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Fulltext Dissemination of streptococcal pyrogenic exotoxin G (spegg) with an IS-like element in fish isolates of Streptococcus dysgalactiae

Abdelsalam M, Chen SC, Yoshida T

FEMS Microbiol Lett, 2010 Aug 1;309(1):105-13.
PMID: 20528946 DOI: 10.1111/j.1574-6968.2010.02024.x

The Lancefield group C alpha-hemolytic Streptococcus dysgalactiae ssp. dysgalactiae (GCSD) causes systemic granulomatous inflammatory disease and high mortality rates in infected fish. Superantigen and streptolysin S genes are the most important virulence factors contributing to an invasive streptococcal infection. PCR amplification revealed that all strains isolated from moribund fish harbored the streptolysin S structural gene (sagA). GCSD fish isolates were PCR negative for emm, speA, speB, speC, speM, smeZ, and ssa. However, the size of the streptococcal pyrogenic exotoxin G (spegg) locus, a superantigen, in positive S. dysgalactiae fish and pig strains was variable. The ORF of the spegg locus of 26 GCSD fish strains and one GCSD pig strain was inserted with IS981SC. Interestingly, the ORF of the spegg locus of two fish strains of GCSD collected in Malaysia was inserted with an IS981SC-IS1161 hybrid IS element. The hybrid IS element was found in all of the GCSD fish isolates and one GCSD pig through PCR screening. Although no insertion sequence (IS) was detected in the spegg locus of S. dysgalactiae ssp. equisimilis (GCSE) strains, a five-nucleotide deletion mutation was detected in the ORF of the spegg locus of one GCSE strain at the supposed site of IS981SC insertion, resulting in a frameshift mutation.
Fulltext Phenotypic and genetic characterizations of Streptococcus dysgalactiae strains isolated from fish collected in Japan and other Asian countries

Abdelsalam M, Chen SC, Yoshida T

FEMS Microbiol Lett, 2010 Jan;302(1):32-8.
PMID: 19895643 DOI: 10.1111/j.1574-6968.2009.01828.x

Lancefield group C Streptococcus dysgalactiae is an emerging fish pathogen, which was first isolated in 2002 in Japan. Streptococcus dysgalactiae isolates collected from diseased fish in Japan (n=12), Taiwan (n=12), China (n=2), Malaysia (n=3), and Indonesia (n=1) were characterized using biased sinusoidal field gel electrophoresis (BSFGE), sodA gene sequence analysis, and antimicrobial susceptibility. These isolates exhibited high phenotypic homogeneity irrespective of the countries from where the strains were collected. Seventeen isolates were found to be resistant to oxytetracycline and carried the tet(M) gene, except for the strains collected in Taiwan and the PP1564 strain collected in China. The sodA gene sequence analysis revealed that 23 isolates were identical, except for one Japanese isolate (KNH07902), in which a single nucleotide differed from that of the other isolates. Based on BSFGE typing by ApaI macrorestriction, the isolates - including the Japanese, Taiwanese, and Chinese isolates - could be grouped into one main cluster at a 70% similarity level. However, the macrorestriction genotypes of some isolates were apparently distinct from those of the main cluster.
Fulltext Genetic diversity of geographically distinct Streptococcus dysgalactiae isolates from fish

Abdelsalam M, Eissa AE, Chen SC

J Adv Res, 2015 Mar;6(2):233-8.
PMID: 25750757 DOI: 10.1016/j.jare.2013.12.003

Streptococcus dysgalactiae is an emerging pathogen of fish. Clinically, infection is characterized by the development of necrotic lesions at the caudal peduncle of infected fishes. The pathogen has been recently isolated from different fish species in many countries. Twenty S. dysgalactiae isolates collected from Japan, Taiwan, Malaysia and Indonesia were molecularly characterized by biased sinusoidal field gel electrophoresis (BSFGE) using SmaI enzyme, and tuf gene sequencing analysis. DNA sequencing of ten S. dysgalactiae revealed no genetic variation in the tuf amplicons, except for three strains. The restriction patterns of chromosomal DNA measured by BSFGE were differentiated into six distinct types and one subtype among collected strains. To our knowledge, this report gives the first snapshot of S. dysgalactiae isolates collected from different countries that are localized geographically and differed on a multinational level. This genetic unrelatedness among different isolates might suggest a high recombination rate and low genetic stability.
Fulltext Evaluation of X-Ray Beam Quality Based on Measurements and Estimations Using SpekCalc and Ipem78 Models

Chen SC, Jong WL, Harun AZ

Malays J Med Sci, 2012 Jul;19(3):22-8.
PMID: 23610546 MyJurnal

Different computational methods have been used for the prediction of X-ray spectra and beam quality in diagnostic radiology. The purpose of this study was to compare X-ray beam qualities based on half-value layers (HVLs) determined through measurements and computational model estimations.
Expression of the serum opacity factor gene and the variation in its upstream region in Streptococcus dysgalactiae isolates from fish

Nishiki I, Minami T, Chen SC, Itami T, Yoshida T

J Gen Appl Microbiol, 2012;58(6):457-63.
PMID: 23337581

Group C Streptococcus dysgalactiae (GCSD) is a pathogen of farmed fish. Almost all GCSD isolates from Asian countries, including Japan, Taiwan, Malaysia, and China, have a serum opacity factor (SOF-FD). Although the SOF-FD sequences in different GCSD isolates are identical, different opacification activities are observed. Three types of variations were observed in the upstream sequence of the sof-FD gene in GCSD isolates with different SOF-FD activities. Type 1 was characterized by insertion of an IS981-like element into the upstream region of the sof-FD gene. In Type 2, an IS981-like element was inserted into the upstream region in a direction opposite to that in Type 1. In Type 3, no IS element was inserted. Type 1 was predominant among Japanese isolates (129 of 133). Isolates from other Asian countries were generally Type 3 (13 of 16). Except for 1 strain, Type 1 strains exhibited opacification activities with optical densities (ODs)>0.6, while Type 2 and Type 3 strains have low opacification activities (ODs >0.2). Only Type 1 strains have putative -10 and -35 promoter regions upstream of the sof-FD gene, and the expression level of the sof-FD gene was higher in Type 1 strains than in Type 2 and Type 3 strains.
Single strand dna breaks in human lymphocytes exposed to para-phenylenediamine and its derivatives

Chye SM, Hseu YC, Liang SH, Chen CH, Chen SC

Bull Environ Contam Toxicol, 2008 Jan;80(1):58-62.
PMID: 18058049

Para-Phenylenediamine (PPD), the main aromatic amines used in the hair dye formation, and its four derivatives (2-chloro-p-phenylenediamine, 4-chloro-o-phenylenediamine, 2-nitro-p-phenylenediamine, and 4-nitro-o-phenylenediamine) were examined for their potential to produce single strand DNA breaks in human lymphocytes using the alkaline comet assay. Results revealed that all the tested chemicals within the range of doses from 100 microM to 500 microM showed the genotoxicity in a dose-dependent manner after the incubation of lymphocytes with these chemicals for 2 h. In this study, we first reported that PPD and its four derivatives can elicit the type of single strand breaks in human lymphocytes.
Fulltext Laparoscopic sleeve gastrectomy in Asia: Long term outcome and revisional surgery

Pok EH, Lee WJ, Ser KH, Chen JC, Chen SC, Tsou JJ, et al.

Asian J Surg, 2016 Jan;39(1):21-8.
PMID: 25964106 DOI: 10.1016/j.asjsur.2015.03.006

Laparoscopic sleeve gastrectomy (LSG) is a popular stand-alone bariatric surgery, despite a paucity of long-term data. Hence, this study is to report the long-term outcome of LSG as primary bariatric procedure and the result of revisional surgery.
Clinical utility of caspofungin eye drops in fungal keratitis

Neoh CF, Daniell M, Chen SC, Stewart K, Kong DC

Int J Antimicrob Agents, 2014 Aug;44(2):96-104.
PMID: 24933448 DOI: 10.1016/j.ijantimicag.2014.04.008

Treatment of fungal keratitis remains challenging. To date, only the polyenes and azoles are commonly used topically in the management of fungal keratitis. Natamycin, a polyene, is the only antifungal eye drop that is commercially available; the remainder are prepared in-house and are used in an 'off-label' manner. Failure of medical treatment for fungal keratitis is common, hence there is a need for more effective topical antifungal therapy. To increase the antifungal eye drop armamentarium, it is important to investigate the utility of other classes of antifungal agents for topical use. Caspofungin, an echinocandin antifungal agent, could potentially be used to address the existing shortcomings. However, little is known about the usefulness of topically administered caspofungin. This review will briefly explore the incidence, epidemiology and antifungal treatment of fungal keratitis. It will focus primarily on evidence related to the efficacy, safety and practicality of using caspofungin eye drops in fungal keratitis.
Echinocandins in the treatment of candidaemia and invasive candidiasis: clinical and economic perspectives

Neoh CF, Slavin M, Chen SC, Stewart K, Kong DC

Int J Antimicrob Agents, 2014 Mar;43(3):207-14.
PMID: 24670423 DOI: 10.1016/j.ijantimicag.2013.08.010

Candidaemia and invasive candidiasis (IC) complicate modern medical therapy, contributing to high morbidity and mortality. Managing candidiasis is costly, with an additional healthcare expenditure of nearly US$300 million annually. Recent consensus guidelines have suggested the use of newer antifungal agents, such as echinocandins, for the treatment of candidaemia and IC owing to promising clinical outcomes compared with older-generation antifungal agents, but at higher drug acquisition and administration costs. Comprehensive cost-effectiveness data for echinocandins in treating candidaemia and IC remain relatively scant, underlining the need for more studies to incorporate robust economic analyses into clinical decisions. Assessment of the cost efficiencies of these expensive antifungal agents is essential for maximising health outcomes within the constraints of healthcare resources. This review will explore the epidemiology of candidaemia and IC in the context of clinical and economic aspects of the antifungal agents used to treat IC, especially the echinocandins. Standardising the outcome measure, methodology and reporting of results used in economic studies is central to ensure validity and comparability of the findings. Future studies comparing the economic advantages of all available antifungal treatment options and in the context of new diagnostic tools for fungal infections are anticipated.
Genotypic and phenotypic analysis of Elizabethkingia meningoseptica in bullfrog Rana catesbeiana isolated in Taiwan

Tsai MA, See MS, Chiu CH, Wang PC, Chen SC

J Fish Dis, 2023 Nov;46(11):1239-1248.
PMID: 37519120 DOI: 10.1111/jfd.13842

Elizabethkingia meningoseptica is a hazardous bacterium for agriculture production and human health. The present study identified E. meningoseptica from the bullfrog, human and reference strain BCRC 10677 by API 20NE, 50S ribosome protein L27 sequencing and pulse field gel electrophoresis to differentiate isolates of E. meningoseptica from aquatic animals and humans. All isolates from bullfrogs and humans were identified as E. meningoseptica by DNA sequencing with 98.8%-100% sequence identity. E. meningoseptica displayed significant genetic diversity when analysed using pulsed-field gel electrophoresis (PFGE). There were six distinct pulsotypes, including one pulsotype found in bullfrog isolates and five pulsotypes found in human isolates. However, E. meningoseptica from bullfrog exhibited one genotype only by PFGE. Overall, molecular epidemiological analysis of PFGE results indicated that the frog E. meningoseptica outbreaks in Taiwan were produced by genetically identical clones. The bullfrog isolates were not genetically related to other E. meningoseptica from human and reference isolates. This research provided the first comparisons of biochemical characteristics and genetic differences of E. meningoseptica from human and bullfrog isolates.
Expanding the scope of "trans-humanism": situating within the framework of life and death education - the importance of a "trans-mystical mindset"

Phan HP, Ngu BH, Hsu CS, Chen SC, Wu L

Front Psychol, 2024;15:1380665.
PMID: 38721316 DOI: 10.3389/fpsyg.2024.1380665

Life and death education, as noted from the literatures, has been studied and researched extensively in China, Malaysia, and Taiwan. Our own research undertakings over the past several years, situated in different sociocultural settings have delved into aspects of life and death that could help advance theoretical understanding of the subject matters (e.g., does the meaning of "effective life functioning" connote differing interpretations for different cultural groups?). Situating within the framework of life and death education, we expand the study of trans-humanism by introducing an extended prefix or nomenclature known as "trans-mystical". Specifically, our philosophized concept of trans-mysticism considers a related concept, which we term as a "trans-mystical mindset". A trans-mystical mindset, differing from an ordinary mindset, from our philosophical rationalization, is defined as "a person's higher-order state of consciousness, espousing her perception, judgment, belief, and attempted interpretation of life and death phenomena that are mystifying and fall outside the ordinary boundaries of human psyche." Our focus of inquiry, as reported in the present article, seeks to advance our proposition: that a trans-mystical mindset, unlike an ordinary mindset, may help a person to rationalize, appreciate, and understand metaphysical contexts, mystical experiences, and the like. This focus, interestingly, serves to highlight an important discourse - namely, that there is a dichotomy in theoretical lenses (i.e., objective reality vs. individual subjectivity) that a person may use to rationalize the significance or non-significance of universal contexts, events, phenomena, etc. (e.g., a person's experience of "premonition"). As such, then, there is an important question that we seek to consider: whether philosophization, or the use of philosophical psychology, would yield perceived "scientific evidence" to support or to reject the study of metaphysicism, mysticism, and the like? For example, does our philosophization of an "equivalency" between a person's trans-mystical mindset and her experience of self-transcendence help to normalize and/or to scientize the subject matters of metaphysicism, mysticism, etc.?
Apoptosis induced by para-phenylenediamine involves formation of ROS and activation of p38 and JNK in chang liver cells

Chye SM, Tiong YL, Yip WK, Koh RY, Len YW, Seow HF, et al.

Environ Toxicol, 2014 Sep;29(9):981-90.
PMID: 23172806 DOI: 10.1002/tox.21828

para-Phenylenediamine (p-PD) is a suspected carcinogen, but it has been widely used as a component in permanent hair dyes. In this study, the mechanism of p-PD-induced cell death in normal Chang liver cells was investigated. The results demonstrated that p-PD decreased cell viability in a dose-dependent manner. Cell death via apoptosis was confirmed by enhanced DNA damage and increased cell number in the sub-G1 phase of the cell cycle, using Hoechst 33258 dye staining and flow cytometry analysis. Apoptosis via reactive oxygen species generation was detected by the dichlorofluorescin diacetate staining method. Mitogen-activated protein kinase (MAPK) activation was assessed by western blot analysis and revealed that p-PD activated not only stress-activated protein kinase (SAPK)/c-Jun N-terminal kinases (JNK) and p38 MAPK but also extracellular signal-regulated kinase (ERK). Cytotoxicity and apoptosis induced by p-PD were markedly enhanced by ERK activation and selectively inhibited by ERK inhibitor PD98059, thus indicating a negative role of ERK. In contrast, inhibition of p38 MAPK activity with the p38-specific inhibitor SB203580 moderately inhibited cytotoxicity and apoptosis induction by p-PD. Similarly, SP600125, an inhibitor of SAPK/JNK, moderately inhibited cytotoxicity and apoptosis induced by p-PD, thus implying that p38 MAPK and SAPK/JNK had a partial role in p-PD-induced apoptosis. Western blot analysis revealed that p-PD significantly increased phosphorylation of p38 and SAPK/JNK and decreased phosphorylation of ERK. In conclusion, the results demonstrated that SAPK/JNK and p38 cooperatively participate in apoptosis induced by p-PD and that a decreased ERK signal contributes to growth inhibition or apoptosis.
Fulltext Six-Year Outcomes in Subjects with Polypoidal Choroidal Vasculopathy in the EVEREST II Study

Teo KYC, Park KH, Ngah NF, Chen SJ, Ruamviboonsuk P, Mori R, et al.

Ophthalmol Ther, 2024 Apr;13(4):935-954.
PMID: 38308746 DOI: 10.1007/s40123-024-00888-0

INTRODUCTION: The EVEREST II study previously reported that intravitreally administered ranibizumab (IVR) combined with photodynamic therapy (PDT) achieved superior visual gain and polypoidal lesion closure compared to IVR alone in patients with polypoidal choroidal vasculopathy (PCV). This follow-up study reports the long-term outcomes 6 years after initiation of the EVEREST II study.
METHODS: This is a non-interventional cohort study of 90 patients with PCV from 16 international trial sites who originally completed the EVEREST II study. The long-term outcomes were assessed during a recall visit at about 6 years from commencement of EVEREST II.
RESULTS: The monotherapy and combination groups contained 41 and 49 participants, respectively. The change in best-corrected visual acuity (BCVA) from baseline to year 6 was not different between the monotherapy and combination groups; - 7.4 ± 23.0 versus - 6.1 ± 22.4 letters, respectively. The combination group had greater central subfield thickness (CST) reduction compared to the monotherapy group at year 6 (- 179.9 vs - 74.2 µm, p = 0.011). Fewer eyes had subretinal fluid (SRF)/intraretinal fluid (IRF) in the combination versus monotherapy group at year 6 (35.4% vs 57.5%, p = 0.032). Factors associated with BCVA at year 6 include BCVA (year 2), CST (year 2), presence of SRF/IRF at year 2, and number of anti-VEGF treatments (years 2-6). Factors associated with presence of SRF/IRF at year 6 include combination arm (OR 0.45, p = 0.033), BCVA (year 2) (OR 1.53, p = 0.046), and presence of SRF/IRF (year 2) (OR 2.59, p = 0.042).
CONCLUSION: At 6 years following the EVEREST II study, one-third of participants still maintained good vision. As most participants continued to require treatment after exiting the initial trial, ongoing monitoring and re-treatment regardless of polypoidal lesion status are necessary in PCV.
TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT01846273.
Pan-Asian adapted ESMO Clinical Practice Guidelines for the management of patients with intermediate and advanced/relapsed hepatocellular carcinoma: a TOS-ESMO initiative endorsed by CSCO, ISMPO, JSMO, KSMO, MOS and SSO

Chen LT, Martinelli E, Cheng AL, Pentheroudakis G, Qin S, Bhattacharyya GS, et al.

Ann Oncol, 2020 03;31(3):334-351.
PMID: 32067677 DOI: 10.1016/j.annonc.2019.12.001

The most recent version of the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of hepatocellular carcinoma (HCC) was published in 2018, and covered the diagnosis, management, treatment and follow-up of early, intermediate and advanced disease. At the ESMO Asia Meeting in November 2018 it was decided by both the ESMO and the Taiwan Oncology Society (TOS) to convene a special guidelines meeting immediately after the Taiwan Joint Cancer Conference (TJCC) in May 2019 in Taipei. The aim was to adapt the ESMO 2018 guidelines to take into account both the ethnic and the geographic differences in practice associated with the treatment of HCC in Asian patients. These guidelines represent the consensus opinions reached by experts in the treatment of patients with intermediate and advanced/relapsed HCC representing the oncology societies of Taiwan (TOS), China (CSCO), India (ISMPO) Japan (JSMO), Korea (KSMO), Malaysia (MOS) and Singapore (SSO). The voting was based on scientific evidence, and was independent of the current treatment practices, the drug availability and reimbursement situations in the individual participating Asian countries.
Fulltext The Psychological Science Accelerator: Advancing Psychology through a Distributed Collaborative Network

Moshontz H, Campbell L, Ebersole CR, IJzerman H, Urry HL, Forscher PS, et al.

Adv Methods Pract Psychol Sci, 2018 Dec;1(4):501-515.
PMID: 31886452 DOI: 10.1177/2515245918797607

Concerns have been growing about the veracity of psychological research. Many findings in psychological science are based on studies with insufficient statistical power and nonrepresentative samples, or may otherwise be limited to specific, ungeneralizable settings or populations. Crowdsourced research, a type of large-scale collaboration in which one or more research projects are conducted across multiple lab sites, offers a pragmatic solution to these and other current methodological challenges. The Psychological Science Accelerator (PSA) is a distributed network of laboratories designed to enable and support crowdsourced research projects. These projects can focus on novel research questions, or attempt to replicate prior research, in large, diverse samples. The PSA's mission is to accelerate the accumulation of reliable and generalizable evidence in psychological science. Here, we describe the background, structure, principles, procedures, benefits, and challenges of the PSA. In contrast to other crowdsourced research networks, the PSA is ongoing (as opposed to time-limited), efficient (in terms of re-using structures and principles for different projects), decentralized, diverse (in terms of participants and researchers), and inclusive (of proposals, contributions, and other relevant input from anyone inside or outside of the network). The PSA and other approaches to crowdsourced psychological science will advance our understanding of mental processes and behaviors by enabling rigorous research and systematically examining its generalizability.
To which world regions does the valence-dominance model of social perception apply?

Jones BC, DeBruine LM, Flake JK, Liuzza MT, Antfolk J, Arinze NC, et al.

Nat Hum Behav, 2021 01;5(1):159-169.
PMID: 33398150 DOI: 10.1038/s41562-020-01007-2

Over the past 10 years, Oosterhof and Todorov's valence-dominance model has emerged as the most prominent account of how people evaluate faces on social dimensions. In this model, two dimensions (valence and dominance) underpin social judgements of faces. Because this model has primarily been developed and tested in Western regions, it is unclear whether these findings apply to other regions. We addressed this question by replicating Oosterhof and Todorov's methodology across 11 world regions, 41 countries and 11,570 participants. When we used Oosterhof and Todorov's original analysis strategy, the valence-dominance model generalized across regions. When we used an alternative methodology to allow for correlated dimensions, we observed much less generalization. Collectively, these results suggest that, while the valence-dominance model generalizes very well across regions when dimensions are forced to be orthogonal, regional differences are revealed when we use different extraction methods and correlate and rotate the dimension reduction solution. PROTOCOL REGISTRATION: The stage 1 protocol for this Registered Report was accepted in principle on 5 November 2018. The protocol, as accepted by the journal, can be found at https://doi.org/10.6084/m9.figshare.7611443.v1 .
Fulltext Author Correction: A multi-country test of brief reappraisal interventions on emotions during the COVID-19 pandemic

Wang K, Goldenberg A, Dorison CA, Miller JK, Uusberg A, Lerner JS, et al.

Nat Hum Behav, 2022 Sep;6(9):1318-1319.
PMID: 36002766 DOI: 10.1038/s41562-022-01441-4
Fulltext A multi-country test of brief reappraisal interventions on emotions during the COVID-19 pandemic

Wang K, Goldenberg A, Dorison CA, Miller JK, Uusberg A, Lerner JS, et al.

Nat Hum Behav, 2021 Aug;5(8):1089-1110.
PMID: 34341554 DOI: 10.1038/s41562-021-01173-x

The COVID-19 pandemic has increased negative emotions and decreased positive emotions globally. Left unchecked, these emotional changes might have a wide array of adverse impacts. To reduce negative emotions and increase positive emotions, we tested the effectiveness of reappraisal, an emotion-regulation strategy that modifies how one thinks about a situation. Participants from 87 countries and regions (n = 21,644) were randomly assigned to one of two brief reappraisal interventions (reconstrual or repurposing) or one of two control conditions (active or passive). Results revealed that both reappraisal interventions (vesus both control conditions) consistently reduced negative emotions and increased positive emotions across different measures. Reconstrual and repurposing interventions had similar effects. Importantly, planned exploratory analyses indicated that reappraisal interventions did not reduce intentions to practice preventive health behaviours. The findings demonstrate the viability of creating scalable, low-cost interventions for use around the world. PROTOCOL REGISTRATION: The stage 1 protocol for this Registered Report was accepted in principle on 12 May 2020. The protocol, as accepted by the journal, can be found at https://doi.org/10.6084/m9.figshare.c.4878591.v1.
Fulltext In COVID-19 Health Messaging, Loss Framing Increases Anxiety with Little-to-No Concomitant Benefits: Experimental Evidence from 84 Countries

Dorison CA, Lerner JS, Heller BH, Rothman AJ, Kawachi II, Wang K, et al.

Affect Sci, 2022 Sep;3(3):577-602.
PMID: 36185503 DOI: 10.1007/s42761-022-00128-3

The COVID-19 pandemic (and its aftermath) highlights a critical need to communicate health information effectively to the global public. Given that subtle differences in information framing can have meaningful effects on behavior, behavioral science research highlights a pressing question: Is it more effective to frame COVID-19 health messages in terms of potential losses (e.g., "If you do not practice these steps, you can endanger yourself and others") or potential gains (e.g., "If you practice these steps, you can protect yourself and others")? Collecting data in 48 languages from 15,929 participants in 84 countries, we experimentally tested the effects of message framing on COVID-19-related judgments, intentions, and feelings. Loss- (vs. gain-) framed messages increased self-reported anxiety among participants cross-nationally with little-to-no impact on policy attitudes, behavioral intentions, or information seeking relevant to pandemic risks. These results were consistent across 84 countries, three variations of the message framing wording, and 560 data processing and analytic choices. Thus, results provide an empirical answer to a global communication question and highlight the emotional toll of loss-framed messages. Critically, this work demonstrates the importance of considering unintended affective consequences when evaluating nudge-style interventions.

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