bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hypertension Outcomes of Adrenalectomy for Unilateral Primary Aldosteronism
Authors: Hartmann Igor , Hruska Frantisek , Vaclavik Jan , Frysak Zdenek , Nesvadbova Marika , Tudos Zbynek , Ctvrtlik Filip , Benesova Klara 
Published: July 2021

Abstract
Purpose: To evaluate laboratory and clinical results after unilateral adrenalectomy in patients with primary aldosteronism (PHA).Methods: A cross-sectional analysis was performed using data from patients who underwent transperitoneal laparoscopic adrenalectomy for PHA, between January 2008 and December 2019. Surgical indications were based on adrenal venous sampling without ACTH stimulation. Analyses included patient demographics; preoperative clinical, pharmacological, laboratory, and radiological data; and postoperative results assessed after a median of 4 months. Antihypertensive drug use was quantified by estimating the daily defined dose (DDD) of antihypertensive medication, thus enabling standardised comparison of dosage between the drug classes. Statistical assessments included univariable and multivariable logistic regression analysis. Results: This study enrolled 87 patients. The patients were taking 5.4 DDD of antihypertensive medication before surgery, and 3.0 DDD after surgery. In 45 cases (52%), the aldosterone-to-renin ratio normalized after surgery (“laboratory cured”), while 21 patients (24%) required no antihypertensive drugs after surgery (“clinically cured”). Among the 66 patients who were not clinically cured, 51 (77%) had a reduction of their DDD. Thus, surgery had a positive effect on hypertension control in 72 cases (83% of all enrolled patients). Multivariable logistic regression showed that clinical cure of hypertension was independently associated with female gender, absence of diabetes mellitus, and DDD < 4.Conclusion: A majority of patients undergoing unilateral adrenalectomy for PHA achieved markedly improved hypertension control, despite almost halving their antihypertensive medication. About a quarter of patients were cured and able to cease using all antihypertensive drugs.
Dissecting the Molecular Response of Human Escs to Iron-Mediated Oxidative Stress by Genetic Silencing of FTH1 Gene
Authors: Scaramuzzino Luana , Lucchino Valeria , Scalise Stefania , Conte Michela Lo , Zannino Clara , Sacco Alessandro , Biamonte Flavia , Parrotta Elvira Immacolata , Costanzo Francesco Saverio , Cuda Giovanni 
Published: July 2021

Abstract
Background: Embryonic stem cells (ESCs) are pluripotent cells with indefinite self-renewal ability and differentiation properties. As such, to function properly and maintain genomic stability, ESCs need to be endowed with an efficient repair system as well as effective redox homeostasis. In this study, we investigated and characterized different aspects involved in ESCs response to iron accumulation following stable knockdown of ferritin heavy chain (FTH1) gene, encoding for a major iron storage protein with ferroxidase activity. Methods: stable FTH1 knockdown of H9-hES cell line was achieved with the use of shRNA lentiviral particles. Upon FTH1 silencing, we speculated whether hESCs still retained their pluripotency capability were first monitored for their capability the pluripotent status,FTH1 stable knock-down ESCs were obtained using lentiviral vector plasmids. The effect of FTH1 silencing on hESCs pluripotency was evaluated through alkaline phosphatase (AP) staining, immunofluorescence and embryoid bodies (EBs) formation assay. Western blotting and qRT-PCR analysis were performed to assess the involvement of nuclear factor (erythroid-derived-2)-like 2 (Nrf2) and pentose phosphate pathway (PPP) in the antioxidant response. ROS levels and mitochondrial functionality were explored by flow cytometry. Seahorse Analyzer was used to evaluate metabolic and bioenergetic profiles. Results: Our findings clearly show that FTH1 silencing in hESCs does not correlate with increased ROS production nor with redox status strengthening the concept that hESCs are extremely resistant and, to certain extent, even refractory to the pattern of results produced in other cell lines. Collectively, our results demonstrate that FTH1 silencing is accompanied by a significant activation of the nuclear factor (erythroid-derived-2)-like 2 (Nrf2) signaling pathway and pentose phosphate pathway (PPP) which crosstalk in driving hESCs antioxidant cascade events able to antagonize the effects of FTH1 silencing.Conclusion: to our knowledge, this is the first evidence of a crosstalk between FTH1 silencing and Nrf2 pathway activation in hESCs, casting a new light on how human ESCs perform under oxidative stress conditions. Our findings go beyond previous reports, showing how the Nrf2 pathway, in combination with PPP activation, regulates the molecular signature underlying ESCs defence mechanisms against oxidative stress mediated by FTH1 downregulation.
Integrated Production and Maintenance Control Policies for Failure-prone Manufacturing Systems Producing Perishable Products
Authors: Kaddachi Rawia , Gharbi Ali , Kenné Jean-Pierre 
Published: July 2021

Abstract
The problem of integrated production and maintenance control of unreliable manufacturing systems evolving in a stochastic and dynamic environment is studied in this paper. The considered system is subject to degradation and the produced products are perishable with random shelf-lives. The literature of operations management for perishable products reports a correlation between the shelf-life of the product and the machine degradation. In fact, the latter results in shelf-lives reduction. Ignoring this correlation effect may result in inaccurate values of the shelf-lives and inefficient control policies. The objective of this paper is to develop a joint production and maintenance control policy that minimizes the total cost composed of backlog, inventory holding, disposal and maintenance costs. The proposed parametrized joint control policy combines a multi hedging point policy and an age-based preventive maintenance policy. The optimization of the parameters of the proposed joint control policy is obtained using a simulation-based optimization approach and sensitivity analyses are provided to confirm its robustness. The obtained results show that the correlation between machine degradation and shelf-life reduction has a major influence on the control parameters and that preventive maintenance interventions can lead to increasing the shelf-life of products and minimizing the total cost. The proposed joint control policy is then compared to three other polices for a wide range of system and cost data. The obtained results show that the proposed joint control policy outperforms the other polices in terms of total incurred costs.
Long-acting granulocyte colony-stimulating factor in primary prophylaxis of early infection in patients with newly diagnosed multiple myeloma
Authors: Ding Xinjing , Ding Jianghua , Gu Hong , Zhong Chuanxiang 
Published: July 2021

Abstract
Purpose
This study sought to compare the efficacy of prophylactic long-acting and standard granulocyte colony-stimulating factor (G-CSF) on febrile neutropenia, early infections, and treatment delay in patients with newly diagnosed multiple myeloma receiving the therapeutic regimen of bortezomib, lenalidomide, and dexamethasone (BLD).
Methods
A prospective study with 68 consecutive patients with multiple myeloma was conducted in three regional hospitals. Participants were randomly treated with the BLD regimen in combination with prophylactic long-acting G-CSF (treatment group) or standard G-CSF (control group). The primary endpoints were the incidence rates of febrile neutropenia, early infection, and treatment delays. The secondary endpoint was clinical outcomes.
Results
Thirty-three patients were assigned to the treatment group and thirty-five patients were assigned to the control group. The incidence of febrile neutropenia was 6.1% and 17.1% in the treatment and control groups, respectively (p = 0.297). However, the rates of early infection and treatment delay were markedly lower in the treatment group than in the control group (6.1% vs. 25.7% and 9.1% vs. 31.4%; p < 0.05). Notably, all early infections occurred during the first four cycles of BLD therapy, and the most common type of infection was pneumonia. No significant difference in clinical efficacy was found between the two groups. All participants achieved at least partial remission.
Conclusions
Prophylactic administration of domestic long-acting G-CSF markedly reduced the rates of early infection and treatment delay as compared with standard G-CSF in patients newly diagnosed with multiple myeloma. Notably, all early infections occurred during the first four cycles of BLD therapy. As such, it seems appropriate to administer long-acting G-CSF with the aim of primary prophylaxis of early infection, particularly within the first four courses of chemotherapy in the setting of newly diagnosed multiple myeloma.
Small Peptide Targeting ANP32A as a Novel Strategy For Acute Myeloid Leukemia Therapy
Authors: Wang Manman , Guo Hao , Zhang Xuechun , Wang Xiyang , Tao Hu , Zhang Tan , Peng Min , Zhang Min , Huang Zan 
Published: July 2021

Abstract
Background: Clinic therapy of acute myeloid leukemia (AML) remains unsatisfactory that urges for development of novel strategy. Recent studies identified ANP32A as a novel biomarker of unfavorable outcome of leukemia, which promoted leukemogenesis by increasing H3 acetylation and the expression of lipid metabolism genes. It is of great significance to investigate whether targeting ANP32A is a novel strategy for leukemia therapy. Results: To target ANP32A, we identified a peptide that competed with ANP32A to bind to histone 3 (termed as H3-binding peptide, H3BP). Disrupting ANP32A and H3 interaction by the overexpression of H3BP-GFP fusion protein mimicked the effect of ANP32A knockdown, impaired H3 acetylation on multiple locus of target genes, reduced proliferation, and caused apoptosis in leukemia cells. Furthermore, a synthesized membrane-penetrating peptide TAT-H3BP effectively entered into leukemia cells and reproduced such effect. In vivo, TAT-H3BP showed potent efficacy against leukemia: Intra-tumor injection of TAT-H3BP significantly reduced the volume of subcutaneous tumors in nude mice and recipient mice engrafted with TAT-H3BP-pretreated 6133/MPL W515L cells exhibited ameliorated leukemia burden and prolonged survival. Noticeably, TAT-H3BP efficiently suppressed proliferation and colony-forming unit of human primary AML cells without affecting normal cord blood cells.Conclusions: Intervening the physical interaction of ANP32A with H3 impairs the oncogenicity of ANP32A and may be a promising therapeutic strategy against AML.
Therapeutic Effects of CXCL9-overexpressing Human Umbilical Cord Mesenchymal Stem Cells on Liver Fibrosis in Rats
Authors: Li Yang , Ye Xueshuai , Zhang Xueqian , Cai Ziqi , Shen Li , Zhang Mengya , Zhang Wentao , Cai Jianhui 
Published: July 2021

Abstract
Background: Umbilical cord mesenchymal stem cells (UC-MSCs) transplantation have become a promising treatment for liver fibrosis. However, UC-MSCs have limited anti-fibrosis ability, and their homing ability of UC-MSCs to the injured liver sites appears to be poor. In this study, we aimed to determining if overexpression of CXCL9 could have the synergistic anti-fibrosis effect with UC-MSCs, and whether it can promote the homing ability of UC-MSCs.Methods: Overexpression of CXCL9 in UC-MSCs (CXCL9-UC-MSCs) was attained by transfection of naive UC-MSCs with the lenti-CXCL9-mCherry. The impact of transplanted CXCL9-UC-MSCs on both repairing of liver fibrosis and homing was evaluated and compared with lenti-mCherry empty vector transfected UC-MSCs (control UC-MSCs).Results: After puromycin screening, UC-MSCs could stably express CXCL9 without affecting the stem and differentiation ability of UC-MSCs. In addition, biochemical analysis showed that the liver function of CXCL9-UC-MSCs was significantly increased in comparison with that of control UC-MSCs (P < 0.05). Futhermore, histopathology after 4 weeks of cell therapy demonstrated that the content of collagen fibers decreased obviously, the pseudo-lobules almost disappeared, and the morphology of hepatic lobules was basically normal. Frozen sections were performed 24 hours and 4 weeks after the cell injection. It can be seen that the fluorescence expression of the CXCL9-UC-MSCs group was significantly higher than that of the control UC-MSCs group, which proved that CXCL9-UC-MSCs have a stronger chemotactic ability, and can stay longer than control UC-MSCs in the injured liver.Conclusion: Overexpression of CXCL9 improves the efficacy of UC-MSC therapy for liver fibrosis repair, thereby promoting the homing and staying of UC-MSCs to injured hepatic sites in a rat model of liver fibrosis.
Ephaptic Coupling in Hybrid Neuronal Model
Authors: Cunha Gabriel Moreno , Corso Gilberto , Miranda José Garcia Vivas , Lima Gustavo Zampier Dos Santos 
Published: July 2021

Abstract
In recent decades, there has been growing interest in the impact of electric fields generated in the brain. Transmembrane ionic currents originate electric fields in the extracellular space and are capable of affecting nearby neurons, a phenomenon called ephaptic neuronal communication. In the present work, the Quadratic Integrate-and-Trigger model (QIF-E) underwent an adjustment/improvement to include the ephaptic coupling behavior between neurons and their results are compared to the empirical results. In this way, the analysis tools are employed according to the neuronal activity regime: (i) for the subthreshold regime, the circular statistic is used to describe the phase differences between the input stimulus signal and the modeled membrane response; (ii) in the suprathreshold regime, the Population Vector and the Spike Field Coherence are employed to estimate phase preferences and the coupling intensity between the input stimulus and the Action Potentials. The results observed are i) in the subthreshold regime the values of the phase differences change with distinct frequencies of an input stimulus; ii) in the supra-threshold regime the preferential phase of Action Potentials changes for different frequencies. In addition, we explore other parameters of the model, such as noise and membrane characteristic-time, in order to understand different types of neurons and extracellular environment related to ephaptic communication. Such results are consistent with results observed in empirical experiments based on ephaptic coupling behavior. In addition, the QIF-E model allows further studies on the physiological importance of ephaptic coupling in the brain, and its simplicity can open a door to simulating ephaptic coupling in neuron networks and evaluating the impact of ephaptic communication in such scenarios.
Intraspinal Sparganosis Diagnosed by Metagenomics Next Generation Sequencing：An Uncommon Infection
Authors: Wang Rongming , Hu Bobin , Jiang Jianning , Su Minghua 
Published: July 2021

Abstract
In this paper, we report a case of lumbago with lower limb fatigue. After a series of biochemical, immunological, imaging, and pathological examinations, the patient was diagnosed with intraspinal sparganosis based on metagenomics next generation sequencing. Due to the length of infection, the presence of multiple complex lesions, and the high risk of surgical treatment with poor prognosis, we did not advocate surgical treatment, but chose to administer a high dose and long course of praziquantel treatment for this case.
Prospective Associations Between Alcohol Consumption and Psychological Well-being in Midlife
Authors: Grønkjær Marie , Wimmelmann Cathrine Lawaetz , Mortensen Erik Lykke , Flensborg-Madsen Trine 
Published: July 2021

Abstract
Background: Alcohol consumption potentially influences psychological well-being in beneficial and harmful ways, but prospective studies on the association show mixed results. Our main purpose was to examine prospective associations between alcohol consumption and psychological well-being in middle-aged men and women. Methods: The study sample included 4,148 middle-aged individuals (80% men) from the Copenhagen Aging and Midlife Biobank who reported their alcohol consumption (average weekly consumption and frequency of binge drinking) at baseline in 2004 or 2006 and reported their psychological well-being (satisfaction with life and vitality) at follow-up in 2009–2011. Analyses were adjusted for sociodemographic factors, lifestyle, social relations, and morbidity.Results: For satisfaction with life at follow-up, lower scores were observed in men and women who were alcohol abstinent at baseline as well as in men with heavy alcohol consumption compared with moderate alcohol consumption at baseline. Moreover, men with moderate frequency of binge drinking (1–3 times/month) at baseline had higher satisfaction with life scores at follow-up than men with less and more frequent binge drinking. In relation to vitality at follow-up, alcohol abstinence at baseline in men and women and heavy alcohol consumption at baseline in men were associated with lower scores compared with moderate alcohol consumption. Conclusions: Alcohol abstinence seems to be prospectively associated with adverse psychological well-being in men and women, while heavy alcohol consumption seems to be prospectively associated with adverse psychological well-being in men. Finally, an inverse u-shaped prospective association between binge drinking and life satisfaction was observed in men.
Amplification, copy number variation, expression and association of non-synonymous SNP of bovine beta-defensin 129 gene with distinct fertility of cattle bull
Authors: Solanki Subhash , Kashyap Poonam ,   Ashutosh vats1, Kumar Vijay , Pukhrambam Martina , De Sachinandan , Kumar Rakesh , Datta* Tirtha Kumar 
Published: July 2021

Abstract

Background: The male reproductive specific class-A β-defensins are adsorbed on sperm surface and enrich sperm functioning thus considered vital for maintaining male fertility. The primate DEFB129 play role in sperm maturation, motility, and fertilization but its contribution to bovine fertility is still unexplored.Method: RLM-RACE and RT-qPCR approaches were used to characterize and expression analysis of Indian cattle BBD129 gene. The polymorphism analysis of the BBD129 gene was done by PCR, sequencing, and absolute RT-qPCR on sperm gDNA from distinct fertility cattle bulls. Bioinformatic analysis was performed to understand the structural and functional implications of SNP on BBD129 protein.Results: The complete coding sequence of the BBD129 gene consists of 582 bp mRNA including UTRs and conserves all beta-defensin-like characteristics. Sequencing results revealed two conserved non-synonymous T169G (rs378737321, S57A) and A329G (rs383285978, N110S) SNPs in the functional protein-coding exon. Based on SNP position and linkage, BBD129 gene haplotypes were categorized into four groups: TA haplotype (169T & 329A), GA haplotype (T169G polymorphism), TG haplotype (A329G polymorphism), and GG haplotype (when T169G & A329G polymorphisms present together). The frequencies distributions of BBD129 haplotypes in the high fertile group (n=105 clones) were: TA (71.42%), GA (1.90%), TG (2.8%), and GG (24.76%), while in the low fertile group of bulls, the frequencies distributions of observed BBD129 haplotypes (n=149 clones) were: TA (36.24%), GA (0%), TG (2.68%), and GG (61.07%). The distributions of TA haplotype were majorly distributed in bulls with a high conception rate (P=0.5256) while double mutated GG haplotype was significantly more abundant in bulls with a lower conception rate (P=0.0001). BBD129 exist as a single-copy gene in the bovine genome and found higher expression in the corpus-epididymis region. Bioinformatic analyses found nsSNPs as neutral and non-deleterious but their structural-distorter could result in altered mRNA secondary structure, protein conformations decreased protein stability, and compromised biological functionalities. The polymorphisms resulted in altered O-glycosylations (deletion S57A and insertion N110S) and an increase in phosphorylations (52T-Threonine and 110S-Serine) post-translational-modifications.Conclusion: BBD129 gene polymorphism could be associated with the fertility performance of cattle bulls.
Establishing Analytical Validity of BeadChip Array Genotype Data by Comparison to Whole-Genome Sequence and Standard Benchmark Datasets
Authors: Cherukuri Praveen F , Soe Melissa M. , Condon David E. , Bartaria Shubhi , Meis Kaitlynn , Gu Shaopeng , Frost Frederick G. , Fricke Lindsay M. , Lubieniecki Krzysztof P. , Lubieniecka Joanna M. , Pyatt Robert E. , Hajek Catherine , Boerkoel Cornelius F. , Carmichael Lynn 
Published: July 2021

Abstract
Background Clinical use of genotype data requires high positive predictive value (PPV) and thorough understanding of the genotyping platform characteristics. BeadChip arrays, such as the Global Screening Array (GSA), potentially offer a high-throughput, low-cost clinical screen for known variants. We hypothesize that quality assessment and comparison to whole-genome sequence and benchmark data establish the analytical validity of GSA genotyping.Methods To test this hypothesis, we selected 263 samples from Coriell, generated GSA genotypes in triplicate, generated whole genome sequence (rWGS) genotypes, assessed the quality of each set of genotypes, and compared each set of genotypes to each other and to the 1000 Genomes Phase 3 (1KG) genotypes, a performance benchmark. For 59 genes (MAP59), we also performed theoretical and empirical evaluation of variants deemed medically actionable predispositions.Results Quality analyses detected sample contamination and increased assay failure along the chip margins. Comparison to benchmark data demonstrated that > 82% of the GSA assays had a PPV of 1. GSA assays targeting transitions, genomic regions of high complexity, and common variants performed better than those targeting transversions, regions of low complexity, and rare variants. Comparison of GSA data to rWGS and 1KG data showed >99.3% concordance across all measured parameters. GSA detection of variation within the MAP59 genes was 3/261 consistent with predictions from prior studies.Conclusion We establish the analytical validity of GSA assays using quality analytics and comparison to benchmark and rWGS data. GSA assays meet the standards of a clinical screen although assays interrogating rare variants, transversions, and variants within low-complexity regions require careful evaluation.