A comprehensive next generation sequencing tissue assay for Asian-prevalent cancers-Analytical validation and performance evaluation with clinical samples.

Introduction: A well-validated diagnostic assay with curated biomarkers complements clinicopathological factors to facilitate early diagnosis and ensure timely treatment delivery. This study focuses on an Asian-centric cancer diagnostic assay designed and thoroughly validated against commercially available standard references and a cohort of over 200 clinical specimens spanning 12 diverse Asian-centric cancer types. Methods: The assay uses hybrid-capture probes capable of profiling DNA aberrations from 572 cancer-related genes and 91 RNA fusion partners. The panel can detect clinically-tractable biomarkers such as microsatellite instability (MSI) and tumor mutation burden (TMB). Results: Analytical evaluation demonstrated 100% specificity and 99.9% sensitivity within a ≥5% VAF limit of detection (LoD) for SNV/Indels. RNA-based fusion features an LoD of ≥5 copies per nanogram input when evaluated against commercial references. Excellent linearity and concordance were observed when benchmarking against orthogonal methods in identifying MSI status, TMB scores and RNA fusions. Actionable genetic alterations were identified in 65% of the clinical samples. Conclusion: These results demonstrate a molecular diagnostic assay that accurately detects genomic alterations and complex biomarkers. The data also supports an excellent performance of this assay for making critical diagnoses and well-informed therapeutic decisions in Asian prevalent cancers.

Neutrophil to lymphocyte ratio and platelet to lymphocyte ratio reflect disease activity and flares in patients with systemic lupus erythematosus - A prospective study.

OBJECTIVES: To determine the association between neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) with disease activity and flares in an inception cohort of patients with systemic lupus erythematosus (SLE) using a prospective study design. METHODS: Consecutive adult patients (age≥21) who fulfilled the 1997 American College of Rheumatology (ACR) or the 2012 Systemic Lupus International Collaboration Clinic Classification (SLICC) Criteria for SLE were followed every 3 months, with SLE disease activity assessed by using SLEDAI-2K, and disease flares defined and captured by the SELENA-SLEDAI Flare Index (SFI). NLR and PLR were computed from the automated machine-counted blood count differentials. Linear mixed model and generalized estimating equation model were constructed to analyze the associations between NLR/PLR and SLEDAI-2K and disease flares, with multivariate adjustments. RESULTS: Of 290 patients recruited, the median (IQR) duration of follow-up and baseline SLEDAI-2K were 4.7 (3.2-6.1) years and 2 (0.5-3.5), respectively. On multivariable analyses, NLR was shown to be positively and significantly associated with SLEDAI-2K (estimate of coefficient (ß)=0.05, P<0.01) and severe disease flares (odds ratio [OR] 1.05, P<0.05), but not with overall disease flares [OR 1.02, non-significant]. While PLR was shown to be positively associated with SLEDAI-2K [ß=0.09, P<0.05], no statistically significant association between PLR and overall or severe disease flares was found [OR 1.00 and OR 1.06 respectively, non-significant]. CONCLUSION: Derived readily from automated blood count differentials, the NLR potentially serves as a surrogate prospective marker of disease activity and severe disease flares in SLE patients.

A meta-analysis of clinical manifestations in asian systemic lupus erythematous: The effects of ancestry, ethnicity and gender.

OBJECTIVES: Systemic lupus erythematosus (SLE) in Asians is a unique patient group that has been thought to present with more severe organ involvement in comparison to their non-Asian counterparts. We set out to perform a meta-analysis to compare clinical manifestations between ancestries, with a focus on Southeast Asian ethnicities and gender. MATERIALS AND METHODS: A cross-sectional study was performed in conjunction with a meta-analysis to identify differences in prevalences of SLE clinical manifestations. Searches were conducted on Medline for articles comparing between: (i) Asian and non-Asian ancestry; (ii) Southeast Asian ethnicities (Chinese, Malay and Indian); and (iii) male and female Asians. Using random effects model, effect sizes as odd ratios were pooled with DerSimonian and Laird's model. RESULTS: A total of 13 articles were identified and pooled together with our study for this meta-analysis. Comparing among patients of Asian with Non-Asian/European ancestries, no significance difference was found in severe organ manifestations such as renal and neurological involvement [odds ratio (OR): 1.398, p= 0.320 and OR: 1.224, p= 0.526 respectively]. There was significantly greater proportion of Asian SLE patients with thrombocytopenia compared to non-Asian SLE. Chinese SLE patients were less likely to have oral ulcers compared to Indian SLE patients. Lastly, Asian male SLE patients had greater incidence of renal involvement and thrombocytopenia compared to Asian female SLE patients. CONCLUSIONS: Severe SLE manifestations such as renal and neurological involvement were not significantly more frequent in Asian SLE compared to non-Asian/European SLE in this analysis.

Disruptive behavior in a high-power distance culture and a three-dimensional framework for curbing it.

BACKGROUND: Disruptive behavior can harm high-quality care and is prevalent in many Western public health systems despite increasing spotlight on it. Comparatively less knowledge about it is available in Asia, a region commonly associated with high-power distance, which may limit its effectiveness in addressing disruptive behavior. PURPOSE: The aim of this study was to develop a comprehensive framework for tackling disruptive behavior among health care professionals in a public health system. METHODOLOGY: A nationwide cross-sectional study relying on the Nurse-Physician Relationship Survey was conducted in Singapore. Four hundred eighty-six public health care professionals responded. RESULTS: Two hundred ninety-eight doctors (95.5%) and 163 nurses (93.7%) had witnessed a form of disruptive behavior. Doctors observed disruptive behavior committed by other doctors and nurses much more frequently than did nurses. Doctors made stronger associations between disruptive behavior and negative employee outcomes and between disruptive behavior and negative patient outcomes. Qualitative analyses of participants' open-ended answers produced a multipronged three-dimensional approach for tackling disruptive behavior: (a) deterrent measures, (b) development of knowledge and skills, and (c) demonstration of organizational commitment through proper norms, empathizing with staff, and structural reforms. PRACTICE IMPLICATIONS: Disruptive behavior is a multifaceted problem requiring a multipronged approach. Our three-dimensional framework is a comprehensive approach for giving health care professionals the capability, opportunity, and motivation to address disruptive behavior effectively.

Experienced incivility in the workplace: A meta-analytical review of its construct validity and nomological network.

Although workplace incivility has received increasing attention in organizational research over the past two decades, there have been recurring questions about its construct validity, especially vis-à-vis other forms of workplace mistreatment. Also, the antecedents of experienced incivility remain understudied, leaving an incomplete understanding of its nomological network. In this meta-analysis using Schmidt and Hunter's [Methods of meta-analysis: Correcting error and bias in research findings (3rd ed.), Sage] random-effect meta-analytic methods, we validate the construct of incivility by testing its reliability, convergent and discriminant validity, as well as its incremental predictive validity over other forms of mistreatment. We also extend its nomological network by drawing on the perpetrator predation framework to systematically study the antecedents of experienced incivility. Based on 105 independent samples and 51,008 participants, we find extensive support for incivility's construct validity. Besides, we demonstrate that demographic characteristics (gender, race, rank, and tenure), personality traits (agreeableness, conscientiousness, neuroticism, negative affectivity, and self-esteem), and contextual factors (perceived uncivil climate and socially supportive climate) are important antecedents of experienced incivility, with contextual factors displaying a stronger association with incivility. In a supplementary primary study with 457 participants, we find further support for the construct validity of incivility. We discuss the theoretical and practical implications of this study. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Fit to be good: Physical fitness is negatively associated with deviance.

While modern organizations generate economic value, they also produce negative externalities in terms of human physical fitness, such that workers globally are becoming physically unfit. In the current research, we focus on a significant but overlooked indirect cost that lack of physical fitness entails-deviance. In contrast to early (and methodologically limited) research in criminology, which suggests that physically fit people are more likely to behave in a deviant manner, we draw on self-control theory to suggest the opposite: That physically fit people are less likely to engage in deviance. In Study 1, we assembled a dataset on 50 metropolitan areas in the U.S. spanning a 9-year period, and found that physical fitness index of a metropolitan area is negatively related to deviance in that area in a concurrent as well as time-lagged fashion. We complemented this aggregate-level theory test with two studies testing the theory at the individual level. In Study 2, we collected multi-source data from 3,925 military recruits who underwent physical training and found that those who score higher on physical fitness test are less likely to engage in deviance. Study 3 conceptually replicated the effect with both concurrent and time-lagged models using a five-wave longitudinal design in a sample of employees working in service roles, and also found that ego depletion mediates the effect of physical activity on workplace deviance. We speculate on economic implications of the observed relationship between physical fitness and deviance and discuss its relevance for organizations and public policy. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Impact of teleconsultation on subsequent disease activity and flares in patients with systemic lupus erythematosus.

OBJECTIVES: Despite the widespread adoption of teleconsultations amid the COVID-19 pandemic, their safety in SLE patients has not been evaluated. Here, we examined subsequent disease activity and flares among SLE patients who received teleconsultation vs in-person consultation. To discern differences in physicians' prescription behaviour during both forms of consultations, we compared corticosteroid dose adjustments. METHODS: We studied adult SLE patients who were seen between 1 February 2020 and 1 February 2021. At each patient-visit, rheumatologists utilized phone/video teleconsultation or physical consultation at their discretion. Disease activity was assessed with SLE Disease Activity Index 2000 (SLEDAI-2K) and flares were defined by the SELENA-SLEDAI Flare Index (SFI). We derived a propensity score for patients who were chosen for physical consultation. Multivariable generalized estimation equations were used to analyse SLEDAI-2k and flare at the next visit, adjusted for the propensity score. RESULTS: A total of 435 visits were recorded, of which 343 (78.9%) were physical visits and 92 (21.1%) were teleconsultations. The modality of consultation did not predict flare [OR for physical consultation (95% CI) 0.42 (0.04, 5.04), P =0.49] or SLEDAI-2k at the next visit [estimate of coefficient for physical consultation (95% CI) -0.19 (-0.80, 0.43), P =0.55]. Adjustments of prednisolone dosages were comparable between the two forms of visits [OR for physical consultation (95% CI) 1.34 (0.77, 2.34), P =0.30]. CONCLUSION: SLE disease activity and flares at the subsequent visit were similar between teleconsultations and physical consultations. Medication prescription behaviour, determined using adjustment in corticosteroid dosages, was not different between the two forms of visits.

Treating resistant Pseudomonas aeruginosa lung disease in young children with cystic fibrosis.

Pseudomonas aeruginosa is a common bacterial pathogen in the evolution of bronchiectasis in cystic fibrosis. The appearance of resistant strains of pseudomonas is increasing with the earlier and more liberal use of a range of anti-pseudomonal antibiotics for the treatment of bacterial chest infections. The rationale for treatment and potential benefits of aggressive treatment of resistant strains of Pseudomonas aeruginosa from early in life are discussed.

Supervisor support: does supervisor support buffer or exacerbate the adverse effects of supervisor undermining?

Empirical investigations concerning the interplay between supervisor support and supervisor undermining behaviors and their effects on employees yielded contradictory findings, with some studies suggesting that support buffers the adverse effects of undermining, and others suggesting that support exacerbates these adverse effects. Seeking to explain such contradictory findings, we integrate uncertainty-management perspectives with coping theory to posit that relational uncertainty is inherent in the mixture of supervisor support and undermining. Hence, whether supervisor support buffers or exacerbates the adverse effects of supervisor undermining on employee health and well-being depends on factors pertaining to employee ability to resolve and manage such relational uncertainty. Specifically, we hypothesize a buffering effect for employees with high self-esteem and high quality of work life, and an exacerbating effect for employees with low self-esteem and low quality of work life. Analyses of 2-wave data collected from a probability stratified sample of U.S. Air Force personnel supported our predictions. Two supplementary studies of the U.S. military replicated our core findings and demonstrated its practical significance.

Family incivility and job performance: a moderated mediation model of psychological distress and core self-evaluation.

This study extends the stress literature by exploring the relationship between family incivility and job performance. We examine whether psychological distress mediates the link between family incivility and job performance. We also investigate how core self-evaluation might moderate this mediated relationship. Data from a 2-wave study indicate that psychological distress mediates the relationship between family incivility and job performance. In addition, core self-evaluation moderates the relationship between family incivility and psychological distress but not the relationship between psychological distress and job performance. The results hold while controlling for general job stress, family-to-work conflict, and work-to-family conflict. The findings suggest that family incivility is linked to poor performance at work, and psychological distress and core self-evaluation are key mechanisms in the relationship.

Microarray with micro- and nano-topographies enables identification of the optimal topography for directing the differentiation of primary murine neural progenitor cells.

During development and tissue repair, progenitor cells are guided by both biochemical and biophysical cues of their microenvironment, including topographical signals. The topographical cues have been shown to play an important role in controlling the fate of cells. Systematic investigation of topographical structures with different geometries and sizes under the identical experimental conditions on the same chip will enhance the understanding of the role of shape and size in cell-topography interactions. A simple customizable multi-architecture chip (MARC) array is therefore developed to incorporate, on a single chip, distinct topographies of various architectural complexities, including both isotropic and anisotropic features, in nano- to micrometer dimensions, with different aspect ratios and hierarchical structures. Polydimethylsiloxane (PDMS) replicas of MARC are used to investigate the influence of different geometries and sizes in neural differentiation of primary murine neural progenitor cells (mNPCs). Anisotropic gratings (2 µm gratings, 250 nm gratings) and isotropic 1 µm pillars significantly promote differentiation of mNPCs into neurons, as indicated by expression of ß-III-tubulin (59%, 58%, and 58%, respectively, compared to 30% on the control). In contrast, glial differentiation is enhanced on isotropic 2 µm holes and 1 µm pillars. These results illustrate that anisotropic topographies enhance neuronal differentiation while isotropic topographies enhance glial differentiation on the same chip under the same conditions. MARC enables simultaneous cost-effective investigation of multiple topographies, allowing efficient optimization of topographical and biochemical cues to modulate cell differentiation.

Graded Nodal/Activin signaling titrates conversion of quantitative phospho-Smad2 levels into qualitative embryonic stem cell fate decisions.

Nodal and Activin are morphogens of the TGFbeta superfamily of signaling molecules that direct differential cell fate decisions in a dose- and distance-dependent manner. During early embryonic development the Nodal/Activin pathway is responsible for the specification of mesoderm, endoderm, node, and mesendoderm. In contradiction to this drive towards cellular differentiation, the pathway also plays important roles in the maintenance of self-renewal and pluripotency in embryonic and epiblast stem cells. The molecular basis behind stem cell interpretation of Nodal/Activin signaling gradients and the undertaking of disparate cell fate decisions remains poorly understood. Here, we show that any perturbation of endogenous signaling levels in mouse embryonic stem cells leads to their exit from self-renewal towards divergent differentiation programs. Increasing Nodal signals above basal levels by direct stimulation with Activin promotes differentiation towards the mesendodermal lineages while repression of signaling with the specific Nodal/Activin receptor inhibitor SB431542 induces trophectodermal differentiation. To address how quantitative Nodal/Activin signals are translated qualitatively into distinct cell fates decisions, we performed chromatin immunoprecipitation of phospho-Smad2, the primary downstream transcriptional factor of the Nodal/Activin pathway, followed by massively parallel sequencing, and show that phospho-Smad2 binds to and regulates distinct subsets of target genes in a dose-dependent manner. Crucially, Nodal/Activin signaling directly controls the Oct4 master regulator of pluripotency by graded phospho-Smad2 binding in the promoter region. Hence stem cells interpret and carry out differential Nodal/Activin signaling instructions via a corresponding gradient of Smad2 phosphorylation that selectively titrates self-renewal against alternative differentiation programs by direct regulation of distinct target gene subsets and Oct4 expression.

Work and nonwork outcomes of workplace incivility: Does family support help?

This study extended incivility research beyond the confines of the workplace by exploring the relationships between incivility, work-to-family conflict and family support. Data collected from 180 employees from various organizations in Singapore showed that incivility is not a rare phenomenon in Asian cultures. Employees experienced more incivility from superiors than coworkers or subordinates, and these experiences were related to different outcomes. Coworker-initiated incivility was associated with decreased coworker satisfaction, increased perceptions of unfair treatment, and increased depression. On the other hand, superior-initiated incivility was associated with decreased supervisor satisfaction and increased work-to-family conflict. Results also revealed that employees with high family support showed stronger relationships between workplace incivility and negative outcomes, compared with employees with low family support.

Personal and workgroup incivility: impact on work and health outcomes.

This article develops a theoretical model of the impact of workplace incivility on employees' occupational and psychological well-being. In Study 1, the authors tested the model on 1,158 employees, finding that satisfaction with work and supervisors, as well as mental health, partially mediated effects of personal incivility on turnover intentions and physical health; this process did not vary by gender. Study 2 cross-validated and extended these results on an independent sample of 271 employees, showing negative effects of workgroup incivility that emerged over and above the impact of personal incivility. In both studies, all results held while controlling for general job stress. Implications for organizational science and practice are discussed.

Interpersonal mistreatment in the workplace: the interface and impact of general incivility and sexual harassment.

This article examined the relationships and outcomes of behaviors falling at the interface of general and sexual forms of interpersonal mistreatment in the workplace. Data were collected with surveys of two different female populations (Ns = 833 and 1,425) working within a large public-sector organization. Findings revealed that general incivility and sexual harassment were related constructs, with gender harassment bridging the two. Moreover, these behaviors tended to co-occur in organizations, and employee well-being declined with the addition of each type of mistreatment to the workplace experience. This behavior type (or behavior combination) effect remained significant even after controlling for behavior frequency. The findings are interpreted from perspectives on sexual aggression, social power, and multiple victimization.