bluuebunny/crossref_metadata_2025_split huggingface dataset:
Psychosocial Impairment and Lower Quality of Life among Childhood Cancer Survivors in Egypt, Single Institution Experince.
Authors: Elsamahy Mona , Abdelmonem Ashraf , Abdelrahman Shahinda 
Published: October 2019

Abstract
Survival itself has, until recently, been the marker of successful cancer therapy, but now more attention is being focused on the long-term effects of cancer therapy and the quality of life (QOL)of the survivors.
OBJECTIVE: To assess health related quality of life and behavior and emotional problems among childhood cancer survivors at Ain Shams Pediatric Oncology Clinic, Cairo, Egypt.
DESIGN: This study was conducted on 30 childhood cancer survivors attending the cancer survivors’ clinic at Ain Sham Children’s University Hospital in the period of October 2004–April 2005. The PedsQL™ 4.0 Generic Core Scales (physical, emotional, social and, school functioning) translated into Arabic language has been utilized. Parallel child self-report and parent proxy-report questionnaire formats have been used. Items were reverse-scored and linearly transformed to a 0–100 scale, so that higher scores indicate better QOL. Assessment of behavioral and emotional disturbance was performed using The Child Behavior Checklist (CBCL)
Results: Age range 6–16 years with a mean age of 10.7±2.9 years, 18 (60%) were males and 12(40%) were females. Seventeen patients (56.6%) were acute leukemia survivors and 10(43.4%) lymphomas and solid tumors. There was statistically significant (p<0.001) decrease in the overall generic PedsQL in cancer survivors (mean 67±11.6) compared to normal children (mean 83.9±12.5) with school functioning area being the most affected (score 47.5±13). ALL survivors had significantly lower mean QOL (62.5±11.8) compared to other cancer survivors (72.8±8.8) (p<0.05). Gender (females) and CNS-directed therapy were risk factors for poorer QOL. Strong agreement between parents and their children QOL rating was seen in most of the QOL domains {overall QOL (p=0.001) physical well being (p=0.04), emotional feelings (p=0.0004), and social interaction (p=0.003) with the strongest correlation in the school domain (p=0.000004)}. Fifty three percent of the survivors showed clinical range of social incompetence with survivors who were diagnosed before the age of 3 were less socially competent than those who were diagnosed after this age (p<0.05), 63% expressed Internalizing behavioral problems and while 23% had Externalizing problems.
CONCLUSION: This results demonstrate Chidhood cancer survivors are at significant risk of poor psychosocial functioning and QOL.
Internet Use by Patients with Lymphoma and Caregivers.
Authors: Garcia-Nieto Antonia A. , Duran Soledad S. , Fernandez-Valle Maria Carmen M.C. , Rios Eduardo E. , Rodriguez Juan Nicolas J.N. , Martin-Reina Maria Vicencia M.V. , Duran Jose J. , Bailen Alicia A. , Lopez Pilar P. , Almagro Manuel M. , Capote Francisco Javier F.J. 
Published: October 2019

Abstract
The Internet is changing the way that people learn about health and illness. At present do not exist data of the use of Internet by patients of lymphoma and her caregivers in Spain.
OBJECTIVE: To investigate the distribution and patterns of Internet use by patients with lymphoma and her caregivers.
PATIENTS AND METHODS: 585 subjects (258 patients, 264 relatives and 63 health professionals), 228 male and 357 female, they have responded a questionnaire on diverse aspects of the use of Internet.
RESULTS: Two hundred fifty (42,7%) subjects use Internet, although only 27% make to obtain data on lymphoma. With respect to the group of patients 31% recognize to use Internet, but only the 23,3% do it by questions related to their disease. The main reasons for Internet use are to obtain information about treatments (74.7%) or second opinion medical (9.3%). The 77,6% have been using Internet for more than 3 years; the 47,2% have university studies and the 58,4% have between 33–50 years. Mainly the information search is made in Spanish language and through the Google finder. They consider that Information on lymphoma is acceptable (44.9%) or of enough quality (43.7%), trustworthy (50.6%) or of enough reliability (33.5%) and useful (45.6%) or quite useful (37.3%).
COMMENTARIES: This study contributes data on the use of Internet by patients with lymphoma and her caregivers in Spain. Oncologists should be familiar with this important resource to help patients access appropriate material.
Therapeutic Dilemma of Chemotherapy Dosing in Morbidly Obese Patient with AML: A Case Report and a Review of the Literature.
Authors: Hussain Sakeer , Glass Jonathan , Ballester Oscar 
Published: October 2019

Abstract
Obesity is a common and increasing problem affecting the developed world. There is no consensus on a standard approach to chemotherapy dosing has been adopted in obese patients. We present a 25 year old white male with worsening fatigue, dyspnea and recurrent cellulites. Physical examination was significant for morbid obesity of 616 lb (BMI 86.4 and BSA 3.43m2). Initial laboratory values were WBC 0.870/ml (3400–9200/ml), Hb 6.5g/dL (11.5–15.4g/dl), platelet count of 35,000/mm3 (130000–400000/mm3), MCV 91 mm3 (80–100mm3). Basic metabolic and coagulation panel was normal except elevated D-dimer and LDH. Peripheral smear consistent with hypochromic normocytic RBC, occasional schistocytes, premature myeloid cells, myeloid blasts 26% with granularity of cytoplasm and a few Auer rods were evident. Bone marrow biopsy was consistent with acute myeloid leukemia. Flowcytometry was positive for CD33, CD 38 and myeloperoxidase. Lymphoid antigens were negative. Cytogenetic analysis revealed normal karyotype and negative for t (15; 17). Patient was treated with standard induction regimen with cytarabine 243mg (100mg/m2) and daunorubicin 109mg (45mg/m2). Chemotherapy dosing was done according to the adjusted body weight (BSA 2.43 m2). Day 14 bone marrow was consistent with significant disease. Reinduction with high dose cytarabine 14000mg (3000mg/m2) had no response. Patient was then received gemtuzumab ozagomycin 22mg (9mg/m2) on day 1 and 14. Bone marrow analysis 30 days after the treatment was consistent with remission. Interestingly patient developed little adverse effect from the initial induction chemotherapy. Hospital course was complicated with Clostridium difficile colitis and neutropenic fever which was treated with antibiotics and voricanazole. Voricanazole dosing was done according to the actual body weight (1000mg IV twice daily). The peak and trough levels were within normal range. Failed response to initial induction treatment could be due to refractory disease or inadequate dosing of chemotherapy in this patient. BSA has been used to calculate the dose in anticancer therapy since 1950s. Experimental studies have demonstrated BSA based dosing failed to standardize the variation in pharmacokinetics of cytotoxic drugs. In obese cancer patients, the pharmacokinetics of the drug demonstrated a prolonged elimination time for several agents. Risk of both under dosing and overdosing can have detrimental affect outcome in obese patients. Prospective studies of chemotherapy pharmacokinetics are needed to address the issue of optimal chemotherapy dosing in obese population.
Can Exposure to Jet Fumes Lead to Acute Leukemia?.
Authors: Khalil Maged F. , Sangal Ashish , Arora Alka , Niak Seema , He Zili , Steier William , Kalavar Madhumati 
Published: October 2019

Abstract
Introduction:
AML/MDS is usually diagnosed in older adults with median age of 64 in patients at time of diagnosis, after occupational exposure to organic solvents, such as benzene, or previous therapeutic exposure to alkylating agents, topoisomerase inhibitors, or ionizing radiation.
We are presenting a case of AML/MDS in a young female without previous history of exposure to alkylating agents or ionizing radiation, but with history of exposure to jet fumes.
Case Report:
This is a 30-year old Carribean woman, chronic smoker, ethanol user, employed for eight years at the airport, working on the ground with heavy direct exposure to jet fumes, who presented with 2 weeks of progressive dyspnea, fatigue and bone pains. She was found to have pancytopenia, hemoglobin 2.8 gm/dL, platelets 37,000/mL, and neutrophils 1100/mL. Peripheral smear showed many nucleated red blood cells and blasts. Bone marrow aspiration was “dry” and bone biopsy revealed hypercellularity with dysplastic changes in erythrocyte, granulocyte and megakaryocytic lineages with 46% blasts. Flow cytometry of peripheral blood showed positivity for CD13, CD33, CD34, and CD117 and HLA-DR with complex cytogenetics showing deletions involving chromosomes 5q, 7q, 12p, 20q and loss of chromosome 17. Fluorescent in situ hybridization (FISH) studies were negative for t(15,17), MLL, t(8,21), inv(16) seen in classical de novo AML. FISH also did not show abnormalities in the probe regions 5q31, 7q31, 8cen and 20q12 of chromosomes 5, 7, 8 and 20 classically seen in de novo MDS. The blast cell morphology suggested acute myelocytic leukemia on a background of myelodysplasia. Precise FAB subtype was not possible in the absence of special stains like myeloperoxidase, and specific and non-specific esterase stains. The patient was treated with two induction courses of cytosine arabinoside and idarubicin. With persistence of 4.5% blasts on the peripheral blood and severe bone marrow aplasia, she was referred for allogeneic stem cell transplantation, in view of failed induction remission and complex cytogenetics at presentation.
Conclusion:
Case-control studies of leukemia demonstrated only slight increase in risk of disease after many years of occupational or chemical exposures. More studies to investigate leukemia incidence in airport employees, or even communities near airports are needed.
Effect of Mild Hemophilia A on Quality of Life Using the SF-36.
Authors: Walsh Meghan C. , Macgregor David , Barrett Brendan , Stuckless Susan , Kawaja Marc , Scully Mary-Frances 
Published: October 2019

Abstract
Using a cross-sectional study design we determined the impact of mild hemophilia A on quality of life. Adult males (n=47) with the same mutation (Val2016ala) were compared to unaffected adult males (n=32). The Short Form-36 (SF-36) and the Health Assessment Questionnaire (HAQ) were used to measure quality of life and physical function. Measures included bleeding history, Body Mass Index (BMI), age, and viral status. Using the SF-36, mild hemophilia was found to be statistically and negatively associated with quality of life in both the general health scale (p<0.039) and role emotional (p<0.005) dimensions. Age (>40) was associated with lower quality of life in four of eight dimensions namely, physical functioning (p<0.023), bodily pain (p<0.049), general health scale (p<0.034) and role emotional (p<0.025). A positive viral status of hepatitis (HCV) was found to be negatively associated with bodily pain (p<0.044) in affected males. Finally, those who experienced bleeding episodes (>2 in previous 5 years) were also associated with lower quality of life in social functioning (p<0.02) and the health transition scale (p<0.043). Additionally, a greater than 5-point difference was found in affected males in five out of eight dimensions when compared to the Canadian male population. No significant differences were found between groups from the HAQ scores. Mild hemophilia A, age, bleeding frequency and a positive hepatitis status were found to negatively affect quality of life in our study.
Twenty Years of Follow-Up among Survivors of Childhood and Young Adult Acute Myeloid Leukemia (AML): A Report from the Childhood Cancer Survivor Study (CCSS).
Authors: Mulrooney Daniel A. , Dover Douglas C. , Yasui Yutaka , Ness Kirsten K. , Mertens Ann C. , Neglia Joseph P. , Sklar Charles A. , Robison Leslie L. , Davies Stella M. 
Published: October 2019

Abstract
Survival rates for childhood AML continue to improve. Limited data exist on the comprehensive assessment of late medical and social effects experienced by these aggressively treated individuals. This analysis includes 272 5-yr survivors of AML participating in the CCSS diagnosed ≤ age 21, between 1970–1986. AML survivors who received a blood or marrow transplant are excluded from the current analysis. Comparisons among treatment groups and to a sibling control group are age and gender adjusted. Survivors (55% female) were on average 7 yrs old at dx and 28 yrs at follow-up, 56% received chemotherapy only, 34% chemotherapy/RT. Average follow-up was 22.6 yrs (16.1–33.5). Among these 5-yr survivors, overall survival was 97% (95% CI, 94–98%) at 10 yrs and 94% (95% CI, 92–97%) at 20 yrs. Six individuals reported 8 recurrences a mean of 11.1 yrs (5.6–16.6) from diagnosis, 2 died from relapse, 1 from congestive heart failure (CHF), and 1 from a myocardial infarction (MI). All cause standardized mortality ratio was 4.7 (95% CI 2.8–7.5). Cumulative incidence of recurrent AML at 10 and 20 years was 1.8% (95% CI 0.2–3.4%) and 3.7% (95% CI 1.4–5.9%), respectively. Eight survivors reported 10 subsequent malignant neoplasms (SMN) (5 breast cancers, 3 CNS tumors, 1 ovarian tumor, 1 salivary gland tumor) a mean of 18.7 yrs (9.2–26.4) from diagnosis, 3 with a history of RT exposure. SMN cumulative incidence at 20 yrs was 1.6% (95% CI 0.02–3.3%) with a standardized incidence ratio of 3.2 (95% CI 1.4–6.0). Six cardiac events (5 CHF and 1 MI) occurred a mean of 16.4 yrs (12.8–18.4) from diagnosis, 20-yr cumulative incidence 2.4% (95% CI 0.5–4.4%). Among those aged 25 yrs or more, marriage rates were similar among AML survivors and the general U.S. population (59%), but lower compared to siblings (69%) (p<0.01). College graduation rates were lower among survivors compared to siblings, but higher than in the general population (42% vs. 52% vs. 34%, respectively, p<0.01). No significant difference in graduation rates was found among those treated with or without CNS directed RT (p=0.9). All survivors and siblings were employed (100%) and most had health insurance (93% vs. 90%). Long-term survival from childhood AML greater than 5 yrs from diagnosis is favorable. Late occurring medical events remain concerning. Marriage and education rates may be lower than expected within individual family units; yet not significantly different from the U.S. population.
In Chronic Lymphocytic Leukemia, Zap70 Identifies a Survival Pathway Signal Cascade Involving p85 PI-3-Kinase, CrkL, and Cbl with Syk En Route to JNK1 and bcl-2.
Authors: Hartman Amy D. , Wilson-Weekes Annique , Cripe Larry D. , Bennett Brydon , Friedman Glenn , Worland Peter , Druker Brian , Ren Shuyue , Skorski Tomasz , Boswell H. Scott 
Published: October 2019

Abstract
Bcl-2 expression is high in CLL and this appears to participate in disease progression. Zap70 expression is a poor prognostic marker for the disease whose function may be to contribute in a pathway promoting heightened bcl-2 levels. We recently identified a pathway to heightened bcl-2 transcriptional expression involving the bcl-2 promoter CRE (TGACGTCA) element and c-jun/ATF-2 downstream of JNK1. Indeed, JNK activation is a known survival pathway in B cell lymphoma (Gururajan, et al. Blood106: 1382, 2005). We confirmed a strict correspondence of Zap70 expression with JNK activity in CLL cell lysates by immunoblot identification of Zap70 and of phospho-S73-c-jun; and we found bcl-2 levels to be high in cells with Zap70 and JNK activity. We uncovered an adaptor/scaffolding pathway physically linking these mediators. By immunoprecipitation from lysates in a series of Zap70+ CLL’s we found JNK1 to coimmunoprecipitate with CrkL, a JNK1 scaffolding that binds by its SH3 domain to polyproline sequences of JNK1, and with p85 and Cbl and Zap70 as well as Syk. By contrast, using GST-p85 as bait in pull-down experiments, a selective interaction was found for Zap70 with p85, particularly of the p85 C-terminal SH2 domain, in lysates with heavy Y319 phosphorylation of Zap70. In parallel pull-downs with such lysates, exclusion of Cbl N-terminal TKB domain binding from Zap70 but not Syk was observed. Zap70+ CLL cell growth stimulated by the cytokine April was inhibited by the novel JNK inhibitor, CC-401, 5 uM, without significant effect on inhibition of NFkB or AKT activations. Such inhibition of JNK1 also led to upregulation of bim mRNA and downregulation of bcl-2 mRNA, and modest-to-moderate bcl-2 protein downregulation, in cells whose nuclear proteins contained abundant phospho-ATF2/c-jun binding activity for the bcl-2 promoter CRE site indicative of a transcriptional connection. Thus, Zap70 represents a point of origin in CLL cells for parallel pathways of Zap70 and Syk signaling to JNK1, involving specific complexes of Zap70 and Syk with p85/CrkL/JNK1(Cbl), respectively. These dual routes to JNK activation promote cell survival, in part, through the ability of JNK to contribute in a bcl-2 regulatory mechanism.
The IL-2 Induced De-Ubiquitinating Enzyme, DUB-2, Is a Nuclear-Cytoplasmic Shuttle Which Requires Catalytic Activity for Nuclear Localization.
Authors: Galardy Paul J. , D’Andrea Alan D. , Ploegh Hidde L. 
Published: October 2019

Abstract
DUB-2 is a T-cell specific de-ubiquitinating enzyme whose expression is induced by IL-2. Expression of DUB-2 results in prolonged STAT5 phosphorylation, enhanced IL-2 induced gene expression, and resistance to apoptosis resulting from cytokine withdrawal. The molecular basis of DUB-2s effects, however, is not understood. In order to better understand the role of DUB-2 in the IL-2 response, we performed a systematic analysis of DUB-2 catalytic activity, subcellular localization, and domain organization. Subcellular localization of DUB-2 was examined using a C-terminal DUB-2-Cherry (enhanced red fluorescence) fusion and live-cell imaging. When expressed in HeLa cells, wild-type DUB-2-Cherry is predominantly localized to the cytoplasm, although 8–10% of cells have a strong nuclear accumulation. Strikingly, the nuclear localization is entirely eliminated by a mutation in the catalytic cysteine (c60s). This effect on DUB-2s localization is not due to changes in cell cycle progression, as we observe identical cell cycle profiles (DNA content) in wt or c60s expressing cells. Conversely, enhanced DUB-2 nuclear localization is seen following nocodazole-induced cell cycle synchronization and with mutant DUB-2-Cherry fusions lacking a duplicated 8-residue sequence within the C-terminal domain.
We next analyzed the catalytic activity of DUB-2 toward ubiquitin and other ubiquitin-like (UbL) molecules using a series of semi-synthetic activity-based probes. These probes consist of full-length Ub or UbL molecules equipped with a C-terminal electrophilic group. These probes act as suicide substrates, forming a covalent bond with the active site cysteine of catalytically active (but not inactive) Ub(L) isopeptidases. Unexpectedly, DUB-2 forms adducts not only with the Ub-based probe, but also the probe derivative of the UbL molecule ISG15, which suggests that it has dual-specificity. The activity towards Ub and ISG15 is abrogated by a mutation in the catalytic cysteine (c60s) of DUB-2, but is not affected by deletions of the poly-lysine or hypervariable domains.
Taken together, these results suggest that DUB-2 is a bi-specific (Ub and ISG15) isopeptidase which shuttles between the cytoplasm and the nucleus in a manner dependent on its catalytic activity. This work, and the ultimate elucidation of the molecular target of DUB-2, will further increase our understanding of DUB-2’s role in IL-2-dependent T-cell proliferation and immunologic tolerance.
Effects of Renal Impairment on the Pharmacology of Rivaroxaban (BAY 59-7939) - An Oral, Direct, Factor Xa Inhibitor.
Authors: Halabi Atef , Maatouk Haidar , Klause Norbert , Lufft Volkmar , Kubitza Dagmar , Zuehlsdorf Michael , Becka Michael , Mueck Wolfgang , Schäfers Rafael , Wand Dominic , Philipp Thomas , Bruck Heike 
Published: October 2019

Abstract
Rivaroxaban (BAY 59-7939) is an oral, direct Factor Xa (FXa) inhibitor in advanced clinical development for the prevention and treatment of thromboembolic disorders. It has predictable pharmacokinetics and pharmacodynamics in healthy subjects. Approximately 30% of rivaroxaban is excreted unchanged in the urine; therefore, renal excretion is an important route of elimination. This multicenter study was performed to evaluate the effect of renal impairment on the tolerability, pharmacokinetics, and pharmacodynamics of a single oral 10 mg dose of rivaroxaban. Subjects (N=32) were allocated to one of four groups (matched by age and gender), based on calculated creatinine clearance (CrCL): ≥80 mL/min (control); 50–79 mL/min (mild impairment); 30–49 mL/min (moderate impairment); and <30 mL/min (severe impairment). Rivaroxaban was well tolerated; treatment-emergent adverse events occurred in 62.5% of control subjects, and 12.5%, 12.5%, and 37.5% of those with mild, moderate, and severe renal impairment, respectively. All adverse events were mild to moderate in severity, and resolved by the end of the study. Decreased CrCL led to increased rivaroxaban plasma concentrations: AUC was 44%, 52%, and 64% higher in subjects with mild, moderate, and severe renal impairment, respectively, compared with control subjects (p<0.05); Cmax was relatively unaffected, and tmax was delayed in subjects with CrCL <50 mL/min (3 hours vs 2 hours for control). Renal clearance of rivaroxaban decreased with decreasing renal function; 29% of rivaroxaban was excreted via the urine in control subjects, compared with 20%, 13%, and 10% in those with mild, moderate, and severe renal impairment, respectively. The pharmacodynamic effects of rivaroxaban (inhibition of FXa activity and prolongation of prothrombin time [PT]) were increased with decreasing renal function. The AUC for inhibition of FXa activity increased by 50% (mild impairment), 86% (moderate impairment), and 100% (severe impairment) (p<0.01; Pearson’s correlation coefficient −0.49), and the AUC for prolongation of PT increased by 33%, 116%, and 144%, respectively (p<0.001; correlation −0.56), compared with control. The maximum effects (Emax) of rivaroxaban on inhibition of FXa activity or prolongation of PT did not differ to a relevant extent among the different groups. In conclusion, rivaroxaban plasma concentrations and, as a result, inhibition of FXa activity and prolongation of PT, are inversely correlated with CrCL. In phase II clinical studies of rivaroxaban, patients with mild or moderate renal impairment were included without dose adjustment. However, whether dose adjustment is necessary in patients with renal impairment will require investigation in future clinical trials.