Novel Approach for Pancreas Transcriptomics Reveals the Cellular Landscape in Homeostasis and Acute Pancreatitis.

BACKGROUND & AIMS: Acinar cells produce digestive enzymes that impede transcriptomic characterization of the exocrine pancreas. Thus, single-cell RNA-sequencing studies of the pancreas underrepresent acinar cells relative to histological expectations, and a robust approach to capture pancreatic cell responses in disease states is needed. We sought to innovate a method that overcomes these challenges to accelerate study of the pancreas in health and disease. METHODS: We leverage FixNCut, a single-cell RNA-sequencing approach in which tissue is reversibly fixed with dithiobis(succinimidyl propionate) before dissociation and single-cell preparation. We apply FixNCut to an established mouse model of acute pancreatitis, validate findings using GeoMx whole transcriptome atlas profiling, and integrate our data with prior studies to compare our method in both mouse and human pancreas datasets. RESULTS: FixNCut achieves unprecedented definition of challenging pancreatic cells, including acinar and immune populations in homeostasis and acute pancreatitis, and identifies changes in all major cell types during injury and recovery. We define the acinar transcriptome during homeostasis and acinar-to-ductal metaplasia and establish a unique gene set to measure deviation from normal acinar identity. We characterize pancreatic immune cells, and analysis of T-cell subsets reveals a polarization of the homeostatic pancreas toward type-2 immunity. We report immune responses during acute pancreatitis and recovery, including early neutrophil infiltration, expansion of dendritic cell subsets, and a substantial shift in the transcriptome of macrophages due to both resident macrophage activation and monocyte infiltration. CONCLUSIONS: FixNCut preserves pancreatic transcriptomes to uncover novel cell states during homeostasis and following pancreatitis, establishing a broadly applicable approach and reference atlas for study of pancreas biology and disease.

Synthesis and Structural Optimization of ATG4B Inhibitors for the Attenuation of Autophagy in Glioblastoma.

Glioblastoma, a prevalent malignant CNS tumor, presents a therapeutic challenge because of resistance to standard treatments, including radiation therapy and temozolomide. Both modalities induce autophagy, thereby paradoxically promoting tumor survival. The cysteine protease ATG4B is implicated in this cellular process, which highlights the enzyme as a viable therapeutic target for glioblastoma. We have developed streamlined syntheses for ATG4B inhibitor NSC185058, its derivatives, and fluorogenic ATG4B substrate pim-FG-PABA-AMC. We leveraged these findings to rapidly identify novel compound MJO445, which demonstrates markedly greater potency biochemically and in cells.

The progranulin cleavage product granulin 3 exerts a dominant negative effect on animal fitness.

Progranulin is an evolutionarily conserved protein that has been implicated in human neurodevelopmental and neurodegenerative diseases. Human progranulin is comprised of multiple cysteine-rich, biologically active granulin peptides. Granulin peptides accumulate with age and stress, however their functional contributions relative to full-length progranulin remain unclear. To address this, we generated C. elegans strains that produced quantifiable levels of both full-length progranulin/PGRN-1 protein and cleaved granulin peptide. Using these strains, we demonstrated that even in the presence of intact PGRN-1, granulin peptides suppressed the activity of the lysosomal aspartyl protease activity, ASP-3/CTSD. Granulin peptides were also dominant over PGRN-1 in compromising animal fitness as measured by progress through development and stress response. Finally, the degradation of human TDP-43 was impaired when the granulin to PGRN-1 ratio was increased, representing a disease-relevant downstream impact of impaired lysosomal function. In summary, these studies suggest that not only absolute progranulin levels, but also the balance between full-length progranulin and its cleavage products, is important in regulating lysosomal biology. Given its relevance in human disease, this suggests that the processing of progranulin into granulins should be considered as part of disease pathobiology and may represent a site of therapeutic intervention.

Validation of the Short Version (TLS-15) of the Triangular Love Scale (TLS-45) across 37 Languages.

Love is a phenomenon that occurs across the world and affects many aspects of human life, including the choice of, and process of bonding with, a romantic partner. Thus, developing a reliable and valid measure of love experiences is crucial. One of the most popular tools to quantify love is Sternberg's 45-item Triangular Love Scale (TLS-45), which measures three love components: intimacy, passion, and commitment. However, our literature review reveals that most studies (64%) use a broad variety of shortened versions of the TLS-45. Here, aiming to achieve scientific consensus and improve the reliability, comparability, and generalizability of results across studies, we developed a short version of the scale-the TLS-15-comprised of 15 items with 5-point, rather than 9-point, response scales. In Study 1 (N = 7,332), we re-analyzed secondary data from a large-scale multinational study that validated the original TLS-45 to establish whether the scale could be truncated. In Study 2 (N = 307), we provided evidence for the three-factor structure of the TLS-15 and its reliability. Study 3 (N = 413) confirmed convergent validity and test-retest stability of the TLS-15. Study 4 (N = 60,311) presented a large-scale validation across 37 linguistic versions of the TLS-15 on a cross-cultural sample spanning every continent of the globe. The overall results provide support for the reliability, validity, and cross-cultural invariance of the TLS-15, which can be used as a measure of love components-either separately or jointly as a three-factor measure.

Exploring Attitudes Toward "Sugar Relationships" Across 87 Countries: A Global Perspective on Exchanges of Resources for Sex and Companionship.

The current study investigates attitudes toward one form of sex for resources: the so-called sugar relationships, which often involve exchanges of resources for sex and/or companionship. The present study examined associations among attitudes toward sugar relationships and relevant variables (e.g., sex, sociosexuality, gender inequality, parasitic exposure) in 69,924 participants across 87 countries. Two self-report measures of Acceptance of Sugar Relationships (ASR) developed for younger companion providers (ASR-YWMS) and older resource providers (ASR-OMWS) were translated into 37 languages. We tested cross-sex and cross-linguistic construct equivalence, cross-cultural invariance in sex differences, and the importance of the hypothetical predictors of ASR. Both measures showed adequate psychometric properties in all languages (except the Persian version of ASR-YWMS). Results partially supported our hypotheses and were consistent with previous theoretical considerations and empirical evidence on human mating. For example, at the individual level, sociosexual orientation, traditional gender roles, and pathogen prevalence were significant predictors of both ASR-YWMS and ASR-OMWS. At the country level, gender inequality and parasite stress positively predicted the ASR-YWMS. However, being a woman negatively predicted the ASR-OMWS, but positively predicted the ASR-YWMS. At country-level, ingroup favoritism and parasite stress positively predicted the ASR-OMWS. Furthermore, significant cross-subregional differences were found in the openness to sugar relationships (both ASR-YWMS and ASR-OMWS scores) across subregions. Finally, significant differences were found between ASR-YWMS and ASR-OMWS when compared in each subregion. The ASR-YWMS was significantly higher than the ASR-OMWS in all subregions, except for Northern Africa and Western Asia.

Quantifying Ligand Binding to the Surface of Metal-Organic Frameworks.

The binding of molecules to the exterior surface of metal-organic frameworks (MOFs) is not a well-understood phenomenon. Herein, the surface chemistry of three MOFs, UiO-66, MIL-88B-NH2, and ZIF-8, is investigated using dye-displacement experiments. MOF particle surfaces were modified with ligand-appended BODIPY dyes. The ability of the coordinated dyes to be displaced by a variety of exogenous ligands was measured by ultraviolet-visible spectroscopy. This method allowed for measurement of apparent binding constants for different ligands to the MOF surface. As might be expected, ligand affinity was dependent on the nature of the underlying metal-ligand composition of the MOF. This work provides a quantitative evaluation of ligand binding to MOF surfaces and important insights for the modulation, modification, and manipulation of MOFs.

Comparing stress and behavioral coping strategies during the early stages of the COVID-19 crisis among domestic and overseas Taiwanese.

This study reported domestic and overseas Taiwanese people's perceived stress levels and examined the mediation effect of their coping strategies during the early stages of the COVID-19 pandemic. We recruited 2727 Taiwanese respondents from the COVIDiSTRESS Global Survey (N = 173,426) between March 30 and May 30, 2020. The self-report questionnaire included a modified 10-item Perceived Stress Scale and a 16-item coping strategy scale. Three stress-coping factors were extracted with principal component analysis and confirmatory factor analysis. Their effects were examined through a regression and mediation analysis. The overseas Taiwanese participants had a significantly higher stress level than domestic counterparts (2.89 to 2.69 in 1-5 scale, p < 0.001). Government guidance was associated with lower stress level among domestic (- 0.097, 95% C.I. [- 0.131, - 0.063]) but not overseas Taiwanese (0.025, [- 0.114, 0.163]). The association of stress level with residency was mediated by coping strategies, for government guidance (0.04, [0.01, 0.07], ref: domestic participants) and supportive social networks (- 0.03, [- 0.05, - 0.01]). All results hold after the propensity score matching on samples. Government guidance on COVID-19 as a channel for coping with stress is correlated with the residency status of the respondents. Public health authorities should recognize the importance of various mental health interventions during pandemics.

Naloxegol versus Alvimopan for Enhancing Postoperative Recovery following Radical Cystectomy for Bladder Cancer.

INTRODUCTION: µ-Opioid-receptor antagonists are a standard component of enhanced recovery after surgery (ERAS) pathways following radical cystectomy (RC) as they reduce ileus and shorten length of stay (LOS). Prior studies have used alvimopan; however, naloxegol is a less expensive medication in the same class. We compared differences in postoperative outcomes between patients receiving alvimopan or naloxegol following RC. METHODS: We retrospectively reviewed all patients undergoing RC over 20 months at an academic center during which standard practice transitioned from using alvimopan to naloxegol, while maintaining all other components of our ERAS pathway. We utilized bivariate comparisons as well as negative binomial and logistic regression to compare return of bowel function, rates of ileus and LOS following RC. RESULTS: Of 117 eligible patients, 59 (50%) received alvimopan and 58 (50%) received naloxegol. There were no differences in baseline clinical, demographic or perioperative factors. Median postoperative LOS was 6 days in each group (p=0.3). Time to flatus (2 versus 2 days, p=0.2) and ileus (14% versus 17%, p=0.6) were similar between the alvimopan and naloxegol groups, respectively. In multivariable models controlling for patient and surgical factors, µ-opioid antagonist agent was associated with neither LOS nor ileus. Cost difference was -$344.20/day, equivalent to a $2,065.20 savings over a 6-day hospital stay with naloxegol. CONCLUSIONS: In patients undergoing RC managed with a standard ERAS pathway, there were no differences in postoperative recovery based on the use of alvimopan versus naloxegol. Substitution of naloxegol for alvimopan may allow for significant cost savings without compromising outcomes.

Genetically Encoded, pH-Sensitive mTFP1 Biosensor for Probing Lysosomal pH.

Lysosomes are important sites for macromolecular degradation, defined by an acidic lumenal pH of ∼4.5. To better understand lysosomal pH, we designed a novel, genetically encoded, fluorescent protein (FP)-based pH biosensor called Fluorescence Indicator REporting pH in Lysosomes (FIRE-pHLy). This biosensor was targeted to lysosomes with lysosomal-associated membrane protein 1 (LAMP1) and reported lumenal pH between 3.5 and 6.0 with monomeric teal fluorescent protein 1 (mTFP1), a bright cyan pH-sensitive FP variant with a pKa of 4.3. Ratiometric quantification was enabled with cytosolically oriented mCherry using high-content quantitative imaging. We expressed FIRE-pHLy in several cellular models and quantified the alkalinizing response to bafilomycin A1, a specific V-ATPase inhibitor. In summary, we have engineered FIRE-pHLy, a specific, robust, and versatile lysosomal pH biosensor, that has broad applications for investigating pH dynamics in aging- and lysosome-related diseases, as well as in lysosome-based drug discovery.

The molecular tweezer CLR01 improves behavioral deficits and reduces tau pathology in P301S-tau transgenic mice.

BACKGROUND: Molecular tweezers (MTs) are broad-spectrum inhibitors of abnormal protein aggregation. A lead MT, called CLR01, has been demonstrated to inhibit the aggregation and toxicity of multiple amyloidogenic proteins in vitro and in vivo. Previously, we evaluated the effect of CLR01 in the 3 × Tg mouse model of Alzheimer's disease, which overexpresses mutant human presenilin 1, amyloid ß-protein precursor, and tau and found that subcutaneous administration of the compound for 1 month led to a robust reduction of amyloid plaques, neurofibrillary tangles, and microgliosis. CLR01 also has been demonstrated to inhibit tau aggregation in vitro and tau seeding in cell culture, yet because in Alzheimer's disease (AD) and in the 3 × Tg model, tau hyperphosphorylation and aggregation are thought to be downstream of Aß insults, the study in this model left open the question whether CLR01 affected tau in vivo directly or indirectly. METHODS: To determine if CLR01 could ameliorate tau pathology directly in vivo, we tested the compound similarly using the P301S-tau (line PS19) mouse model. Mice were administered 0.3 or 1.0 mg/kg per day CLR01 and tested for muscle strength and behavioral deficits, including anxiety- and disinhibition-like behavior. Their brains then were analyzed by immunohistochemical and biochemical assays for pathological forms of tau, neurodegeneration, and glial pathology. RESULTS: CLR01 treatment ameliorated muscle-strength deterioration, anxiety-, and disinhibition-like behavior. Improved phenotype was associated with decreased levels of pathologic tau forms, suggesting that CLR01 exerts a direct effect on tau in vivo. Limitations of the study included a relatively short treatment period of the mice at an age in which full pathology is not yet developed. In addition, high variability in this model lowered the statistical significance of the findings of some outcome measures. CONCLUSIONS: The findings suggest that CLR01 is a particularly attractive candidate for the treatment of AD because it targets simultaneously the two major pathogenic proteins instigating and propagating the disease, amyloid ß-protein (Aß), and tau, respectively. In addition, our study suggests that CLR01 can be used for the treatment of other tauopathies in the absence of amyloid pathology.

Influencing overseas Chinese by tweets: text-images as the key tactic of Chinese propaganda.

The literature on China's social media foreign propaganda mostly focuses on text-format contents in English, which may miss the real target and the tool for analysis. In this article, we traced 1256 Twitter accounts echoing China government's #USAVirus propaganda before and after Twitter removed state-linked operations on June 12, 2020. The 3567 tweets with #USAVirus we collected, albeit many written in English, 74% of them attached with a lengthy simplified Chinese text-image. Distribution of the post-creation time fits the working-hour in China. Overall, 475 (37.8%) accounts we traced were later suspended after Twitter's disclosure. Our dataset enables us to analyze why and why not Twitter suspends certain accounts. We apply the decision tree, random forest, and logit regression to explain the suspensions. All models suggest that the inclusion of a text-image is the most important predictor. The importance outweighs the number of followers, engagement, and the text content of the tweet. The prevalence of simplified Chinese text-images in the #USAVirus trend and their impact on Twitter account suspensions both evidence the importance of text-image in the study of state-led propaganda. Our result suggests the necessity of extracting and analyzing the content in the attached text-image.

Racial disparities in post-stroke functional outcomes in young patients with ischemic stroke.

BACKGROUND AND PURPOSE: Recent studies show rising incidence of stroke in the young, for which risk factors are not well characterized. There is evidence of increased risk in certain racial and ethnic groups. We assessed racial differences in risk factors, stroke etiology, and outcomes among young stroke patients. METHODS: Using data from our inpatient registry for ischemic stroke, we reviewed patients aged 18-50 who were admitted 01/2013 to 04/2018. Race/ethnicity were characterized as non-Hispanic White (NHW), non-Hispanic Black (NHB), Hispanic (HIS). For univariate comparisons Chi-square and Kruskal-Wallis tests were performed as appropriate. Multivariable logistic regression was used to assess impact of race on day seven modified Rankin score (mRS). RESULTS: Among 810 patients with race and outcome data who were admitted in the study period, median age was 43, 57.1% were male, and 36.5% NHW, 43.2% NHB, 20.2% HIS. History of hypertension (HTN), type II diabetes (DM II), smoking, heart failure (CHF), prior stroke, and end-stage renal disease varied significantly by race. Compared to NHW, NHB had higher odds of HTN (OR 2.28, 1.65-3.15), CHF (OR 2.17, 1.06-4.46), and DM II 1.92 (1.25-2.94) while HIS had higher odds of DM II (OR 2.52, 1.55-4.10) and lower odds of smoking (OR 0.56, 0.35-0.90). Arrival NIHSS was higher in NHB, but etiology and rates of tpA treatment and thrombectomy did not vary by race. Compared to NHW patients, NHB (OR 0.50 CI (0.31-0.78)) and HIS (OR 0.37 CI (0.21-0.67)) were less likely to have good functional outcome (mRS <2) at day 7 in adjusted analyses. CONCLUSIONS: In this study, there was a higher prevalence of several modifiable risk factors in NHB and HIS young stroke patients and early functional outcome was worse in these groups. Our study suggests a need for targeted prevention efforts for younger populations at highest risk for stroke.

Allele-Specific QTL Fine Mapping with PLASMA.

Although quantitative trait locus (QTL) associations have been identified for many molecular traits such as gene expression, it remains challenging to distinguish the causal nucleotide from nearby variants. In addition to traditional QTLs by association, allele-specific (AS) QTLs are a powerful measure of cis-regulation that are concordant with traditional QTLs but typically less susceptible to technical/environmental noise. However, existing methods for estimating causal variant probabilities (i.e., fine mapping) cannot produce valid estimates from asQTL signals due to complexities in linkage disequilibrium (LD). We introduce PLASMA (Population Allele-Specific Mapping), a fine-mapping method that integrates QTL and asQTL information to improve accuracy. In simulations, PLASMA accurately prioritizes causal variants over a wide range of genetic architectures. Applied to RNA-seq data from 524 kidney tumor samples, PLASMA achieves a greater power at 50 samples than conventional QTL-based fine mapping at 500 samples, with more than 17% of loci fine mapped to within five causal variants, compared to 2% by QTL-based fine mapping, and a 6.9-fold overall reduction in median credible set size compared to QTL-based fine mapping when applied to H3K27AC ChIP-seq from just 28 prostate tumor/normal samples. Variants in the PLASMA credible sets for RNA-seq and ChIP-seq were enriched for open chromatin and chromatin looping, respectively, at a comparable or greater degree than credible variants from existing methods while containing far fewer markers. Our results demonstrate how integrating AS activity can substantially improve the detection of causal variants from existing molecular data.

Increased Vascular Pathology in Older Veterans With a Purple Heart Commendation or Chronic Post-Traumatic Stress Disorder.

The goal of this retrospective cohort study was to determine whether stressors related to military service, determined by a diagnosis of chronic post-traumatic stress disorder (cPTSD) or receiving a Purple Heart (PH), are associated with an increased risk of vascular risk factors and disease, which are of great concern for veterans, who constitute a significant portion of the aging US population. The Veterans Integrated Service Network (VISN) 16 administrative database was searched for individuals 65 years or older between October 1, 1997 to September 30, 1999 who either received a PH but did not have cPTSD (PH+/cPTSD-; n = 1499), had cPTSD without a PH (PH-/cPTSD+; n = 3593), had neither (PH-/cPTSD-; n = 5010), or had both (PH+/cPTSD+; n = 153). In comparison to the control group (PH-/cPTSD-), the PH+/cPTSD- group had increased odds ratios for incidence and prevalence of diabetes mellitus, hypertension, and hyperlipidemia. The PH-/cPTSD+ group had increased odds ratios for prevalence of diabetes mellitus and for the incidence and prevalence of hyperlipidemia. The PH-/cPTSD+ and PH+/cPTSD- groups were associated with ischemic heart disease and cerebrovascular disease, but not independently of the other risk factors. The PH+/cPTSD+ group was associated only with an increase in the incidence and prevalence of hyperlipidemia, though this group's much smaller sample size may limit the reliability of this finding. We conclude that certain physical and psychological stressors related to military service are associated with a greater incidence of several vascular risk factors in veterans aged 65 years or older, which in turn are associated with greater rates of ischemic heart disease and cerebrovascular disease.

Impact of an immunization platform in community pharmacies.

OBJECTIVES: To assess the impact of incorporating a bidirectional immunization forecasting and reporting platform in the workflow of a regional community pharmacy chain with the use of time and motion methodologies. SETTING: Six Bartell Drugs Pharmacies in Seattle, Washington. PRACTICE DESCRIPTION: Bartell Drugs is a 63-store family-owned regional community pharmacy chain that offers all routine vaccinations and travel vaccinations. PRACTICE INNOVATION: Six pharmacies were selected based on immunization performance the previous year. These pharmacies were divided into 3 immunization performance groups. Within each performance group, one store had implemented the bidirectional immunization forecasting and reporting platform (intervention) and the other had not (control). EVALUATION: Observations were conducted for 4 to 8 hours at each store to determine the time required for each immunization encounter. Each encounter was divided into 7 time subcategories, which were assigned to the pharmacist, technician, or patient. Time and motion methodologies were used to estimate total pharmacist and technician time and the number of immunizations administered per patient encounter. All data were analyzed with the use of descriptive statistics. RESULTS: Ten vaccinations were administered during 5 patient encounters in the intervention group compared with 8 vaccinations during 8 patient encounters in the control group. The average time spent on each patient encounter in the intervention group was 24.8 minutes, compared with 18.5 minutes in the control group. In the intervention group, pharmacists spent an average of 9.3 minutes per patient encounter compared with 7.6 minutes in the control group. In the intervention group, technicians spent an average of 10.8 minutes per encounter compared with 9.1 minutes in the control group. CONCLUSION: Incorporation of a bidirectional immunization platform into the workflow of a community pharmacy increased staff time but also resulted in a greater number of immunizations per patient, suggesting enhanced immunization care in the intervention pharmacies.

Multi-Granulin Domain Peptides Bind to Pro-Cathepsin D and Stimulate Its Enzymatic Activity More Effectively Than Progranulin in Vitro.

Progranulin (PGRN) is an evolutionarily conserved glycoprotein associated with several disease states, including neurodegeneration, cancer, and autoimmune disorders. This protein has recently been implicated in the regulation of lysosome function, whereby PGRN may bind to and promote the maturation and activity of the aspartyl protease cathepsin D (proCTSD, inactive precursor; matCTSD, mature, enzymatically active form). As the full-length PGRN protein can be cleaved into smaller peptides, called granulins, we assessed the function of these granulin peptides in binding to proCTSD and stimulating matCTSD enzyme activity in vitro. Here, we report that full-length PGRN and multi-granulin domain peptides bound to proCTSD with low to submicromolar binding affinities. This binding promoted proCTSD destabilization, the magnitude of which was greater for multi-granulin domain peptides than for full-length PGRN. Such destabilization correlated with enhanced matCTSD activity at acidic pH. The presence and function of multi-granulin domain peptides have typically been overlooked in previous studies. This work provides the first in vitro quantification of their binding and activity on proCTSD. Our study highlights the significance of multi-granulin domain peptides in the regulation of proCTSD maturation and enzymatic activity and suggests that attention to PGRN processing will be essential for the future understanding of the molecular mechanisms leading to neurodegenerative disease states with loss-of-function mutations in PGRN.

Tau/MAPT disease-associated variant A152T alters tau function and toxicity via impaired retrograde axonal transport.

Mutations in the microtubule-associated protein tau (MAPT) underlie multiple neurodegenerative disorders, yet the pathophysiological mechanisms are unclear. A novel variant in MAPT resulting in an alanine to threonine substitution at position 152 (A152T tau) has recently been described as a significant risk factor for both frontotemporal lobar degeneration and Alzheimer's disease. Here we use complementary computational, biochemical, molecular, genetic and imaging approaches in Caenorhabditis elegans and mouse models to interrogate the effects of the A152T variant on tau function. In silico analysis suggests that a threonine at position 152 of tau confers a new phosphorylation site. This finding is borne out by mass spectrometric survey of A152T tau phosphorylation in C. elegans and mouse. Optical pulse-chase experiments of Dendra2-tau demonstrate that A152T tau and phosphomimetic A152E tau exhibit increased diffusion kinetics and the ability to traverse across the axon initial segment more efficiently than wild-type (WT) tau. A C. elegans model of tauopathy reveals that A152T and A152E tau confer patterns of developmental toxicity distinct from WT tau, likely due to differential effects on retrograde axonal transport. These data support a role for phosphorylation of the variant threonine in A152T tau toxicity and suggest a mechanism involving impaired retrograde axonal transport contributing to human neurodegenerative disease.

Patience moderates the class cleavage in demand for redistribution.

Previous studies on class voting have yielded mixed results linking income and demand for redistribution. Why do some poor people oppose redistribution, while some rich people support it? This article argues that an individual's level of patience, an important personal characteristic that influences how people calculate immediate and distinct outcomes, may moderate the effect of class on redistributive preference. In a one-shot game, redistribution between the rich and the poor is zero sum. When people extend their time horizons, however, the poor see the possibility of upward mobility, while the rich emphasize future losses, such as unemployment and economic instability. Consistent with the hypotheses, analyses of the 2014 Cooperative Congressional Election Study and a representative Taiwanese dataset from 2016 reveal a clear class cleavage in demand for redistribution among impatient poor and rich respondents, but the cleavage between their patient counterparts diminished. This pattern of convergence extends previous studies on upward mobility and risk perception theory.