bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predicting engagement and performance through firm’s internal factors
Authors: Ali Zulqurnain , Sabir Sadia , Mehreen Aqsa 
Published: June 2019

PurposeThe purpose of this paper is to investigate how the firm’s internal factors influence employee engagement (EE), which, in turn, enhances the performance of textile employees. Furthermore, the present study pursues to address the indirect effect of EE on the relationship between the firm’s internal factors and employee performance.Design/methodology/approachData were taken from 355 participants working in textile mills through a survey approach. Structural equation modeling was run to confirm the proposed model and structural relationships.FindingsResults highlight that internal communication and reward and recognition are significantly related to EE, except for work‒life balance. Furthermore, EE has a significant effect on the performance of textile employees.Practical implicationsThe present study helps the textile managers to improve employee performance while focusing on the firm’s internal factors of engagement. Proactive internal communication and reward system will help to bring a competitive edge and achieve the organizational goals. The findings also provide managers the information to reduce the organization interruptions in enhancing EE and performance.Originality/valueThis study covered the hidden gap in the previous literature on EE and performance, especially in the field of the textile sector by employing Kahn’s theory of engagement.
Leadership behaviors during lean healthcare implementation: a review and longitudinal study
Authors: Tortorella Guilherme , van Dun Desirée H. , de Almeida Amanda Gundes 
Published: June 2019

PurposeThe purpose of this paper is to examine leadership behaviors associated with lean healthcare (LH) implementation and how they develop throughout the change process.Design/methodology/approachAfter a systematic literature review of 107 peer-reviewed articles on lean leaders’ behaviors, the authors undertook a one-year mixed-methods study of 12 leaders within a Brazilian public hospital undergoing LH implementation. Multivariate data analysis techniques were employed.FindingsThe literature review showed some convergence between effective lean leader behaviors in both manufacturing and healthcare work settings, implying that lean leaders’ behaviors are generalizable to other contexts than manufacturing. The empirical findings suggest that LH implementation needs leaders to demonstrate a set of task-oriented behaviors, especially if short-term results are mandatory. More mature lean leaders should also continue developing their relations-oriented behaviors.Research limitations/implicationsWhile the contingency theory assumes that contexts influence (lean) practices adoption, leadership behaviors may not be bound to the work context. The finding resembles the augmentation effect of leadership whereby more mature lean leaders adopt both task- and relations-oriented behaviors.Originality/valueLongitudinal studies in this field are scarce, regardless of the industrial setting. Many manufacturing and healthcare organizations crave for knowledge about lean leader behaviors throughout the lean implementation journey in order to enhance the effectiveness of their often-struggling lean initiatives. The insights derived from this study could help organizations to adjust their expectations as well as identify behavioral gaps and needs in terms of soft skills development among their leaders.
Knowledge-intensive entrepreneurship: a systematic review and future directions
Authors: Sousa Caio , Silva Luciana Soares 
Published: June 2019

PurposeThis study aims to propose a framework based on the main theoretical and empirical contributions present in the literature and articulate the main paths for future studies in knowledge-intensive entrepreneurship (KIE).Design/methodology/approachUsing the systematic review method from a survey of 85 articles,related to the KIE focal issue, originated from the Web of Science, it was possible to exhaustively analyze the studies and to divide the theme into key categories.FindingsThe present research has raised the relationship of five categories to KIE conceptualizations; the data suggest that although the literature indicates a distancing from KIE research, there are multidisciplinary themes and approaches interlinked in the studies.Originality/valueThe systematic approach in the main theoretical and empirical contributions in KIE enabled us to relate five categories (entrepreneurs, innovation, internationalization, location and triple alliance), and finally, to understand the gaps suggested by the researchers.
Intermittent Oral Dosing of Roxadustat in Peritoneal Dialysis Chronic Kidney Disease Patients with Anemia: A Randomized, Phase 3, Multicenter, Open‐Label Study
Authors: Akizawa Tadao , Otsuka Tetsuro , Reusch Michael , Ueno Mai 
Published: June 2019

AbstractRoxadustat is an oral hypoxia‐inducible factor prolyl hydroxylase inhibitor developed to treat anemia in chronic kidney disease (CKD) patients. This Phase 3, randomized, open‐label, 24‐week study investigated the efficacy and safety of roxadustat in Japanese CKD patients with anemia on peritoneal dialysis (PD) who were previously treated or not treated with erythropoiesis stimulating agents (ESAs). Patients not previously receiving ESA (ESA‐Naïve group) were randomized to roxadustat at a starting dose of 50 or 70 mg three times weekly; patients previously receiving ESA (ESA‐Converted group) switched from ESA to roxadustat 70 or 100 mg three times weekly depending on the prior ESA dose. Outcomes included maintenance rate of average hemoglobin (Hb) level within 10–12 g/dL at weeks 18–24, cumulative response rate at end of treatment (Hb thresholds, 10.0 g/dL or 10.5 g/dL; Hb increase, ≥1.0 g/dL), and average Hb levels at weeks 18–24. Safety was assessed by occurrence of treatment‐emergent adverse events (TEAEs). Fifty‐six patients were enrolled (ESA‐Naïve, n = 13; ESA‐Converted, n = 43). Maintenance rates (weeks 18–24) were 92.3% (95% CI: 64.0–99.8; ESA‐Naïve) and 74.4% (95% CI: 58.8–86.5; ESA‐Converted). Cumulative response rate was 100.0% in the ESA‐Naïve group. Average Hb levels (weeks 18–24) were 11.05 g/dL (95% CI: 10.67–11.42; ESA‐Naïve) and 10.93 g/dL (95% CI: 10.73–11.13; ESA‐Converted). Common TEAEs included nasopharyngitis and back pain. Roxadustat was well tolerated and effective in maintaining target Hb levels in CKD patients on PD who were previously treated or not treated with ESA.
Effect of alcohol on the sense of agency in healthy humans
Authors: De Pirro Silvana , Lush Peter , Parkinson Jim , Duka Theodora , Critchley Hugo D. , Badiani Aldo 
Published: June 2019

AbstractEven at low to moderate doses, ingestion of the widely used recreational drug alcohol (ethanol) can impact cognitive and emotional processing. Recent studies show that the sense of agency (SoA; ie, the subjective experience of voluntary control over actions) can be modulated by specific pharmacological manipulations. The SoA, as quantified by the intentional binding (IB) paradigm, is enhanced by direct or indirect dopaminergic agonists in patients with Parkinson's disease and by ketamine (an N‐methyl‐D‐aspartate (NMDA) receptor antagonist) in healthy individuals. These findings implicate dopaminergic and glutamatergic neurotransmission in mechanisms underlying SoA. Alcohol has a complex set of actions, including disinhibition of dopaminergic neurotransmission and allosteric antagonism at NMDA receptors. Here, we tested the hypothesis that low to moderate doses of alcohol would enhance SoA, and impact impulsivity and subjective emotional state. We conducted two experiments in 59 healthy male and female social drinkers, who ingested either a placebo “vehicle,” or one of two doses of ethanol: 0.4 and 0.6 g/kg. In both experiments, we observed increased SoA/IB at both doses of alcohol exposure, relative to the placebo condition. We found no correlation between the effects of alcohol on IB and on impulsivity or subjective emotional state. Our findings might have implications for social and legal responsibility related to alcohol use, particularly in states prior to overt intoxication. Further studies are necessary to investigate the effects of alcohol and other addictive substances on the SoA.
The development and validation of the Score for the Prediction of Postoperative Respiratory Complications (SPORC‐2) to predict the requirement for early postoperative tracheal re‐intubation: a hospital registry study
Authors: Lukannek C. , Shaefi S. , Platzbecker K. , Raub D. , Santer P. , Nabel S. , Lecamwasam H.S. , Houle T.T. , Eikermann M. 
Published: June 2019

SummaryPostoperative pulmonary complications are associated with an increase in mortality, morbidity and healthcare utilisation. The Agency for Healthcare Research and Quality recommends risk assessment for postoperative respiratory complications in patients undergoing surgery. In this hospital registry study of adult patients undergoing non‐cardiac surgery between 2005 and 2017 at two independent healthcare networks, a prediction instrument for early postoperative tracheal re‐intubation was developed and externally validated. This was based on the development of the Score for Prediction Of Postoperative Respiratory Complications. For predictor selection, stepwise backward logistic regression and bootstrap resampling were applied. Development and validation cohorts were represented by 90,893 patients at Partners Healthcare and 67,046 patients at Beth Israel Deaconess Medical Center, of whom 699 (0.8%) and 587 (0.9%) patients, respectively, had their tracheas re‐intubated. In addition to five pre‐operative predictors identified in the Score for Prediction Of Postoperative Respiratory Complications, the final model included seven additional intra‐operative predictors: early post‐tracheal intubation desaturation; prolonged duration of surgery; high fraction of inspired oxygen; high vasopressor dose; blood transfusion; the absence of volatile anaesthetic use; and the absence of lung‐protective ventilation. The area under the receiver operating characteristic curve for the new score was significantly greater than that of the original Score for Prediction Of Postoperative Respiratory Complications (0.84 [95%CI 0.82–0.85] vs. 0.76 [95%CI 0.75–0.78], respectively; p < 0.001). This may allow clinicians to develop and implement strategies to decrease the risk of early postoperative tracheal re‐intubation.
A systematic review of cannabidiol dosing in clinical populations
Authors: Millar S.A. , Stone N.L. , Bellman Z.D. , Yates A.S. , England T.J. , O'Sullivan S.E. 
Published: June 2019

AimsCannabidiol (CBD) is a cannabis‐derived medicinal product with potential application in a wide‐variety of contexts; however, its effective dose in different disease states remains unclear. This review aimed to investigate what doses have been applied in clinical populations, in order to understand the active range of CBD in a variety of medical contexts.MethodsPublications involving administration of CBD alone were collected by searching PubMed, EMBASE and ClinicalTrials.gov.ResultsA total of 1038 articles were retrieved, of which 35 studies met inclusion criteria covering 13 medical contexts. Twenty‐three studies reported a significant improvement in primary outcomes (e.g. psychotic symptoms, anxiety, seizures), with doses ranging between <1 and 50 mg/kg/d. Plasma concentrations were not provided in any publication. CBD was reported as well tolerated and epilepsy was the most frequently studied medical condition, with all 11 studies demonstrating positive effects of CBD on reducing seizure frequency or severity (average 15 mg/kg/d within randomised controlled trials). There was no signal of positive activity of CBD in small randomised controlled trials (range n = 6–62) assessing diabetes, Crohn's disease, ocular hypertension, fatty liver disease or chronic pain. However, low doses (average 2.4 mg/kg/d) were used in these studies.ConclusionThis review highlights that CBD has a potential wide range of activity in several pathologies. Pharmacokinetic studies as well as conclusive phase III trials to elucidate effective plasma concentrations within medical contexts are severely lacking and highly encouraged.
Simultaneous phenotyping of CYP2E1 and CYP3A using oral chlorzoxazone and midazolam microdoses
Authors: Hohmann Nicolas , Blank Antje , Burhenne Jürgen , Suzuki Yosuke , Mikus Gerd , Haefeli Walter E. 
Published: June 2019

AimsChlorzoxazone is the paradigm marker substrate for CYP2E1 phenotyping in vivo. Because at the commonly used milligram doses (250–750 mg) chlorzoxazone acts as an inhibitor of the CYP3A4/5 marker substrate midazolam, previous attempts failed to combine both drugs in a common phenotyping cocktail. Microdosing chlorzoxazone could circumvent this problem.MethodWe enrolled 12 healthy volunteers in a trial investigating the dose–exposure relationship of single ascending chlorzoxazone oral doses over a 10,000‐fold range (0.05–500 mg) and assessed the effect of 0.1 and 500 mg of chlorzoxazone on oral midazolam pharmacokinetics (0.003 mg).ResultsChlorzoxazone area under the concentration–time curve was dose‐linear in the dose range between 0.05 and 5 mg. A nonlinear increase occurred with doses ≥50 mg, probably due to saturated presystemic metabolic elimination. While midazolam area under the concentration–time curve increased 2‐fold when coadministered with 500 mg of chlorzoxazone, there was no pharmacokinetic interaction between chlorzoxazone and midazolam microdoses.ConclusionThe chlorzoxazone microdose did not interact with the CYP3A marker substrate midazolam, enabling the simultaneous administration in a phenotyping cocktail. This microdose assay is now ready to be further validated and tested as a phenotyping procedure assessing the impact of induction and inhibition of CYP2E1 on chlorzoxazone microdose pharmacokinetics.
Do we have a right to an unmanipulated genome? The human genome as the common heritage of mankind
Authors: Primc Nadia 
Published: June 2019

AbstractThe human genome is commonly regarded as a ‘natural’ connection between all human beings, as it has been handed down to us by our predecessors. As such, it is believed to represent common heritage of humanity, e.g. a resource of outstanding value that should be the object of special protection and international concern. Some critics argue that germline manipulation would disrupt this natural heritage and that we have a duty to preserve the integrity of the human germline. However, a closer look reveals that the concept of common heritage of humanity does not necessarily imply the impermissibility of germline manipulation. If it is restricted to the prevention of severe diseases, germline manipulation does not represent a threat to the unity and identity of the human species, even though this would create a new form of relationship between human beings, namely that between a designer and a genetically designed person.
The role of values in scientific theory selection and why it matters to medical education
Authors: Ellis Rebecca D. 
Published: June 2019

AbstractIn this paper, I argue that the role of values in theory selection is an important issue within medical education. I review the underdetermination argument, which is the idea within philosophy of science that the data serving as evidence for theories are by themselves not sufficient to support a theory to the exclusion of alternatives. There are always various explanations compatible with the data, and we ultimately appeal to certain values as our grounds for choosing one theory over another. I explore some of the ways contemporary feminist philosophers have chosen to grapple with the problem of underdetermination and proposed solutions to systematize how values might be incorporated into theory choice, drawing primarily from the work of Helen Longino and Elizabeth Anderson. I conclude by discussing how value‐laden inquiry should be incorporated within medical education to promote reflection towards medicine’s normative underpinnings.
Anxiety among women experiencing medically complicated pregnancy: A systematic review and meta‐analysis
Authors: Abrar Ambar , Fairbrother Nichole , Smith André P. , Skoll Amanda , Albert Arianne Y. K. 
Published: June 2019

AbstractBackgroundSymptoms of anxiety are common among pregnant and postpartum women, and 15%‐20% of pregnancies are affected by medical complications. Despite this, little is known about the relationship of medical complications in pregnancy and women's experience of anxiety. The purpose of this research was to conduct a systematic review and meta‐analysis of differences in anxiety symptom severity among women experiencing a medically complicated versus a medically uncomplicated pregnancy.MethodsThis work was guided by the PRISMA reporting process. Electronic databases MEDLINE and PsycINFO were searched to identify studies that met the inclusion criteria. An adaptation of the Newcastle‐Ottawa Quality Assessment Scale for case‐control studies was used to perform a quality assessment review. A random‐effects meta‐analysis was used to calculate the estimated average standardized mean differences.ResultsBased on the five studies which met our inclusion criteria, findings provide evidence of higher levels of anxiety symptoms among pregnant women experiencing a medically complicated versus a medically uncomplicated pregnancy. Despite considerable heterogeneity, all mean difference estimates are in the direction of greater anxiety in the high‐risk groups.ConclusionsWomen experiencing a medically complex pregnancy report higher levels of anxiety symptoms compared to women experiencing a medically uncomplicated pregnancy.
The immune response‐related mutational signatures and driver genes in non‐small‐cell lung cancer
Authors: Chen Hao , Chong Wei , Teng Changcai , Yao Yueliang , Wang Xin , Li Xue 
Published: June 2019

AbstractImmune checkpoint blockade (ICB) therapy has achieved remarkable clinical benefit in non‐small‐cell lung cancer (NSCLC), but our understanding of biomarkers that predict the response to ICB remain obscure. Here we integrated somatic mutational profile and clinicopathologic information from 113 NSCLC patients treated by ICB (CTLA‐4/PD‐1). High tumor mutation burden (TMB) and neoantigen burden were identified significantly associated with improved efficacy in NSCLC immunotherapy. Furthermore, we identified apolipoprotein B mRNA editing enzyme, catalytic polypeptide‐like (APOBEC) mutational signature was markedly associated with responding of ICB therapy (log‐rank test, P = .001; odds ratio (OR), 0.18 [95% CI, 0.06‐0.50], P < .001). The association with progression‐free survival remained statistically significant after controlling for age, sex, histological type, smoking, PD‐L1 expression, hypermutation, smoking signature and mismatch repair (MMR) (HR, 0.30 [95% CI, 0.12‐0.75], P = .010). Combined high TMB with APOBEC signature preferably predict immunotherapy responders in NSCLC cohort. The CIBERSORT algorithm revealed that high APOBEC mutational activity samples were associated with increased infiltration of CD4 memory activated T cells, CD8+ T cells and natural killer (NK) cells, but reduced infiltration of regulatory T cells. Besides, individual genes mutation of IFNGR1 or VTCN1 were only found in responders; however, the PTEN mutation was only found in non‐responders (Fisher's exact test, all P < .05). These findings may be applicable for guiding immunotherapy for patients with NSCLC.
Effect of hyperinsulinaemia and insulin resistance on endocrine, metabolic and fertility outcomes in women with polycystic ovary syndrome undergoing ovulation induction
Authors: Zhang Duojia , Yang Xinming , Li Jian , Yu Jiarui , Wu Xiaoke 
Published: June 2019

AbstractObjectiveThe aim of this study was to evaluate the effects of hyperinsulinaemia and insulin resistance (IR) on reproductive and metabolic disorders and fertility in women with polycystic ovary syndrome (PCOS).Design, Setting, Participants and MeasurementsThis was a multicenter, randomized controlled trial involving a total of 1000 women diagnosed with PCOS according to the modified Rotterdam criteria at 21 sites (27 hospitals). We evaluated the effects of serum insulin levels and HOMA‐IR on parameters and outcomes. The main outcome measures were anthropometric, biometric and ultrasound parameters at baseline and the clinical outcomes of ovulation, conception, pregnancy, live birth and pregnancy loss.ResultsThe relevant analysis between hyperinsulinaemia and IR and clinical characteristics showed that weight, waist and hip circumference, BMI, waist‐to‐hip ratio, acanthosis nigricans score and menstrual period were significantly correlated with fasting insulin (FIN) and HOMA‐IR. There was no significant correlation between the hirsutism score or acne score with FIN or HOMA‐IR. The relevant analysis between hyperinsulinaemia and IR and circulating sex steroids and gonadotrophins showed that FAI was significantly correlated with FIN and HOMA‐IR (r = 0.240, P < 0.001 and r = 0.191, P < 0.001, respectively). Free testosterone was significantly correlated with FIN after adjusting for the influence of age. LH and LH/FSH were not related to FIN or HOMA‐IR after statistical correction for differences in BMI. The relevant analysis between hyperinsulinaemia and IR and metabolic profile showed that FIN and HOMA‐IR were positively associated with fasting glucose, cholesterol, triglycerides, low‐density lipoprotein, Apo B, and the incidence of metabolic syndrome and were negatively associated with high‐density lipoprotein. The predictive analysis between hyperinsulinaemia and IR with fertility showed that the levels of FIN and HOMA‐IR were related to the fertility outcome (ovulation, pregnancy, conception or live birth) in patients with PCOS. After adjustments for age, total testosterone and free testosterone, increasing serum insulin levels and HOMA‐IR were significantly associated with decreased cycle ovulation, conception, pregnancy and live birth rates.ConclusionsHyperinsulinaemia and IR are associated with reproductive and metabolic disorders and can predict the fertility outcomes in PCOS patients.
14‐3‐3ζ targeting induced senescence in Hep‐2 laryngeal cancer cell through deneddylation of Cullin1 in the Skp1‐Cullin‐F‐box protein complex
Authors: Seo Sung Bin , Baek Ji‐Ye , Lim Ji‐Hee , Jin Xuyan , Lee Mun‐Yong , Lee Jeong‐Hwa 
Published: June 2019

AbstractObjectivesDespite of the aberrant expression of 14‐3‐3ζ in head and neck squamous cell carcinoma (HNSCC), little is known about the role of 14‐3‐3ζ in the regulation of senescence in HNSCC. This study was performed to investigate whether 14‐3‐3ζ is implicated in senescence evasion of Hep‐2 laryngeal cancer cells.MethodsThe expression of 14‐3‐3ζ was suppressed using RNA interference strategy. Senescence induction was determined by senescence‐associated β‐galactosidase staining and the numbers of promyelocytic leukaemia nuclear body. Real‐time PCR, western blotting and immunohistochemistry were applied for the expression of corresponding proteins. Xenograft experiment was performed to show in vivo effect of 14‐3‐3ζ silencing on tumour growth.Results14‐3‐3ζ silencing significantly induced senescence phenotypes via 27 accumulations. Subsequently, we demonstrated that p27 accumulation is linked to inactivation of SCFSkp2 complex activity, probably due to the deneddylation of cullin‐1 (Cul‐1) as follows. (a) Neddylated Cul‐1 is decreased by 14‐3‐3ζ silencing. (b) Blocking neddylation using MLN4924 reproduces senescence phenotypes. (c) Knockdown of CSN5, which functions as a deneddylase, was shown to restore the senescence phenotypes induced by 14‐3‐3ζ depletion. Finally, we demonstrated that 14‐3‐3ζ depletion effectively hindered the proliferation of Hep‐2 cells implanted into nude mice.Conclusion14‐3‐3ζ negatively regulates senescence in Hep‐2 cells, suggesting that 14‐3‐3ζ targeting may serve to suppress the expansion of laryngeal cancer via induction of senescence through the Cul‐1/SCFSkp2/p27 axis.