bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Future of Work is a ‘Work in Progress’
Authors: A S Vasudevan 
Published: December 2020

This article is a phenomenological interpretation of the myriad processes that influence the transient nature of ‘work’ and measures to retrieve the dignity it deserves. Vasu is an emerging organisational futurist whose passion is to develop management educational approaches that ensure a positive outlook of the uncertain future ahead. The differences between Eastern and Western history, especially Indian history is ingrained with a unique resilience to catastrophic events, invasions and embedded diversity. Leaning more in defence of human dignity at work according to Pablo Gilbert, Victor Frankl, World Happiness Report 2012 and the contemporary theory of autopoiesis, he conjectures a ‘FUTOPIA’ rising in the horizon, where humanistic valuing of work becomes culture. The corporate world is realizing the shifting paradigms—from end goals of profit-centric strategies and exploitation of human futures to partnerships with associates and ‘working resources’ that optimize creative contribution from work environments. At a meta level, the nation-building agenda of development is talking the language of equal opportunity for and treatment of women at work, with equitable wage parity and abolition of forced labour in the United States. Recent bills in the Indian Parliament on education and farmers’ rights and tailoring of the archaic labour laws will strengthen the negotiation for equitable fund allocation. The spirit of enterprise will boost small and medium sectors, especially farming and food product preservation, innovation and research and development (R&D), and rapid skill development will for sure retrieve the dignity tag for academics, farm labourers and those in the service sector, such as paramedics, the police, etc. According to thought leaders, corporate founders and contemporary authors, the future of work can be seen as a promising work in progress towards a new work ethic. This article risks suggesting radical steps needed in challenging traditional leadership styles and human resource (HR) practices of a growth economy that draws on patriarchal alpha-male prominence. What will replace traditional leadership styles is compassionate servant leadership, with leaders who will become designers of future ‘work’ environments.
Fecal microbiota diversity disruption and clinical outcomes after auto-HCT: a multicenter observational study
Authors: Khan Niloufer , Lindner Sarah , Gomes Antonio L. C. , Devlin Sean M. , Shah Gunjan L. , Sung Anthony D. , Sauter Craig S. , Landau Heather J. , Dahi Parastoo B. , Perales Miguel-Angel , Chung David J. , Lesokhin Alexander M. , Dai Anqi , Clurman Annelie , Slingerland John B. , Slingerland Ann E. , Brereton Daniel G. , Giardina Paul A. , Maloy Molly , Armijo Gabriel K. , Rondon-Clavo Carlos , Fontana Emily , Bohannon Lauren , Ramalingam Sendhilnathan , Bush Amy T. , Lew Meagan V. , Messina Julia A. , Littmann Eric , Taur Ying , Jenq Robert R. , Chao Nelson J. , Giralt Sergio , Markey Kate A. , Pamer Eric G. , van den Brink Marcel R. M. , Peled Jonathan U. 
Published: December 2020

Abstract
We previously described clinically relevant reductions in fecal microbiota diversity in patients undergoing allogeneic hematopoietic cell transplantation (allo-HCT). Recipients of high-dose chemotherapy and autologous HCT (auto-HCT) incur similar antibiotic exposures and nutritional alterations. To characterize the fecal microbiota in the auto-HCT population, we analyzed 1161 fecal samples collected from 534 adult recipients of auto-HCT for lymphoma, myeloma, and amyloidosis in an observational study conducted at 2 transplantation centers in the United States. By using 16S ribosomal gene sequencing, we assessed fecal microbiota composition and diversity, as measured by the inverse Simpson index. At both centers, the diversity of early pretransplant fecal microbiota was lower in patients than in healthy controls and decreased further during the course of transplantation. Loss of diversity and domination by specific bacterial taxa occurred during auto-HCT in patterns similar to those with allo-HCT. Above-median fecal intestinal diversity in the periengraftment period was associated with decreased risk of death or progression (progression-free survival hazard ratio, 0.46; 95% confidence interval, 0.26-0.82; P = .008), adjusting for disease and disease status. This suggests that further investigation into the health of the intestinal microbiota in auto-HCT patients and posttransplant outcomes should be undertaken.
Statin use is associated with reduced mortality after respiratory viral infection
Authors: Franco-Peláez Juan Antonio , Esteban-Lucia Laura , Zambrano Chacón María de los Ángeles , Pello-Lázaro Ana María , Venegas Rodriguez Ana María , Nieto Roca Luis , García-Talavera Camila Sofia , Kallmeyer Mayor Andrea , Villar Alvarez Felipe , Fernandez Roblas Ricardo , Gonzalez-Lorenzo Oscar , Tuñón José , Ibañez Borja , Aceña Alvaro 
Published: December 2020

BackgroundSeveral studies suggest that statins, besides reducing cardiovascular disease, have anti-inflammatory properties which might provide a benefit in downregulating the immune response after a respiratory viral infection (RVI) and, hence, decreasing subsequent complications. We aim to analyse the effect of statins on mortality after RVI.MethodsA single-centre, observational and retrospective study was carried out including all adult patients with a RVI confirmed by PCR tests from October 2, 2017 to May 20, 2018. Patients were divided between statin users and non-statin users and followed-up for 1 year, and all causes of death were recorded. In order to analyse the effect of statin treatment on mortality after RVI we planned two different approaches, a multivariate Cox regression model with the overall population and a univariate Cox model with a propensity-score matched population.ResultsWe included 448 patients, 154 (34.4%) of whom were under statin treatment. Statin users had a worse clinical profile (older population with more comorbidities). During the 1-year follow-up, 67 patients died, 17 (11.0%) in the statin group and 50 (17.1%) in the non-statin group. Multivariate Cox analysis showed that statins were associated with mortality benefit (HR 0.47, 95% CI 0.26–0.83; p=0.01). In a matched population (101 statins users and 101 non-statins users) statins also remained associated with mortality benefit (HR 0.32, 95% CI 0.14–0.72; p=0.006). Differences were mainly driven by non-cardiovascular mortality (HR 0.31, 95% CI 0.13–0.73; p=0.004).ConclusionsChronic statin treatment was associated with reduced 1-year mortality in patients with laboratory-confirmed RVI. Further studies are needed to determine the exact role of statin therapy after RVI.
First clinical trials of the inhaled epithelial sodium channel inhibitor BI 1265162 in healthy volunteers
Authors: Mackie Alison , Rascher Juliane , Schmid Marion , Endriss Verena , Brand Tobias , Seibold Wolfgang 
Published: December 2020

BackgroundInhibition of the epithelial sodium channel (ENaC) represents a mutation-agnostic therapeutic approach to restore airway surface liquid hydration and mucociliary clearance in patients with cystic fibrosis. BI 1265162 is an inhaled ENaC inhibitor with demonstrated preclinical efficacy.MethodsThree phase I trials of BI 1265162 in healthy male subjects are presented:NCT03349723(single-rising-dose trial evaluating safety, tolerability and pharmacokinetics (PK));NCT03576144(multiple-rising-dose trial evaluating safety, tolerability and PK); andNCT03907280(absolute bioavailability trial).ResultsBI 1265162 single doses ≤1200 µg and multiple doses of 600 µg were well tolerated. Adverse events were balanced across treatment groups, were of mainly mild or moderate intensity and resolved by trial-end. One subject discontinued from trial medication on day 7 (asymptomatic hyperkalaemia adverse event; recovered day 8). One subject experienced a serious adverse event (neuropathia vestibularis) leading to hospitalisation and missed one of the four dosing periods. Both events were not considered to be drug-related and subjects recovered. BI 1265162 displayed dose-proportional, time-independent PK; maximum accumulation was 1.6-fold; calculated effective elimination half-life was 3.6–8.7 h over the dose ranges tested. Renal excretion was not a major drug elimination route. Oral and inhaled dosing (±activated oral charcoal) absolute bioavailability was 0.50% and ∼40%, respectively.ConclusionBI 1265162 single or multiple doses up to 6.5 days were well tolerated. Systemic exposures mainly represent drug absorbed through the lungs and not the gastrointestinal tract, with ∼40% of the inhaled dose reaching the systemic circulation. Accumulation was minimal. Twice-daily dosing is supported for future development.
Characterisation of cough evoked by inhaled treprostinil and treprostinil palmitil
Authors: Chapman Richard W. , Corboz Michel R. , Fernandez Carlos , Sullivan Eugene , Stautberg Andy , Plaunt Adam J. , Konicek Donna M. , Malinin Vladimir , Li Zhili , Cipolla David , Perkins Walter 
Published: December 2020

Cough is induced by inhaled prostacyclin analogues including treprostinil (TRE), and, at higher doses, treprostinil palmitil (TP), a prodrug of TRE. In this report, we have investigated mechanisms involved in TRE- and TP-induced cough, using a dry powder formulation of TP (TPIP) to supplement previous data obtained with an aqueous suspension formulation of TP (TPIS).Experiments in guinea pigs and rats investigated the prostanoid receptor subtype producing cough and whether it involved activation of sensory nerves in the airways and vasculature. Experiments involved treatment with prostanoid, tachykinin and bradykinin receptor antagonists, a cyclooxygenase inhibitor and TRE administration to the isolated larynx or intravenously.In guinea pigs, cough with inhaled TRE (1.23 µg·kg−1) was not observed with an equivalent dose of TPIP and required higher inhaled doses (12.8 and 35.8 µg·kg−1) to induce cough. TRE cough was blocked with IP and tachykinin NK1receptor antagonists but not with EP1, EP2, EP3, DP1or bradykinin B2antagonists or a cyclooxygenase inhibitor. TRE administered to the isolated larynx or intravenously in rats produced no apnoea or swallowing, whereas citric acid, capsaicin and hypertonic saline had significant effects.The mechanisms inducing cough with inhaled TRE likely involves the activation of prostanoid IP receptors on jugular C-fibres in the tracheobronchial airways. Cough induced by inhaled dry powder and nebulised formulations of TP occurs at higher inhaled doses than TRE, presumably due to the slow, sustained release of TRE from the prodrug resulting in lower concentrations of TRE at the airway sensory nerves.
High sensitivity of PD-L1 analysis from pleural effusion in nonsmall cell lung cancer
Authors: Hagmeyer Lars , Schäfer Stephan , Engels Marianne , Pietzke-Calcagnile Anja , Treml Marcel , Herkenrath Simon-Dominik , Heldwein Matthias , Hekmat Khosro , Matthes Sandhya , Scheel Andreas , Wolf Jürgen , Büttner Reinhard , Randerath Winfried 
Published: December 2020

Background:Programmed cell death protein 1 (PD-1)/programmed cell death protein ligand 1 (PD-L1) immune checkpoint inhibitors have been approved for monotherapy of metastatic nonsmall cell lung cancer (mNSCLC) depending on tumour cells' PD-L1 expression. Pleural effusion is common in mNSCLC. The significance of immunocytochemistry PD-L1 analysis from pleural effusion samples is unclear.Aim:The aim of the study was to analyse the sensitivity regarding immunocytochemistry PD-L1 analysis of pleural effusion in NSCLC as compared to immunohistochemistry of pleural biopsies.Patients and Methods:Fifty consecutive subjects (17 female, median age 72.5 years, seven never-smokers) were enrolled in this prospective controlled two-centre study. Inclusion criteria were pleural effusion, suspected or known lung cancer, indication for pleural puncture and thoracoscopy, and written informed consent. Immunocytochemistry and immunohistochemistry PD-L1 analyses were performed with the Dako-PDL1-IHC-22C3pharmDx assay. Analysis for sensitivity, specificity, and positive and negative predictive value was performed for PD-L1 detection from pleural effusion.Results:50 subjects underwent pleural puncture and thoracoscopy. Pathological diagnoses were lung cancer (48), lymphoma (1) and mesothelioma (1). Sensitivity, specificity, positive predictive value and negative predictive value of PD-L1-testing with expression ≥50% defined as positive were 100% (95% CI 46–100%), 63% (36–84%), 45% (18–75%) and 100% (66–100%), and with expression ≥1% defined as positive 86% (56–97%), 43% (12–80%), 75% (47–92%) and 60% (17–93%).Conclusion:PD-L1 analysis in tumour-positive pleural effusion samples shows a very high sensitivity and negative predictive value, especially regarding PD-L1 expression levels ≥50% (European Medicines Agency approval). Negative results are reliable and help in the decision against a first-line checkpoint inhibitor monotherapy. However, a 1% cut-off level (United States Food and Drug Administration approval) leads to a markedly lower negative predictive value, making other invasive procedures necessary (NCT02855281).
A fast, efficient and high-throughput procedure involving laser microdissection and RT droplet digital PCR for tissue-specific expression profiling of rice roots
Authors: Mounier Thibault , Navarro-Sanz Sergi , Bureau Charlotte , Antoine Lefeuvre , Varoquaux Fabrice , Durandet Franz , Périn Christophe 
Published: December 2020

AbstractBackgroundIn rice, the cortex and outer tissues play a key role in submergence tolerance. The cortex differentiates into aerenchyma, which are air-containing cavities that allow the flow of oxygen from shoots to roots, whereas exodermis suberification and sclerenchyma lignification limit oxygen loss from the mature parts of roots by forming a barrier to root oxygen loss (ROL). The genes and their networks involved in the cellular identity and differentiation of these tissues remain poorly understood. Identification and characterization of key regulators of aerenchyma and ROL barrier formation require determination of the specific expression profiles of these tissues.ResultsWe optimized an approach combining laser microdissection (LM) and droplet digital RT-PCR (ddRT-PCR) for high-throughput identification of tissue-specific expression profiles. The developed protocol enables rapid (within 3 days) extraction of high-quality RNA from root tissues with a low contamination rate. We also demonstrated the possibility of extracting RNAs from paraffin blocks stored at 4 °C without any loss of quality. We included a detailed troubleshooting guide that should allow future users to adapt the proposed protocol to other tissues and/or species. We demonstrated that our protocol, which combines LM with ddRT-PCR, can be used as a complementary tool to in situ hybridization for tissue-specific characterization of gene expression even with a low RNA concentration input. We illustrated the efficiency of the proposed approach by validating three of four potential tissue-specific candidate genes detailed in the RiceXpro database.ConclusionThe detailed protocol and the critical steps required to optimize its use for other species will democratize tissue-specific transcriptome approaches combining LM with ddRT-PCR for analyses of plants.
Differential gene expression reveals mechanisms related to habitat divergence between hybridizing orchids from the Neotropical coastal plains
Authors: Leal Bárbara Simões Santos , Brandão Marcelo Mendes , Palma-Silva Clarisse , Pinheiro Fabio 
Published: December 2020

Abstract
Background
Closely related hybridizing species are ideal systems for identifying genomic regions underlying adaptive divergence. Although gene expression plays a central role in determining ecologically-based phenotypic differences, few studies have inferred the role of gene expression for adaptive divergence in Neotropical systems. In this study, we conduct genome-wide expression analysis alongside soil elemental analysis in sympatric and allopatric populations of Epidendrum fulgens and E. puniceoluteum (Orchidaceae), which occur in contrasting adjacent habitats in the Neotropical coastal plains.

Results
These species were highly differentiated by their gene expression profiles, as determined by 18–21% of transcripts. Gene ontology (GO) terms associated with reproductive processes were enriched according to comparisons between species in both allopatric and sympatric populations. Species showed differential expression in genes linked to salt and waterlogging tolerance according to comparisons between species in sympatry, and biological processes related to environmental stimulus appeared as representative among those transcripts associated with edaphic characteristics in each sympatric zone. Hybrids, in their turn, were well differentiated from E. fulgens, but exhibited a similar gene expression profile to flooding-tolerant E. puniceolutem. When compared with parental species, hybrids showed no transcripts with additive pattern of expression and increased expression for almost all transgressive transcripts.

Conclusions
This study sheds light on general mechanisms promoting ecological differentiation and assortative mating, and suggests candidate genes, such as those encoding catalase and calcium-dependent protein kinase, underling adaptation to harsh edaphic conditions in the Neotropical coastal plains. Moreover, it demonstrates that differential gene expression plays a central role in determining ecologically-based phenotypic differences among co-occurring species and their hybrids.
TaClpS1, negatively regulates wheat resistance against Puccinia striiformis f. sp. tritici
Authors: Yang Qian , Islam Md Ashraful , Cai Kunyan , Tian Shuxin , Liu Yan , Kang Zhensheng , Guo Jun 
Published: December 2020

AbstractBackgroundThe degradation of intracellular proteins plays an essential role in plant responses to stressful environments. ClpS1 and E3 ubiquitin ligase function as adaptors for selecting target substrates in caseinolytic peptidase (Clp) proteases pathways and the 26S proteasome system, respectively. Currently, the role of E3 ubiquitin ligase in the plant immune response to pathogens is well defined. However, the role of ClpS1 in the plant immune response to pathogens remains unknown.ResultsHere, wheat (Triticum aestivum) ClpS1 (TaClpS1) was studied and resulted to encode 161 amino acids, containing a conserved ClpS domain and a chloroplast transit peptide (1–32 aa). TaClpS1 was found to be specifically localized in the chloroplast when expressed transiently in wheat protoplasts. The transcript level ofTaClpS1in wheat was significantly induced during infection byPuccinia striiformisf. sp.tritici(Pst). Knockdown ofTaClpS1via virus-induced gene silencing (VIGS) resulted in an increase in wheat resistance againstPst, accompanied by an increase in the hypersensitive response (HR), accumulation of reactive oxygen species (ROS) and expression ofTaPR1andTaPR2, and a reduction in the number of haustoria, length of infection hypha and infection area ofPst. Furthermore, heterologous expression ofTaClpS1inNicotiana benthamianaenhanced the infection byPhytophthora parasitica.ConclusionsThese results suggest that TaClpS1 negatively regulates the resistance of wheat toPst.
Combined proteomics, metabolomics and physiological analyses of rice growth and grain yield with heavy nitrogen application before and after drought
Authors: Du Jie , Shen Tianhua , Xiong Qiangqiang , Zhu Changlan , Peng Xiaosong , He Xiaopeng , Fu Junru , Ouyang Linjuan , Bian Jianmin , Hu Lifang , Sun Xiaotang , Zhou Dahu , He Haohua , Zhong Lei , Chen Xiaorong 
Published: December 2020

Abstract
Background
Nitrogen application can effectively mitigate the damage to crop growth and yield caused by drought. However, the efficiency of heavy nitrogen application before drought (NBD) and heavy nitrogen application after drought (NAD) to regulate rice response to drought stress remains controversial. In this study, we profiled physiology, proteomics and metabolomics in rice variety Wufengyou 286 of two nitrogen management modes (NBD and NAD) to investigate their yield formation and the mechanism of nitrogen regulation for drought resistance.

Results
Results revealed that the yield of NBD and NAD decreased significantly when it was subjected to drought stress at the stage of young panicle differentiation, while the yield of NBD was 33.85 and 36.33% higher than that of NAD in 2017 and 2018, reaching significant levels. Under drought conditions, NBD increased chlorophyll content and net photosynthetic rate in leaves, significantly improved the activities of antioxidant enzymes such as superoxide dismutase (SOD), peroxidase and catalase, and decreased malondialdehyde (MDA) content compared with NAD. NBD promoted nitrogen assimilation in leaves, which was characterized by increased activities of nitrate reductase (NR) and glutamine synthetase (GS). In addition, NBD significantly increased the contents of osmotic regulatory substances such as soluble sugar, soluble protein and free proline. Gene ontology and KEGG enrichment analysis of 234 differentially expressed proteins and 518 differential metabolites showed that different nitrogen management induced strong changes in photosynthesis pathway, energy metabolism pathway, nitrogen metabolism and oxidation-reduction pathways.

Conclusion
Different nitrogen management methods have significant differences in drought resistance of rice. These results suggest that heavy nitrogen application before drought may be an important pathway to improve the yield and stress resistance of rice, and provide a new ecological perspective on nitrogen regulation in rice.