bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of a distal RXFP1 gene enhancer with differential activity in fibrotic lung fibroblasts involving AP-1
Authors: Chen Ting-Yun , Li Xiaoyun , Goobie Gillian C. , Hung Ching-Hsia , Hamilton Kyle , Bahudhanapati Harinath , Tan Jiangning , Kass Daniel J. , Zhang Yingze 
Published: July 2021

AbstractRelaxin/insulin-like family peptide receptor 1 (RXFP1) mediates relaxin’s antifibrotic effects and has reduced expression in the lung and skin of patients with fibrotic interstitial lung disease (fILD) including idiopathic pulmonary fibrosis (IPF) and systemic sclerosis (SSc). This may explain the failure of relaxin-based anti-fibrotic treatments in SSc, but the regulatory mechanisms controlling RXFP1 expression remain largely unknown. This study aimed to identify regulatory elements of RXFP1 that may function differentially in fibrotic fibroblasts.We identified and evaluated a distal regulatory region of RXFP1 in lung fibroblasts using a luciferase reporter system. Using serial deletions, an enhancer upregulating pGL3-promoter activity was localized to the distal region between -584 to -242bp from the distal transcription start site (TSS). This enhancer exhibited reduced activity in IPF and SSc lung fibroblasts. Bioinformatic analysis identified two clusters of activator protein 1 (AP-1) transcription factor binding sites within the enhancer. Site-directed mutagenesis of the binding sites confirmed that only one cluster reduced activity (−358 to -353 relative to distal TSS). Co-expression of FOS in lung fibroblasts further increased enhancer activity. In vitro complex formation with a labeled probe spanning the functional AP-1 site using nuclear proteins isolated from lung fibroblasts confirmed a specific DNA/protein complex formation. Application of antibodies against JUN and FOS resulted in the complex alteration, while antibodies to JUNB and FOSL1 did not. Analysis of AP-1 binding in 5 pairs of control and IPF lung fibroblasts detected positive binding more frequently in control fibroblasts. Expression of JUN and FOS was reduced and correlated positively with RXFP1 expression in IPF lungs.In conclusion, we identified a distal enhancer of RXFP1 with differential activity in fibrotic lung fibroblasts involving AP-1 transcription factors. Our study provides insight into RXFP1 downregulation in fILD and may support efforts to reevaluate relaxin-based therapeutics alongside upregulation of RXFP1 transcription.
Correlational networking guides the discovery of cryptic natural product biosynthetic enzymes
Authors: Xue Dan , Older Ethan A. , Zhong Zheng , Shang Zhuo , Chen Nanzhu , Dittenhauser Nolan , Hou Lukuan , Walla Michael D. , Dong Shi-Hui , Tang Xiaoyu , Nagarkatti Prakash , Nagarkatti Mitzi , Li Yong-Xin , Li Jie 
Published: July 2021

AbstractBacterial natural product biosynthetic genes, canonically clustered, have been increasingly found to rely on cryptic enzymes encoded elsewhere in the genome for completion of biosynthesis. The study and application of lanthipeptides are frequently hindered by cryptic proteases required for final maturation. Here, we establish a global correlation network bridging the gap between lanthipeptide precursors and cryptic proteases. Applying our analysis to 161,954 bacterial genomes, we establish 5,209 correlations between precursors and cryptic proteases, with 91 prioritized. We use network predictions and co-expression analysis to reveal a previously missing protease for the maturation of class I lanthipeptide paenilan. We further discover widely distributed bacterial M16B metallopeptidases of previously unclear biological function as a new family of lanthipeptide proteases. We show the involvement of a pair of bifunctional M16B proteases in the production of novel class III lanthipeptides with high substrate specificity. Together, these results demonstrate the strength of our correlational networking approach to the discovery of cryptic lanthipeptide proteases and potentially other missing enzymes for natural products biosynthesis.Graphical abstract
Protection of human ACE2 transgenic Syrian hamsters from SARS CoV-2 variants by human polyclonal IgG from hyper-immunized transchromosomic bovines
Authors: Gilliland Theron , Liu Yanan , Li Rong , Dunn Matthew , Cottle Emily , Terada Yutaka , Ryckman Zachary , Alcorn Maria , Vasilatos Shauna , Lundy Jeneveve , Larson Deanna , Wu Hua , Luke Thomas , Bausch Christoph , Egland Kristi , Sullivan Eddie , Wang Zhongde , Klimstra William B. 
Published: July 2021

ABSTRACTPandemic SARS CoV-2 has been undergoing rapid evolution during spread throughout the world resulting in the emergence of many Spike protein variants, some of which appear to either evade antibody neutralization, transmit more efficiently, or potentially exhibit increased virulence. This raises significant concerns regarding the long-term efficacy of protection elicited after primary infection and/or from vaccines derived from single virus Spike (S) genotypes, as well as the efficacy of anti-S monoclonal antibody based therapeutics. Here, we used fully human polyclonal human IgG (SAB-185), derived from hyperimmunization of transchromosomic bovines with DNA plasmids encoding the SARS-CoV-2 Wa-1 strain S protein or purified ectodomain of S protein, to examine the neutralizing capacity of SAB-185 in vitro and the protective efficacy of passive SAB-185 antibody (Ab) transfer in vivo. The Ab preparation was tested for neutralization against five variant SARS-CoV-2 strains: Munich (Spike D614G), UK (B.1.1.7), Brazil (P.1) and SA (B.1.3.5) variants, and a variant isolated from a chronically infected immunocompromised patient (Spike Δ144-146). For the in vivo studies, we used a new human ACE2 (hACE2) transgenic Syrian hamster model that exhibits lethality after SARS-Cov-2 challenge and the Munich, UK, SA and Δ144-146 variants. SAB-185 neutralized each of the SARS-CoV-2 strains equivalently on Vero E6 cells, however, a control convalescent human serum sample was less effective at neutralizing the SA variant. In the hamster model, prophylactic SAB-185 treatment protected the hamsters from fatal disease and minimized clinical signs of infection. These results suggest that SAB-185 may be an effective treatment for patients infected with SARS CoV-2 variants.
A new perspective on sales outcome controls: an inside sales perspective
Authors: Conde Richard , Prybutok Victor , Thompson Kenneth 
Published: July 2021

PurposePrevious sales control research has limited the definition of outcome controls exclusively to sales outcomes in an outside sales context. In addition to sales outcome controls, inside sales managers use phone operational outcomes to influence inside sales agent performance, supporting the need to expand the broader definition of outcome controls. Hence, the purpose of this paper is to explore the need to bifurcate outcome controls into two distinct variables: sales and phone operational controls. Researchers know little about the application of sales outcome controls beyond sales-only outcomes, which, in turn, limits the definition of outcome controls.Design/methodology/approachThrough the utilization of survey, secondary operational data and sales manager’s feedback, this paper demonstrates that the definition of outcome controls needs to be divided into two distinct areas, sales and phone operational controls for inside sales agents, which, in turn, acts collectively to impact an inside sales agent’s job performance and satisfaction.FindingsThis research demonstrates that inside sales managers depend on both sales and phone operational outcome controls to drive sales agent performance, varying in degrees by industry. Even as inside sales managers focus on creating an employee-centric autonomous motivational work culture, the overarching controlling factors associated with phone operational outcomes dampen an inside sales agent’s performance and job satisfaction.Research limitations/implicationsTo the best of the authors’ knowledge, as the first sales control research to examine an inside sales context, this study provides support to further study sales controls in an inside sales context. This research can be enhanced by examining business-to-consumer inside sales environments, behavior controls, greater sample size and additional work outcomes such as turnover and tenure.Practical implicationsThe findings have important implications because they can help practitioners understand the effect that both sales and phone operational outcomes have on sales agent performance. It also illuminates the need for inside sales managers to be less controlling in their focus on phone operational outcomes, as such a practice has a negative influence on key sales agent job outcomes.Originality/valueTo the best of the authors’ knowledge, this study is the first to triangulate multiple data sources to illustrate the need to evaluate both sales and phone operational outcomes as broader components of sales outcome controls. The study of sales controls in a different sales context suggests that sales management controls may differ by sales context, opening the door to extend the vast sales control literature beyond its current context of outside sales.
Opening-up as entrepreneurial internationalisation in Chinese higher education
Authors: Zhong Zhou 
Published: July 2021

PurposeThis study describes and elucidates higher education internationalisation with an in-depth case study of China and its Tsinghua University using international entrepreneurship concepts. The study examines internationalisation as a dynamic reciprocal interplay between opening-up policy and higher education policy, especially world-class university policy.Design/methodology/approachThis is a qualitative mixed-method single case study. In desktop research, the study reviewed China's national policy documents on educational opening-up, Tsinghua's institutional strategy papers and research literature concerning internationalisation, entrepreneurship, Chinese higher education and Tsinghua University. In fieldwork research, the present researcher engaged in action, participatory and collaborative research about university internationalisation in her capacity as both a faculty and an international office administrator at Tsinghua.FindingsEntrepreneurial internationalisation in Chinese higher education has served multiple purposes simultaneously: (1) a pillar to support domestic confidence in educational opening-up for modernisation while also contributing to global development; (2) a cost-effective way to cultivate Chinese talent by accessing the international education market; (3) a quality imperative to stimulate domestic reform and innovation through Sino-foreign exchange and collaboration; (4) a public diplomacy measure building a global network of educational engagement; and (5) a differentiation strategy to stretch the capacity of the nation's top universities by benchmarking their global competitiveness.Originality/valueConceptualising opening-up as entrepreneurial internationalisation is key to understand China's higher education development. This study expounds this special term by connecting it with basic concepts in international entrepreneurship research. The analyses at system and institutional levels reinforce one another to forge a synthetic view by integrating policy and practice.
Equity crowdfunding and financial literacy of individual investors in Japan
Authors: Fujii Masatoshi , Hosomi Chie , Nose Yoshiaki 
Published: July 2021

PurposeThis study aims to fill the gap in previous research that focuses on the superficial aspects of equity crowdfunding (ECF) campaigns and financial practices by examining financial literacy aspects, such as due diligence and valuation, in terms of factors that influence Japanese individual investors' investments in ECF.Design/methodology/approachThe status of information disclosure in ECF campaigns is checked. In addition, the feasibility of the initial due diligence and valuation using this information is verified. Specifically, the lack of financial literacy hypothesis is developed and (1) expected market capitalization in the final fiscal year of the business plan and (2) expected returns on investment (IRR: internal rate of return) are estimated.FindingsECF campaigns in Japan disclose information equivalent to that obtained by professional venture capitalists. Analysis of the disclosed business plan allows for initial due diligence and valuation. By contrast, due diligence reveals that some projects are unlikely to be listed even if their business plans are met, and others have low IRRs. In addition, a stock acquisition rights project, in which even professional investors are unable to calculate IRRs, is completed at the same rate as a common stock project; this suggests that individual investors lack financial literacy.Originality/valueAnalyzing ECF from financial literacy aspects, such as due diligence and valuation, is unique. Such aspects are essential for private equity investments but have not been addressed in previous studies.
Knowledge management capabilities and organizational outcomes: contemporary literature and future directions
Authors: Imran Muhammad Kashif , Fatima Tehreem , Sarwar Ambreen , Amin Shahid 
Published: July 2021

PurposeThe purpose of this systematic review is to summarize the possible organizational outcomes related to knowledge management capabilities (KMCs). It aims at offering the modern-day dynamic organizations a path, through which they can utilize KMC at hand for gaining competitive advantage and positive organizational outcomes. The review is based on previous studies in the field of knowledge management and explains how KMCs are associated with various organizational outcomes.Design/methodology/approachA systematic approach was utilized to collect, examine, interpret and synthesize researches regarding KMCs and their usefulness for various organizational outcomes. The meta-synthesis method was adopted to review 106 research papers after careful selection.FindingsIt was evident from this integrated review that KMCs help in promoting organizational effectiveness, innovative ability, organizational change, value creation, competitive advantage, organizational learning and performance. Furthermore, the current review suggests research avenues and knowledge gaps in current literature to provide future researchers unique research opportunities.Originality/valueThe review revealed a profound opinion that organizations have to develop an optimal mix of KMCs to achieve better organizational outcomes. The study identified how KMCs set a basis and build positive support to enhance the key organizational outcomes such as organizational effectiveness, innovative ability, organizational change, value creation, competitive advantage, organizational learning and performance. However, cooperation bias is one of the most considerable limitations in research studies included in this systematic literature review.
Navigating dual-careers: the challenge for professional couples
Authors: Scurry Tracy , Clarke Marilyn 
Published: July 2021

PurposeDual-careers are an increasingly common typology among professionals yet very few studies have considered how two potentially competing career trajectories are managed in relation to the broader aspects of life, such as family and personal life. This article addresses the gap through an exploration of the strategies adopted by dual-career professional couples as they seek to navigate these challenges whilst satisfying individual and shared goals and aspirations.Design/methodology/approachSemi-structured, face-to-face interviews were carried out with 18 couples (dyads) from a range of professional occupations. Interviews were conducted individually, and then responses analysed and compared for key themes.FindingsRather than focusing on how couples manage work–life balance on a day-today basis this study shows how couples incorporate a more strategic approach to dual-careers so that both careers are able to progress, albeit within situational constraints.Practical implicationsTo satisfy personal, business and economic performance goals, organisations and governments will need to find more creative ways to support employees as they seek to navigate careers while balancing the work and nonwork needs of themselves and their partner. The challenges faced by dual-career couples have implications for human resource managers as they seek to attract and retained talent within their organisations.Social implicationsDemographic and social changes at the household level will ultimately require changes at an organisational and broader societal level to meet the work and family needs of this growing cohort.Originality/valueRather than focusing on how couples manage work-life balance on a day-today basis this study shows how couples incorporate a more strategic approach to dual-careers so that both careers are able to progress, albeit within situational constraints.
Impact of the availability of midurethral slings on treatment strategies for stress urinary incontinence: a cost‐effectiveness analysis
Authors: Chang OH , Cadish LA , Kailasam A , Ridgeway BM , Shepherd JP 
Published: July 2021

ObjectiveTo perform a cost‐effectiveness analysis for the surgical and non‐surgical management of stress urinary incontinence (SUI) with and without the availability of midurethral sling.DesignCost‐effectiveness analysis.SettingUSA, 2019.PopulationWomen with stress urinary incontinence.MethodsWe modelled SUI treatment pathways with and without the availability of midurethral slings, including no treatment, incontinence pessary, pelvic floor muscle physical therapy, urethral bulking injection, open and laparoscopic Burch colposuspension, and pubovaginal autologous sling. Time horizon was 2 years after initial treatment.Main outcome measuresCosts (2019 US$) included index surgery, surgical retreatment, and complications including urinary retention, de novo urgency and mesh exposure. The incremental cost‐effectiveness ratio (ICER) was calculated for non‐dominated treatment strategies.ResultsThe least costly treatment strategies were incontinence pessary, pelvic floor physical therapy, no treatment and midurethral sling, respectively. Midurethral slings had the highest effectiveness. The strategy with the lowest effectiveness was no treatment. The three cost‐effective strategies included pessary, pelvic floor muscle physical therapy and midurethral slings. No other surgical options were cost‐effective. If midurethral slings were not available, all other surgical options were still dominated by pelvic floor muscle physical therapy. Multiple one‐way sensitivity analyses confirmed model robustness. The only reasonable threshold in which outcomes would change, was if urethral bulking costs decreased 12.6%.ConclusionsThe midurethral sling is the most effective SUI treatment and the only cost‐effective surgical option.Tweetable abstractMidurethral sling is the only cost‐effective surgical treatment option for stress urinary incontinence.
Nursing diagnosis neonatal hyperbilirubinemia: A survival analysis
Authors: Dantas Anna Virginia V. C. , Guedes Nirla G. , da Silva Leonardo A. , Lopes Marcos V. de O. , da Silva Viviane M. 
Published: July 2021

AbstractPurposeTo analyze the short‐term survival of the nursing diagnosis of neonatal hyperbilirubinemia in hospitalized neonates within the first 24 h of life and over a maximum of 7 days.MethodsA prospective open cohort study with a longitudinal design was developed with 120 newborns during the first 24 h of life. The survival rate after a nursing diagnosis of neonatal hyperbilirubinemia was analyzed for 7 days.FindingsThe number of new cases of neonatal hyperbilirubinemia during the follow‐up was 82 (RR: 90.1%, daily incidence rate: 34.17%). The greatest manifestation of the diagnosis occurred in the first three days (n = 97). The median diagnostic survival time was 2 days (95% CI: 2–2). Yellow‐orange skin color (RR = 8.08), yellow mucous membranes (RR = 2.05), yellow sclera (RR = 1.99), and female gender (RR = 1.36) had the highest risk ratios.ConclusionsA rapid impairment of neonatal hyperbilirubinemia in hospitalized neonates was observed. Some clinical indicators were associated with an increased risk for this diagnosis.Implications for nursing practiceStudies on the prognostic capacity of the clinical indicators of nursing diagnoses like neonatal hyperbilirubinemia strengthen the clinical reasoning of nurses and subsidize diagnostic inferences and accurate clinical decisions.
Evidence for a hijacked brain reward system but no desensitized threat system in quitting‐motivated smokers: An fMRI study
Authors: Kunas Stefanie L. , Stuke Heiner , Heinz Andreas , Ströhle Andreas , Bermpohl Felix 
Published: July 2021

AbstractBackground and aimsSeveral aspects of how quitting‐motivated tobacco use disorder (TUD) subjects and never‐smokers differ in terms of reward and threat processing remain unresolved. We aimed to examine aberrant reward and threat processes in TUD and the association with smoking characteristics.DesignA between‐ and within‐subjects functional magnetic resonance imaging (fMRI) experiment with a 2 (groups) × 4 (stimulus type) factorial design. The experimental paradigm had four conditions: pictures of (1) cigarettes served as drug‐related‐positive cues, (2) food as alternative reward cues, (3) long‐term consequences of smoking as drug‐related‐negative cues and (4) neutral pictures as control.Setting/participantsAdult participants (n = 38 TUD subjects and n = 42 never‐smokers) were recruited in Berlin, Germany.MeasurementsAs contrasts of primary interest, the interactions of group × stimulus‐type were assessed. Significance threshold correction for multiple testing was carried out with the family‐wise error method. Correlation analyses were used to test the association with smoking characteristics.FindingsThe 2 × 2 interaction of smoking status and stimulus type revealed activations in the brain reward system to drug‐related‐positive cues in TUD subjects (between‐subjects effect: P‐values ≤ 0.036). As a response to drug‐related‐negative cues, TUD subjects showed no reduced activation of the aversive brain network. Within the TUD group, a significant negative association was found between response of the aversive brain system to drug‐related‐negative cues (within‐subjects effect: P‐values ≤ 0.021) and the number of cigarettes smoked per day (right insula r = −0.386, P = 0.024; left insula r = −0.351, P = 0.042; right ACC r = −0.359, P = 0.037).ConclusionsModerate smokers with tobacco use disorder appear to have altered brain reward processing of drug‐related‐positive (but not negative) cues compared with never smokers.
Dear Sylvie: A Handful of Letters to Nearly Perfect Strangers
Authors: Edmiston Paige 
Published: July 2021

SummaryIn this collection of letters addressed to nearly perfect strangers, I consider the ways fleeting connections can move with and shape us despite never becoming deep relationships. Drawing on the anthropology of care and kinship, I revisit the summer my father and I spent living in an apartment building for cancer patients and their caregivers. My journal entries from that summer are filled with stories about people I hardly knew and, in some cases, whose names I never learned. The letters in this essay are written to and about these strangers, who landed in my journal right alongside the people in the world I hold most dear. They are the words I wish I would have said to them then and what I would like to say to them now. Read together, these letters suggest that chance encounters need not transform into ongoing relationships to play a part in making us who we are.