modification could contribute to transcriptional shut-down and chromatin compaction during semi-quiescence.

Results
We made use of nano-spray tandem mass spectrometry to perform a precursor ion scan to detect an m/z 126 immonium ion, diagnostic of an Nε-acetylated lysine residue that allowed unambiguous identification of acetylated as opposed to tri-methylated lysine. The fragmentation spectra of peptides thus identified were searched with Mascot against the Swiss-Prot database, and the y-ion and b-ion fragmentation series subsequently analyzed for mass shifts compatible with acetylated lysine residues. We found that K9, K14 and K36 of histone H3 and K12 and K16 of histone H4 were acetylated in exponential phase (bulk histones), but could not detect these modifications in histones isolated from stationary phase cells at the sensitivity level of the mass spectrometer. The corresponding un-acetylated peptides were, however, observed. A significantly higher level of acetylation of these residues in exponential phase was confirmed by immuno-blotting.

Conclusion
H4K16 acetylation was previously shown to disrupt formation of condensed chromatin in vitro. We propose that de-acetylation of H4K16 allowed formation of condensed chromatin in stationary phase, and that acetylation of H3K9, H3K14, H3K36, and H4K12 reflected the active transcriptional state of the yeast genome in exponential phase.
Biochemical characterization of trans-sialidase TS1 variants from Trypanosoma congolense
Authors: Koliwer-Brandl Hendrik , Gbem Thaddeus T , Waespy Mario , Reichert Olga , Mandel Philipp , Drebitz Eric , Dietz Frank , Kelm Sørge 
Published: July 2011

Abstract

Background
Animal African trypanosomiasis, sleeping sickness in humans and Nagana in cattle, is a resurgent disease in Africa caused by Trypanosoma parasites. Trans-sialidases expressed by trypanosomes play an important role in the infection cycle of insects and mammals. Whereas trans-sialidases of other trypanosomes like the American T. cruzi are well investigated, relatively little research has been done on these enzymes of T. congolense.

Results
Based on a partial sequence and an open reading frame in the WTSI database, DNA sequences encoding for eleven T. congolense trans-sialidase 1 variants with 96.3% overall amino acid identity were amplified. Trans-sialidase 1 variants were expressed as recombinant proteins, isolated and assayed for trans-sialylation activity. The purified proteins produced α2,3-sialyllactose from lactose by desialylating fetuin, clearly demonstrating their trans-sialidase activity. Using an HPLC-based assay, substrate specificities and kinetic parameters of two variants were characterized in detail indicating differences in substrate specificities for lactose, fetuin and synthetic substrates. Both enzymes were able to sialylate asialofetuin to an extent, which was sufficient to reconstitute binding sites for Siglec-4. A mass spectrometric analysis of the sialylation pattern of glycopeptides from fetuin revealed clear but generally similar changes in the sialylation pattern of the N-glycans on fetuin catalyzed by the trans-sialidases investigated.

Conclusions
The identification and characterization of a trans-sialidase gene family of the African parasite T. congolense has opened new perspectives for investigating the biological role of these enzymes in Nagana and sleeping sickness. Based on this study it will be interesting to address the expression pattern of these genes and their activities in the different stages of the parasite in its infection cycle. Furthermore, these trans-sialidases have the biotechnological potential to be used for enzymatic modification of sialylated glycoconjugates.