bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fzr1 Preserves Hematopoietic Stem Cell Quiescence through Inhibiting Runx1
Authors: Zhou Chengfang , Kuang Mei , Chen Jieping , Hou Yu 
Published: February 2021

Regulated blood production is achieved through the hierarchical organization of dormant hematopoietic stem cell (HSC) subsets that differ in self-renewal potential and division frequency, with long-term (LT)-HSCs dividing the least. FZR1, as a regulatory subunit of anaphase promoting complex/cyclosome (APC), is a master regulator of cell cycle, but little is known with regard to its role in HSC quiescence. Thus, we examined the function of Fzr1 in HSCs during steady-state hematopoiesis and under stress. We demonstrate that Fzr1 deletion led to perturbed hematopoiesis with an approximately 2-fold decrease in HSC pool size, as consequence of Fzr1 loss driving HSC from quiescence into rapid cycling (~70.1% to ~28.4%), elevating proliferation (~4.58% to ~18.5%) and apoptosis (~0.23% to ~2.86%) in HSC. As shown by serial bone marrow transplantation and competitive repopulation assays, self-renewal capacity and regenerative capacity were impaired, but differentiation of HSCs was not affected post Fzr1 deletion. Mechanistically, Fzr1 loss led to upregulation of Runx1 expression, in line with the protein expression, the ubiquitin sites of the gene was also obviouly decreased, knockdown Runx1 can rescue the Fzr1-deficient phenotype in HSC. Together, our data therefore support that Fzr1 acts a positive regulator of HSC quiescence and self-renewal capacity through inhibiting Runx1 expression.

Disclosures
No relevant conflicts of interest to declare.
Incidence and Risk Factors for 30-Day Readmission after Inpatient Chemotherapy Among Acute Lymphoblastic Leukemia Patients
Authors: Dalal Mansi , Slayton William , Tran Phuong Tan , Brown Joshua David 
Published: February 2021

Background: chemotherapy for acute lymphoblastic leukemia (ALL) patients is complex and intense, resulting in their high readmission rate. Modifiable risk factors may exist to reduce their readmission.
Objectives: To identify the incidence, causes, and risk factors of readmission following inpatient chemotherapy among ALL patients.
Design: A retrospective cohort using the 2016 National Readmission Database.
Subjects: ALL children and adults receiving inpatient chemotherapy.
Measurements: We applied three different definitions of 30-day readmission: (1) nonelective readmission based on readmission type reported by hospitals, (2) unplanned readmission defined by the algorithm developed by the Center for Medicare and Medicaid Services, and (3) unintentional readmission, combining of (1) and (2). We used a weighted survey procedure to calculate incidence and unweighted, multivariable Poisson regression with robust variance estimates for risk factors analysis, including patient-, hospital- and admission-related characteristics.
Results: Percentage for nonelective, unplanned, and unintentional readmission were 33.3%, 22.4%, and 18.5%, respectively. Top three causes for unplanned readmissions were neutropenia/agranulocytosis (27.8%), septicemia (15.3%) and pancytopenia (11.5%). Risk ratios for unintentional readmission were 1.21 (1.08-1.36) for nonelective vs elective admission, 1.19 (1.06-1.33) for public vs private insurance enrollees, 0.96 (0.95-0.98) for each day of hospital stay, 0.77 (0.62-0.95) for large, teaching, and 0.87 (0.70-1.08) for small teaching vs non-teaching hospitals.
Conclusions: Possible strategies to reduce readmission among ALL patients could be shortening the gap in quality of care among teaching vs non-teaching hospitals, understanding the difference of privately vs publicly insured patients, and avoiding aggressive discharge after chemotherapy.

Disclosures
No relevant conflicts of interest to declare.
Weakness Ranking Method for Subsystems of Heavy-Duty Machine Tools Based on FMECA Information
Authors: Yang Zhaojun , Guo Jinyan , Tian Hailong , Chen Chuanhai , Zhu Yongfu , Liu Jia 
Published: February 2021

AbstractHeavy-duty machine tools are composed of many subsystems with different functions, and their reliability is governed by the reliabilities of these subsystems. It is important to rank the weaknesses of subsystems and identify the weakest subsystem to optimize products and improve their reliabilities. However, traditional ranking methods based on failure mode effect and critical analysis (FMECA) does not consider the complex maintenance of products. Herein, a weakness ranking method for the subsystems of heavy-duty machine tools is proposed based on generalized FMECA information. In this method, eight reliability indexes, including maintainability and maintenance cost, are considered in the generalized FMECA information. Subsequently, the cognition best worst method is used to calculate the weight of each screened index, and the weaknesses of the subsystems are ranked using a technique for order preference by similarity to an ideal solution. Finally, based on the failure data collected from certain domestic heavy-duty horizontal lathes, the weakness ranking result of the subsystems is obtained to verify the effectiveness of the proposed method. An improved weakness ranking method that can comprehensively analyze and identify weak subsystems is proposed herein for designing and improving the reliability of complex electromechanical products.
Coupled mixed model for joint genetic analysis of complex disorders with two independently collected data sets
Authors: Wang Haohan , Pei Fen , Vanyukov Michael M. , Bahar Ivet , Wu Wei , Xing Eric P. 
Published: February 2021

AbstractBackgroundIn the last decade, Genome-wide Association studies (GWASs) have contributed to decoding the human genome by uncovering many genetic variations associated with various diseases. Many follow-up investigations involvejoint analysisof multiple independently generated GWAS data sets. While most of the computational approaches developed for joint analysis are based on summary statistics, the joint analysis based on individual-level data with consideration of confounding factors remains to be a challenge.ResultsIn this study, we propose a method, called Coupled Mixed Model (CMM), that enables a joint GWAS analysis on two independently collected sets of GWAS data with different phenotypes. The CMM method does not require the data sets to have the same phenotypes as it aims to infer the unknown phenotypes using a set of multivariate sparse mixed models. Moreover, CMM addresses the confounding variables due to population stratification, family structures, and cryptic relatedness, as well as those arising during data collection such as batch effects that frequently appear in joint genetic studies. We evaluate the performance of CMM using simulation experiments. In real data analysis, we illustrate the utility of CMM by an application to evaluating common genetic associations for Alzheimer’s disease and substance use disorder using datasets independently collected for the two complex human disorders. Comparison of the results with those from previous experiments and analyses supports the utility of our method and provides new insights into the diseases. The software is available athttps://github.com/HaohanWang/CMM.
Comparative transcriptome analysis reveals novel insights into transcriptional responses to phosphorus starvation in oil palm (Elaeis guineensis) root
Authors: Kong Sze-Ling , Abdullah Siti Nor Akmar , Ho Chai-Ling , Musa Mohamed Hanafi bin , Yeap Wan-Chin 
Published: February 2021

Abstract
Background
Phosphorus (P), in its orthophosphate form (Pi) is an essential macronutrient for oil palm early growth development in which Pi deficiency could later on be reflected in lower biomass production. Application of phosphate rock, a non-renewable resource has been the common practice to increase Pi accessibility and maintain crop productivity in Malaysia. However, high fixation rate of Pi in the native acidic tropical soils has led to excessive utilization of P fertilizers. This has caused serious environmental pollutions and cost increment. Even so, the Pi deficiency response mechanism in oil palm as one of the basic prerequisites for crop improvement remains largely unknown.

Results
Using total RNA extracted from young roots as template, we performed a comparative transcriptome analysis on oil palm responding to 14d and 28d of Pi deprivation treatment and under adequate Pi supply. By using Illumina HiSeq4000 platform, RNA-Seq analysis was successfully conducted on 12 paired-end RNA-Seq libraries and generated more than 1.2 billion of clean reads in total. Transcript abundance estimated by fragments per kilobase per million fragments (FPKM) and differential expression analysis revealed 36 and 252 genes that are differentially regulated in Pi-starved roots at 14d and 28d, respectively. Genes possibly involved in regulating Pi homeostasis, nutrient uptake and transport, hormonal signaling and gene transcription were found among the differentially expressed genes.

Conclusions
Our results showed that the molecular response mechanism underlying Pi starvation in oil palm is complexed and involved multilevel regulation of various sensing and signaling components. This contribution would generate valuable genomic resources in the effort to develop oil palm planting materials that possess Pi-use efficient trait through molecular manipulation and breeding programs.
Screening the elite chemotypes of Gloriosa superba L. in India for the production of anticancer colchicine: simultaneous microwave-assisted extraction and HPTLC studies
Authors: Pandey Devendra Kumar , Kaur Prabhjot , Kumar Vijay , Banik R. M. , Malik Tabarak , Dey Abhijit 
Published: February 2021

Abstract
Background
Gloriosa superba L. (Colchicaceae) is a high-value medicinal plant indigenous to Africa and Southeast Asia. Its therapeutic benefits are well-established in traditional medicines including Ayurveda. It is well known for its natural bioactive compound colchicine which exhibits a wide range of pharmacological activities i.e. rheumatism, gout and was also introduced into clinical practices. The increasing demand as well as its illegal harvesting has brought this valuable plant under threatened category.

Methods
The present investigation describes a microwave assisted extraction (MAE) strategy coupled with a densitometric-high performance thin layer chromatographic (HPTLC) methodology for the analysis of colchicine from 32 different populations of G. superba. A Box-Behnken statistical design (3 level factor) has been employed to optimize MAE, in which power of microwave, time of irradiation, aqueous ethanol and pH were used as independent variables whereas colchicine was used as the dependent variables. Chromatography was carried out on Silica gel 60 F254 TLC plates with toluene: methanol, 85:15 (v/v) being used as solvent system. Densitometric measurement was performed at λ=254 nm following post-derivatization (10% methanolic sulphuric acid).

Results
Optimal conditions for extraction to obtain the maximum colchicine yield was found to be 7.51 mg g− 1 which was very close to be predicted response 7.48 mg g− 1 by maintaining microwave power (460 W), irradiation time (6.4 min), aqueous ethanol-30, pH -3. Colchicine content ranged between 2.12–7.58 mg g− 1 among 32 G. superba populations in which only three chemotypes viz. GS- 1, GS- 3, and GS- 2 collected from West Bengal and Sikkim, respectively exhibited maximum yield of colchicine.

Conclusion
Therefore, this newly developed optimized MAE coupled with HPTLC densitometry methodology not only quantifies colchicine in order to identify elite chemotypes of G. superba, but it also encourages in selecting high yielding populations of the plants for industrial use and economic boost for the farmers. This validated, simple and reproducible HPTLC protocol is being used for the first time to estimate colchicine from natural populations of G. superba obtained from 32 different geographical regions of India.

Graphical abstract
Complex chronic patients as an emergent group with high risk of intracerebral haemorrhage: an observational cohort study
Authors:   on behalf Ebrictus Research Group, Lorman-Carbó Blanca , Clua-Espuny Josep Lluís , Muria-Subirats Eulàlia , Ballesta-Ors Juan , González-Henares Maria Antònia , Fernández-Sáez José , Martín-Luján Francisco M. 
Published: February 2021

Abstract
Background
Demographic aging is a generalised event and the proportion of older adults is increasing rapidly worldwide with chronic pathologies, disability, and complexity of health needs. The intracerebral haemorrhage (ICH) has devastating consequences in high risk people. This study aims to quantify the incidence of ICH in complex chronic patients (CCP).

Methods
This is a multicentre, retrospective and community-based cohort study of 3594 CCPs followed up from 01/01/2013 to 31/12/2017 in primary care without a history of previous ICH episode. The cases were identified from clinical records encoded with ICD-10 (10th version of the International Classification of Diseases) in the e-SAP database of the Catalan Health Institute. The main variable was the ICH episode during the study period. Demographic, clinical, functional, cognitive and pharmacological variables were included. Descriptive and logistic regression analyses were carried out to identify the variables associated with suffering an ICH. The independent risk factors were obtained from logistic regression models, ruling out the variables included in the HAS-BLED score, to avoid duplication effects. Results are presented as odds ratio (OR) and 95% confidence interval (CI). The analysis with the resulting model was also stratified by sex.

Results
161 (4.4%) participants suffered an ICH episode. Mean age 87 ± 9 years; 55.9% women. The ICH incidence density was 151/10000 person-years [95%CI 127–174], without differences by sex. Related to subjects without ICH, presented a higher prevalence of arterial hypertension (83.2% vs. 74.9%; p = 0.02), hypercholesterolemia (55.3% vs. 47.4%, p = 0.05), cardiovascular disease (36.6% vs. 28.9%; p = 0.03), and use of antiplatelet drugs (64.0% vs. 52.9%; p = 0.006). 93.2% had a HAS-BLED score ≥ 3. The independent risk factors for ICH were identified: HAS-BLED ≥3 [OR 3.54; 95%CI 1.88–6.68], hypercholesterolemia [OR 1.62; 95%CI 1.11–2.35], and cardiovascular disease [OR 1.48 IC95% 1.05–2.09]. The HAS_BLED ≥3 score showed a high sensitivity [0.93 CI95% 0.89–0.97] and negative predictive value [0.98 (CI95% 0.83–1.12)].

Conclusions
In the CCP subgroup the incidence density of ICH was 5–60 times higher than that observed in elder and general population. The use of bleeding risk score as the HAS-BLED scale could improve the preventive approach of those with higher risk of ICH.

Trial registration
This study was retrospectively registered in ClinicalTrials.gov (NCT03247049) on August 11/2017.
Effect of balanced crystalloids versus saline on urinary biomarkers of acute kidney injury in critically ill adults
Authors:   for the SMART Investigators, Funke Blake E. ,   the Pragmatic Critical Care Research Group, Jackson Karen E. , Self Wesley H. , Collins Sean P. , Saunders Christina T. , Wang Li , Blume Jeffrey D. , Wickersham Nancy , Brown Ryan M. , Casey Jonathan D. , Bernard Gordon R. , Rice Todd W. , Siew Edward D. , Semler Matthew W. 
Published: February 2021

Abstract
Background
Recent trials have suggested use of balanced crystalloids may decrease the incidence of major adverse kidney events compared to saline in critically ill adults. The effect of crystalloid composition on biomarkers of early acute kidney injury remains unknown.

Methods
From February 15 to July 15, 2016, we conducted an ancillary study to the Isotonic Solutions and Major Adverse Renal Events Trial (SMART) comparing the effect of balanced crystalloids versus saline on urinary levels of neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) among 261 consecutively-enrolled critically ill adults admitted from the emergency department to the medical ICU. After informed consent, we collected urine 36 ± 12 h after hospital admission and measured NGAL and KIM-1 levels using commercially available ELISAs. Levels of NGAL and KIM-1 at 36 ± 12 h were compared between patients assigned to balanced crystalloids versus saline using a Mann-Whitney U test.

Results
The 131 patients (50.2%) assigned to the balanced crystalloid group and the 130 patients (49.8%) assigned to the saline group were similar at baseline. Urinary NGAL levels were significantly lower in the balanced crystalloid group (median, 39.4 ng/mg [IQR 9.9 to 133.2]) compared with the saline group (median, 64.4 ng/mg [IQR 27.6 to 339.9]) (P < 0.001). Urinary KIM-1 levels did not significantly differ between the balanced crystalloid group (median, 2.7 ng/mg [IQR 1.5 to 4.9]) and the saline group (median, 2.4 ng/mg [IQR 1.3 to 5.0]) (P = 0.36).

Conclusions
In this ancillary analysis of a clinical trial comparing balanced crystalloids to saline among critically ill adults, balanced crystalloids were associated with lower urinary concentrations of NGAL and similar urinary concentrations of KIM-1, compared with saline. These results suggest only a modest reduction in early biomarkers of acute kidney injury with use of balanced crystalloids compared with saline.

Trial registration
ClinicalTrials.gov number: NCT02444988. Date registered: May 15, 2015.
Safety and efficacy of Hypofractionated stereotactic radiosurgery for high-grade Gliomas at first recurrence: a single-center experience
Authors: Guan Yun , Xiong Ji , Pan Mingyuan , Shi Wenyin , Li Jing , Zhu Huaguang , Gong Xiu , Li Chao , Mei Guanghai , Liu Xiaoxia , Pan Li , Dai Jiazhong , Wang Yang , Wang Enmin , Wang Xin 
Published: February 2021

Abstract
Background
The optimal treatment for recurrent high-grade gliomas (rHGGs) remains uncertain. This study aimed to investigate the efficacy and safety of hypofractionated stereotactic radiosurgery (HSRS) as a first-line salvage treatment for in-field recurrence of high-grade gliomas.

Methods
Between January 2016 and October 2019, 70 patients with rHGG who underwent HSRS were retrospectively analysed. The primary endpoint was overall survival (OS), and secondary endpoints included both progression-free survival (PFS) and adverse events, which were assessed according to Common Toxicity Criteria Adverse Events (CTCAE) version 5. The prognostic value of key clinical features (age, performance status, planning target volume, dose, use of bevacizumab) was evaluated.

Results
A total of 70 patients were included in the study. Forty patients were male and 30 were female. Forty-nine had an initial diagnosis of glioblastoma (GBM), and the rest (21) were confirmed to be WHO grade 3 gliomas. The median planning target volume (PTV) was 16.68 cm3 (0.81–121.96 cm3). The median prescribed dose was 24 Gy (12–30 Gy) in 4 fractions (2–6 fractions). The median baseline of Karnofsky Performance Status (KPS) was 70 (40–90). With a median follow-up of 12.1 months, the median overall survival after salvage treatment was 17.6 months (19.5 and 14.6 months for grade 3 and 4 gliomas, respectively; p = .039). No grade 3 or higher toxicities was recorded. Multivariate analysis showed that concurrent bevacizumab with radiosurgery and KPS > 70 were favourable prognostic factors for grade 4 patients with HGG.

Conclusions
Salvage HSRS showed a favourable outcome and acceptable toxicity for rHGG. A prospective phase II study (NCT04197492) is ongoing to further investigate the value of hypofractionated stereotactic radiosurgery (HSRS) in rHGG.
Life-conditions and anthropometric variables as risk factors for oral health in children in Ladakh, a cross-sectional survey
Authors: Cagetti Maria Grazia , Cocco Fabio , Calzavara Ezio , Augello Davide , Zangpoo Phunchok , Campus Guglielmo 
Published: February 2021

Abstract
Background
The aim of this survey was to evaluate the severity of dental caries among children living in Zanskar Valley (Ladakh, India) and its association with anthropometric and background variables.

Methods
This cross‐sectional survey was conducted on schoolchildren divided into four age groups (< 6, ≥ 6 < 11, ≥ 11 < 14 and > 14 years of age). A total of 1474 schoolchildren (607 males, 41.2%) were examined. Actual caries prevalence (dt/DT) and gingival bleeding were recorded by four calibrated dentists. An ad hoc questionnaire evaluated general health, eating habits, oral hygiene and the self-perception of oral conditions. Height, weight, waist circumference, heart-rate and oxygen-saturation were also collected directly by examiners. Responses to questionnaire items were treated as categorical or ordinal variables. The relationship between children’s caries data, gingival bleeding, gender, Body Mass Index (BMI) following the International Obesity Task Force, waist circumference and questionnaire items was assessed using the Kruskal–Wallis test and Pearson correlation. Conditional ordinal logistic regression was used to analyse associations among caries severity, gender, BMI, waist circumference, oxygen saturation and questionnaire items. A forward stepwise logistic regression procedure was also carried-out to estimate the ORs of gingival bleeding prevalence and the covariates derived from examination or questionnaire.

Results
Caries was almost ubiquitarian with only 10.0% of caries-free children (dt/DT = 0). Caries severity, in both primary and permanent dentitions, was statistically significantly related to gender, waist circumference, BMI, oral hygiene frequency and self-reported chewing problems (p < 0.01 in both dentitions). An increasing relative risk for caries in permanent dentition compared to caries-free subjects was observed in children with a low BMI (RRR = 1.67, 95%CI = 1.54/2.83 for subjects with 1–3 caries lesions and RRR = 1.52, 95%CI = 1.36/1.74 for subjects with > 3 caries lesions); also, children with reduced waist circumference had a higher relative risk to have 1–3 caries lesions (RRR = 2.16, 95%CI = 1.84/2.53) and an even higher risk to have more than 3 caries lesions (RRR = 4.22, 95%CI = 3.33/5.34).

Conclusions
A significant impact of untreated caries lesions was observed in Ladakh schoolchildren; low BMI values and reduced waist circumference showed to be the main caries risk predictors. Preventive and intervention programmes should be implemented to improve children's oral health.