bluuebunny/crossref_metadata_2025_split huggingface dataset:
Concordance between flow cytometry CLL scores
Authors: Sorigue Marc , Raya Minerva , Vergara Sara , Junca Jordi 
Published: May 2021

AbstractIntroductionMultiple flow cytometry scores/diagnostic systems for the classification of leukemic lymphoproliferative disorders (LPD) have been published but few have been compared between them.Patients and MethodsWe classified a cohort of leukemic LPD based on eleven published flow cytometry scores/diagnostic systems and compared their classification as chronic lymphocytic leukemia (CLL) or non‐CLL LPD.Results329 patients were included. Patients classified as CLL ranged from 46% to 73%, depending on the score/diagnostic system used. All eleven scores/diagnostic systems agreed in 184/324 (57%) of patients while in 58/324 (18%) at least two scores/diagnostic systems classified the patient differently (from the majority). Fleiss kappa was 0.74, but pairwise agreement was variable (Cohen's kappa: 0.48 to 0.87).ConclusionThis study found a suboptimal agreement between published flow cytometry scores/diagnostic systems for the classification of LPD.
Development of a model to predict closure of chronic wounds in Germany: Claims data analysis
Authors: Hagenström Kristina , Protz Kerstin , Petersen Jana , Augustin Matthias 
Published: May 2021

AbstractPatients with chronic leg ulcer, pressure ulcer, or diabetic foot ulcer suffer from significant disease burden. With a view to improving healthcare provision sustainably, a predictive model of time to closure (time‐to‐event analysis) based on claims data was developed. To identify potential predictors of wound closure, clinical information absent from statutory health insurance (SHI) data was modelled. In patients with leg ulcers, age of the patient (hazard ratios [HR] 0.99), increasing number of comorbidities (HR 0.94), inpatient stays (HR 0.74), and treatment by a specialised wound care professional (HR 1.18) were significant predictors of time to closure (adjusted model). In almost all models, the number of inpatient stays and of comorbidities predicted a lower probability of healing. In addition, the age and the sex of the patient were found to be significant predictors in some models (leg ulcer: HR 0.99; pressure ulcer: HR 0.99). Increasing number of comorbidities and inpatient stays were predictors for closure time in all models. Since these predictors may give an indication of wound severity, further clinical information should be considered in future models, as also indicated by the moderate values of thec‐statistics. This requires future data linkage between SHI and primary studies (eg, registers).
Nintedanib attenuates peritoneal fibrosis by inhibiting mesothelial‐to‐mesenchymal transition, inflammation and angiogenesis
Authors: Liu Feng , Yu Chao , Qin Huan , Zhang Shenglei , Fang Lu , Wang Yi , Wang Jun , Cui Binbin , Hu Susie , Liu Na , Zhuang Shougang 
Published: May 2021

AbstractNintedanib, an Food and Drug Administration (FDA) approved multiple tyrosine kinase inhibitor, exhibits an anti‐fibrotic effect in lung and kidneys. Its effect on peritoneal fibrosis remains unexplored. In this study, we found that nintedanib administration lessened chlorhexidine gluconate (CG)‐induced peritoneal fibrosis and reduced collagen I and fibronectin expression. This coincided with suppressed phosphorylation of platelet‐derived growth factor receptor, fibroblast growth factor receptors, vascular endothelial growth factor receptor and Src family kinase. Mechanistically, nintedanib inhibited injury‐induced mesothelial‐to‐mesenchymal transition (MMT), as demonstrated by decreased expression of α‐smooth muscle antigen and vimentin and preserved expression of E‐cadherin in the CG‐injured peritoneum and cultured human peritoneal mesothelial cells exposed to transforming growth factor‐β1. Nintedanib also suppressed expression of Snail and Twist, two transcription factors associated with MMT in vivo and in vitro. Moreover, nintedanib treatment inhibited expression of several cytokines/chemokines, including tumour necrosis factor‐α, interleukin‐1β and interleukin‐6, monocyte chemoattractant protein‐1 and prevented infiltration of macrophages to the injured peritoneum. Finally, nintedanib reduced CG‐induced peritoneal vascularization. These data suggest that nintedanib may attenuate peritoneal fibrosis by inhibiting MMT, inflammation, and angiogenesis and have therapeutic potential for the prevention and treatment of peritoneal fibrosis in patients on peritoneal dialysis.
Metabolic changes during carbon monoxide poisoning: An experimental study
Authors: Simonsen Carsten , Magnusdottir Sigriður Olga , Andreasen Jan Jesper , Wimmer Reinhard , Rasmussen Bodil Steen , Kjærgaard Benedict , Maltesen Raluca Georgiana 
Published: May 2021

AbstractCarbon monoxide (CO) is the leading cause of death by poisoning worldwide. The aim was to explore the effects of mild and severe poisoning on blood gas parameters and metabolites. Eleven pigs were exposed to CO intoxication and had blood collected before and during poisoning. Mild CO poisoning (carboxyhaemoglobin, COHb 35.2 ± 7.9%) was achieved at 32 ± 13 minutes, and severe poisoning (69.3 ± 10.2% COHb) at 64 ± 23 minutes from baseline (2.9 ± 0.5% COHb). Blood gas parameters and metabolites were measured on a blood gas analyser and nuclear magnetic resonance spectrometer, respectively. Unsupervised principal component, analysis of variance and Pearson's correlation tests were applied. A P‐value ≤ .05 was considered statistically significant. Mild poisoning resulted in a 28.4% drop in oxyhaemoglobin (OHb) and 12‐fold increase in COHb, while severe poisoning in a 65% drop in OHb and 24‐fold increase in COHb. Among others, metabolites implicated in regulation of metabolic acidosis (lactate, P < .0001), energy balance (pyruvate, P < .0001; 3‐hydroxybutyrc acid, P = .01), respiration (citrate, P = .007; succinate, P = .0003; fumarate, P < .0001), lipid metabolism (glycerol, P = .002; choline, P = .0002) and antioxidant‐oxidant balance (glutathione, P = .03; hypoxanthine, P < .0001) were altered, especially during severe poisoning. Our study adds new insights into the deranged metabolism of CO poisoning and leads the way for further investigation.
Telomerase/myocardin expressing mesenchymal cells induce survival and cardiovascular markers in cardiac stromal cells undergoing ischaemia/reperfusion
Authors: Madonna Rosalinda , Guarnieri Simone , Kovácsházi Csenger , Görbe Aniko , Giricz Zoltán , Geng Yong‐Jian , Mariggiò Maria Addolorata , Ferdinandy Péter , De Caterina Raffaele 
Published: May 2021

AbstractCardiac stromal cells (CSCs) contain a pool of cells with supportive and paracrine functions. Various types of mesenchymal stromal cells (MSCs) can influence CSCs in the cardiac niche through their paracrine activity. Ischaemia/reperfusion (I/R) leads to cell death and reduction of the paracrine activity of CSCs. The forced co‐expression of telomerase reverse transcriptase (TERT) and myocardin (MYOCD), known to potentiate anti‐apoptotic, pro‐survival and pro‐angiogenic activities of MSCs isolated from the adipose tissue (AT‐MSCs), may increase CSC survival, favouring their paracrine activities. We aimed at investigating the hypothesis that CSCs feature improved resistance to simulated I/R (SI/R) and increased commitment towards the cardiovascular lineage when preconditioned with conditioned media (CM) or extracellular vesicles (EV) released from AT‐MSCs overexpressing TERT and MYOCD (T/M AT‐MSCs). Murine CSCs were isolated with the cardiosphere (CSps) isolation technique. T/M AT‐MSCs and their secretome improved spontaneous intracellular calcium changes and ryanodine receptor expression in aged CSps. The cytoprotective effect of AT‐MSCs was tested in CSCs subjected to SI/R. SI/R induced cell death as compared to normoxia (28 ± 4 vs 10 ± 3%, P = .02). Pre‐treatment with CM (15 ± 2, P = .02) or with the EV‐enriched fraction (10 ± 1%, P = .02) obtained from mock‐transduced AT‐MSCs in normoxia reduced cell death after SI/R. The effect was more pronounced with CM (7 ± 1%, P = .01) or the EV‐enriched fraction (2 ± 1%, P = .01) obtained from T/M AT‐MSCs subjected to SI/R. In parallel, we observed lower expression of the apoptosis marker cleaved caspase‐3 and higher expression of cardiac and vascular markers eNOS, sarcomeric α‐actinin and cardiac actin. The T/M AT‐MSCs secretome exerts a cytoprotective effect and promotes development of CSCs undergoing SI/R towards a cardiovascular phenotype.
Glucose‐lowering action through targeting islet dysfunction in type 2 diabetes: Focus on dipeptidyl peptidase‐4 inhibition
Authors: Ahrén Bo 
Published: May 2021

AbstractDipeptidyl peptidase‐4 (DPP‐4) inhibition is a glucose‐lowering medication for type 2 diabetes. It works through stimulation of insulin secretion and inhibition of glucagon secretion in a glucose‐dependent manner, resulting in lowered fasting and postprandial glycemia with low risk of hypoglycemia. As impaired insulin secretion and augmented glucagon secretion are key factors underlying hyperglycemia in type 2 diabetes, DPP‐4 inhibition represents a therapy that targets the underlying mechanisms of the disease. If insufficient in monotherapy, it can preferably be used in combination with metformin, which targets insulin resistance, and also in combination with sodium–glucose cotransporter 2 inhibition, thiazolidinediones and insulin, which target other mechanisms. In individuals of East Asian origin, islet dysfunction is of particular importance for the development of type 2 diabetes. Consequently, it has been shown in several studies that DPP‐4 is efficient in these populations. This mini‐review highlights the islet mechanisms of DPP‐4 inhibition, islet dysfunction as a key factor for hyperglycemia in type 2 diabetes and that, consequently, DPP‐4 is of particular value in populations where islet dysfunction is central, such as in individuals of East Asian origin.
Active share: A blessing and a curse
Authors: Cline Brandon N. , Gilstrap Collin 
Published: May 2021

AbstractWe examine the implications of active mutual fund management across manager skill levels. We find that funds in the highest active share quintile outperform funds in the lowest active share quintile on a risk‐adjusted basis. When sorted on both active share and capture ratio, only managers with high skill and high active share experience positive future performance. Funds with high active share and low skill experience negative future risk‐adjusted returns, and these funds underperform all funds with low active share. We conclude that only funds with both high active management and high manager skill are preferable to index funds.
‘It was quite a shock’: A qualitative study of the impact of organisational and personal factors on newly qualified nurses' experiences
Authors: Ho Szu‐Szu , Stenhouse Rosie , Snowden Austyn 
Published: May 2021

AbstractAims and objectivesTo explore how newly qualified nurses’ work experiences are constructed through the interplay between self, workplace and home‐life influencing their retention.BackgroundNurses are critical to achieving the goal of universal health coverage. However, shortages of nursing staff are endemic. Of particular concern, newly qualified nurses are more likely to leave the nursing workforce. The point of transition to working as a newly qualified nurse is a time of vulnerability. Most studies attempt to discover why nurses leave. This study uses the concept of job embeddedness to examine the experience of this transition and first two years of practice to understand what might help newly qualified nurses stay.DesignQualitative approach using semi‐structured telephone interviews.MethodsSelf‐selecting sample of nurses (n = 23) who participated 1‐year (n = 12) and 2 years (n = 11) post‐qualification. Participants were part of a larger longitudinal cohort (n = 867) study which has followed them since September 2013 when they entered nurse education in two Scottish universities. Thematic analysis was used to understand the interplay between organisation/workplace and the individual.ResultsThree themes were developed: transition shock; workplace factors and work/life balance. Two further subthemes were developed: experience of support and belonging; and feeling unsupported and alienated. Eight participants had changed job or left, and two were looking to leave nursing.ConclusionThis study highlights how the experience of transition shock can be positively or negatively impacted by the workplace environment, and how in turn this impacts the home environment. Ultimately, this impacts retention of newly qualified nurses.Relevance to clinical practiceHaving adequate support resources, such as staffing, supportive team morale, professional development and family‐friendly work environment, can create a work environment where they feel the purpose and meaningfulness of working as a nurse. This ‘job embeddedness’ can potentially enhance nurse retention. Reporting follows the COREQ checklist.
Tubal stump pregnancy after salpingectomy—Does the time interval from surgical intervention to conception matter?
Authors: Melcer Yaakov , Naaman Hilli Zur , Hausman Reut , Vaknin Zvi , Levinsohn‐Tavor Orna , Maymon Ron , Smorgick Noam 
Published: May 2021

AbstractAimEctopic pregnancy implantation on the tubal stump after salpingectomy is a rare location for extrauterine pregnancy, whose pathogenesis is still unknown. The purpose of this study was to examine whether the time interval elapsed from salpingectomy may predispose the embryo to implantation on the tubal stump in the next pregnancy subsequent to tube removal.MethodsNine women operated for stump pregnancy (study group) between 2008 and 2019 were retrospectively identified. For each case in the study group, 12 consecutive cases that underwent laparoscopic salpingectomy constituted the control group. A sample size of 100 control patients was calculated to achieve statistical power (97.8%) and an α of 0.05. The control groups were triple‐matched with the study group for patients' age, indications for salpingectomy (tubal pregnancy or hydrosalpinx prior to in vitro fertilization treatment) and mode of conception of the subsequent pregnancy following salpingectomy.ResultsNine women underwent surgery for stump pregnancy during the study period. All women had a surgical history of laparoscopic salpingectomy. The time interval from prior salpingectomy to subsequent pregnancy was significantly shorter in study group than in the control group (4.3 ± 2.1 months vs. 15.6 ± 13.7 months, respectively, p = 0.016).ConclusionA possible association between the short time interval from prior salpingectomy to ectopic implantation on the tubal stump in the subsequent pregnancy was found. The clinical implications of these findings and in particular whether patients should be advised to wait at least 4 months from the salpingectomy to the subsequent pregnancy remain unclear.
Transcriptome analysis and identification of genes and single‐nucleotide polymorphisms associated with growth traits in the Chinese soft‐shelled turtle, Pelodiscus sinensis
Authors: Zeng Dan , Xiong Gang , Wang Xiaoqing , Zhou Xianwen , Wang Pei , Peng Na , Luo Zhijia , Li Xiao 
Published: May 2021

AbstractThe Chinese soft‐shelled turtle, Pelodiscus sinensis, is an important aquaculture species in China. Understanding the molecular mechanisms of growth regulation may contribute to its genetic improvement and lead to increases in the production. Growth rate in this species varies greatly among individuals, and the variation apparently has a genetic basis. To identify growth‐related genes and explore the molecular mechanism of its growth regulation, fast‐growing and slow‐growing turtles were selected from two growth stages, juveniles or adults, respectively, for transcriptome sequencing with liver tissue using the Illumina sequencing platform. Analyses showed that, in juveniles, 303 genes were differentially expressed, of which 217 genes were expressed at higher levels in the fast‐growing turtles. In adults, 1,093 genes were differentially expressed, of which 682 genes were expressed at higher levels in the fast‐growing turtles. Gene Ontology (GO) enrichment of differentially expressed genes (DEGs) identifies three functional groups being significantly enriched in juveniles, but 71 functional groups in adults. Kyoto Encyclopedia of Genes and Genomes enrichment analysis of DEGs in juveniles identified only one pathway being significantly enriched, the proxisome proliferator‐activated receptor (PPAR) signaling pathway, while eight pathways mostly related to fatty acid metabolism were identified in adults. These findings suggest that regulation of growth is more complicated and involves more genes and pathways in adults compared with juveniles, and metabolic or metabolic‐related genes may relate to the growth difference of P. sinensis. Some key genes related to growth were identified from another six growth‐related signaling pathways, and DEGs in GH‐IGF 1 axis genes and Jak–STAT signaling pathway might play important roles in the growth difference of P. sinensis. In addition, 73 single‐nucleotide polymorphisms (SNPs) from 23 growth‐related genes were successfully genotyped. Growth association analysis in 280 individuals revealed that 2 SNPs in 2 key genes (IGF2R and SLC27A2) were associated with growth of P. sinensis. This study provides information on key genes, SNPs, and biological processes that may be involved in growth and highlights the differentiation of growth regulation in different growth stages of P. sinensis.
Exclusive breastfeeding among working mothers in Kenya: Perspectives from women, families and employers
Authors: Ickes Scott B. , Sanders Hannah , Denno Donna M. , Myhre Jennifer A. , Kinyua Joyceline , Singa Benson , Lemein Hellen Sankaine , Iannotti Lora L. , Farquhar Carey , Walson Judd L. , Nduati Ruth 
Published: May 2021

AbstractExclusive breastfeeding (EBF) for the first 6 months of life improves survival, growth and development. In Kenya, recent legislation and policies advocate for maternity leave and workplace support for breastfeeding and breast milk expression. We conducted a qualitative study to describe factors influencing EBF for 6 months among mothers employed in commercial agriculture and tourism. We interviewed employed mothers (n = 42), alternate caregivers and employed mothers' husbands (n = 20), healthcare providers (n = 21), daycare directors (n = 22) and commercial flower farm and hotel managers (n = 16) in Naivasha, Kenya. Despite recognizing the recommended duration for EBF, employed mothers describe the early cessation of EBF in preparation for their return to work. Managers reported supporting mothers through flexible work hours and duties. Yet, few workplaces have lactation spaces, and most considered adjusting schedules more feasible than breastfeeding during work. Managers and healthcare providers believed milk expression could prolong EBF but thought mothers lack experience with pumping. The most frequently suggested interventions for improving EBF duration were to expand schedule flexibility (100% of groups), provide on‐site daycare (80% of groups) and workplace lactation rooms (60% of groups), improve milk expression education and increase maternity leave length (60% of groups). Returning to work corresponds with numerous challenges including lack of proximate or on‐site childcare and low support for and experience with milk expression. These factors currently make EBF for 6 months unattainable for most mothers in these industries. Interventions and supports to improve breastfeeding upon return to work are recommended to strengthen employed mothers' opportunity for EBF.
Critically ill patients' experience of agitation: A qualitative meta‐synthesis
Authors: Freeman Samantha , Yorke Janelle , Dark Paul 
Published: May 2021

AbstractBackgroundAcute episodes of agitation are frequently experienced by patients during critical illness, yet what is not understood is the experience of agitation from the patient and family perspectives.Aims and objectivesTo search existing literature, appraise it and then provide a synthesized interpretation to broaden the understanding of patients' and their families' experience of agitation during an adult critical care admission.DesignQualitative meta‐synthesis.MethodsA qualitative meta‐synthesis based on a systematic literature search registered with PROSPERO. The search conducted between July and September 2019 was applied to ProQuest, Cumulative Index to Nursing and Allied Health, British Nursing Index, Cochrane Library, Ovid Medline, Web of Science, and PsycINFO databases. We appraised the selected literature and presented a synthesized interpretation. Analysis was based on the approach of Gadamerian hermeneutics. Due to the lack of data identified; the family experiences of agitation could not be addressed within the review.ResultsIn total, 8 studies were included capturing the experiences of 494 patients, aged between 18 and 92 years, with 225 (45%) women. The analysis generated three core themes: (a) What is real, what is not, (b) loss of communication and dependency, and (c) what helps, what does not. Fear of death, the emotion of anxiety, and feelings of pain alongside transient periods of fluctuating conscious levels provoked a feeling of intense vulnerability. The loss of effective communication and the feeling of dependence incite agitation and distress.ConclusionsThe patient's recollection of their critical illness can be completely or partially absent and disjointed with uncertainty around what is real and what is not. Family members observe the full effect of the patient's critical care illness and could be a wealth of untapped information.Relevance to clinical practiceIncreasing awareness of the critically ill patients' experience of agitation highlights possible contributing factors to agitation development, such as staff interaction and communication skills, and the critical care environment.
Preclinical development of plant‐based oral immune modulatory therapy for haemophilia B
Authors: Srinivasan Aparajitha , Herzog Roland W. , Khan Imran , Sherman Alexandra , Bertolini Thais , Wynn Tung , Daniell Henry 
Published: May 2021

SummaryAnti‐drug antibody (ADA) formation is a major complication in treatment of the X‐linked bleeding disorder haemophilia B (deficiency in coagulation factor IX, FIX). Current clinical immune tolerance protocols are often not effective due to complications such as anaphylactic reactions against FIX. Plant‐based oral tolerance induction may address this problem, as illustrated by the recent first regulatory approval of orally delivered plant cells to treat peanut allergy. Our previous studies showed that oral delivery of plant cells expressing FIX fused to the transmucosal carrier CTB (cholera toxin subunit B) in chloroplasts suppressed ADA in animals with haemophilia B. We report here creation of the first lettuce transplastomic lines expressing a coagulation factor, in the absence of antibiotic resistance gene. Stable integration of the CTB‐FIX gene and homoplasmy (transformation of ˜10 000 copies in each cell) were maintained in both T1 and T2 generation marker‐free plants. CTB‐FIX expression in lyophilized leaves of T1 and T2 marker‐free plants was 1.0–1.5 mg/g dry weight, confirming that the marker excision did not affect antigen levels. Oral administration of CTB‐FIX to Sprague Dawley rats at 0.25, 1 or 2.5 mg/kg did not produce overt adverse effects or toxicity. The no‐observed‐adverse‐effect level (NOAEL) is at least 2.5 mg/kg for a single oral administration in rats. Oral administration of CTB‐FIX at 0.3 or 1.47 mg/kg either mixed in food or as an oral suspension to Beagle dogs did not produce any observable toxicity. These toxicology studies should facilitate filing of regulatory approval documents and evaluation in haemophilia B patients.