bluuebunny/crossref_metadata_2025_split huggingface dataset:
Compound interaction screen on a photoactivatable cellulose membrane (CISCM) identifies drug targets
Authors: Melder Teresa , Lindemann Peter , Welle Alexander , Trouillet Vanessa , Heißler Stefan , Nazaré Marc , Selbach Matthias 
Published: April 2022

AbstractIdentifying the protein targets of drugs is an important but tedious process. Existing proteomic approaches enable unbiased target identification but lack the throughput needed to screen larger compound libraries. Here, we present a compound interaction screen on a photoactivatable cellulose membrane (CISCM) that enables target identification of several drugs in parallel. To this end, we use diazirine-based undirected photoaffinity labeling (PAL) to immobilize compounds on cellulose membranes. Functionalized membranes are then incubated with protein extract and specific targets are identified via quantitative affinity purification and mass spectrometry. CISCM reliably identifies known targets of natural products in less than three hours of analysis time per compound. In summary, we show that combining undirected photoimmobilization of compounds on cellulose with quantitative interaction proteomics provides an efficient means to identify the targets of natural products.
RNA methylation influences TDP43 binding and disease pathogenesis in models of amyotrophic lateral sclerosis and frontotemporal dementia
Authors: McMillan M , Gomez N , Bekier M , Li X , Miguez R , Tank EM , Barmada SJ 
Published: April 2022

AbstractMethylation of RNA at the N6 position of adenosine (m6A) is one of the most common RNA modifications, impacting RNA stability as well as its transport and translation. Previous studies uncovered RNA destabilization in models of amyotrophic lateral sclerosis (ALS), in association with accumulation of the RNA-binding protein TDP43, which is itself mislocalized from the nucleus in >95% of those with ALS. Here, we show that TDP43 recognizes m6A-modified RNA, and that RNA methylation is critical for both TDP43 binding and autoregulation. We also observed extensive hypermethylation of coding and non-coding transcripts in ALS spinal cord, many of which overlap with methylated TDP43 target RNAs. Emphasizing the importance of m6A for TDP43 binding and function, we identified several m6A factors that enhance or suppress TDP43-mediated toxicity via a single-cell CRISPR/Cas9 candidate-based screen in primary neurons. The most promising genetic modifier among these—the canonical m6A reader YTHDF2— accumulated within spinal motor neurons in ALS postmortem sections, and its knockdown prolonged the survival of human neurons carrying ALS-associated mutations. Collectively, these data show that m6A modifications modulate RNA binding by TDP43, and that m6A is pivotal for TDP43-related neurodegeneration in ALS.
Protein-Peptide Turnover Profiling reveals wiring of phosphorylation during protein maturation
Authors: Hammarén Henrik M. , Geissen Eva-Maria , Potel Clement , Beck Martin , Savitski Mikhail M. 
Published: April 2022

SummaryPost-translational modifications (PTMs) regulate various aspects of protein function, including degradation. Mass spectrometric methods that rely on pulsed metabolic labeling are very popular to quantify turnover rates on a proteome-wide scale. Such data have often been interpreted in the context of protein proteolytic stability. Here, we combine theoretical kinetic modeling with experimental pulsed stable isotope labeling of amino acids in cell culture (pSILAC) for the study of protein phosphorylation. We demonstrate that metabolic labeling combined with PTM-specific enrichment does not measure effects of PTMs on protein stability. Rather, it reveals the relative order of PTM addition and removal along a protein’s lifetime—a fundamentally different metric. We use this framework to identify temporal phosphorylation sites on cell cycle-specific factors and protein complex assembly intermediates. Our results open up an entirely new aspect in the study of PTMs, by tying them into the context of a protein’s lifetime.
CD169+ macrophages orchestrate plasmacytoid dendritic cell arrest and retention for optimal priming in the bone marrow of malaria-infected mice
Authors: Fried Jamie , Paul Mahinder , Jing Zhixin , Fooksman David , Lauvau Grégoire 
Published: April 2022

AbstractPlasmacytoid dendritic cells (pDC) are the most potent producer of type I interferon (IFN), but how pDC are primed in vivo is poorly defined. Using a mouse model of severe malaria, we have previously established that upon priming by CD169+ macrophages (MP), pDC initiate type I IFN-I secretion in the bone marrow (BM) of infected mice via cell-intrinsic TLR7 sensing and cell-extrinsic STING sensing. Herein we show that CD169+ MP and TLR7-sensing are both required for pDC arrest during priming, suggesting CD169+ MP are the source of TLR7 ligands. We establish that TLR7 sensing in pDC and chemotaxis are both required for pDC arrest and functional clustering with CD169+ MP in the BM. Lastly, we demonstrate that STING-sensing in CD169+ MP control pDC initiation of type I IFN production while also regulating pDC clustering and egress from the BM. Collectively, these results link pDC acquisition of type I IFN secreting capacity with changes in their motility, homing and interactions with CD169+ MP during infection. Thus, targeting this cellular interaction may help modulate type I IFN to improve outcomes of microbial infections and autoimmune diseases.
Estimating the number of breakthrough COVID-19 deaths in the United States
Authors: Smith Jinkinson 
Published: April 2022

AbstractWhile there is compelling evidence of the effectiveness of COVID-19 vaccines, increasing attention has also been paid to the fact that, like all vaccines, they are not 100% effective. Therefore, some fully vaccinated people have developed “breakthrough” cases of COVID-19, and some of these individuals have died as a result. The purpose of this study was to estimate the number of fully vaccinated or “breakthrough” deaths from COVID-19 in the United States. Data was compiled from state COVID-19 dashboards and various other sources for as many states as possible. As of March 27, 2022 based on data from 46 U.S. states and the District of Columbia, an estimated minimum of 57,617 breakthrough COVID-19 deaths had occurred in the United States. Furthermore, based on this incomplete data, a total of 12.8% of all COVID-19 deaths in the included regions and time periods were among fully vaccinated individuals (whether boosted or not). Extrapolating this data to the entire United States implies that the minimum total number of such deaths as of March 27, 2022 was 79,917. Data from a MMWR article, if similarly extrapolated to the entire country, implies a significantly larger number of breakthrough deaths throughout the United States: 99,152.
A simple algorithm based on initial Ct values predicts the duration to SARS-CoV-2 negativity and allows more efficient test-to-release and return-to-work schedules
Authors: Anastasiou Olympia E. , Khanh Le-Trilling Vu Thuy , Trilling Mirko 
Published: April 2022

AbstractEspecially during global pandemics but also in the context of epidemic waves, the capacity for diagnostic qRT-PCRs rapidly becomes a limiting factor. Furthermore, excessive testing incurs high costs and can result in an overstrained work force in diagnostics departments. Obviously, people aim to shorten their isolation periods, hospitals need to discharge convalescent people, and re-employ staff members after infection. The aim of the study was to optimize retesting regimens for test-to-release from isolation and return-to-work applications. For this purpose, we investigated the association between Ct values at the first diagnosis of SARS-CoV-2 infection and the period until test negativity was reached, or at least until the Ct value exceeded 30, which is considered to indicate the transition to a non-infectious state. We included results from the testing of respiratory material samples for the detection of SARS-CoV-2 RNA, tested from 01 March 2020 to 31 January 2022.Lower initial Ct values were associated with longer periods of SARS-CoV-2 RNA positivity. Starting with Ct values of <20, 20-25, 25-30, 30-35, and >35, it took median intervals of 20 (interval: 14-25), 16 (interval: 10-21), 12 (interval: 7-16), 7 (interval: 5-14), and 5 (interval: 2-7) days, respectively, until the person tested negative. Accordingly, a Ct threshold of 30 was surpassed after 13 (interval: 8-19), 9 (interval: 6-14), 7 (interval: 6-11), 6 (interval: 4-10), and 3 (interval: 1-6) days, respectively, in individuals with aforementioned start Ct values. Furthermore, the time to negativity was longer for adults versus children, wild-type SARS-CoV-2 variant versus other variants of concern, and in patients who were treated in the intensive care units.Based on these data, we propose an adjusted retesting strategy according to the initial Ct value in order to optimize available PCR resources.
Dark accumulation of downstream glycolytic intermediates confers robust initiation of photosynthesis in cyanobacteria
Authors: Tanaka Kenya , Shirai Tomokazu , Vavricka Christopher J. , Matsuda Mami , Kondo Akihiko , Hasunuma Tomohisa 
Published: April 2022

AbstractPhotosynthesis must maintain stability and robustness throughout fluctuating natural environments. In cyanobacteria, dark-to-light transition leads to drastic metabolic changes from dark respiratory metabolism to CO2 fixation through the Calvin-Benson-Bassham (CBB) cycle using energy and redox equivalents provided by photosynthetic electron transfer. Previous studies showed that catabolic metabolism supports the smooth transition into CBB cycle metabolism. However, metabolic mechanisms for robust initiation of photosynthesis are poorly understood due to lack of dynamic metabolic characterizations of dark-to-light transitions. Here, we show rapid (on a time scale of seconds) dynamic changes in absolute metabolite concentrations and 13C tracer incorporation after strong or weak light irradiation in the cyanobacterium Synechocystis sp. PCC 6803. Integration of this data enables estimation of time-resolved nonstationary metabolic flux underlying CBB cycle activation. This dynamic metabolic analysis indicates that downstream glycolytic intermediates including phosphoglycerate and phosphoenolpyruvate accumulate under dark conditions as major substrates for initial CO2 fixation. Compared with wild-type Synechocystis, significant delays in the initiation of oxygen evolution are observed in 12 h dark preincubated mutants deficient in glycogen degradation or oxidative pentose phosphate pathway (Δzwf, Δgnd, and ΔglgP). Accordingly, the degree of delay in the oxygen evolution initiation is proportional to the accumulated pool size of the glycolytic intermediates. These observations indicate that the accumulation of glycolytic intermediates is essential for efficient metabolism switching under fluctuating light environments.
(How) do advanced data and analyses enable HR analytics success? A neo-configurational analysis
Authors: Strohmeier Stefan , Collet Julian , Kabst Rüdiger 
Published: April 2022

PurposeEnabled by increased (“big”) data stocks and advanced (“machine learning”) analyses, the concept of human resource analytics (HRA) is expected to systematically improve decisions in human resource management (HRM). Since so far empirical evidence on this is, however, lacking, the authors' study examines which combinations of data and analyses are employed and which combinations deliver on the promise of improved decision quality.Design/methodology/approachTheoretically, the paper employs a neo-configurational approach for founding and conceptualizing HRA. Methodically, based on a sample of German organizations, two varieties (crisp set and multi-value) of qualitative comparative analysis (QCA) are employed to identify combinations of data and analyses sufficient and necessary for HRA success.FindingsThe authors' study identifies existing configurations of data and analyses in HRM and uncovers which of these configurations cause improved decision quality. By evidencing that and which combinations of data and analyses conjuncturally cause decision quality, the authors' study provides a first confirmation of HRA success.Research limitations/implicationsMajor limitations refer to the cross-sectional and national sample and the usage of subjective measures. Major implications are the suitability of neo-configurational approaches for future research on HRA, while deeper conceptualizing and researching both the characteristics and outcomes of HRA constitutes a core future task.Originality/valueThe authors' paper employs an innovative theoretical-methodical approach to explain and analyze conditions that conjuncturally cause decision quality therewith offering much needed empirical evidence on HRA success.
Patanjali Ayurved Limited: role reversal in competitive advertising
Authors: Singh Harvinder , Aggarwal Rashmi Kumar , Rishi Bikramjit 
Published: April 2022

Learning outcomes
Leraning outcomes are as follows: demonstrating how companies in the Indian market are using competitive advertising; giving participants an overview of the regulatory framework for advertising in India; highlighting the complexities arising out of the multiplicity of advertising regulations and institutions in India; appreciating the legal and ethical perspectives of advertisements and self-regulation; and evaluating the stance taken by both the parties in this particular case to develop multi-stakeholder perspective.

Case overview/Synopsis
A recent advertisement by international conglomerate Hindustan Unilever Limited was severely criticized for insulting Indian values by Baba Ramdev, promoter of India's largest Ayurvedic Company selling Indian indigenous and natural alternate medicinal products. It was in a complete reversal of the scenario between 2015 and 2018 when other Indian consumer goods companies complained against advertisements released by Patanjali. Indian fast moving consumer goods sector is witnessing a trend of competitive advertising in which companies are downplaying and criticizing the competitors. Though quite old, this trend caught momentum when Patanjali Ayurved Limited, a new player in the market, started advertising aggressively in 2015–2016. It resulted in many complaints by the aggrieved parties in the industry bodies and different courts of law in India. A part of the confusion comes from the diversity of advertising regulations across different Indian platforms and the absence of a clearly defined institutional framework for resolving such disputes. Consequently, most such disputes land up in the court of law in India. The case study builds an understanding of the legal framework within which companies are governed for brand promotions and creates a contextual ethical dilemma to drive the discourse on advertising through self-regulation in India.

Complexity academic level
This case is meant to benefit students pursuing a graduate or upper-level undergraduate degree in management or law/business law.

Supplementary materials
Teaching notes are available for educators only.

Subject code
CSS 8: Marketing.
Towards an understanding of consumers’ FinTech adoption: the case of Open Banking
Authors: Chan Rebecca , Troshani Indrit , Rao Hill Sally , Hoffmann Arvid 
Published: April 2022

PurposeThis study aims to identify key factors driving consumers' adoption of Open Banking. It extends the Unified Theory of Acceptance and Use of Technology (UTAUT) by integrating perceived risk, initial trust and financial literacy into an overarching conceptual model.Design/methodology/approachMeasurement items of the theoretical constructs included in the conceptual model were adapted from related literature and a set of hypotheses was developed. The hypotheses of the conceptual model were subsequently assessed with partial least squares structural equation modeling using a dataset of 456 Australian survey respondents.FindingsThe model has strong explanatory power with anR2of 69.5%. Performance expectancy, effort expectancy, social influence and perceived risk are direct antecedents of consumers' usage intention of Open Banking. Social influence has a strong mediating effect on usage intention through performance expectancy. The effect of perceived risk is alleviated by effort expectancy and initial trust, while initial trust positively affects the effects of performance expectancy and effort expectancy on consumers' usage intention of Open Banking. Finally, financial literacy lowers initial trust towards Open Banking, possibly inducing consumer skepticism.Practical implicationsThe results suggest that practitioners should focus on performance expectancy as a primary driver of Open Banking adoption, while understanding the role of other drivers, such as social influence and perceived risk in developing marketing strategies. Policy makers are recommended to adopt a governance approach to build initial trust amongst consumers.Originality/valueThis research contributes by providing an integrated and comprehensive model for explaining consumers' FinTech adoptions by extending the existing technology adoption model UTAUT to the Open Banking domain and integrating perceived risk, initial trust and financial literacy, thereby advancing and enriching the conceptual horizon of the extant literature.
Internet penetration, financial access and new business formation: evidence from developing economies
Authors: Haini Hazwan , Pang Wei Loon 
Published: April 2022

PurposeThis study examines whether Internet penetration has a complementary effect on the relationship between financial access and new business formation in 57 developing economies from 2006 to 2018.Design/methodology/approachUsing the generalised least squares estimator, the authors employ a framework that allows us to distinguish between the marginal impact of financial access on new business formation in developing economies with high and low levels of Internet penetration rates. Furthermore, the authors distinguish between financial institutions and financial markets.FindingsThe authors find that increased accessibility for financial institutions promotes entrepreneurial activity, while financial market access has a negative relationship with new business formation. Furthermore, the authors find that the marginal impact of financial institution access increases in magnitude as Internet penetration increases. The effect does not hold for financial markets.Research limitations/implicationsThe major limitation lies in the measurement of new business formation, as it focuses on the formal entrepreneurial sector and overlooks the informal economy and entrepreneurs operating as sole proprietors.Practical implicationsPolicymakers should continue to promote the development of the information communication and technology sector and digitalisation policy while increasing financial accessibility in the financial system.Originality/valueThis study provides new empirical evidence on the greasing role of technology to leverage the impact of financial access on new business formation. Furthermore, the study distinguishes this effect by differentiating between financial institutions and markets.
Looking beyond violence prevention climate – exploring line managers' violence preventive practices in two high-risk sectors
Authors: Jaspers Sofie Østergaard , Raaby Andersen Dorte , Karlsen Iben Louise , Sønderbo Andersen Lars Peter , Conway Paul Maurice , Dyreborg Johnny , Aust Birgit 
Published: April 2022

PurposeWork-related violence is a major occupational safety and health (OSH) issue. According to the concept of violence prevention climate, managers play a pivotal role in preventing the risk of violence at work. However, research on this is scarce. The objective of this study was, therefore, to examine line managers' use of violence preventive practices in high-risk sectors.Design/methodology/approach The authors employed three different sources of data (semi-structured interviews and field notes from both leadership seminars and coaching sessions) that were collected in the context of an intervention study in Denmark aimed at improving violence prevention. The authors conducted a thematic analysis of violence prevention experiences among 16 line managers – eight from the prison and probation services and eight from psychiatric hospitals.FindingsUsing an existing prevention framework, the authors categorized the descriptions into three types of violence preventive practices used by the line managers across the two sectors: “preventing violence”, “managing episodes of violence” and “promoting the positive”. Especially the category “promoting the positive” is often neglected in the intervention literature.Originality/value The study identified new aspects of managers' violence preventive practices than those included in the violence prevention climate concept. Such knowledge may help organizations devise improved systems for violence prevention in high-risk sectors.
An empirical assessment of the sustainable development goals compass based on consumer sentiment
Authors: Anwar Abdou Yasmin , El-Bassiouny Noha , Becker-Ritterspach Florian 
Published: April 2022

PurposeThis research aims to provide an empirical assessment of consumer sentiment towards corporate sustainability practices in the context of developing countries, specifically Egypt.Design/methodology/approachA survey was deployed to measure the importance of corporate sustainability activities to consumers.FindingsThe results demonstrate that consumers are concerned with all the measured dimensions of corporate sustainability practices, yet some of the dimensions are more critical to them than others.Originality/valueBy providing an overview of how consumers' purchase behavior is affected by corporate sustainability practices, this research contributes to knowledge on understanding more about sustainable consumer behavior in developing countries, which is scarce. Moreover, this research goes further by segmenting sustainable consumers into groups based on their sustainability concerns.
A trust model for consumer conversion in community-based group buying: the dual roles of group leaders
Authors: Ying Huajing , Ji Huanhuan , Shi Xiaoran , Wang Xinyue 
Published: April 2022

PurposeIn the presence of coronavirus disease 2019 (COVID-19), due to the social distance restriction, consumers' regular consumption behaviors and patterns have been changing fundamentally. Thereafter, an innovative group buying model has emerged and developed explosively with a specific focus on consumer's location, known as community-based group buying (CGB). The purpose of this paper is to investigate the transfer mechanism of user's trust in dyadic contexts of social and commercial role-playing in the CGB program.Design/methodology/approachThis study adopts an empirical research method, with an online and offline questionnaire survey, a total of 382 responses have been obtained. Then, both descriptive analysis and hierarchical regression analysis are conducted to explore the dual roles of group leader and its corresponding effects on consumers' trust (i.e. emotional trust and behavioral trust) and engagement actions (i.e. purchase and share) in the CGB program.FindingsResults indicate that resident's trust and their perception of group leader's friend role can positively enhance their engagement actions in the CGB programs. Meanwhile, for the purpose of profit maximization, the group leader is more willing to play a friend role in transactions no matter whether the role conflict exists.Originality/valueResearch findings provide some managerial insights for CGB platform on the selection and training of group leaders and the incentive mechanism design.