bluuebunny/crossref_metadata_2025_split huggingface dataset:
Medication errors on oral chemotherapy in children with acute lymphoblastic leukemia in a developing country
Authors: Oberoi Sapna , Trehan Amita , Marwaha Ram Kumar 
Published: August 2014

BackgroundMedication errors occur universally. Inappropriate administration of chemotherapy drugs can have adverse effects in cancer patients. Our objective was to assess the rate and type of medication errors in children with acute lymphoblastic leukemia (ALL) receiving oral chemotherapy in outpatient setting.ProcedurePrescription and administration of oral chemotherapy drugs in children with ALL were evaluated prospectively to determine rate and type of medication errors. Errors were defined as prescription (physician) level or administration (patient) level errors.ResultsTwo hundred eighty‐nine drugs were prescribed to 121 patients. Medication errors occurred in 36 (12.5%) prescriptions; 21(7.3%) were administration errors, 13 (4.5%) were prescribing errors, and two errors occurred at both levels. Mercaptopurine (6‐MP) was significantly associated with higher rates of errors (Odds ratio [OR] = 2.1, 95% CI [confidence interval] 1–4.1) whereas lapses were less with dexamethasone (OR = 0.25, 95% CI 0.09–0.67). As a result of medication errors 28 (23.1%) patients received inappropriate doses. Twenty five (21%) patients received sub‐optimal doses whereas three got higher doses of chemotherapy. On univariate analysis, socioeconomic status, education status of the caregiver, 6‐MP and methotrexate were significantly associated with errors (P ≤ 0.05). On multivariate analysis, ≤ primary school education of the caregiver and prescription of methotrexate were independent predictors of errors.ConclusionsMedication errors affected nearly one fourth of the children receiving oral chemotherapy. Future studies are needed to look at effective interventions to avoid chemotherapy associated errors especially amongst the lower strata of society. Pediatr Blood Cancer 2014;61:2218–2222. © 2014 Wiley Periodicals, Inc.
Sequential and hierarchical chromosomal changes and chromosome instability are distinct features of high hyperdiploid pediatric acute lymphoblastic leukemia
Authors: Alpár Donát , Pajor Gábor , Varga Péter , Kajtár Béla , Pótó László , Mátics Róbert , Vojcek Ágnes , Ottoffy Gábor , Szuhai Károly , Pajor László 
Published: August 2014

BackgroundPathogenesis of the non‐random accumulation of extra chromosomes in the low and high hyperdiploid (HeL, HeH) pre‐B pediatric acute lymphoblastic leukemia (B‐pALL) is largely unknown, and has been clarified with respect only to tetrasomic chromosomes. We analyzed the hierarchy of changes in chromosome number and chromosomal instability, as well as clonal heterogeneity and evolution, in the untreated bone marrow cell samples from 214 B‐pALL patients.ProcedureApplying relocation, 2 × 4 color interphase fluorescence in situ hybridization was used to detect copy number alterations (CNAs) of the most commonly involved chromosomes, 4, 6, 10, 14, 17, 18, 21, and X. This approach allowed us to acquire a dataset correlated for all eight parameters.ResultsBased on chromosome number, an average of 6.9 and 10.2, whereas according to unique constellation 15.3 and 26.7 subclones could be identified in the HeL and HeH subgroups, respectively. Cluster analysis revealed the order of CNAs to chromosomes was highly conserved, and network analysis indicated changes in chromosome number were sequential for 80–90% of all numerical aberrations. Significant chromosome instability was revealed in both subgroups of leukemia.ConclusionsData generated using this new approach indicate that chromosomal instability, which causes heterogeneity in the subclonal landscape, and the sequential changes to chromosome numbers, are both determining factors in the pathomechanism of the hyperdiploid B‐pALL. These new observations could prompt research into the mitotic machinery of leukemic cells to identify new therapeutic targets for treating this disease. Pediatr Blood Cancer 2014;61:2208–2214. © 2014 Wiley Periodicals, Inc.
Reduced‐intensity conditioning for hematopoietic cell transplantation of chronic granulomatous disease
Authors: Oshrine Benjamin , Morsheimer Megan , Heimall Jennifer , Bunin Nancy 
Published: August 2014

AbstractHematopoietic cell transplantation (HCT) is the only available curative therapy for chronic granulomatous disease (CGD), but its use is limited by transplant‐related mortality (TRM) in patients who often come to transplant with existing infections or organ dysfunction. Reduction in the intensity of the preparative regimen mitigates these risks, but increases the potential for mixed donor‐recipient chimerism (MC) that may progress to graft loss. Recently a busulfan‐based reduced‐intensity conditioning (RIC) regimen has been described with excellent survival and little MC. We report our experience with a similar RIC regimen at our institution, demonstrating problems with donor chimerism and graft loss. Pediatr Blood Cancer 2015;62:359–361. © 2014 Wiley Periodicals, Inc.
Transient abnormal myelopoiesis of a newborn not associated with chromosome 21 abnormalities or GATA1 mutations
Authors: Nakashima Megan O. , Shetty Shashirekha , Chicka Michael , Flagg Aron , Eng Charis , Cotta Claudiu V. 
Published: August 2014

AbstractTransient abnormal myelopoiesis (TAM) is a disorder of Down syndrome newborns characterized by megakaryocytic blasts indistinguishable from acute myeloid leukemia (AML), which undergoes spontaneous remission. Acquired GATA1 mutations are present in blasts of both TAM and the subsequent AML which sometimes develops. We present a unique case of a newborn with leukemic megakaryoblasts indistinguishable from those of TAM who had neither extra material from chromosome 21 in the germline or blasts, nor evidence of GATA1 mutations. These findings suggest there are other genetic abnormalities that can lead to TAM besides GATA1 mutation in the setting of trisomy 21. Pediatr Blood Cancer 2015;62:353–355. © 2014 Wiley Periodicals, Inc.
Lung function at 6 and 18 months after preterm birth in relation to severity of bronchopulmonary dysplasia
Authors: Thunqvist Per , Gustafsson Per , Norman Mikael , Wickman Magnus , Hallberg Jenny 
Published: September 2014

SummaryMany preterm infants with bronchopulmonary dysplasia (BPD) demonstrate impaired lung function and respiratory symptoms during infancy. The relationships between initial BPD severity, lung function and respiratory morbidity are not fully understood. We aimed to investigate the association between BPD severity and subsequent lung function and whether lung function impairment is related to respiratory morbidity.Study design and methodsIn this longitudinal cohort study, 55 infants born preterm (23–30 weeks of gestation) with mild or moderate/severe BPD, based on oxygen requirement at 36 gestational weeks, were followed up at 6 and 18 months postnatal age. Respiratory symptoms, such as recurrent or chronic chough and wheeze, were noted and patient records were scrutinized. Lung function was assessed by passive lung mechanics, whole body plethysmography, and tidal and raised volume rapid thoraco‐abdominal compression techniques. Results were related to published normative values.ResultsBesides residual functional capacity (FRC) and respiratory system compliance (Cso) assessed at 18 months, all measures of lung function were significantly below normative values. Moderate/severe BPD differed significantly from mild BPD only with respect to reduced Cso. At follow‐up at 6 and 18 months, participants with respiratory symptoms showed lower; maximal forced expiratory flow at FRC (FRC) (P = 0.006, P = 0.001), forced mid‐expiratory flows (MEF50) (P = 0.006, P = 0.048), and Cso (P = 0.004, P = 0.015) as compared to participants without symptoms.ConclusionsIn the present study BPD severity did not predict lung function, but may be associated with impaired alveolarization, indicated by reduced Cso. Respiratory morbidity was associated with reduced airway function and respiratory compliance in infancy after preterm birth. Pediatr Pulmonol. 2015; 50:978–986. © 2014 Wiley Periodicals, Inc.
Clinical activity of enzalutamide in Docetaxel‐naïve and Docetaxel‐pretreated patients with metastatic castration‐resistant prostate cancer
Authors: Nadal Rosa , Zhang Zhe , Rahman Hibba , Schweizer Michael T. , Denmeade Samuel R. , Paller Channing J. , Carducci Michael A. , Eisenberger Mario A. , Antonarakis Emmanuel S. 
Published: August 2014

AbstractBACKGROUNDTwo randomized clinical trials have demonstrated a survival advantage with enzalutamide over placebo in both docetaxel (D)‐pretreated and D‐naïve metastatic castration‐resistant prostate cancer (mCRPC) patients. Cross‐resistance between androgen receptor‐directed therapies and taxanes has been suggested, possibly leading to lower efficacy of enzalutamide in the post‐D setting.METHODSWe aimed to examine the impact of prior D treatment on the clinical activity of enzalutamide in patients with mCRPC. We retrospectively reviewed an institutional database to identify men with mCRPC treated with standard‐of‐care enzalutamide. Patients were classified as D‐naïve or D‐pretreated. The efficacy end points were prostate‐specific antigen (PSA) response rates (≥ 50% PSA decline), time to PSA progression (TTPP) and clinical/radiographic progression‐free survival (PFS) in response to enzalutamide. Differences between groups (D‐naïve and D‐pretreated) were assessed by univariate and multivariable analyses using logistic and Cox regression models.RESULTSOne‐hundred‐seven (107) consecutive patients were included: 60 were D‐pretreated and 47 were D‐naïve. PSA responses were 43.2% in D‐naïve patients and 25.4% in D‐pretreated patients (P = 0.089). Median TTPP was 7.2 months (95% CI = 4.5 – 17.2) in the D‐naïve group versus 2.6 mo (95% CI = 1.9 – 3.5) in the D‐pretreated group (P < 0.0001). Median PFS was not reached for D‐naïve men and was 3.3 mo (95% CI = 2.5 – 4.8) for D‐pretreated men (P < 0.0001). After adjusting for potential confounders including prior abiraterone use, differences remained statistically significant for TTPP (HR = 2.32; 95% CI = 1.19 – 4.50; P = 0.013) and marginally significant for PFS (HR = 1.90; 95% CI = 0.94 – 3.84; P = 0.073) in multivariable analyses. Among patients who achieved a PSA response to enzalutamide (n = 34), results suggested a trend towards shorter duration of response in D‐pretreated patients.CONCLUSIONSThe clinical activity of enzalutamide appears to be blunted in patients who have previously received docetaxel chemotherapy. These results support the concept of cross‐resistance between these two agents. Prostate 74:1560–1568, 2014. © 2014 Wiley Periodicals, Inc.
Performance of serum prostate‐specific antigen isoform [‐2]proPSA (p2PSA) and the prostate health index (PHI) in a Chinese hospital‐based biopsy population
Authors: Na Rong , Ye Dingwei , Liu Fang , Chen Haitao , Qi Jun , Wu Yishuo , Zhang Guiming , Wang Meilin , Wang Wenying , Sun Jielin , Yu Guopeng , Zhu Yao , Ren Shancheng , Zheng S. Lilly , Jiang Haowen , Sun Yinghao , Ding Qiang , Xu Jianfeng 
Published: August 2014

BACKGROUNDThe use of serum [‐2]proPSA (p2PSA) and its derivative, the prostate health index (PHI), in detecting prostate cancer (PCa) have been consistently shown to have better performance than total prostate‐specific antigen (tPSA) in discriminating biopsy outcomes in western countries. However, little is known about their performance in Chinese men. Our objective is to test the performance of p2PSA and PHI and their added value to tPSA in discriminating biopsy outcomes in Chinese men.METHODSConsecutive patients who underwent prostate biopsy in three tertiary hospitals in Shanghai, China during 2012–2013 were recruited. Serum tPSA, free PSA (fPSA), and p2PSA were measured centrally using Beckman Coulter's DxI 800 Immunoassay System. The primary outcome is PCa and the secondary outcome is high‐grade PCa (Gleason Score of 4 + 3 or worse). Discriminative performance was assessed using the area under the receiver operating characteristic curve (AUC), detection rate and Decision Curve Analysis (DCA).RESULTSAmong 636 patients who underwent prostate biopsy, PHI was a significant predictor of biopsy outcomes, independent of other clinical variables. The AUC in discriminating PCa from non‐PCa was consistently higher for PHI than tPSA in the entire cohort (0.88 vs. 0.81) as well as in patients with tPSA at 2–10 ng/ml (0.73 vs. 0.53), at 10.1–20 ng/ml (0.81 vs. 0.58), and at tPSA >20 ng/ml (0.90 vs. 0.80). The differences were statistically significant in all comparisons, P < 0.01. To detect 90% of all PCa in the cohort, 362 and 457 patients would need to be biopsied based on PHI and tPSA cutoff, respectively, a 21% reduction for PHI. Similar results were found for discriminating high‐grade PCa.CONCLUSIONSPHI provides added value over tPSA in discriminating PCa and high‐grade PCa in patients who underwent prostate biopsy in China. Prostate 74:1569–1575, 2014. © 2014 Wiley Periodicals, Inc.
Pcgf6, a Polycomb Group Protein, Regulates Mesodermal Lineage Differentiation in Murine ESCs and Functions in iPS Reprogramming
Authors: Zdzieblo D. , Li X. , Lin Q. , Zenke M. , Illich D. J. , Becker M. , Müller Albrecht M. 
Published: September 2014

Abstract
Polycomb group (PcG) proteins comprise evolutionary conserved factors with essential functions for embryonic development and adult stem cells. PcG proteins constitute two main multiprotein polycomb repressive complexes (PRC1 and PRC2) that operate in a hierarchical manner to silence gene transcription. Functionally distinct PRC1 complexes are defined by Polycomb group RING finger protein (Pcgf) paralogs. So far, six Pcgf paralogs (Pcgf1–6) have been identified as defining components of different PCR1-type complexes. Paralog-specific functions are not well understood. Here, we show that Pcgf6 is the only Pcgf paralog with high expression in undifferentiated embryonic stem cells (ESCs). Upon differentiation Pcgf6 expression declines. Following Pcgf6 kockdown (KD) in ESCs, the expression of pluripotency genes decreased, while mesodermal- and spermatogenesis-specific genes were derepressed. Concomitantly with the elevated expression of mesodermal lineage markers, Pcgf6 KD ESCs showed increased hemangioblastic and hematopoietic activities upon differentiation suggesting a function of Pcgf6 in repressing mesodermal-specific lineage genes. Consistant with a role in pluripotency, Pcgf6 replaced Sox2 in the generation of germline-competent induced pluripotent stem (iPS) cells. Furthermore, Pcgf6 KD in mouse embryonic fibroblasts reduced the formation of ESC-like colonies in OSKM-driven reprogramming. Together, these analyses indicate that Pcgf6 is nonredundantly involved in maintaining the pluripotent nature of ESCs and it functions in iPS reprogramming. Stem Cells 2014;32:3112–3125
Human Embryonic Stem Cells Prevent T-Cell Activation by Suppressing Dendritic Cells Function via TGF-Beta Signaling Pathway
Authors: Leshansky Lucy , Aberdam Daniel , Itskovitz-Eldor Joseph , Berrih-Aknin Sonia 
Published: September 2014

Abstract
Human embryonic stem cells (hESCs) represent a potential source of transplantable cells for regenerative medicine, but development of teratoma even in syngenic recipients represents a critical obstacle to safe stem cell-based therapies. We hypothesized that hESCs escape the immune surveillance by regulating the environmental immune system. Using cocultures of hESCs with allogenic peripheral blood mononuclear cells, we demonstrated that hESCs prevent proliferation and activation of human CD4+ T lymphocytes, an effect dependent upon monocytes. Altered expression of key signaling molecules responsible for the crosstalk of monocytes with T cells was detected in the presence of hESCs. Analyzing the mechanism of action, we demonstrated that hESCs were able to downregulate intracellular glutathione levels in both monocytes and CD4+ cells by suppressing glutamate cysteine ligase expression and to alter MHCII and CD80 expression in monocytes. These effects were achieved at least partially via TGF-beta signaling, and both monocyte phenotype and GCLC expression were affected by Caspase-3 proteolytic activity. Altogether, our results demonstrate a novel immune-suppressive mechanism used by hESCs. Stem Cells 2014;32:3137–3149
Pluripotent Stem Cells Derived From Mouse Primordial Germ Cells by Small Molecule Compounds
Authors: Kimura Tohru , Kaga Yoshiaki , Sekita Yoichi , Fujikawa Keita , Nakatani Tsunetoshi , Odamoto Mika , Funaki Soichiro , Ikawa Masahito , Abe Kuniya , Nakano Toru 
Published: September 2014

Abstract
Primordial germ cells (PGCs) can give rise to pluripotent stem cells known as embryonic germ cells (EGCs) when cultured with basic fibroblast growth factor (bFGF), stem cell factor (SCF), and leukemia inhibitory factor. Somatic cells can give rise to induced pluripotent stem cells (iPSCs) by introduction of the reprogramming transcription factors Oct4, Sox2, and Klf4. The effects of Sox2 and Klf4 on somatic cell reprogramming can be reproduced using the small molecule compounds, transforming growth factor-β receptor (TGFβR) inhibitor and Kempaullone, respectively. Here we examined the effects of TGFβR inhibitor and Kempaullone on EGC derivation from PGCs. Treatment of PGCs with TGFβR inhibitor and/or Kempaullone generated pluripotent stem cells under standard embryonic stem cell (ESC) culture conditions without bFGF and SCF, which we termed induced EGCs (iEGCs). The derivation efficiency of iEGCs was dependent on the differentiation stage and sex. DNA methylation levels of imprinted genes in iEGCs were reduced, with the exception of the H19 gene. The promoters of genes involved in germline development were generally hypomethylated in PGCs, but three germline genes showed comparable DNA methylation levels among iEGs, ESCs, and iPSCs. These results show that PGCs can be reprogrammed into pluripotent state using small molecule compounds, and that DNA methylation of these germline genes is not maintained in iEGCs. Stem Cells 2015;33:45–55
Lineage Tracing of Stem and Progenitor Cells of the Murine Corneal Epithelium
Authors: Amitai-Lange Aya , Altshuler Anna , Bubley Jeffrey , Dbayat Noora , Tiosano Beatrice , Shalom-Feuerstein Ruby 
Published: September 2014

Abstract
Accumulating evidence supports the dogma that the corneal epithelium is regenerated by stem cells located exclusively in the limbal niche, at the corneal periphery. Accordingly, limbal stem cells (LSCs) give rise to progenitors that proliferate and migrate centripetally to repopulate the corneal epithelium, which has a short turnover. Moreover, LSC loss leads to corneal opacity and blindness, while limbal grafting restores patients' vision. However, contradicting data suggested that the limbus does not participate in corneal homeostasis and that the cornea contains stem cells. As of today, only indirect evidence for limbal cell migration under homeostasis or injury has been demonstrated. Here, we performed lineage tracing experiments using R26R-Confetti mice to follow K14+ limbal/corneal epithelial cells stochastically induced to express one out of four fluorescent genes. In homeostasis, radial limbal stripes of slow migrating cells proceeded toward the corneal center while, infrequently, slow cycling limbal clones resembling quiescent stem cells were observed. Additionally, rare corneal clones that did not migrate centripetally, but survived for over 4 months, were inspected. In contrast to limbal stripes, corneal clusters had minor contribution to tissue replenishment in homeostasis. Corneal cells, however, significantly contributed to mild wound repair while large limbal streaks appeared within a week following severe wounding that coincided with partial loss of corneal transparency. This data suggest that the mouse limbus largely contributes to corneal renewal while corneal progenitor cells have a long turnover and, therefore, may be able to maintain the corneal epithelium for several months. Stem Cells 2015;33:230–239
Percutaneous Injection of Autologous Bone Marrow Concentrate Cells Significantly Reduces Lumbar Discogenic Pain Through 12 Months
Authors: Pettine Kenneth A. , Murphy Matthew B. , Suzuki Richard K. , Sand Theodore T. 
Published: September 2014

Abstract
Degenerative disc disease (DDD) induces chronic back pain with limited nonsurgical options. In this open label pilot study, 26 patients (median age 40 years; range 18–61) received autologous bone marrow concentrate (BMC) disc injections (13 one level, 13 two levels). Pretreatment Oswestry disability index (ODI) and visual analog scale (VAS) were performed to establish baseline pain scores (average 56.5 and 79.3, respectively), while magnetic resonance imaging was independently scored according to the modified Pfirrmann scale. Approximately 1 ml of BMC was analyzed for total nucleated cell (TNC) content, colony-forming unit-fibroblast (CFU-F) frequency, differentiation potential, and phenotype characterization. The average ODI and VAS scores were reduced to 22.8 and 29.2 at 3 months, 24.4 and 26.3 at 6 months, and 25.0 and 33.2 at 12 months, respectively (p ≤ .0001). Eight of twenty patients improved by one modified Pfirrmann grade at 1 year. The average BMC contained 121 × 106 TNC/ml with 2,713 CFU-F/ml (synonymous with mesenchymal stem cells). Although all subjects presented a substantial reduction in pain, patients receiving greater than 2,000 CFU-F/ml experienced a significantly faster and greater reduction in ODI and VAS. Subjects older than 40 years who received fewer than 2,000 CFU-F/ml experienced an average pain reduction of 33.7% (ODI) and 29.1% (VAS) at 12 months, while all other patients' average reduction was 69.5% (ODI, p = .03) and 70.6% (VAS, p = .01). This study provides evidence of safety and feasibility in the nonsurgical treatment of DDD with autologous BMC and indicates an effect of mesenchymal cell concentration on discogenic pain reduction. Stem Cells 2015;33:146–156
Single molecular shuttle-junction: Shot noise and decoherence
Authors: Lai Wenxi , Zhang Chao , Ma Zhongshui 
Published: September 2014

Abstract
Single molecular shuttle-junction is one kind of nanoscale electromechanical tunneling system. In this junction, a molecular island oscillates depending on its charge occupation, and this charge dependent oscillation leads to modulation of electron tunneling through the molecular island. This paper reviews recent development on the study of current, shot noise and decoherence of electrons in the single molecular shuttle-junction. We will give detailed discussion on this topic using the typical system model, the theory of fully quantum master equation and the Aharonov-Bohm interferometer.