bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeting the bone marrow microenvironment in multiple myeloma
Authors: Kawano Yawara , Moschetta Michele , Manier Salomon , Glavey Siobhan , Görgün Güllü T. , Roccaro Aldo M. , Anderson Kenneth C. , Ghobrial Irene M. 
Published: December 2014

SummaryMultiple myeloma (MM) is characterized by clonal expansion of malignant plasma cells in the bone marrow (BM). Despite the significant advances in treatment, MM is still a fatal malignancy. This is mainly due to the supportive role of the BM microenvironment in differentiation, migration, proliferation, survival, and drug resistance of the malignant plasma cells. The BM microenvironment is composed of a cellular compartment (stromal cells, osteoblasts, osteoclasts, endothelial cells, and immune cells) and a non‐cellular compartment. In this review, we discuss the interaction between the malignant plasma cell and the BM microenvironment and the strategy to target them.
Do we need more drugs for chronic myeloid leukemia?
Authors: Holyoake Tessa L. , Helgason G. Vignir 
Published: December 2014

SummaryThe introduction of protein tyrosine kinase inhibitors (TKIs) in 1998 transformed the management of chronic myeloid leukemia (CML), leading to significantly reduced mortality and improved 5 year survival rates. However, the CML community is faced with several clinical issues that need to be addressed. Ten to 15% of CML patients are diagnosed in advanced phase, and small numbers of chronic phase (CP) cases experience disease progression each year during treatment. For these patients, TKIs induce only transient responses and alternative treatment strategies are urgently required. Depending on choice of first line TKI, approximately 30% of CML CP cases show suboptimal responses, due to a combination of poor compliance, drug intolerance, and drug resistance, with approximately 50% of TKI‐resistance caused by kinase domain mutations and the remainder due to unknown mechanisms. Finally, the chance of successful treatment discontinuation is on the order of only 10–20% related to disease persistence. Disease persistence is a poorly understood phenomenon; all CML patients have functional Philadelphia positive (Ph+) stem and progenitor cells in their bone marrows and continue to express BCR‐ABL1 by DNA PCR, even when in very deep remission and following treatment discontinuation. What controls the maintenance of these persisting cells, whether it is necessary to fully eradicate the malignant clone to achieve cure, and how that might be approached therapeutically are open questions.
Role of the ubiquitin proteasome system in hematologic malignancies
Authors: Sahasrabuddhe Anagh A. , Elenitoba‐Johnson Kojo S. J. 
Published: December 2014

SummaryUbiquitination is a post‐translational modification process that regulates several critical cellular processes. Ubiquitination is orchestrated by the ubiquitin proteasome system (UPS), which constitutes a cascade of enzymes that transfer ubiquitin onto protein substrates. The UPS catalyzes the destruction of many critical protein substrates involved in cancer pathogenesis. This review article focuses on components of the UPS that have been demonstrated to be deregulated by a variety of mechanisms in hematologic malignancies. These include E3 ubiquitin ligases and deubiquitinating enzymes. The prospects of specific targeting of key enzymes in this pathway that are critical to the pathogenesis of particular hematologic neoplasia are also discussed.
TET proteins and 5‐methylcytosine oxidation in hematological cancers
Authors: Ko Myunggon , An Jungeun , Pastor William A. , Koralov Sergei B. , Rajewsky Klaus , Rao Anjana 
Published: December 2014

SummaryDNA methylation has pivotal regulatory roles in mammalian development, retrotransposon silencing, genomic imprinting, and X‐chromosome inactivation. Cancer cells display highly dysregulated DNA methylation profiles characterized by global hypomethylation in conjunction with hypermethylation of promoter CpG islands that presumably lead to genome instability and aberrant expression of tumor suppressor genes or oncogenes. The recent discovery of ten‐eleven‐translocation (TET) family dioxygenases that oxidize 5mC to 5‐hydroxymethylcytosine (5hmC), 5‐formylcytosine (5fC), and 5‐carboxylcytosine (5caC) in DNA has led to profound progress in understanding the mechanism underlying DNA demethylation. Among the three TET genes, TET2 recurrently undergoes inactivating mutations in a wide range of myeloid and lymphoid malignancies. TET2 functions as a bona fide tumor suppressor particularly in the pathogenesis of myeloid malignancies resembling chronic myelomonocytic leukemia (CMML) and myelodysplastic syndromes (MDS) in human. Here we review diverse functions of TET proteins and the novel epigenetic marks that they generate in DNA methylation/demethylation dynamics and normal and malignant hematopoietic differentiation. The impact of TET2 inactivation in hematopoiesis and various mechanisms modulating the expression or activity of TET proteins are also discussed. Furthermore, we also present evidence that TET2 and TET3 collaborate to suppress aberrant hematopoiesis and hematopoietic transformation. A detailed understanding of the normal and pathological functions of TET proteins may provide new avenues to develop novel epigenetic therapies for treating hematological malignancies.
New themes in the biological functions of 5‐methylcytosine and 5‐hydroxymethylcytosine
Authors: Moen Erika L. , Mariani Christopher J. , Zullow Hayley , Jeff‐Eke Meselle , Litwin Edward , Nikitas John N. , Godley Lucy A. 
Published: December 2014

Summary5‐methylcytosine (5‐mC) and 5‐hydroxymethylcytosine (5‐hmC) play a critical role in development and normal physiology. Alterations in 5‐mC and 5‐hmC patterns are common events in hematopoietic neoplasms. In this review, we begin by emphasizing the importance of 5‐mC, 5‐hmC, and their enzymatic modifiers in hematological malignancies. Then, we discuss the functions of 5‐mC and 5‐hmC at distinct genic contexts, including promoter regions, gene bodies, intron‐exon boundaries, alternative promoters, and intragenic microRNAs. Recent advances in technology have allowed for the study of 5‐mC and 5‐hmC independently and specifically permitting distinction between the bases that show them to have transcriptional effects that vary by their location relative to gene structure. We extend these observations to their functions at enhancers and transcription factor binding sites. We discuss dietary influences on 5‐mC and 5‐hmC levels and summarize the literature on the effects of folate and vitamin C on 5‐mC and 5‐hmC, respectively. Finally, we discuss how these new themes in the functions of 5‐mC and 5‐hmC will likely influence the broader research field of epigenetics.
Genome‐Wide Identification of MicroRNAs Responsive to High Temperature in Rice (Oryza sativa) by High‐Throughput Deep Sequencing
Authors: Li J. , Wu L.‐Q. , Zheng W.‐Y. , Wang R.‐F. , Yang L.‐X. 
Published: December 2014

AbstractMicroRNAs (miRNAs) are known to play important roles in plant growth and stress response. Heat stress is a severe abiotic stresses by adversely affecting plant growth and yield. To identify heat‐responsive miRNAs at the genome‐wide level in rice (Oryza sativa), we constructed two small RNA libraries from young panicles treated or not with heat conditions. Ion torrent sequencing of the two libraries identified 294 known miRNAs and 539 novel miRNAs. Differential expression analysis showed that 26 miRNAs were downregulated and 21 miRNAs were upregulated in response to heat stress. Among them, five heat‐responsive miRNAs, including miR162b, miR529a‐p5, PC‐5P‐62245‐9, miR171b and miR169n, were validated by quantitative real‐time polymerase chain reaction. A total of 44 target genes of the differentially expressed miRNAs were predicted. These target genes are most significantly overrepresented in the cell growth process. The results demonstrated that rice miRNAs play critical roles in the heat stress response. This study opens up a new avenue for understanding the regulatory mechanisms of miRNAs involvement in the heat stress response in rice.
Enhanced clinical pharmacy service targeting tools: risk‐predictive algorithms
Authors: El Hajji Feras W. D. , Scullin Claire , Scott Michael G. , McElnay James C. 
Published: December 2014

AbstractRationale, aims and objectivesThis study aimed to determine the value of using a mix of clinical pharmacy data and routine hospital admission spell data in the development of predictive algorithms. Exploration of risk factors in hospitalized patients, together with the targeting strategies devised, will enable the prioritization of clinical pharmacy services to optimize patient outcomes.MethodsPredictive algorithms were developed using a number of detailed steps using a 75% sample of integrated medicines management (IMM) patients, and validated using the remaining 25%. IMM patients receive targeted clinical pharmacy input throughout their hospital stay. The algorithms were applied to the validation sample, and predicted risk probability was generated for each patient from the coefficients. Risk threshold for the algorithms were determined by identifying the cut‐off points of risk scores at which the algorithm would have the highest discriminative performance. Clinical pharmacy staffing levels were obtained from the pharmacy department staffing database.ResultsNumbers of previous emergency admissions and admission medicines together with age‐adjusted co‐morbidity and diuretic receipt formed a 12‐month post‐discharge and/or readmission risk algorithm. Age‐adjusted co‐morbidity proved to be the best index to predict mortality. Increased numbers of clinical pharmacy staff at ward level was correlated with a reduction in risk‐adjusted mortality index (RAMI).ConclusionsAlgorithms created were valid in predicting risk of in‐hospital and post‐discharge mortality and risk of hospital readmission 3, 6 and 12 months post‐discharge. The provision of ward‐based clinical pharmacy services is a key component to reducing RAMI and enabling the full benefits of pharmacy input to patient care to be realized.
A feasibility study of behavioural activation for depressive symptoms in adults with intellectual disabilities
Authors: Jahoda A. , Melville C. A. , Pert C. , Cooper S.‐A. , Lynn H. , Williams C. , Davidson C. 
Published: December 2014

AbstractBackgroundImportant work has been carried out adapting cognitive behavioural therapy for people with intellectual disabilities. However, there is a lack of alternative psychological therapies available for people with intellectual disabilities and emotional difficulties. Behavioural activation for depression is less reliant on verbal communication and focuses on increasing purposeful activity and reducing avoidance.MethodThis feasibility study involved the development and piloting of an adapted manual of behavioural activation for people with intellectual disabilities. The intervention consisted of 10–12 sessions and a key adaptation was that the therapist worked with the clients alongside a significant other in their life, either a paid carer or family member. Baseline, post‐intervention (3 months after entering the study) and 6‐month quantitative follow‐up data were obtained. Primary outcome data were gathered, concerning depressive symptoms, participants' levels of activity and general well‐being.ResultsTwenty‐three adults with intellectual disabilities with symptoms of depression were recruited from specialist health services. In terms of acceptability, the behavioural activation intervention was well received and only two individuals dropped out, with a further two lost to follow‐up. The main measures of depression appeared to be sensitive to change. Pre‐ to post‐intervention data showed a significant reduction in self‐report of depressive symptoms with a strong effect size (r = 0.78), that was maintained at follow‐up (r = 0.86). Positive change was also obtained for informant reports of depressive symptoms from pre‐ to post‐intervention, with a strong effect size (r = 0.7). Once again, this positive change was maintained at follow‐up (r = 0.72).ConclusionsThe study suggested that behavioural activation may be a feasible and worthwhile approach to tackling depression in people with intellectual disabilities. However, a randomised controlled trial would be required to establish its effectiveness, with more sensitive measurement of change in activity.
Development of the human infrahepatic inferior caval and azygos venous systems
Authors: Hikspoors Jill P. J. M. , Soffers Jelly H. M. , Mekonen Hayelom K. , Cornillie Pieter , Köhler S. Eleonore , Lamers Wouter H. 
Published: December 2014

AbstractDifferences in opinion regarding the development of the infrahepatic inferior caval and azygos venous systems in mammals centre on the contributions of ‘caudal cardinal’, ‘subcardinal’, ‘supracardinal’, ‘medial and lateral sympathetic line’ and ‘sacrocardinal’ veins. The disagreements appear to arise from the use of topographical position rather than developmental origin as criterion to define separate venous systems. We reinvestigated the issue in a closely spaced series of human embryos between 4 and 10 weeks of development. Structures were visualized with the Amira® reconstruction and Cinema4D® remodelling software. The vertebral level and neighbouring structures were used as topographic landmarks. The main results were that the caudal cardinal veins extended caudally from the common cardinal vein between CS11 and CS15, followed by the development of the subcardinal veins as a plexus sprouting ventrally from the caudal cardinal veins. The caudal cardinal veins adapted their course from lateral to medial relative to the laterally expanding lungs, adrenal glands, definitive kidneys, sympathetic trunk and umbilical arteries between CS15 and CS18, and then became interrupted in the part overlaying the regressing mesonephroi (Th12‐L3). The caudal part of the left caudal cardinal vein then also regressed. The infrarenal part of the inferior caval vein originated from the right caudal cardinal vein, while the renal part originated from subcardinal veins. The azygos veins developed from the remaining cranial part of the caudal cardinal veins. Our data show that all parts of the inferior caval and azygos venous systems developed directly from the caudal cardinal veins or from a plexus sprouting from these veins.
Perivascular Enhancement in a Patient with Neuromyelitis Optica Spectrum Disease during an Optic Neuritis Attack
Authors: Pekcevik Yeliz , Izbudak Izlem 
Published: December 2014

ABSTRACTWe present a case with neuromyelitis optica spectrum disease (NMOSD) who had perivascular enhancement during an optic neuritis attack. Cloud‐like enhancement, pencil‐thin enhancement, and leptomeningeal enhancement have been defined as specific enhancement patterns to neuromyelitis optica (NMO). Perivascular enhancement has not been described before in NMO/NMOSD. This finding suggests that perivascular enhancement may also be seen in NMO/NMOSD patients.
Prevalence of human papillomaviruses in the healthy oral mucosa of women with high‐grade squamous intra‐epithelial lesion and of their partners as compared to healthy controls
Authors: Tatár Tímea Zsófia , Kis Andrea , Szabó Éva , Czompa Levente , Boda Róbert , Tar Ildikó , Szarka Krisztina 
Published: December 2014

Oral human papillomavirus (HPV) carriage rates were investigated in relation to genital HPV carriage in women with HPV‐associated cervical lesions and male partner of such women, including several couples, in comparison with healthy individuals. Buccal and lingual mucosa of 60 males and 149 females with healthy oral mucosa and without known genital lesion, genital and oral mucosa of further 40 females with cervical high‐grade squamous intraepithelial lesion (HSIL) and 34 male sexual partners of women with HSIL (including 20 couples) were sampled. HPV DNA was detected using MY/GP PCR. Genotype was determined by sequencing or restriction fragment length polymorphism. Virus copy numbers were determined by real‐time PCR. Overall, oral HPV carriage rate was 5.7% (12/209) in healthy individuals; average copy number was 5.8 × 102 copies/1 μg DNA; male and female rates were comparable. Oral carriage in women with HSIL was significantly higher, 20.0% (8/40, P = 0.003); males with partners with HSIL showed a carriage rate of 17.6% (6/34), copy numbers were similar to the healthy controls. In contrast, genital carriage rate (52.9%, 18/34 vs. 82.5%, 33/40; P = 0.006) and average copy number were lower in males (5.0 × 105 vs. 7.8 × 105 copies/1 μg DNA; P = 0.01). Oral copy numbers in these groups and in healthy individuals were comparable. High‐risk genotypes were dominant; couples usually had the same genotype in the genital sample. In conclusion, genital HPV carriage is a risk factor of oral carriage for the individual or for the sexual partner, but alone is not sufficient to produce an oral HPV infection in most cases.
Cognitive function and endogenous cytokine levels in children with chronic hepatitis C
Authors: Abu Faddan N. H. , Shehata G. A. , Abd Elhafeez H. A. , Mohamed A. O. , Hassan H. S. , Abd El Sameea F. 
Published: December 2014

SummaryLittle is known about how hepatitis C (HCV) infection affects cognitive function in children. The aim of the study was to assess the impact of HCV infection on cognitive function of children with normal liver functions and their relationships to endogenous IFN‐α, IL‐6 and TNF‐α. IFN‐α, IL‐6 and TNF‐α were measured and the Arabic version of the Stanford–Binet test used to assess cognitive functions in 35 children with HCV infection and 23 controls. Serum levels of IL‐6 and IFN‐α were significantly higher in patients compared to controls. There was a significant effect on vocabulary, comprehension, and abstract visual reasoning, quantitative reasoning and bead memory tests, as well as total short‐term memory and intelligence quotient in patients compared to controls. There was a significant positive correlation between IFN‐α and IL‐6. Also there were significant negative correlations between IFN‐α and Abstract visual reasoning test, Quantitative reasoning test, Bead memory test, Total short‐term memory and Intelligence quotient; and between IL‐6 and Abstract visual reasoning test, Quantitative reasoning test and Intelligence quotient. There was no significant correlation between TNF‐α and any of the cognitive functions. Cytokine levels were not related to demographic characteristics of the patients or viral load (PCR). Children with chronic hepatitis C infection in its early stages showed signs of cognitive impairment, with the memory tasks being mostly affected. There was a significant correlation between endogenous cytokines and cognitive impairment in these children. Further studies are needed to define the effect of successful antiviral treatment.
Non‐invasive score system for fibrosis in chronic hepatitis: proposal for a model based on biochemical, FibroScan and ultrasound data
Authors: Gaia Silvia , Campion Daniela , Evangelista Andrea , Spandre Maurizio , Cosso Loretta , Brunello Franco , Ciccone Giovannino , Bugianesi Elisabetta , Rizzetto Mario 
Published: December 2014

AbstractBackground & AimsWe elaborate a non‐invasive score system for liver fibrosis (NISF), exploring its diagnostic performance and comparing its accuracy to FibroScan in patients with chronic viral hepatitis (CH) and non‐alcoholic fatty liver disease (NAFLD).MethodsClinical, biochemical, elastographic and ultrasound parameters derived from patients with CH (n = 83) or NAFLD (n = 58), undergoing liver biopsy for fibrosis assessment, were prospectively collected as potential predictors of fibrosis. Each parameter was evaluated for its correlation with the liver biopsy (Gold Standard). Candidate predictors with good interobserver agreement and correlation with histological stages were combined into two algorithms (NISF) to predict fibrosis in chronic viral hepatitis and NAFLD.ResultsThe CH‐NISF included six parameters: bluntness of liver edges, irregularity of left lobe surface, diameter of segment 4, liver stiffness measurement, platelet count and ALT values. The ability of the model to discriminate F3–F4 vs F0–F1 stages and F2 vs F0‐F1 was high (AUROC of 0.95 and 0.83 respectively) and better than FibroScan alone, especially in intermediate stages (F2 vs F0‐F1), AUROC 0.83 vs 0.57 (P = 0.003). The resulting algorithm is available as mathematical formula, nomogram or free online link. [http://health.mafservizi.it/NISF_Calculator/liver.htm]The NAFLD‐NISF included liver stiffness, platelet count and AST levels, had good ability to discriminate F0–F1 vs F2–F3–F4 stages (AUROC 0.86), however, not significantly higher than FibroScan.ConclusionsCH‐NISF can be proposed as preliminary and easily available staging tool, superior to FibroScan alone in predicting histological fibrosis, especially in intermediate stages. Further validations are needed to improve NISF accuracy in NAFLD.
Internet addiction and physical and psychosocial behavior problems among rural secondary school students
Authors: Gür Kamer , Yurt Seher , Bulduk Serap , Atagöz Sinem 
Published: December 2014

AbstractThe aim of this study was to determine secondary school students' levels of Internet addiction and the physical and psychosocial behavior problems they face while using the Internet. This descriptive study was conducted in three state secondary schools in a rural area in the western part of Turkey. This study's sample consisted of 549 students who agreed to participate, with the consent of their families, and who had an Internet connection at home. The data were evaluated using t‐tests and variance analyses. In this study the students' score of Internet addiction was at medium level (mean addiction score 44.51 ± 17.90). There were significant differences between the students' Internet addiction scores and the presence of physical behavior problems (going to bed late, skipping meals, eating meals in front of the computer) and psychosocial behavior problems (suffering from conditions such as restlessness, anger, heart palpitations, or tremors when they could not connect to the Internet, decreased relationships with family and friends, feelings of anger, arguing with parents, and finding life boring and empty without an Internet connection).
A comparison of methods for the detection of the r′s haplotype
Authors: Moulds Joann M. , Noumsi Ghislain T. , Billingsley Katrina L. 
Published: December 2014

BackgroundThe r′s haplotype is found in 5% to 15% of individuals of African descent. Persons with this haplotype have a partial C antigen and weakened e and can produce anti‐C or other “e‐like” alloantibodies. Thus, for these chronically transfused patients, accurate detection of the r′s haplotype is important for selection of matched units.Study Design and MethodsAfrican‐American donors were genotyped using the human erythrocyte antigen (HEA) microarray. Samples (n = 125) identified as “possible r′s” were then tested by IDCORE XT and RHD and RHCE microarrays. DNA sequencing was used to resolve discordant samples. The genotyping results were compared to serologic testing using a monoclonal anti‐C reagent (Clone MS24).ResultsOf the 125 possible r′s samples identified by HEA, only 94 (75%) were confirmed by both RHD and RHCE microarrays. The IDCORE XT accurately detected 93 of 94 (99%) of the confirmed r′s and had no false positives. DNA sequencing of the one discordant sample revealed the presence of a compound heterozygote with RHD* DIII.4/RHCE*ceVS.02 as one haplotype and r′s Type 2 as the other. The 31 unconfirmed r′s samples carried RHCE*ceVS.03 not linked to the hybrid RHD‐CE‐D. This occurred most often with RHD*DIIIa (55%) or RHD*01 (19%) and rarely with DIII.4, DIII.6, DAU3, and weak D Type 14. Serologic testing with anti‐C gave 100% concordance with the r′s samples.ConclusionsThe predominant type of r′s in African‐Americans is Type 1, which can be detected either by a reagent anti‐C containing Clone MS24 or by IDCORE XT. However, serology cannot differentiate between a normal C allele and the hybrid.