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[PMID]: 25666624
[Au] Autor:Heim KP; Sullan RM; Crowley PJ; El-Kirat-Chatel S; Beaussart A; Tang W; Besingi R; Dufrene YF; Brady LJ
[Ad] Address:From the Department of Oral Biology, University of Florida, Gainesville, Florida 32610 and....
[Ti] Title:Identification of a Supramolecular Functional Architecture of Streptococcus mutans Adhesin P1 on the Bacterial Cell Surface.
[So] Source:J Biol Chem;290(14):9002-19, 2015 Apr 3.
[Is] ISSN:1083-351X
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:P1 (antigen I/II) is a sucrose-independent adhesin of Streptococcus mutans whose functional architecture on the cell surface is not fully understood. S. mutans cells subjected to mechanical extraction were significantly diminished in adherence to immobilized salivary agglutinin but remained immunoreactive and were readily aggregated by fluid-phase salivary agglutinin. Bacterial adherence was restored by incubation of postextracted cells with P1 fragments that contain each of the two known adhesive domains. In contrast to untreated cells, glutaraldehyde-treated bacteria gained reactivity with anti-C-terminal monoclonal antibodies (mAbs), whereas epitopes recognized by mAbs against other portions of the molecule were masked. Surface plasmon resonance experiments demonstrated the ability of apical and C-terminal fragments of P1 to interact. Binding of several different anti-P1 mAbs to unfixed cells triggered release of a C-terminal fragment from the bacterial surface, suggesting a novel mechanism of action of certain adherence-inhibiting antibodies. We also used atomic force microscopy-based single molecule force spectroscopy with tips bearing various mAbs to elucidate the spatial organization and orientation of P1 on living bacteria. The similar rupture lengths detected using mAbs against the head and C-terminal regions, which are widely separated in the tertiary structure, suggest a higher order architecture in which these domains are in close proximity on the cell surface. Taken together, our results suggest a supramolecular organization in which additional P1 polypeptides, including the C-terminal segment originally identified as antigen II, associate with covalently attached P1 to form the functional adhesive layer.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1504
[Cu] Class update date: 150404
[Lr] Last revision date:150404
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1074/jbc.M114.626663

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[PMID]: 25725588
[Au] Autor:Price KA; Cohen EE
[Ad] Address:Division of Medical Oncology, Mayo Clinic, Rochester, MN, USA. Electronic address: price.katharine@mayo.edu.
[Ti] Title:Mechanisms of and therapeutic approaches for overcoming resistance to epidermal growth factor receptor (EGFR)-targeted therapy in squamous cell carcinoma of the head and neck (SCCHN).
[So] Source:Oral Oncol;51(5):399-408, 2015 May.
[Is] ISSN:1879-0593
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:The majority of squamous cell carcinoma of the head and neck (SCCHN) overexpress epidermal growth factor receptor (EGFR), which has been associated with poor treatment response and survival. However, only modest success has been achieved with the use of single agents that target EGFR, possibly due to primary and acquired resistance. This review will discuss key mechanisms of and therapeutic approaches to overcoming resistance to EGFR-targeted therapy in SCCHN. Recent preclinical and clinical investigations have demonstrated that other ErbB family receptors (eg, HER2 and HER3) and other horizontal resistance mechanisms, as well as activation of downstream signaling pathways, epigenetic events, and nuclear EGFR, are possible mediators of resistance to anti-EGFR therapeutics. Key downstream pathways that may be implicated in EGFR resistance include phosphatidylinositol-3-kinase/protein kinase B, vascular endothelial growth factor (VEGF), and mammalian target of rapamycin (mTOR). Multiple agents that target EGFR and other ErbB family members (ie, lapatinib, afatinib, and dacomitinib), as well as combination therapies that target EGFR and selected other pathways (eg, VEGF, mTOR, and c-Met) are being investigated clinically. In addition, several phase II and III trials continue to investigate strategies to enhance the efficacy of EGFR-targeted therapy in SCCHN.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1504
[Cu] Class update date: 150404
[Lr] Last revision date:150404
[Js] Journal subset:IM
[St] Status:In-Data-Review

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[PMID]: 25726728
[Au] Autor:Lehman W; Medlock G; Li XE; Suphamungmee W; Tu AY; Schmidtmann A; Ujfalusi Z; Fischer S; Moore JR; Geeves MA; Regnier M
[Ad] Address:Department of Physiology & Biophysics, Boston University School of Medicine, 72 East Concord Street, Boston, MA 02118, USA. Electronic address: wlehman@bu.edu....
[Ti] Title:Phosphorylation of Ser283 enhances the stiffness of the tropomyosin head-to-tail overlap domain.
[So] Source:Arch Biochem Biophys;571:10-5, 2015 Apr 1.
[Is] ISSN:1096-0384
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:The ends of coiled-coil tropomyosin molecules are joined together by nine to ten residue-long head-to-tail "overlapping domains". These short four-chained interconnections ensure formation of continuous tropomyosin cables that wrap around actin filaments. Molecular Dynamics simulations indicate that the curvature and bending flexibility at the overlap is 10-20% greater than over the rest of the molecule, which might affect head-to-tail filament assembly on F-actin. Since the penultimate residue of striated muscle tropomyosin, Ser283, is a natural target of phosphorylating enzymes, we have assessed here if phosphorylation adjusts the mechanical properties of the tropomyosin overlap domain. MD simulations show that phosphorylation straightens the overlap to match the curvature of the remainder of tropomyosin while stiffening it to equal or exceed the rigidity of canonical coiled-coil regions. Corresponding EM data on phosphomimetic tropomyosin S283D corroborate these findings. The phosphorylation-induced change in mechanical properties of tropomyosin likely results from electrostatic interactions between C-terminal phosphoSer283 and N-terminal Lys12 in the four-chain overlap bundle, while promoting stronger interactions among surrounding residues and thus facilitating tropomyosin cable assembly. The stiffening effect of D283-tropomyosin noted correlates with previously observed enhanced actin-tropomyosin activation of myosin S1-ATPase, suggesting a role for the tropomyosin phosphorylation in potentiating muscle contraction.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1504
[Cu] Class update date: 150404
[Lr] Last revision date:150404
[Js] Journal subset:IM
[St] Status:In-Data-Review

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[PMID]: 25834323
[Au] Autor:Tyng CJ; Almeida MF; Barbosa PN; Bitencourt AG; Berg JA; Maciel MS; Coimbra FJ; Schiavon LH; Begnami MD; Guimarães MD; Zurstrassen CE; Chojniak R
[Ad] Address:Chiang J Tyng, Maria Fernanda A Almeida, Paula N V Barbosa, Almir G V Bitencourt, José Augusto A G Berg, Macello S Maciel, Luiz Henrique O Schiavon, Marcos D Guimarães, Charles E Zurstrassen, Rubens Chojniak, Department of Imaging, AC Camargo Cancer Center, São Paulo, SP 09015-010, Brazil....
[Ti] Title:Computed tomography-guided percutaneous core needle biopsy in pancreatic tumor diagnosis.
[So] Source:World J Gastroenterol;21(12):3579-86, 2015 Mar 28.
[Is] ISSN:2219-2840
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:AIM: To evaluate the techniques, results, and complications related to computed tomography (CT)-guided percutaneous core needle biopsies of solid pancreatic lesions. METHODS: CT-guided percutaneous biopsies of solid pancreatic lesions performed at a cancer reference center between January 2012 and September 2013 were retrospectively analyzed. Biopsy material was collected with a 16-20 G Tru-Core needle (10-15 cm; Angiotech, Vancouver, CA) using a coaxial system and automatic biopsy gun. When direct access to the lesion was not possible, indirect (transgastric or transhepatic) access or hydrodissection and/or pneumodissection maneuvers were used. Characteristics of the patients, lesions, procedures, and histologic results were recorded using a standardized form. RESULTS: A total of 103 procedures included in the study were performed on patients with a mean age of 64.8 year (range: 39-94 year). The mean size of the pancreatic lesions was 45.5 mm (range: 15-195 mm). Most (75/103, 72.8%) procedures were performed via direct access, though hydrodissection and/or pneumodissection were used in 22.2% (23/103) of cases and indirect transhepatic or transgastric access was used in 4.8% (5/103) of cases. Histologic analysis was performed on all biopsies, and diagnoses were conclusive in 98.1% (101/103) of cases, confirming 3.9% (4/103) of tumors were benign and 94.2% (97/103) were malignant; results were atypical in 1.9% (2/103) of cases, requiring a repeat biopsy to diagnose a neuroendocrine tumor, and surgical resection to confirm a primary adenocarcinoma. Only mild/moderate complications were observed in 9/103 patients (8.7%), and they were more commonly associated with biopsies of lesions located in the head/uncinate process (n = 8), than of those located in the body/tail (n = 1) of the pancreas, but this difference was not significant. CONCLUSION: CT-guided biopsy of a pancreatic lesion is a safe procedure with a high success rate, and is an excellent option for minimally invasive diagnosis.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1504
[Cu] Class update date: 150404
[Lr] Last revision date:150404
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.3748/wjg.v21.i12.3579

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[PMID]: 25834671
[Au] Autor:Nishijima DK; Melnikow J; Tancredi DJ; Shahlaie K; Utter GH; Galante JM; Rudisill N; Holmes JF
[Ad] Address:University of California, Davis, Department of Emergency Medicine, Davis, California....
[Ti] Title:Long-term Neurological Outcomes in Adults with Traumatic Intracranial Hemorrhage Admitted to ICU versus Floor.
[So] Source:West J Emerg Med;16(2):284-90, 2015 Mar.
[Is] ISSN:1936-9018
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:INTRODUCTION: The objective of this study was to compare long-term neurological outcomes in low-risk patients with traumatic intracranial hemorrhage (tICH) admitted to the ICU (intensive care unit) versus patients admitted to the floor. METHODS: This retrospective study was conducted at a Level 1 trauma center from October 1, 2008, to February 1, 2013. We defined low-risk patients as age less than 65 years, isolated head injury, normal admission mental status, and no shift or swelling on initial head CT (computed tomography). Clinical data were abstracted from a trauma registry and linked to a brain injury database. We compared the Extended Glasgow Outcome Scale (GOS-E) score at six months between patients admitted to the ICU and patients admitted to the floor. We did a risk-adjusted analysis of the influence of floor admission on a normal GOS-E. RESULTS: We identified 151 patients; 45 (30%) were admitted to the floor and 106 (70%) to the ICU. Twenty-three (51%; 95% CI [36-66%]) patients admitted to the floor and 55 (52%; 95% CI [42-62%]) patients admitted to the ICU had a normal GOS-E. On adjusted analysis; the odds ratio for floor admission was 0.77 (95% CI [0.36-1.64]) for a normal GOS-E at six months. CONCLUSION: Long-term neurological outcomes in low-risk patients with tICH were not markedly different between patients admitted to the ICU and those admitted to the floor. However, we were unable to demonstrate non-inferiority on adjusted analysis. Future work aimed at a larger, prospective cohort may better evaluate the relative impacts of admission type on outcomes.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1504
[Cu] Class update date: 150404
[Lr] Last revision date:150404
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.5811/westjem.2015.1.23356

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[PMID]: 25765648
[Au] Autor:Fan HF; Cheng YS; Ma CH; Jayaram M
[Ad] Address:Department of Life Sciences and Institute of Genome Sciences, National Yang Ming University, Taipei 112, Taiwan hffan2@ym.edu.tw....
[Ti] Title:Single molecule TPM analysis of the catalytic pentad mutants of Cre and Flp site-specific recombinases: contributions of the pentad residues to the pre-chemical steps of recombination.
[So] Source:Nucleic Acids Res;43(6):3237-55, 2015 Mar 31.
[Is] ISSN:1362-4962
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:Cre and Flp site-specific recombinase variants harboring point mutations at their conserved catalytic pentad positions were characterized using single molecule tethered particle motion (TPM) analysis. The findings reveal contributions of these amino acids to the pre-chemical steps of recombination. They suggest functional differences between positionally conserved residues in how they influence recombinase-target site association and formation of 'non-productive', 'pre-synaptic' and 'synaptic' complexes. The most striking difference between the two systems is noted for the single conserved lysine. The pentad residues in Cre enhance commitment to recombination by kinetically favoring the formation of pre-synaptic complexes. These residues in Flp serve a similar function by promoting Flp binding to target sites, reducing non-productive binding and/or enhancing the rate of assembly of synaptic complexes. Kinetic comparisons between Cre and Flp, and between their derivatives lacking the tyrosine nucleophile, are consistent with a stronger commitment to recombination in the Flp system. The effect of target site orientation (head-to-head or head-to-tail) on the TPM behavior of synapsed DNA molecules supports the selection of anti-parallel target site alignment prior to the chemical steps. The integrity of the synapse, whose establishment/stability is fostered by strand cleavage in the case of Flp but not Cre, appears to be compromised by the pentad mutations.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1504
[Cu] Class update date: 150404
[Lr] Last revision date:150404
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1093/nar/gkv114

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[PMID]: 25834715
[Au] Autor:Beheshti Maal K; Soleimani Delfan A; Salmanizadeh S
[Ad] Address:Department of Microbiology, Faculty of Biological Sciences, Falavarjan Branch, Islamic Azad University, Isfahan, IR Iran.
[Ti] Title:Isolation and Identification of Two Novel Escherichia coli Bacteriophages and Their Application in Wastewater Treatment and Coliform's Phage Therapy.
[So] Source:Jundishapur J Microbiol;8(3):e14945, 2015 Mar.
[Is] ISSN:2008-3645
[Cp] Country of publication:Iran
[La] Language:eng
[Ab] Abstract:BACKGROUND: Phage therapy or use of lytic bacteriophages for eliminating bacterial populations has been developed for several aspects of human affairs such as medicine, agriculture and food industries. OBJECTIVES: The high load of coliforms of treated wastewater effluents that are discharged into the rivers or agricultural lands is a serious concern of the Iran Department of Environment and the reduction of coliforms using phages to overcome this problem is an asset. This research aimed to isolate and identify specific lytic coliphages and investigate their effects on native and standard Escherichia coli strains as well as coliform populations in municipal wastewater. MATERIALS AND METHODS: The wastewater sample was cultured on selective culture media to isolate a native coliform strain and characterized using molecular methods. River water was centrifuged and passed through a 0.45 µm filter and its lytic coliphages were enriched and purified against a native E. coli as well as a standard E. coli strain. Municipal wastewater was treated with isolated lytic coliphages and most probable number (MPN) reduction was examined. RESULTS: E. coli SBSWF27, which is a native strain of E. coli from Isfahan municipal wastewater treatment plant, was isolated and characterized. Also two novel bacteriophages related to Myoviridae and Podoviridae families of bacteriophages from Zayandehrood River (Isfahan, Iran) were isolated. These coliphages had lytic effects on E. coli PTCC1399 and E. coli SBSWF27 as coliform's index. The myovirus had a hexagonal head measuring 27.28 nm and a noncontractile tail measuring 204.5 × 13.63 nm. The podovirus had an oval head measuring 98 × 35 nm and a tail, 14 nm in diameter. The treatment of municipal sewage with the coliphage mixture resulted in a 22-fold decrease of the coliform's MPN from 2400 to 110 after two hours of incubation. CONCLUSIONS: This is the first report on isolation and identification of two novel lytic myovirus and podovirus from Zayandehrood River in Isfahan that had lytic effects on E. coli PTCC1399 and E. coli SBSWF27 strains as well as coliform's population of Isfahan municipal wastewater. We suggest that the use of these lytic coliphages for reduction of coliform's population in sewage could be considered as an effective and simple alternative for costly replacement of instruments and establishments of the old wastewater treatment plants.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1504
[Cu] Class update date: 150404
[Lr] Last revision date:150404
[Da] Date of entry for processing:150402
[St] Status:PubMed-not-MEDLINE
[do] DOI:10.5812/jjm.14945

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[PMID]: 25834572
[Au] Autor:Kikuchi K; Ishige T; Ide F; Ito Y; Saito I; Hoshino M; Inoue H; Miyazaki Y; Nozaki T; Kojima M; Kusama K
[Ad] Address:Division of Pathology, Department of Diagnostic and Therapeutic Sciences, Meikai University School of Dentistry, 1-1 Keyakidai, Sakado, Saitama 350-0283, Japan....
[Ti] Title:Overexpression of Activation-Induced Cytidine Deaminase in MTX- and Age-Related Epstein-Barr Virus-Associated B-Cell Lymphoproliferative Disorders of the Head and Neck.
[So] Source:J Oncol;2015:605750, 2015.
[Is] ISSN:1687-8450
[Cp] Country of publication:Egypt
[La] Language:eng
[Ab] Abstract:Recent research has shown that activation-induced cytidine deaminase (AID) triggers somatic hypermutation and recombination, in turn contributing to lymphomagenesis. Such aberrant AID expression is seen in B-cell leukemia/lymphomas, including Burkitt lymphoma which is associated with c-myc translocation. Moreover, Epstein-Barr virus (EBV) latent membrane protein-1 (LMP-1) increases genomic instability through early growth transcription response-1 (Egr-1) mediated upregulation of AID in B-cell lymphoma. However, few clinicopathological studies have focused on AID expression in lymphoproliferative disorders (LPDs). Therefore, we conducted an immunohistochemical study to investigate the relationship between AID and LMP-1 expression in LPDs (MTX-/Age-related EBV-associated), including diffuse large B-cell lymphomas (DLBCLs). More intense AID expression was detected in LPDs (89.5%) than in DLBCLs (20.0%), and the expression of LMP-1 and EBER was more intense in LPDs (68.4% and 94.7%) than in DLBCLs (10.0% and 20.0%). Furthermore, stronger Egr-1 expression was found in MTX/Age-EBV-LPDs (83.3%) than in DLBCLs (30.0%). AID expression was significantly constitutively overexpressed in LPDs as compared with DLBCLs. These results suggest that increased AID expression in LPDs may be one of the processes involved in lymphomagenesis, thereby further increasing the survival of genetically destabilized B-cells. AID expression may be a useful indicator for differentiation between LPDs and DLBCLs.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1504
[Cu] Class update date: 150404
[Lr] Last revision date:150404
[Da] Date of entry for processing:150402
[St] Status:PubMed-not-MEDLINE
[do] DOI:10.1155/2015/605750

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[PMID]: 25834586
[Au] Autor:Kovács G
[Ad] Address:Interdisciplinary Brachytherapy Unit, University of Lübeck/University Hospital Schleswig-Holstein Campus Lübeck, Germany.
[Ti] Title:Modern head and neck brachytherapy: from radium towards intensity modulated interventional brachytherapy.
[So] Source:J Contemp Brachytherapy;6(4):404-16, 2015 Jan.
[Is] ISSN:1689-832X
[Cp] Country of publication:Poland
[La] Language:eng
[Ab] Abstract:Intensity modulated brachytherapy (IMBT) is a modern development of classical interventional radiation therapy (brachytherapy), which allows the application of a high radiation dose sparing severe adverse events, thereby further improving the treatment outcome. Classical indications in head and neck (H&N) cancers are the face, the oral cavity, the naso- and oropharynx, the paranasal sinuses including base of skull, incomplete resections on important structures, and palliation. The application type can be curative, adjuvant or perioperative, as a boost to external beam radiation as well as without external beam radiation and with palliative intention. Due to the frequently used perioperative application method (intraoperative implantation of inactive applicators and postoperative performance of radiation), close interdisciplinary cooperation between surgical specialists (ENT-, dento-maxillary-facial-, neuro- and orbital surgeons), as well interventional radiotherapy (brachytherapy) experts are obligatory. Published results encourage the integration of IMBT into H&N therapy, thereby improving the prognosis and quality of life of patients.
[Pt] Publication type:JOURNAL ARTICLE; REVIEW
[Em] Entry month:1504
[Cu] Class update date: 150404
[Lr] Last revision date:150404
[Da] Date of entry for processing:150402
[St] Status:PubMed-not-MEDLINE
[do] DOI:10.5114/jcb.2014.47813

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[PMID]: 25832685
[Au] Autor:Vainshtein JM; Moon DH; Feng FY; Chepeha DB; Eisbruch A; Stenmark MH
[Ad] Address:Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan....
[Ti] Title:Long-term quality of life after swallowing and salivary-sparing chemo-intensity modulated radiation therapy in survivors of human papillomavirus-related oropharyngeal cancer.
[So] Source:Int J Radiat Oncol Biol Phys;91(5):925-33, 2015 Apr 1.
[Is] ISSN:1879-355X
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:PURPOSE: To evaluate long-term health-related quality of life (HRQOL) in 2 prospective studies of chemo-intensity modulated radiation therapy (chemo-IMRT) for oropharyngeal cancer (OPC). METHODS AND MATERIALS: Of 93 patients with stage III/IV OPC treated on prospective studies of swallowing and salivary organ-sparing chemo-IMRT, 69 were eligible for long-term HRQOL assessment. Three validated patient-reported instruments, the Head and Neck QOL (HNQOL) questionnaire, the University of Washington quality of life (UWQOL) questionnaire, and the Xerostomia Questionnaire (XQ), previously administered from baseline through 2 years in the parent studies, were readministered at long-term follow-up, along with the Short-Form 36. Long-term changes in HRQOL from before treatment and 2 years were evaluated. RESULTS: Forty patients (58%) with a median follow-up of 6.5 years participated, 39 of whom (97.5%) had confirmed human papillomavirus-positive OPC. Long term, no clinically significant worsening was detected in mean HRQOL scores compared with 2 years, with stable or improved HRQOL from before treatment in nearly all domains. "Moderate" or greater severity problems were uncommon, reported by 5% of patients for eating, 5% for swallowing, and 2.5% and 5% by HNQOL and UWQOL summary scores, respectively. Freedom from percutaneous endoscopic gastrostomy tube dependence and stricture dilation beyond 2 years was 97.5% and 95%, respectively. Eleven percent and 14% of patients reported "moderate" or "severe" long-term worsening in HNQOL Pain and Overall Bother domains, respectively, which were associated with mean dose to the cervical esophagus, larynx, and pharyngeal constrictors. CONCLUSIONS: At more than 6 years' median follow-up, OPC patients treated with swallowing and salivary organ-sparing chemo-IMRT reported stable or improved HRQOL in nearly all domains compared with both before treatment and 2-year follow-up. New late toxicity after 2 years was uncommon. Further emphasis on sparing the swallowing organs may yield additional HRQOL gains for long-term OPC survivors.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1504
[Cu] Class update date: 150404
[Lr] Last revision date:150404
[Js] Journal subset:IM
[St] Status:In-Data-Review


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