bluuebunny/crossref_metadata_2025 huggingface dataset:
Methodological Problems of Using Arabic-Language Twitter as a Gauge for Arab Attitudes Toward Politics and Society
Authors: Isani Mujtaba Ali
Published: December 2020

Public opinion research in the Middle Eastern context has seen a proliferation of data research that aims to track changes in the state of Arab attitudes. Yet, it remains unclear what is being measured and how representative the data is. This article aims to address this question by reviewing the extent to which and how the existing literature has addressed the issues of representativeness of Twitter communities and the validity of opinion measures derived from sentiment analysis in the Middle Eastern context. While some studies aim no further than to gauge the dynamics of Twitter debates, many others seek to generalize the larger public opinion trends. This raises questions about how representative Twitter users are of the general public, how asymmetric social media use is, and how participation routines vary. Furthermore, to what extent can sentiment analysis translate individual tweets into meaningful measures of expressed opinion, and how sensitive are means of aggregating opinions from sentiment analysis to variation in terms of tone and amount of text within and across individuals? Following a comprehensive review of existing research in the context of the Middle East, this article also aims to derive a clearer understanding of how collective Twitter opinion relates to public opinion and make some suggestions of ways to design sampling and coding procedures, as well as validation exercises to address measurement bias and error.
Terrorism and Counterterrorism in Saudi Arabia
Authors: Qurtuby Sumanto Al , Aldamer Shafi
Published: December 2020

Since 2001, the Kingdom of Saudi Arabia has been fighting domestic terrorism and adopting policies and strategies in countering radicalism and terrorism. How effective are these policies, strategies, and tactics in combating terrorist ideology, reducing the number of terrorist activists and sympathizers, as well as preventing terrorist acts in the Kingdom? Although the government’s roles and efforts in counterterrorism programs are fruitful and advantageous, further strategic actions are necessary.
How Culture Wars Delay Herd Immunity: Christian Nationalism and Anti-vaccine Attitudes
Authors: Whitehead Andrew L. , Perry Samuel L.
Published: December 2020

Prior research demonstrates that a number of cultural factors—including politics and religion—are significantly associated with anti-vaccine attitudes. This is consequential because herd immunity is compromised when large portions of a population resist vaccination. Using a nationally representative sample of American adults that contains a battery of questions exploring views about vaccines, the authors demonstrate how a pervasive ideology that rejects scientific authority and promotes allegiance to conservative political leaders—what we and others call Christian nationalism—is consistently one of the two strongest predictors of anti-vaccine attitudes, stronger than political or religious characteristics considered separately. Results suggest that as Americans evaluate decisions to vaccinate themselves or their children, those who strongly embrace Christian nationalism—close to a quarter of the population—will be much more likely to abstain, potentially prolonging the threat of certain illnesses. The authors conclude by discussing the immediate implications of these findings for a possible coronavirus disease 2019 (COVID-19) vaccine.
Can You Hear Me Now? The Communication Challenge
Authors: Forray Jeanie M. , Knott Melissa J.
Published: December 2020

Undergraduate students, particularly those with limited experience in business, struggle to appreciate the complexity of organizational communication dynamics. Communication complexities such as role conflict, position power, and individual perception—and their influence on effective communication—are particularly challenging for this population. This article describes a classroom exercise based on the children’s game “Telephone” that connects organizational communication with considerations of role conflict, power and influence tactics, and individual perceptions as they influence engagement with communication involving a new initiative. During the full class reflection and debrief, students identify the connections between their role in the activity and how individual organizational elements and experiences may inform effective communication. Designed for an undergraduate organizational behavior course, the exercise is adaptable to other management topics or levels where communication is a consideration.
Six Steps to Achieve Meaning, Wellness, and Avoid Burnout in a Residency Program
Authors: Stamm Brian , Yu Margaret , Lineback Christina M , Bega Danny
Published: December 2020

Burnout has become an increasingly recognized problem in higher medical education and is particularly prevalent within the field of Neurology and its training programs. Many previously reported wellness initiatives in other residencies focused mainly on community/team building. We developed a comprehensive Wellness Curriculum (WC) and established a new role of Resident Wellness Liaison in order to facilitate wellness across the department and training program. Here we present a 6-step outline of our WC which can easily be adapted to the needs of other programs. The steps include creating a Wellness Committee with a Resident Wellness Liaison, identification and optimization of institutional resources, identifying and troubleshooting barriers to wellness, providing education and reflection on wellness, showing appreciation to each other, and assessing the impact of the implemented strategies. In order to measure the impact of our WC and to perform a needs assessment for future directions, we posed questions—grounded in the theory of drivers of burnout and engagement—to our residents (N = 24) at a noon conference in the summer of 2020. Interventions implemented at our institution have been very well received by residents, as evidenced by their comments and feedback. Themes that were highlighted by residents include enjoying flexibility, having a welcoming social support system at work, and being able to find meaning in the day-to-day work. The creation of a comprehensive WC is a feasible and meaningful intervention for addressing resident wellness in a Neurology training program and could be adapted to other programs.
Strategies for the Development of Science, Technology and Innovation as a Public and Social Good
Authors: Hogenschurz Lukas
Published: December 2020

There is growing interest in the understanding how science, technology and innovation can be utilized for the benefit for society. Therefore, this article explores the literature on science, technology and innovation and their characteristics as a public and social good. It then outlines the importance of firms to transfer newly created knowledge into a useful social and economic entity. In this context citizen entrepreneurship is delineated as an effective mean to transform knowledge from science and innovation into a social benefit. Based on this understanding eight strategies to support the formation of citizen entrepreneurship in a region involved in science and the development of innovation are outlined. These strategies focus on strengthening (1) individuals, (2) institutions and (3) networks.
A speculative discussion of four animal carcinogens endogenously produced in humans and a formula for cancer development
Authors: Adamson Richard H
Published: December 2020

The major factors (macro) which cause human cancer have been elucidated and include tobacco use, diet, infection, reproductive and sexual behavior and, to a lesser extent, alcohol consumption and occupational factors. Several reports have been published about endogenous chemicals made in humans which produce DNA adducts; however, few have linked them to possible carcinogenic activity. This paper discussed four chemicals made in humans (formaldehyde, acetaldehyde, isoprene and ethylene oxide), pathways of their formation, their animal carcinogenicity and questions about these and other endogenous chemicals’ possible role in human cancer. In addition, the author posits a simplified formula for development of cancer and a formula for causing mutations by various agents.
Affective bureaucratic relations: File practices in a European deportation unit and criminal court
Authors: Wissink Lieke , Oorschot Irene van
Published: December 2020

Indifference has long been acknowledged as a crucial affect to the continuation of bureaucratic practices. Recently, the production of more diverse and layered affective modes in bureaucratic institutions is increasingly highlighted. However, how affects differ within and between sites saturated with ‘paper work’ remains an understudied terrain. In this paper we focus on the relations that are formed in daily file-work within two state institutions: a Deportation Unit and a Criminal Court. We draw on ethnographic fieldwork in order to show that a) affects are locally produced in the relations that are mobilized in file-work b) these affects are unevenly produced within and between different bureaucratic practices. By comparing two different bureaucratic settings yet related in the subjugation they demand of the bureaucratic referent of their practices, we aim to put forward how differences in bureaucratic practice come with their own specific affective modes, showing that bureaucratic practices are saturated in, and thrive on, diverse affects of varying intensity. Bureaucratic action is a deeply affective practice, within which the relationship between caseworker, casefile, and the file’s referent is carefully calibrated. With this intervention we position ourselves within scholarship that complicates perceived dichotomies between rationality, still often associated with bureaucracy, and affect. Developing sensitivities towards such variety of bureaucratic affect offers nuanced perspectives on file-work and what kind of sovereign power the relations that are made through file-work subsequently allow to be reproduced.
Impact assessment and a fiscal recovery policy for tsunami risk: GIS and the general equilibrium approach in Hakodate city, Japan
Authors: Tanaka Hajime , Huang Michael C
Published: December 2020

Given Japan’s substantial exposure to many kinds of natural hazards, such as earthquakes, tsunamis, and typhoons, it has been a priority to invest in resilience, guided by evidence-based modeling. In 2011, the Great East Japan Earthquake and Tsunami became the costliest natural disaster ever recorded. This study applied a geographic information system using assumed tsunami-affected data calibrated in a recursive computable general equilibrium model to perform an economic impact assessment and an estimated recovery budget. We simulated 100 years of tsunamis and a 10-year sectoral recovery package for the sectors related to the ocean economy, such as kelp, net fishery, squid, other fisheries, food processing, and recreation, with a capital-use subsidy policy regarding investment strategy. We found that the aqua sector is incredibly vulnerable and would not recover with the capital-use subsidy within Hakodate City’s financial capability. Nevertheless, the recovery policy could still ease output price changes. On the other hand, the recreation sector could recover to pre-disaster conditions, but at huge fiscal and social costs. Meanwhile, the food processing sector’s recovery could generate social benefits and have a spillover effect on other fisheries sectors. The application of geographic information system in tsunami-prone areas could strengthen the precision of economic analysis. Such evidence-based modeling could visualize the economic impact to assist policymakers and stakeholders in foreseeing disaster risk and implementing more effective building resilience measures.
Risk of Infectious Endophthalmitis From a Resident-Performed Intravitreal Injection
Authors: Day H. Russell , Law Janice C. , Lindsey Jennifer L.
Published: December 2020

Purpose:

This work assesses the safety of resident-performed intravitreal injections by comparing the incidence of postinjection endophthalmitis associated with residents vs surgical retina attendings.

Methods:

In this retrospective noninferiority cohort study, the Current Procedural Technology code for an intravitreal injection was used to identify patients from July 1, 2015, to October 31, 2018, at a single-center Veterans Affairs hospital where patients receive intravitreal injections from attending vitreoretinal surgeons and residents. The medical record for each injection was reviewed for the training level of the proceduralist, indication, medication, and laterality. The main outcome was the incidence of postinjection endophthalmitis occurring within 30 days of an intravitreal injection, which was confirmed by at least 2 medical-record reviewers.

Results:

In this cohort of 593 patients, most were male (97.0%), and the average age was 70.3 years (±10.8 years). Of the 6934 injections given, 3877 (55.9%) were performed by residents and 3057 (44.1%) by attendings. Of the 5 cases of endophthalmitis identified, 3 were associated with a resident-performed injection in his or her fourth year of postgraduate training. The difference (0.012%; 95% CI, –0.168% to 0.169%) in the incidence of postinjection endophthalmitis between residents (0.077%) and attendings (0.065%) did not cross the predetermined noninferiority limit (0.200%).

Conclusions:

At our teaching clinic, resident-performed injections were not associated with an elevated risk of endophthalmitis when compared with attending-performed injections. Under varying levels of supervision, residents appeared to demonstrate appropriate sterile injection technique.
The opioid epidemic and headache: Experience of a general neurology consult service
Authors: Fearon Conor , Moloney Kevin , Chalissery Albi , Ferguson Damien , Redmond Janice
Published: December 2020

Background:

Headaches represent a significant proportion of referrals to any neurology consult service, of which many are migrainous. Regular use of opioids can lead to medication overuse headache in these patients and in some cases, dependence. The epidemic of opioid abuse represents a serious public health concern, with long term use of opioids associated with risk of misuse, abuse, addiction and even overdose.

Methods:

We audited headache referrals to the neurology consult service in an acute tertiary hospital over three 6-month periods between 2012 and 2019. Appropriateness of referrals with respect to NICE guidelines and initial treatments strategies were assessed.

Results:

The majority of headache disorders seen were migrainous and we found an alarming and repeated trend of early opioid prescribing in the initial acute setting (up to 56%).

Conclusions:

Further education of healthcare professionals and patients is urgently required to prevent this group becoming victims of the growing global opioid epidemic.
How U.S. teams advanced communication and resolution program adoption at local, state and national levels
Authors: LeCraw Florence R , Stearns Sally C , McCoy Michael J
Published: December 2020

Widespread adoption of evidence-based new healthcare practice guidelines can take years to occur. Policy leaders frequently make decisions based on incomplete and often incorrect information. These policy decisions can result in wasteful healthcare spending and poor health outcomes. Proponents of a medicolegal policy, Communication-and-Resolution Program (CRP), were successful in their endeavor to get hospitals to implement CRP, state legislators to pass state laws to encourage CRP adoption by hospitals, and national medical societies to endorse CRP to their members. The purpose of this paper is to explain the methods used by nine teams in their efforts to accomplish these goals. We identify reasons for the successes, failures, and obstacles faced by the teams in their effort to advance CRP. Our hope is to educate groups on a potentially more expeditious method to advance evidence-based policy than other methods. We propose that advocates of an innovation determine the concerns and goals of all stakeholder groups impacted by the policy. The specific concerns of each group should be the focus of the message to that group. Teams should identify the opinion leaders of each stakeholder group who can champion the new policy to their peers. Teams can aid the opinion leaders in their communication efforts to their peer group. National groups should be organized to help teams in their endeavor to advance evidence-based policies.
Integrative Analysis of Gene-Specific DNA Methylation and Untargeted Metabolomics Data from the ELEMENT Cohort
Authors: Goodrich Jaclyn M , Hector Emily C , Tang Lu , LaBarre Jennifer L , Dolinoy Dana C , Mercado-Garcia Adriana , Cantoral Alejandra , Song Peter XK , Téllez-Rojo Martha Maria , Peterson Karen E
Published: December 2020

Epigenetic modifications, such as DNA methylation, influence gene expression and cardiometabolic phenotypes that are manifest in developmental periods in later life, including adolescence. Untargeted metabolomics analysis provide a comprehensive snapshot of physiological processes and metabolism and have been related to DNA methylation in adults, offering insights into the regulatory networks that influence cellular processes. We analyzed the cross-sectional correlation of blood leukocyte DNA methylation with 3758 serum metabolite features (574 of which are identifiable) in 238 children (ages 8-14 years) from the Early Life Exposures in Mexico to Environmental Toxicants (ELEMENT) study. Associations between these features and percent DNA methylation in adolescent blood leukocytes at LINE-1 repetitive elements and genes that regulate early life growth ( IGF2, H19, HSD11B2) were assessed by mixed effects models, adjusting for sex, age, and puberty status. After false discovery rate correction (FDR q < 0.05), 76 metabolites were significantly associated with LINE-1 DNA methylation, 27 with HSD11B2, 103 with H19, and 4 with IGF2. The ten identifiable metabolites included dicarboxylic fatty acids (five associated with LINE-1 or H19 methylation at q < 0.05) and 1-octadecanoyl-rac-glycerol ( q < 0.0001 for association with H19 and q = 0.04 for association with LINE-1). We then assessed the association between these ten known metabolites and adiposity 3 years later. Two metabolites, dicarboxylic fatty acid 17:3 and 5-oxo-7-octenoic acid, were inversely associated with measures of adiposity ( P < .05) assessed approximately 3 years later in adolescence. In stratified analyses, sex-specific and puberty-stage specific (Tanner stage = 2 to 5 vs Tanner stage = 1) associations were observed. Most notably, hundreds of statistically significant associations were observed between H19 and LINE-1 DNA methylation and metabolites among children who had initiated puberty. Understanding relationships between subclinical molecular biomarkers (DNA methylation and metabolites) may increase our understanding of genes and biological pathways contributing to metabolic changes that underlie the development of adiposity during adolescence.
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.
Polypropylene nanocomposite fibers: A review of current trends and new developments
Authors: Tsioptsias C , Leontiadis K , Tzimpilis E , Tsivintzelis I
Published: December 2020

In this review, traditional and novel techniques for producing micro- and nano- fibers are discussed and various nanofillers, their modifications and polypropylene (PP) functionalization routes are presented. Their influence on PP properties is discussed and new PP composite fiber applications are presented. This review reveals interesting conclusions, such as that in terms of mechanical reinforcement, there is no nano-filler that can improve tensile strength to the extent that it is improved by drawing. However, in some cases, composite drawn fibers are characterized by higher tensile strength than drawn neat PP. With some notable exceptions, the PP nanocomposites lack of “dramatic” properties improvement is mainly due to the non-polar nature of the hydrocarbon chain, which does not favor strong intermolecular interactions with most popular (mainly inorganic) nano-fillers. However, other properties such as electric conductivity, water contact angle and others can be effectively altered using various nanofillers in PP matrices.
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

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

Background

Several 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.

Methods

A 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.

Results

We 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).

Conclusions

Chronic 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

Background

Inhibition 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.

Methods

Three 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).

Results

BI 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.

Conclusion

BI 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

Background

In 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.

Results

We 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.

Conclusion

The 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

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

Background

The 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.

Results

Here, 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.

Conclusions

These 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

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.
A novel nomogram to predict perioperative acute kidney injury following isolated coronary artery bypass grafting surgery with impaired left ventricular ejection fraction
Authors: Lin Hongyuan , Hou Jianfeng , Tang Hanwei , Chen Kai , Sun Hansong , Zheng Zhe , Hu Shengshou
Published: December 2020

Background and objective

Heart failure (HF) is a global health issue, and coronary artery bypass graft (CABG) is one of the most effective surgical treatments for HF with coronary artery disease. Unfortunately, the incidence of postoperative acute kidney injury (AKI) is high in HF patients following CABG, and there are few tools to predict AKI after CABG surgery for such patients. The aim of this study is to establish a nomogram to predict the incidence of AKI after CABG in patients with impaired left ventricular ejection fraction (LVEF).

Methods

From 2012 to 2017, Clinical information of 1208 consecutive patients who had LVEF< 50% and underwent isolated CABG was collected to establish a derivation cohort. A novel nomogram was developed using the logistic regression model to predict postoperative AKI among these patients. According to the same inclusion criteria and the same period, we extracted the data of patients from 6 other large cardiac centers in China (n = 540) from the China Heart Failure Surgery Registry (China-HFSR) database for external validation of the new model. The nomogram was compared with 3 other available models predicting renal failure after cardiac surgery in terms of calibration, discrimination and net benefit.

Results

In the derivation cohort (n = 1208), 90 (7.45%) patients were diagnosed with postoperative AKI. The nomogram included 7 independent risk factors: female, increased preoperative creatinine(> 2 mg/dL), LVEF< 35%, previous myocardial infarction (MI), hypertension, cardiopulmonary bypass(CPB) used and perioperative blood transfusion. The area under the receiver operating characteristic curve (AUC) was 0.738, higher than the other 3 models. By comparing calibration curves and decision curve analyses (DCA) with other models, the novel nomogram showed better calibration and greater net benefit. Among the 540 patients in the validation cohort, 104 (19.3%) had postoperative AKI, and the novel nomogram performed better with respect to calibration, discrimination and net benefit.

Conclusions

The novel nomogram is a reliable model to predict postoperative AKI following isolated CABG for patients with impaired LVEF.
Qualitative research methods in medical dissertations: an observational methodological study on prevalence and reporting quality of dissertation abstracts in a German university
Authors: Ullrich Charlotte , Stürmlinger Anna , Wensing Michel , Krug Katja
Published: December 2020

Background

Qualitative methods offer a unique contribution to health research. Academic dissertations in the medical field provide an opportunity to explore research practice. Our aim was to assess the use of qualitative methods in dissertations in the medical field.

Methods

By means of a methodological observational study, an analysis of all academic medical dissertations’ abstracts between 1998 and 2018 in a repository databank of a large medical university faculty in Germany was performed. This included MD dissertations (Dr. med. (dent.)) and medical science dissertations (Dr. sc. hum.). All abstracts including “qualitativ*” were screened for studies using qualitative research methods. Data were extracted from abstracts using a category grid considering a) general characteristics (year, language, degree type), b) discipline, c) study design (mixed methods/qualitative only, data conduction, data analysis), d) sample (size and participants) and e) technologies used (data analysis software and recording technology). Thereby reporting quality was assessed.

Results

In total, 103 abstracts of medical dissertations between 1998 and 2018 (1.4% of N = 7619) were included, 60 of MD dissertations and 43 of medical sciences dissertations. Half of the abstracts (n = 51) referred to dissertations submitted since 2014. Most abstracts related to public health/hygiene (n = 27) and general practice (n = 26), followed by medical psychology (n = 19). About half of the studies (n = 47) used qualitative research methods exclusively, the other half (n = 56) used mixed methods. For data collection, primarily individual interviews were used (n = 80), followed by group interviews (n = 33) and direct observation (n = 11). Patients (n = 36), physicians (n = 36) and healthcare professionals (n = 17) were the most frequent research participants. Incomplete reporting of participants and data analysis was common (n = 67). Nearly half of the abstracts (n = 46) lacked information on how data was analysed, most of the remaining (n = 43) used some form of content analysis. In summary, 36 abstracts provided all crucial data (participants, sample size,; data collection and analysis method).

Conclusion

A small number of academic dissertations used qualitative research methods. About a third of these reported all key aspects of the methods used in the abstracts. Further research on the quality of choice and reporting of methods for qualitative research in dissertations is recommended.