bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dana Farber Protocol (DFCP) for Treatment of Adolescents and Young Adults with ALL, Single Institution Experience in Saudi Arabia
Authors: Alabdulwahab Amal S. , ELSayed Hussein G. , Sherisher Mohamed Atia , Elbjeirami Wafa M. 
Published: April 2020

Abstract
Background :
Recent reports indicate that adolescents and young adults (AYA) have a better outcome when treated with pediatric protocols rather than adult ones. Many explanations were raised to explain that including the more intense pediatric protocols and different disease biology.
Patients & Methods : This is a retrospective study that included AYA patients diagnosed as ALL and treated at King Abdulla Medical City (KAMC),Saudi Arabia, in the period from mid 2011- March 2015.
Results: 37 patients were included in this study including 25 males and 12 females with a ratio of 2:1. The median age at diagnosis was 19.4 y. At presentation the mean number of WbCs was 63.7 x 109/L + 103.4 (range 1.9 to 500,000 x109/L), HB 8.87 + 2.3 gm/L (range 6.5-15.2 gm/L), platelets 59 x 109/L + 43.9 (range 8-100,000 x109/L. Bone marrow blasts ranged from 35 -99% with a mean and median of 80.3 + 18.5, 84 % respectively. B-cell phenotype constituted the majority of cases 29/37(78.3%). Cytogenetics using karyotyping and FISH Panel for ALL (done in Mayo clinic,USA) revealed Very high risk cytogenetics (Philadelphia, MLL, complex cytogenetics, hypodiploidy in 14/37 (37.8%) patients, Intermediate / high 16 patients (43.2%) and 7 (18.9%) with favorable cytogenetics (hyperdiploidy, tetraploidy, del p16).
Complete remission was confirmed in 35 of 37 patients (94.5%). (one did not achieve remission while response was not evaluable in another patient who died during induction due to hepatic failure). Repeat cytogenetics at the time of D28 BM evaluation was done in 29/37 patients while in 8/37 it was not done for technical reasons. Cytogenetic remission was confirmed in 18 out of 21 with cytogenetic abnormality (85.7%).
After a median follow up period of 12 m (range 3-52.5 m).. Leukemia free survival ranged from 3 to 52.5 m with a median of 10.5 m, mean 17.5 {CI (95%) 12.61-22.53}: while median survival was 12m with a mean of 18.5m {CI (95%) 13.6-23.5}.
As a whole 6 cases relapsed (5 in the first 18 m and 1 after 4 Y) and 1 was primary resistant constituting (7/35 18.9% of cases) while response could not be documented in one patient who died during induction. Of the 6 relapsed cases, 4 of them due to disease progression and non-responsive to salvage treatment or transplant procedure
Toxicity included febrile neutropenia in virtually all patients with negative cultures in 20/37 patients (54%) while Gram negative sepsis was confirmed in 12/37 patients (32%). Major complications occurred in 9/37 patients (24.3%) and include: septic shock that required ICU (1 patient), typhilitis (1 patient), pancreatitis (2 patients), avascular necrosis of head of femur (2 patients).neuropathy ≥ GIII (2 patients)
In conclusion : Although DFCP is an effective treatment for AYA with ALL, Yet toxicity can not be overlooked.

Disclosures
No relevant conflicts of interest to declare.
Retrovirally Transduced Human Dendritic Cells Express a Normal Phenotype and Potent T-Cell Stimulatory Capacity
Authors: Szabolcs Paul , Gallardo H.F. , Ciocon David H. , Sadelain Michel , Young James W. 
Published: April 2020

AbstractDendritic cells are attractive candidates for vaccine-based immunotherapy because of their potential to function as natural adjuvants for poorly immunogenic proteins derived from tumors or microbes. In this study, we evaluated the feasibility and consequences of introducing foreign genetic material by retroviral vectors into dendritic cell progenitors. Proliferating human bone marrow and cord blood CD34+ cells were infected by retroviral vectors encoding the murine CD2 surface antigen. Mean transduction efficiency in dendritic cells was 11.5% from bone marrow and 21.2% from cord blood progenitors. Transduced or untransduced dendritic cell progeny expressed comparable levels of HLA-DR, CD83, CD1a, CD80, CD86, S100, and p55 antigens. Granulocytes, macrophages, and dendritic cells were equally represented among the transduced and mock-transduced cells, thus showing no apparent alteration in the differentiation of transduced CD34+ precursors. The T-cell stimulatory capacity of retrovirally modified and purified mCD2-positive allogeneic or nominal antigen-pulsed autologous dendritic cells was comparable with that of untransduced dendritic cells. Human CD34+ dendritic cell progenitors can therefore be efficiently transduced using retroviral vectors and can differentiate into potent immunostimulatory dendritic cells without compromising their T-cell stimulatory capacity or the expression of critical costimulatory molecules and phenotypic markers. These results support ongoing efforts to develop genetically modified dendritic cells for immunotherapy.
On the utility of RNA sample pooling to optimize cost and statistical power in RNA sequencing experiments
Authors: Takele Assefa Alemu , Vandesompele Jo , Thas Olivier 
Published: April 2020

Abstract
Background
In gene expression studies, RNA sample pooling is sometimes considered because of budget constraints or lack of sufficient input material. Using microarray technology, RNA sample pooling strategies have been reported to optimize both the cost of data generation as well as the statistical power for differential gene expression (DGE) analysis. For RNA sequencing, with its different quantitative output in terms of counts and tunable dynamic range, the adequacy and empirical validation of RNA sample pooling strategies have not yet been evaluated. In this study, we comprehensively assessed the utility of pooling strategies in RNA-seq experiments using empirical and simulated RNA-seq datasets.

Result
The data generating model in pooled experiments is defined mathematically to evaluate the mean and variability of gene expression estimates. The model is further used to examine the trade-off between the statistical power of testing for DGE and the data generating costs. Empirical assessment of pooling strategies is done through analysis of RNA-seq datasets under various pooling and non-pooling experimental settings. Simulation study is also used to rank experimental scenarios with respect to the rate of false and true discoveries in DGE analysis. The results demonstrate that pooling strategies in RNA-seq studies can be both cost-effective and powerful when the number of pools, pool size and sequencing depth are optimally defined.

Conclusion
For high within-group gene expression variability, small RNA sample pools are effective to reduce the variability and compensate for the loss of the number of replicates. Unlike the typical cost-saving strategies, such as reducing sequencing depth or number of RNA samples (replicates), an adequate pooling strategy is effective in maintaining the power of testing DGE for genes with low to medium abundance levels, along with a substantial reduction of the total cost of the experiment. In general, pooling RNA samples or pooling RNA samples in conjunction with moderate reduction of the sequencing depth can be good options to optimize the cost and maintain the power.
Construction of a high-density genetic map and mapping of growth related QTLs in the grass carp (Ctenopharyngodon idellus)
Authors: Huang Xiaoli , Jiang Yanxin , Zhang Wanting , Cheng Yingyin , Wang Yaping , Ma Xiaocui , Duan You , Xia Lei , Chen Yaxin , Wu Nan , Shi Mijuan , Xia Xiao-Qin 
Published: April 2020

AbstractBackgroundGrass carp (Ctenopharyngodon idellus) are important species in Asian aquaculture. A draft genome for grass carp has already been published in 2015. However, there is still a requirement for a suitable genetic linkage map to arrange scaffolds on chromosomal frameworks. QTL analysis is a powerful tool to detect key locations for quantitative traits, especially in aquaculture. There no growth related QTLs of grass carp have been published yet. Even the growth trait is one of the focuses in grass carp culture.ResultsIn this study, a pair of distantly related parent grass carps and their 100 six-month-old full-sib offspring were used to construct a high-density genetic map with 6429 single nucleotide polymorphisms (SNPs) by 2b-RAD technology. The total length of the consensus map is 5553.43 cM with the average marker interval of 1.92 cM. The map has a good collinearity with both the grass carp draft genome and the zebrafish genome, and it assembled 89.91% of the draft genome to a chromosomal level. Additionally, according to the growth-related traits of progenies, 30 quantitative trait loci (QTLs), including 7 for body weight, 9 for body length, 5 for body height and 9 for total length, were identified in 16 locations on 5 linkage groups. The phenotypic variance explained for these QTLs varies from 13.4 to 21.6%. Finally, 17 genes located in these regions were considered to be growth-related because they either had functional mutations predicted from the resequencing data of the parents.ConclusionA high density genetic linkage map of grass carp was built and it assembled the draft genome to a chromosomal level. Thirty growth related QTLs were detected. After the cross analysis of Parents resequencing data, 17 candidate genes were obtained for further researches.
Clinical utility of serum cystatin C for prediction of multi-vessel disease by coronary angiography in type 2 diabetes mellitus patients with normal renal function
Authors: Wang Shaoyi , Liu Qiaohui , Guo Fangfang , Zhou Xiaocong , Shi Jie , Xie Qing 
Published: April 2020

Abstract
Background
The aim of this study was to evaluate whether serum cystatin C could serve as a predictor of multivessel coronary artery disease identified by coronary angiography in type 2 diabetes patients with normal renal function and to suggest the cutoff point of serum cystatin C for predicting multivessel disease.

Methods
Serum cystatin C concentrations were measured by using particle-enhanced immunonephelometric assays before coronary angiography in 135 consecutive type 2 diabetes patients and 179 nondiabetic patients with normal renal function. Routine anthropometric and serologic data were collected. The severity of multivessel disease was assessed with the Gensini score after coronary angiography. The associations of serum cystatin C with the Gensini score were investigated, and the independent risk factors associated with multivessel disease were assessed.

Results
Serum cystatin C and the Gensini score were significantly elevated in diabetes patients. Cystatin C had a positive correlation with Gensini score. A multiple logistic regression analysis demonstrated that cystatin C was independently associated with the presence of multivessel disease (the OR score is 2.21, P = 0.003). Based on the ROC curve, a cystatin C level of 0.865 mg/L showed 67.7% sensitivity and 76.3% specificity with an AUC of 0.748 in diabetes patients for detecting multivessel disease.

Conclusion
Serum cystatin C is significantly correlated with the presence of multivessel disease, suggesting that cystatin C might be utilized as a screening tool for predicting multivessel disease in type 2 diabetes mellitus patients with normal renal function.
Value of appendicular skeletal muscle mass to total body fat ratio in predicting obesity in elderly people: a 2.2-year longitudinal study
Authors: Zhang Yu-Jie , Fu Shi-Hui , Wang Jing-Xin , Zhao Xin , Yao Yao , Li Xiao-Ying 
Published: April 2020

Abstract
Background
Obesity is a disease characterized by much fat accumulation and abnormal distribution, which was related to cardiovascular diseases, diabetes mellitus (DM) and muscular skeletal diseases. The aim of this study was to evaluate the usefulness of appendicular skeletal muscle mass to total body fat ratio (ASM/TBF) in screening for the risk of obesity in elderly people.

Methods
A prospective study was carried out with 446 participants (non-obese elderly people with body mass index (BMI) < 28 kg/m2) who underwent baseline and an average around 2.2-year follow-up health check-up examinations.

Results
The mean age at baseline was 63.6 years. The incidence of new obesity was 5.4% during follow-up. Linear regression demonstrated that baseline ASM/TBFs were negatively correlated with follow-up BMIs in both men and women (β = − 1.147 (− 1.463—-0.831) for men and − 4.727 (− 5.761—-3.692) for women). The cut-off points of baseline ASM/TBF in elderly people for obesity were 1.24 in men and 0.90 in women which were identified by Classification and Regression Tree (CART). Logistic regression showed that both men and women with decreased ASM/TBF had higher risks of obesity over the follow-up period (Relative Risk (RRs) = 5.664 (1.879–17.074) for men and 34.856 (3.930–309.153) for women).

Conclusions
Elderly people with a low ASM/TBF had a higher risk of new obesity, which suggested that ASM/TBF should be considered in obesity management in the elderly.
Molecular diagnosis of autochthonous human anaplasmosis in Austria – an infectious diseases case report
Authors: Hoepler Wolfgang , Markowicz Mateusz , Schoetta Anna-Margarita , Zoufaly Alexander , Stanek Gerold , Wenisch Christoph 
Published: April 2020

Abstract
Background
The diagnosis of human anaplasmosis remains elusive and is probably often missed. This case report highlights the efficacy of molecular diagnostic techniques.

Case presentation
We would like to report the case of a 74-year-old man who was admitted to hospital because of a high fever, marked chills, transient diplopic images and vertigo, 6 weeks after multiple tick bites. The laboratory results showed mild anemia, marked thrombocytopenia and leukopenia and a moderately elevated C-reactive protein. The initial serology seemed to indicate an active infection with Borrelia spp., and Anaplasma phagocytophilum was detected in peripheral blood by polymerase chain reaction (PCR) and subsequent sequencing. The patient received intravenous ceftriaxone for 14 days and oral doxycycline for 4 weeks and made a fast and complete recovery.

Conclusions
While human anaplasmosis has been reported very rarely in Austria, it should be considered as a differential diagnosis in febrile patients with low leukocyte and platelet counts with elevated levels of C-reactive protein after exposure to tick bites. Molecular detection of A. phagocytophilum is the technique of choice allowing rapid and reliable diagnosis.
A case report of NPHP1 deletion in Chinese twins with nephronophthisis
Authors: Chen Feng , Dai Limeng , Zhang Jun , Li Furong , Cheng Jinbo , Zhao Jinghong , Zhang Bo 
Published: April 2020

Abstract
Background
Nephronophthisis (NPHP) is a rare autosomal recessive inherited disorder with high heterogeneity. The majority of NPHP patients progress to end-stage renal disease (ESRD) within the first three decades of life. As an inherited disorder with highly genetic heterogeneity and clinical presentations, NPHP still poses a challenging task for nephrologists without special training to make a well-judged decision on its precise diagnosis, let alone its mechanism and optimal therapy.

Case presentation
A Chinese family with NPHP was recruited in current study. The clinical characteristics (including findings from renal biopsy) of NPHP patients were collected from medical records and the potential responsible genes were explored by the whole exome sequencing (WES). A homozygous deletion of NPHP1 (1–20 exons) was found in both affected patients, which was further confirmed by quantitative PCR.

Conclusions
Homozygous full gene deletion of the NPHP1 gene was identified in a Chinese family with NPHP, which was the molecular pathogenic basis of this disorder. Furthermore, identification of the pathogenic genes for those affected patients can help to have a full knowledge on NPHP’s molecular mechanism and precise treatment.
Maternal ABVD chemotherapy for Hodgkin lymphoma in a dichorionic diamniotic pregnancy: a case report
Authors: Cotteret Camille , Pham Yen-Vi , Marcais Ambroise , Driessen Marine , Cisternino Salvatore , Schlatter Joël 
Published: April 2020

Abstract
Background
Hodgkin lymphoma (HL) is the most common hematological malignancy during pregnancy. The first-line treatment for HL in pregnancy is the standard ABVD regimen without any drug and/or dose adjustment. However, data on chemotherapy during twin pregnancies are sparse, and a better understanding of the mechanisms involved in exposure to and the toxic effects of anticancer drugs in the fetuses is needed.

Case presentation
A 41-year-old dichorionic diamniotic pregnant patient was given ABVD treatment for HL at a gestational age of 28 weeks and 3 days. The patient received 2 cycles of chemotherapy with a 15-day therapeutic window including an actual 25 mg/m2 dose of doxorubicin per cycle. Unlike the female twin, the male twin presented four days after birth a left cardiac dysfunction. Doxorubicin cardiotoxicity in the male newborn was also supported by high blood levels of troponin. At one month of age, echocardiography findings were normal. We investigated literature data on physiological aspects of pregnancy that may influence doxorubicin pharmacokinetics, and pharmacodynamic and pharmacokinetic data on the use of doxorubicin in pregnancy. We detailed the role of the transporters in doxorubicin placenta distribution, and tried to understand why only one fetus was affected.

Conclusions
Fetal safety depends at least on maternal doxorubicin pharmacokinetics.Because of drug interactions (i.e. drug metabolism and drug transport), care should always be taken to avoid maternal pharmacokinetic variability. The toxic effects were discrepant between the dizygotic twins, suggesting additional fetus-specific pharmacokinetic/pharmacodynamic factors in doxorubicin toxicity.
Hospitalization and definitive radiotherapy in lung cancer: incidence, risk factors and survival impact
Authors: Hazell Sarah Z. , Mai Nicholas , Fu Wei , Hu Chen , Friedes Cole , Negron Alex , Voong Khinh Ranh , Feliciano Josephine L. , Han Peijin , Myers Samantha , McNutt Todd R. , Hales Russell K. 
Published: April 2020

Abstract
Background
Unplanned hospitalization during cancer treatment is costly, can disrupt treatment, and affect patient quality of life. However, incidence and risks factors for hospitalization during lung cancer radiotherapy are not well characterized.

Methods
Patients treated with definitive intent radiation (≥45 Gy) for lung cancer between 2008 and 2018 at a tertiary academic institution were identified. In addition to patient, tumor, and treatment related characteristics, specific baseline frailty markers (Charlson comorbidity index, ECOG, patient reported weight loss, BMI, hemoglobin, creatinine, albumin) were recorded. All cancer-related hospitalizations during or within 30 days of completing radiation were identified. Associations between baseline variables and any hospitalization, number of hospitalizations, and overall survival were identified using multivariable linear regression and multivariable Cox proportional-hazards models, respectively.

Results
Of 270 patients included: median age was 66.6 years (31–88), 50.4% of patients were male (n = 136), 62% were Caucasian (n = 168). Cancer-related hospitalization incidence was 17% (n = 47), of which 21% of patients hospitalized (n = 10/47) had > 1 hospitalization. On multivariable analysis, each 1 g/dL baseline drop in albumin was associated with a 2.4 times higher risk of any hospitalization (95% confidence interval (CI) 1.2–5.0, P = 0.01), and baseline hemoglobin ≤10 was associated with, on average, 2.7 more hospitalizations than having pre-treatment hemoglobin > 10 (95% CI 1.3–5.4, P = 0.01). After controlling for baseline variables, cancer-related hospitalization was associated with 1.8 times increased risk of all-cause death (95% CI: 1.02–3.1, P = 0.04).

Conclusions
Our data show baseline factors can predict those who may be at increased risk for hospitalization, which was independently associated with increased mortality. Taken together, these data support the need for developing further studies aimed at early and aggressive interventions to decrease hospitalizations during treatment.
Prevalence and significance of potential drug-drug interactions among cancer patients receiving chemotherapy
Authors: Ismail Mohammad , Khan Sehrash , Khan Fahadullah , Noor Sidra , Sajid Hira , Yar Shazia , Rasheed Irum 
Published: April 2020

Abstract
Background
Cancer patients often receive multiple drugs to maximize their therapeutic benefit, treat co-morbidities and counter the adverse effects of chemotherapy. Concomitant administration of multiple drugs increases the risk of drug interactions leading to compromised therapeutic efficacy or safety of therapy. The purpose of this study was to identify the prevalence, levels and predictors of potential drug-drug interactions (pDDIs) among cancer patients.

Methods
Six hundred and 78 patients receiving chemotherapy from two tertiary care hospitals were included in this cross-sectional study. Patient medication profiles were screened for pDDIs using the Micromedex® database. Logistic regression analysis was performed to identify the predictors of pDDIs.

Results
The overall prevalence of pDDIs was 78%, majority of patients had 1–2 pDDIs (39.2%). A total of 1843 pDDIs were detected. Major-pDDIs were most frequent (67.3%) whereas, a significant association of pDDIs was found between > 7 all prescribed drugs (p < 0.001) and ≥ 3 anti-cancer drugs (p < 0.001). Potential adverse outcomes of these interactions include reduced therapeutic effectiveness, QT interval prolongation, tendon rupture, bone marrow suppression and neurotoxicity.

Conclusions
Major finding of this study is the high prevalence of pDDIs signifying the need of strict patient monitoring for pDDIs among cancer patients. Patients at higher risk to pDDIs include those prescribed with > 7 any types of drugs or ≥ 3 anticancer drugs. Moreover, list of most frequently identified major and moderate interactions will aid health care professional in timely identification and prevention of pDDIs.
Astigmatism in school students of eastern China: prevalence, type, severity and associated risk factors
Authors: Wang Jianyong , Cheng Qianqian Ellie , Fu Xiaojin , Zhang Ronghua , Meng Jia , Gu Fang , Li Juanjuan , Ying Gui-shuang 
Published: April 2020

Abstract
Background
China has been undergoing dramatic economic development, accompanied by increased education load on the young children. This study is to investigate the prevalence, type, severity, and associated risk factors of astigmatism in school students in eastern China.

Method
In this cross-sectional school-based study, students underwent refraction using NIDEK non-cycloplegic autorefractor. Astigmatism was defined as cylinder 1.5 diopter (D) or greater, and high astigmatism was defined as cylinder 3.0 D or greaterMultivariate regression models were used to determine factors associated with astigmatism.

Results
Among 4801 children (55% male) with mean age (±standard deviation) 12.3 (±3.8) years, 680 (14.2, 95% confidence interval (95% CI): 13.2–15.2%) had astigmatism (85% were with-the-rule) and 103 (2.2, 95% CI: 1.8–2.6%) had high astigmatism. The prevalence rate of astigmatism was 7–8% in grades 4 or below, 15–16% in grades 6–8, 20% in grade 9, and 20–25% in grade 10 or above. In multivariate analyses, higher grade and male gender were associated with higher prevalence of astigmatism (all p < 0.0001) and high astigmatism (p = 0.04 for grade, p = 0.001 for gender). When multivariate models were further adjusted by spherical equivalent, only gender remained statistically associated with astigmatism (odds ratio (OR) = 1.65, p < 0.0001) and high astigmatism (OR = 2.21, p = 0.0004), myopic and hyperopic refractive error were significantly associated with higher risk of astigmatism and high astigmatism (all p < 0.0001).

Conclusion
Astigmatism is common in Chinese school-age children and increases with grade. Majority of astigmatism is with-the-rule. Male gender and myopic or hyperopic refractive error are significantly associated with higher prevalence and severity of astigmatism.