bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prediction of Inadequate Bowel Preparation Using Total and Segmental Colon Transit Time in Patients with Chronic Constipation: Some Different Outcomes
Authors: Zhai Chunying , Huang Qiyang , Chai Ningli , Zhang Wengang , Linghu Enqiang 
Published: October 2019

Aims. Radio-opaque markers have been widely used in the study of colon motility in patients with chronic functional constipation (FC). Here, we evaluate the relationship between the colon transit time (CTT) and the Boston Bowel Preparation Scale (BBPS) to determine whether CTT is a sufficient predictor of bowel preparation in patients with chronic functional constipation. Methods. A total of fifty-six patients with constipation and fifty-two healthy controls (HC) were enrolled in this study. All subjects underwent the colonic transit study using radio-opaque markers and were given a follow-up colonoscopy examination on day 3 to 7 to determine BBPS. The correlation between total and segmental CTT and BBPS was evaluated, and risk factors for predicting inadequate bowel preparation were determined. Results. In our study, we found some distinct outcomes compared with previous studies. The mean total CTT (TCTT) was determined to be 43.37±18.82 h in the FC group and 23.08±10.18 h in the HC group. This difference was found to be significant for both the total and segmental CTTs between the two groups (P<0.05). Further, TCTT was negatively correlated with BBPS both in the FC (r=−0.899, 95% CI -0.748 to -0.925, P<0.001) and the HC (r=−0.978, 95% CI -0.854 to -1.003, P=0.004) groups, as was segmental CTTs and segmental BBPS (P<0.05). In the case of patients with slow transit constipation, multivariate logistic regression analysis indicated that prolonged TCTT (OR 0.722, 95% CI 0.589-0.885, P=0.002) was independently associated with poor bowel preparation. The total and right to left CTTs were found to predict inadequate bowel preparation and exhibited the best sensitivity and specificity at 48.0 h, 15.5 h, 17.5 h, and 19.0 h, based on ROC curve analysis. Conclusions. The CTT test represents a valuable method for predicting the level of bowel preparation prior to a colonoscopy examination. That is, both total and segmental CTTs can be considered an objective predictor of bowel preparation prior to colonoscopy. The present study demonstrates some distinct results relative to previous studies, including STC subtype proportion in FC, the proportion of inadequate bowel preparation in the STC subtype, and the cut-off value of TCTT for predicting inadequate bowel preparation.
The phylum Cnidaria: A review of phylogenetic patterns and diversity 300 years after Linnaeus*
Authors: DALY MARYMEGAN , BRUGLER MERCER R. , CARTWRIGHT PAULYN , COLLINS ALLEN G. , DAWSON MICHAEL N. , FAUTIN DAPHNE G. , FRANCE SCOTT C. , MCFADDEN CATHERINE S. , OPRESKO DENNIS M. , RODRIGUEZ ESTEFANIA , ROMANO SANDRA L. , STAKE JOEL L. 
Published: October 2019

Systema Naturae includes representatives of every major lineage of the animal phylum Cnidaria. However, Linnaeus did not classify the members of the phylum as is now done, and the diversity of the group is not well represented. We contrast the Linnaean perspective on cnidarian diversity with the modern, phylogenetic perspective. For each order, we detail diversity at the family level, providing phylogenetic context where possible.
Carl Linnaeus and his scale insects (Hemiptera: Coccoidea)*
Authors: WILLIAMS D. J. 
Published: October 2019

Carl Linnaeus named 22 species of scale insects in the genus Coccus, another in the genus Aphis, and one other probably unintentionally. All are redescribed and discussed. It is established that Coccus betulae L. is a nomen nudum and that the name was validly described later by Fabricius. A brief history of Linnaeus’ collection is summarised and his scale insect collection described. Linnaeus’ descriptions of scale insects are here translated into English and all the references to scale insect literature cited by Linnaeus are listed in bibliographical form and annotated. Lectotypes are designated for the species names Coccus aonidum Linnaeus, Aphis urticae Linnaeus and Coccus uvaeursi Linnaeus. One species, Coccus phalaridis, is here considered incertae sedis. Coccus pilosellae is recognised as a syn.nov. of Porphyrophora polonica (L.). Coccus rusci is recognised as Ceroplastes rusci (L.), not Columnea rusci.
Phylogeny, classification, and species-level taxonomy of ants (Hymenoptera: Formicidae)*
Authors: WARD PHILIP S. 
Published: October 2019

The current state of ant systematics is reviewed. In recent years substantial progress has been made in identifying the major clades of ants and the relationships among them. Earlier inferences about ant phylogeny based on morphology have been refined and modified as a result of a recent influx of molecular (DNA sequence) data and new fossil discoveries. It is now apparent that much of the biological and taxonomic diversity of ants is contained within the “formicoid clade” which comprises 14 of the 20 extant subfamilies and about 90% of all species. Whether the remaining groups of extant ants (Leptanillinae and the poneroid subfamilies) represent a clade or a grade at the base of the ant tree remains unresolved. The fossil record for crown group ants extends back to 90–100 mya. Stem ants (sphecomyrmines, armaniines) were also present during this period. Molecular divergence date estimates that take into account the fossil record of both ants and other Hymenoptera suggest that crown group ants arose ~115–135 mya. Most of the extant ant subfamilies and genera are well defined morphologically and likely monophyletic, but there are some notable exceptions including the subfamily Cerapachyinae and several large and ambiguously delimited genera such as Pachycondyla. Several tribes in the large subfamilies Formicinae and Myrmicinae also represent artificial assemblages. Finally, while the species-level taxonomy of some ant genera is in a satisfactory state, taxonomic anarchy reigns in others, with numerous ill-defined species and many names of uncertain applicability. Progress in this area of ant systematics will require sustained individual efforts, expansion of job opportunities, enlistment of new technologies, and a deeper understanding of the nature of ant species and the differences between them.
Molecular Pathways of Response to Recombinant Human Erythropoietin (rHuEpo) in Myelodysplastic patients Assayed with Macroarrays.
Authors: Agostino Cortelezzi , Gualtiero Colombo , Caterina Pellegrini , Ilaria Silvestris , Silvano Bosari , Giorgio Lambertenghi Deliliers , Nicola Fracchiolla S. 
Published: October 2019

Abstract
Recently, among myelodysplastic syndromes with IPSS low/intermediate 1 risk classes, promising results have been obtained in the treatment of anemia by high dosage recombinant human erythropoietin (rHuEPO) treatment, in the cases with low endogenous erythropoietin (EPO). We have reproduced these clinical results in the patients treated at our Institution. Based on these premises, in order to evaluate the molecular basis of the rHuEPO response in MDS patients, we investigated the differential gene expression in the bone marrow erythroid cells expressing glycophorin (Gly+) of EPO-responders (ER) and EPO-non responders (ENR) MDS patients, using commercially available macroarrays (Clontech), comparing gene level of expression with a baseline represented by a pool of erythoid cells isolated from normal bone marrow donors. We analysed 4 ER and 4 ENR MDS patients (RA and RARS). BM erythroid cells, after Ficoll density gradient, were separated by positive selection using an immunomagnetic procedure (MACS, glycophorin isolation kit; Miltenyi Biotech, Auburn, CA). The purity of Gly+ cells after magnetic immunosorting was tested by flow-cytometry and was superior to 97%, in all the cases. RNA extraction, cDNA synthesis and macroarrays hybridization and analysis were performed following manufacturer instructions (Clontech Laboratories, Palo Alto, CA). The data were validated on 4 differentially expressed genes by real time RT-PCR TaqMan technology, obtaining results that were superimposable to the macroarrays ones. Using a cut off of an at least two fold difference in gene expression, we obtained a differential pattern of expression in ER and ENR patients, BM Gly+ erythroid cells, with respect to normal donors. In particular, ER patients presented the up-regulation of interleukin-1 beta, apolipoprotein E precursor, CREB2, high mobility group protein (HMG-I), transducin beta-1 subunit and the down regulation of protein kinase MLK-3, cAMP-dependent phosphodiesterase (PDE43), IL-5R-alpha, caspase-9. On the other hand, in ENR group, we found a down regulation of proliferating cyclic nuclear antigen (PCNA), B-myb, prothymosin alpha, phenylethanolamine N-methyltransferase, thymosin beta-10 and an up regulation of homeobox protein HOX-A5, monocarboxylate transporter 1, interleukin-6, deoxyribonuclease II, sterol regulatory element-binding protein, metalloproteinase inhibitor 1 precursor, rap1 GTPase activating protein 1 (RAP1GAP). In conclusion, ER and ENR MDS patients erythroid cells present a different pattern of gene expression with respect to normal. These results may provide the basis for early testing of the genes differentially expressed in ER and ENR patients in order to elucidate their role in the prognostication of rHuEPO response in MDS patients with low endogenous EPO levels.
Telomere Length Reduction in Patients with Early Myelodysplastic Syndrome (MDS) Is Connected with Presence of Karyotype Abnormalities and with Shortened Survival and May Serve as an Additional Prognostic Factor.
Authors: Sieglova Zuzana , Cermak Jaroslav , Zilovcova Sona , Zizkova Hana , Michalova Kyra 
Published: October 2019

Abstract
The degree of telomere shortening was studied in 74 patients with primary MDS or acute myeloid leukemia arising from MDS (sAML) classified according to either FAB ( 30xRA, 3xRARS, 19xRAEB, 3xRAEB-T, 6xCMML, 13x sAML) or WHO classification (11xRA, 3xRARS, 17xRCMD, 2x5q-syndrome, 13xRAEB I, 6xRAEB II, 16x sAML). The telomere lengths were measured in mononuclear bone marrow cell fraction using Terminal Repeat Fragment method (TRF) based on non-radioactive chemiluminiscent detection of hybridization products obtained by digestion of high molecular weight DNA with Hinf I and RsaI restriction enzymes. In accordance with our previous studies performed on age-matched healthy controls, TRF shorter than 7.5 kbp was considered a significant marker of telomere reduction. A significant difference in TRF was found between RA/RARS patients and RAEB/RAEB-T/sAML patients according to FAB criteria ( P=0.048) and between RA/RARS/RCMD and RAEB/sAML patients according to WHO criteria (P=0.035). These results reflected a gradual shortening of telomeres in increased number of patients observed during progression of the disease as well as an inverse correlation between telomere length and number of bone marrow blasts (r = −0.427, P=0.048). Significantly shorter telomeres in a subgroup of patients with karyotype abnormalities (detected by routine cytogenetics and by FISH) in comparison to patients with normal karyotype were present in RA/RARS subtype according to FAB (P=0.042) and in RCMD subgroup according to WHO (P=0.010). Median survival and estimated 3 years survival in RA/RARS patients (FAB) with reduced telomere length were 25,3 months and 76% compared to 48,5 months and 86% in those with normal telomeres (P=0.01). In patients classified according to WHO, median survival and estimated 3 years survival were: RA/RARS+ shortened TRF - 27,0 months,82%, RA/RARS+normal TRF - 92,5 months,100%, RCMD+ shortened TRF - 19,0 months, 50%, RCMD+ normal TRF - 48,5 months, 86%. In patients with advanced disease (RAEB, RAEB-T, sAML), no significant differences were observed either in TRF between patients with normal or abnormal karyotype or in survival between patients with normal or reduced TRF. Since the reduction of telomere length in MDS patients probably represents later but important step in development of pathological clone leading to genetic instability and disease progression, the occurrence of shortened TRF in early MDS may be a consequence of an underlying complex disorder of hematopoiesis with potencially adverse outcome. Thus, measurement of TRF in patients with early disease may serve as an additional prognostic factor.
Phagocytic Signaling Molecules in Lipid Rafts of COS-1 Cells Transfected with FcγRIIA.
Authors: Mansfield Pamela J. , Hinkovska-Galcheva Vania , Borofsky Michael , Shayman James A. , Boxer Laurence A. 
Published: October 2019

Abstract
FcγRIIA-mediated phagocytosis involves a number of signaling proteins and lipids, which increasingly are viewed as localizing subcellularly in plasma membrane microdomains providing a framework for their interaction. COS-1 cells stably transfected with FcγRIIA were used as a model to demonstrate co-localization of several enzymes shown to be important in polymorphonuclear leukocyte (PMN) phagocytic signaling. Previously we developed a model wherein FcγRIIA engagement in PMNs resulted in activation of phospholipase D (PLD), producing phosphatidic acid, which is hydrolyzed to diglyceride, an activator of PKC. PKCδ and Raf-1 then activate the MAP kinase pathway and subsequently myosin to allow pseudopod formation. In COS-1 cells as in PMNs, PLD in the membrane fraction was activated during phagocytosis. COS-1 PLD was found almost exclusively in lipid rafts identified by the presence of caveolin, while two of its cofactors, RhoA and ARF1, were enriched in rafts. PKCδ and Raf-1 translocated to the plasma membrane, and were enriched in lipid rafts, reaching highest levels 5 to 10 min after phagocytosis was initiated. Rottlerin, a specific inhibitor of PKCδ, completely inhibited phagocytosis, suggesting that PKCδ regulates phagocytosis in COS-1 cells; however, translocation of PKCδ to rafts was not inhibited by rottlerin. Chelation of intracellular calcium with BAPTA-AM inhibited phagocytosis by only 25%, suggesting that PKCα or PKCβ, which both require calcium, were not important regulators of phagocytosis. A specific inhibitor of MEK (which is activated by Raf and activates MAP kinase), PD098059, inhibited phagocytosis by about 35%, suggesting that the MAP kinase pathway is involved in, but not the key factor required for, COS-1 cell phagocytosis. Extracellular signal-regulated kinase-2 (ERK2), a MAP kinase, was present in the raft fraction. In PMNs, phagocytosis and activation of MAP kinase are inhibited by exogenous ceramide, and endogenous ceramide levels increase during phagocytosis, indicating that FcγRIIA engagement initiates ceramide generation. Applying this model, we transfected COS-1 cells with FcγRIIA that had been mutated in the ITAM region (Y282F and Y298F), rendering them unable to ingest particles. When the mutant receptors were engaged, ceramide was generated and MAP kinase was activated normally, thus these processes did not require actual ingestion of particles. Previously we showed that ceramide 1-phosphate (C1P), the product of ceramide kinase (CERK), promotes membrane fusion in PMNs. Here we found that C1P increased in COS-1 cells during phagocytosis. CERK was found to be enriched in lipid rafts, translocating during phagocytosis. These results indicate that signaling proteins for phagocytosis are either constitutively present in, or are recruited to, lipid rafts where they are readily available to activate one another.
Effects of the Genetic Background on the Myelofibrosis Induced by the GATA-1Low Mutation.
Authors: Migliaccio Anna Rita , Martelli Fabrizio , Panetta Barbara , Alfani Elena , Migliaccio Giovanni , Gatta Valentina , Di Baldassarre Angela , Pancrazi Alessandro , Bogani Costanza , Paoletti Francesco , Vannucchi Alessandro M. 
Published: October 2019

Abstract
We have reported that CD1 mice harboring the GATA-1low mutation develop myelofibrosis, a syndrome similar to human idiopathic myelofibrosis, that manifests itself at 12 months of age with marrow fibrosis and with anemia, increased stem/progenitor cell trafficking and extramedullary hemopoiesis in the liver from 15 months onward (Vannucchi et al., Blood100: 1123–1132, 2002). The trait is expressed by homozygote and heterozygote females alike with 100% penetrance. The aim of these experiments was to assess the eventual effects of the genetic background on the severity of the myelofibrotic trait induced by the GATA-1low mutation. To harbour the GATA-1low in different backgrounds, it was exploited the fact that the GATA-1 gene is located on the X chromosome. Therefore, normal C57BL/6 and DBA2 females were crossed with GATA-1low males. Their heterozygote F1 female offspring (50% C57BL/6 or DBA/2, respectively) was backcrossed with wild type males (either C57BL/6 or DBA/2, as appropriate) and the F2 offspring (75% C57BL/6 or DBA72) analysed at 12 (by histological criteria) and at 15 months (by cytofluorimetric criteria) for the expression of the myelofibrotic trait. The results obtained are summarized in the Table below. In summary, all of the mice (independently from the background) developed marrow fibrosis while aging. However, a great variegation was observed in the progression of the disease in the different strains. It is proposed that such a variegation may represent a model to investigate the extreme variability of the clinical picture of the disease in humans.
Summary of the GATA-1low trait in the different backgrounds
C57BL/6 CD1 DBA2 Perinatal Mortality yes no no Thrombocytopenia yes yes yes Myelofibrosis Anemia no 15 months no Tear drop poikilocytes 12 months 15 months no Marrow fibrosis yes yes yes Osteosclerosis yes limited no Progenitor cell trafficking no yes no Extramedullary hemopoiesis no yes no
Mitochondria and Caspase-Independent Cell-Death Triggered by GCS-100, a Novel Carbohydrate-Based Therapeutic in Multiple Myeloma (MM) Cells.
Authors: Chauhan Dharminder , Li Guilan , Podar Klaus , Hideshima Teru , Ishitsuka Kenji , Catley Laurence , Sattler Martin , Tai Yu-Tzu , Burger Renate , Richardson Paul , Chang Yan , Schindler Joanne , Carver Bradley , Anderson Kenneth C. 
Published: October 2019

Abstract
GCS-100 is a carbohydrate-based therapeutic in clinical development for the treatment of cancer. Here we show that GCS-100 directly targets MM cells and their bone marrow (BM) microenvironment. Treatment of various MM cell lines, including those resistant to conventional anti-MM agents such as, dexamethasone, melphalan, or doxorubicin, with GCS-100 triggers growth arrest and apoptosis. Examination of purified patient MM cells demonstrated similar results, without significant toxicity against normal peripheral blood mononuclear cells. Importantly, GCS-100 decreases viability of bortezomib-resistant MM patient cells. GCS-100 blocks MM cell growth induced by both adhesion to bone marrow stromal cells (BMSCs) and related cytokine secretion, thereby inhibiting growth and survival in MM cells conferred by the BM microenvironment. GCS-100 overcomes drug-resistance conferred by anti-apoptotic protein Bcl-2 and heat shock protein-27. Although GCS-100 induces MM cell death evidenced by morphological and DNA fragmentation analysis, no activation of caspases-8, -9 and -3 was noted at the IC50 dose. Conversely, the pan caspase inhibitor Z-VAD-fmk failed to abrogate GCS-100-induced apoptosis. Furthermore, GCS-100 does not alter mitochondrial membrane potential, suggesting a mitochondria- and caspase-independent cell death-signaling pathway. These data provided the rationale for combining GCS-100 with an agent that specifically triggers mitochondrial apoptotic signaling in MM cells. For example, combining a conventional agent dexamethasone, a known inducer of Smac release from mitochondria and activator of caspase-9/3 cascade, with GCS-100 shows additive anti-MM activity; and combining GCS-100 with an antagonist to mitochondrial peripheral benzodiazepine receptor PK-11195 shows synergistic anti-MM activity, associated with profound mitochondrial cell-death signaling and activation of caspase-9 and -3. Collectively, these findings lay the framework for clinical evaluation of GCS-100, either alone or in combination with dexamethasone or PK-11195, to overcome drug resistance and improve patient outcome in MM.
Ascorbic Acid Overcomes Drug Resistance in Myeloma and Significantly Increases the Anti-Myeloma Effects of both Arsenic Trioxide and Melphalan in Vitro and in Vivo.
Authors: Campbell Richard A. , Chen Haiming , Zhu Daocheng , Santos Janice C. , Bonavida Benjamin , Pang Shen , Said Jonathan , Berenson James R. 
Published: October 2019

Abstract
Glutathione levels have previously been shown to be associated with the development of resistance to a variety of anti-myeloma therapies. Ascorbic acid (AA) depletes intracellular glutathione levels which, in turn, should increase the sensitivity of tumor cells to anti-myeloma agents such as arsenic trioxide (ATO) and melphalan. To determine the synergistic effects of combining AA, with ATO and/or melphalan, we evaluated the effects of these combinations with MTT assays on myeloma cell lines in vitro and using our severe combined immunodeficient (SCID)-hu murine myeloma models. We determined the synergistic effects of combining AA with ATO and/or melphalan on the myeloma cell lines RPMI8226, 8226/dox, U266, and U266/dox in vitro. MTT assays demonstrated marked synergistic anti-proliferative effects of AA at 10 mM when added to these cell lines in the presence of ATO concentrations ranging from 5x10−5 M – 5x10−9 M, and melphalan concentrations ranging from 3x10−5 M – 3x10−9 M. In order to provide further evidence for the clinical relevance of these synergistic effects of AA, we investigated the potential of AA to increase the efficacy of current anti-myeloma therapies in our SCID-hu murine model of human myeloma LAGλ–1 (Yang H et al. Blood 2002). Each SCID mouse was implanted with a 0.5 cm3 LAGλ–1 tumor fragment into the left hind limb muscle. Twenty-eight days following implantation, mice then received treatment intraperitoneally (IP) with either AA (300 mg/kg) daily x5/week, ATO (1.25 mg/kg) daily x5/week, or melphalan (3.0 mg/kg) x1/week, or the combination of these agents. AA, ATO, and melphalan alone have no anti-myeloma effects at these doses, whereas AA+melphalan results in significantly decreased tumor burden and paraprotein levels. The most profound anti-myeloma effects were observed in animals treated with all three drugs together. These data show not only the additional synergistic anti-myeloma effects of AA on both ATO and melphalan in vitro but for the first time suggest that these effects are also present in vivo. This provides the rationale for combining AA with these agents in myeloma patients with resistant disease. In support of this, early results of clinical trials using the combination of AA, ATO and low doses of oral melphalan are promising.