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Equity crowdfunding campaign overfunding occurs when a campaign generates funds in excess of the funding goal and has hence been touted as the mark of an extraordinarily successful campaign. However, a novel theoretical lens is needed to comprehend funders' enthusiasm in their support of such campaigns. Building on the extant literature on contagion effect, we constructed a research model that posits confidence contagion invoked by confidence cues embedded in campaign materials as a key driver of overfunding. Our hypotheses were validated in two complementary empirical studies. In Study 1, we manipulated confidence cues in a controlled experiment to verify the activation of confidence contagion at the individual level. Analytical results indicate that individual funders detect self-confidence traits from confidence cues embedded in campaign materials and assimilate the fundraiser's confidence via a spontaneous social appraisal mechanism. In turn, confidence contagion drives funders to congregate and invest in campaigns. In Study 2, we analyzed a secondary dataset collected from a leading equity crowdfunding platform to discern how confidence contagion drives overfunding at the collective level. By modeling funding activities as a Hawkes process, we derived three key metrics that govern the emergence and magnitude of funding surges. We demonstrated that these metrics of funding surges mediate the impact of confidence cues on the level of overfunding for equity crowdfunding campaigns. The findings from this study could inform future research seeking to untangle the interdependencies between individual and collective mechanisms underlying crowd phenomena, provide strategic guidance to fundraisers interested in promoting the overfunding of their campaigns, and help crowdfunding platforms predict the potential extent of overfunding and advise fundraisers accordingly. [ABSTRACT FROM AUTHOR]

When people share their prosocial behavior on social media, they face a dilemma. By making prosocial disclosures, they risk being perceived as self-promoting or even selfish and thus less likable. By staying silent, they fail to spread awareness about prosocial activities they value. Drawing on attribution theory, we study the digital reaction of likes to the self-disclosure of prosocial activities that involve multiple stakeholders to understand the affordances and constraints of social media. Leveraging field data on a social networking site, we found that reporting a higher level of self-effort increases the digital reaction of likes. To our surprise, expressing gratitude for the sponsor's efforts also increased likes for such selfdisclosures. Through lab experiments that emulated this context, we dissected this paradox by separating the positive effect of expressing gratitude and the negative effect of sharing credit with other stakeholders on likes. Further, we underscore the salience of expressing gratitude, even when gratitude was extended to sponsors with bad reputations. Our study contributes to the design of a more humane digital world where individuals share and promote prosocial activities without compromising their likability and offers valuable insights for navigating the evolving landscape of social networking platforms. [ABSTRACT FROM AUTHOR]

Patients with type 2 diabetes (T2D) are more susceptible to severe respiratory viral infections, but the underlying mechanisms remain elusive. Here, we show that patients with T2D and coronavirus disease 2019 (COVID-19) infections, and influenza-infected T2D mice, exhibit defective T helper 1 (Th1) responses, which are an essential component of anti-viral immunity. This defect stems from intrinsic metabolic perturbations in CD4+ T cells driven by hyperglycemia. Mechanistically, hyperglycemia triggers mitochondrial dysfunction and excessive fatty acid synthesis, leading to elevated oxidative stress and aberrant lipid accumulation within CD4+ T cells. These abnormalities promote lipid peroxidation (LPO), which drives carbonylation of signal transducer and activator of transcription 4 (STAT4), a crucial Th1-lineage-determining factor. Carbonylated STAT4 undergoes rapid degradation, causing reduced T-bet induction and diminished Th1 differentiation. LPO scavenger ameliorates Th1 defects in patients with T2D who have poor glycemic control and restores viral control in T2D mice. Thus, this hyperglycemia-LPO-STAT4 axis underpins reduced Th1 activity in T2D hosts, with important implications for managing T2D-related viral complications. [Display omitted] • T2D hosts exhibit impaired anti-viral Th1 responses • Hyperglycemia impedes Th1 differentiation by triggering lipid peroxidation (LPO) • LPO induces protein carbonylation of STAT4 and accelerates its degradation • LPO scavenger mitigates Th1 defects and improves viral control in T2D hosts Patients with T2D are more susceptible to severe viral respiratory infections, yet the underlying mechanism remains elusive. Here, Gray et al. reveal that hyperglycemia triggers lipid peroxidation (LPO) in CD4+ T cells. LPO-derived reactive carbonyl species modify STAT4 and expedite its degradation, leading to diminished anti-viral Th1 responses. [ABSTRACT FROM AUTHOR]

Peritoneal metastasis (PM) in gastric cancer (GC) is associated with poor prognosis and significant morbidity. We sought to understand the genomic, transcriptomic, and tumor microenvironment (TME) features that contribute to peritoneal organotropism in GC. We conducted a comprehensive multi-omic analysis of 548 samples from 326 patients, including primary tumors, matched normal tissues; peritoneal metastases, and adjacent-normal peritoneal tissues. We used whole exome sequencing, whole transcriptome sequencing, and digital spatial profiling to investigate molecular alterations, gene expression patterns, and TME characteristics associated with PM. Our analysis identified specific genomic alterations in primary tumors, including mutations in ELF3 , CDH1 , and PIGR , and TME signatures, such as stromal infiltration and M2 macrophage enrichment, associated with increased risk of PM. We observed distinct transcriptional programs and immune compositions in GCPM compared with liver metastases, highlighting the importance of the TME in transcoelomic metastasis. We found differential expression of therapeutic targets between primary tumors and PM, with lower CLDN18.2 and FGFR2b expression in PM. We unravel the roles of the TME in niche reprogramming within the peritoneum, and provide evidence of pre-metastatic niche conditioning even in early GC without clinical PM. These findings were further validated using a humanized mouse model, which demonstrated niche remodeling in the peritoneum during transcoelomic metastasis. Our study provides a comprehensive molecular characterization of GCPM and unveils key biological principles underlying transcoelomic metastasis. The identified predictive markers, therapeutic targets, and TME alterations offer potential avenues for targeted interventions and improved patient outcomes. [Display omitted] In the largest study of its kind, we identified key molecular changes that contribute to the spread of stomach cancer to the peritoneum (the lining of the abdomen). [ABSTRACT FROM AUTHOR]

Some contemporary articulator systems claim to be highly precise in their interchangeability, with tolerances below 10 μm in vertical error; however, the claims have not been independently verified. The purpose of this study was to investigate the interchangeability of calibrated semiadjustable articulators in service over time. A calibrated mounting articulator served as the master articulator, while the test groups were used articulators with a minimum of 1-year use by predoctoral dental students (n=10); used articulators with a minimum of 1-year use by prosthodontic residents (n=10); and new articulators (n=10). One set of mounted maxillary and mandibular master models was positioned in the master and test articulators. High-precision reference markers on the master models were used to determine interarch 3D distance distortions (dR R , dR C , and dR L), interocclusal 3D distance distortion (dR M), interocclusal 2D distance distortions (dx M , dy M , and dz M), and interocclusal angular distortion (dθ M) relative to the master articulator. All measurements were conducted three times using a coordinate measuring machine and then averaged to derive the final data set. For interarch 3D distance distortion, the mean dR R ranged from 4.6 ±21.6 μm for new articulators to 56.3 ±47.6 μm for articulators used by prosthodontic residents; mean dR C ranged from 65 ±48.6 μm for new articulators to 119.0 ±58.8 μm for articulators used by prosthodontic residents; and mean dR L ranged from 12.7 ±39.7 μm for articulators used by prosthodontic residents to 62.8 ±75.2 μm for new articulators. For interocclusal 3D distance distortion, the mean dR M ranged from 21.5 ±49.8 μm for new articulators to 68.6 ±64.9 μm for articulators used by predoctoral dental students. For the 2D distance distortions, the mean dx M ranged from −17.9 ±43.4 μm for articulators used by predoctoral dental students to −61.9 ±48.3 μm for articulators used by prosthodontic residents; mean dy M ranged from 18.1 ±59.4 μm for new articulators to 69.3 ±115.1 μm for articulators used by prosthodontic residents; and mean dz M ranged from 29.5 ±20.2 μm for new articulators to 70.1 ±37.8 μm for articulators used by prosthodontic residents. Mean dθ M ranged from −0.018 ±0.289 degree for new articulators to 0.141 ±0.267 degree for articulators used by prosthodontic residents. One-way ANOVA by articulator type revealed statistically significant differences among the test groups for dR R (P =.007) and dz M (P =.011) only, where articulators used by prosthodontic residents fared significantly poorer than the other test groups. The new and used articulators tested did not fulfill the manufacturer's claim of accuracy of up to 10 μm in the vertical dimension. Up to 1 year of time in service, none of the investigated test groups fulfilled the criterion for articulator interchangeability, even if the more lenient threshold of 166 μm were accepted. [ABSTRACT FROM AUTHOR]

• Anti-fibrotic therapy of pirfenidone and nintedanib can limit the decline in lung function based on FVC in non-IPF PF-ILD patients. • However, overall improvements in 6MWD, all-cause mortality, or hospitalization were not noted between the group of patients receiving anti-fibrotic versus those receiving placebo. • The clinical benefits of anti-fibrotic therapy need to be weighed against the adverse risks of nausea/vomiting, diarrhea, anorexia/weight loss, and neurological disorders. Anti-fibrotics can reduce restrictive impairment in idiopathic pulmonary fibrosis (IPF). However, its effectiveness in non-IPF progressive fibrosing interstitial lung disease (non-IPF PF-ILD) remains uncertain. We assess the efficacy and safety of anti-fibrotics pirfenidone and nintedanib versus placebo among non-IPF PF-ILD adult patients. Meta-analysis was performed using PubMed, SCOPUS, and Cochrane databases to identify randomized controlled trials (RCTs). At respective centers, non-IPF PF-ILD was defined as clinical and radiological findings inconsistent with IPF and greater than 5 % forced vital capacity (FVC) decline, worsening radiological fibrosis or respiratory symptoms. Among seven RCTs involving 1,816 non-IPF PF-ILD patients, anti-fibrotics significantly reduced decline in FVC from baseline in milliliters (MD -66.80milliliters; P < 0.01) and percent predicted (MD -1.80 %; P < 0.01) compared to placebo. However, severity of FVC decline was less than 10 % (P = 0.33) in both groups. No significant difference in the decline of 6MWD from baseline in meters (P = 0.19) while on anti-fibrotics, although those on pirfenidone had less decline in 6MWD (MD -25.12 m; P < 0.01) versus placebo. The rates of all-cause mortality (P = 0.34), all-cause hospitalization (P = 0.44), and hospitalization for respiratory etiology (P = 0.06) were comparable in both groups. Adverse events of nausea/vomiting (54.2 % vs. 20.3 %; P < 0.01), diarrhea (65.2 % vs. 27.6 %; P = 0.02), anorexia/weight loss (23.0 % vs. 7.7 %; P < 0.01), neurological disorders (20.8 % vs. 12.6 %; P < 0.01), and events requiring therapy discontinuation were higher (18.4 % vs. 9.9 %; P < 0.01) in the anti-fibrotic group. Other adverse events of skin (P = 0.18) and respiratory disorders (P = 0.20) were equal. The advent of anti-fibrotics offers alternative treatment to reduce lung function decline. [ABSTRACT FROM AUTHOR]

Microbiota and feeding modes influence the susceptibility of premature newborns to necrotizing enterocolitis (NEC) through mechanisms that remain unknown. Here, we show that microbiota colonization facilitated by breastmilk feeding promotes NOD-like receptor family CARD domain containing 5 (Nlrc5) gene expression in mouse intestinal epithelial cells (IECs). Notably, inducible knockout of the Nlrc5 gene in IECs predisposes neonatal mice to NEC-like injury in the small intestine upon viral inflammation in an NK1.1+ cell-dependent manner. By contrast, formula feeding enhances neonatal gut colonization with environment-derived tilivalline-producing Klebsiella spp. Remarkably, tilivalline disrupts microbiota-activated STAT1 signaling that controls Nlrc5 gene expression in IECs through a PPAR-γ-mediated mechanism. Consequently, this dysregulation hinders the resistance of neonatal intestinal epithelium to self-NK1.1+ cell cytotoxicity upon virus infection/colonization, promoting NEC development. Together, we discover the underappreciated role of intestinal microbiota colonization in shaping a disease tolerance program to viral inflammation and elucidate the mechanisms impacting NEC development in neonates. [Display omitted] • Breastmilk-fed gut microbiota sparks STAT1 to shift IECs into an NLRC5highTAP1high state • Formula feeding enhances tilivalline (TV)-producing Klebsiella spp. colonization • TV confers IECs with an NLRC5lowTAP1low state via PPAR-γ-mediated STAT1 inhibition • NLRC5lowTAP1low IECs are killed by self-NK cells upon viral inflammation, leading to NEC Subramanian, Geng, and colleagues discover that formula-feeding facilitates neonatal gut colonization with environment-derived tilivalline-producing Klebsiella spp., which impedes STAT1-NLRC5 axis maturation in intestinal epithelial cells through tilivalline-induced PPAR-γ activation. This dysregulation causes the epithelium to lose resistance to autologous NK cell cytotoxicity, leading to necrotizing enterocolitis (NEC) during virus colonization/infection. [ABSTRACT FROM AUTHOR]

• Cognitive function affects self-care via sense of coherence and health practices. • Those with higher sense of coherence have capacities to execute complex self-care. • The findings concur with the shift towards community care in the ageing population. • The salutogenic model can be integrated into interventions to facilitate self-care. With the trend towards ageing population globally, the salutogenic model can be integrated in interventions for pre-ageing and older adults to better support healthy ageing. However, there is limited research examining the salutogenic model's pathway amongst pre-ageing and older adults. Hence, this study aims to investigate pathways of the salutogenic model amongst pre-ageing and older adults with chronic diseases. Two hundred and eight pre-ageing and older adults were recruited from 11 Senior Activity Centres in Singapore. Data was collected using a self-reported questionnaire and analysed using path analyses. The indirect pathway from Subjective Cognitive Complaints to self-care abilities via sense of coherence and health practices were significant. Participants with higher sense of coherence may have increased capacities to execute more complex forms of self-care. Future interventions integrating the salutogenic model could enhance pre-ageing and older adults' self-care abilities to cope with chronic diseases and contribute to healthy ageing. [ABSTRACT FROM AUTHOR]

Four novel macrocyclic trichothecenes, termed mytoxins D−G (1 − 4), along with four known analogs (5 − 8), were isolated from the ethyl acetate extract of fermented rice inoculated with the fungus Myrothecium verrucaria PA57. Each compound features a tricyclic 12,13-epoxytrichothec-9-ene (EPT) core. Notably, mytoxin G (4) represents the first instance of a macrocyclic trichothecene incorporating a glucosyl unit within the trichothecene structure. The structures of the newly identified compounds were elucidated through comprehensive spectroscopic analysis combined with quantum chemical calculations. All isolated compounds demonstrated cytotoxic activity against the CAL27 and HCT116 cell lines, which are models for human oral squamous cell carcinoma and colorectal cancer, respectively. Specifically, mytoxin D (1) and mytoxin F (3) exhibited pronounced cytotoxic effects against both cancer cell lines, with IC 50 values ranging from 3 to 6 nmol·L−1. Moreover, compounds 1 and 3 were found to induce apoptosis in HCT116 cells by activating caspase-3. [ABSTRACT FROM AUTHOR]

Background: The impact of atrial fibrillation (AF) among patients with amyloidosis on in‐hospital outcomes is not well‐established. We aimed to examine in‐hospital outcomes among patients admitted with a primary diagnosis of AF with and without amyloidosis. Methods and Results: We queried the Nationwide Readmissions Database to compare the in‐hospital outcomes among AF patients with and without amyloidosis. Our study demonstrated that in‐hospital all‐cause mortality, adverse events, and 30‐day readmission were comparable between the two groups. Conclusions: Patients with AF and concurrent amyloidosis did not have worse in‐hospital outcomes than those with AF alone. [ABSTRACT FROM AUTHOR]

To compare the clinical and cost effectiveness of the Collaborative Model of Care between Orthopaedics and Allied Healthcare Professionals (CONNACT), a community-based, stratified, multidisciplinary intervention consisting of exercise, education, psychological and nutrition delivered through a chronic care model to usual hospital care in adults with knee osteoarthritis (OA). Pragmatic, parallel-arm, single-blinded superiority RCT trial. Community-dwelling, ambulant adults with knee OA (Kellgren-Lawrence grade > 1; Knee Injury and OA Outcome Score (KOOS 4) ≤75) were enrolled. Primary outcome was KOOS 4 at 12-months; secondary outcomes included: quality of life, physical performance measures, symptom satisfaction, psychological outcomes, dietary habits, and global perceived effect. Intention-to-treat analysis using generalized linear model (GLM) and regression modeling were conducted. Economic evaluation through a societal approach was embedded. 110 participants (55 control, 55 intervention) were randomized. No between-group difference found for the primary outcome (MD [95%CI]: −1.86 [−9.11. 5.38]), although both groups demonstrated within-group improvement over 12-months. Among the secondary outcomes, the CONNACT group demonstrated superior dietary change (12 months) and physical performance measures (3 months), and global perceived effect (6 months). While there was no between-group difference in total cost, significant productivity gains (reduced indirect cost) were seen in the CONNACT group. CONNACT was not superior to usual care at 1 year. Further efforts are needed to understand the underlying contextual and implementation factors in order to further improve and refine such community-based, stratified care models moving forward. Clinicaltrials.gov Identifier: NCT03809975. Registered January 18, 2019. https://clinicaltrials.gov/ct2/show/NCT03809975 [ABSTRACT FROM AUTHOR]

This study evaluated the cost-effectiveness of open, laparoscopic, and robotic liver resection. A comprehensive literature review and Bayesian network meta-analysis were conducted. Surface under cumulative ranking area values, mean difference, odds ratio, and 95% credible intervals were calculated for all outcomes. Cluster analysis was performed to determine the most cost-effective clustering approach. Costs-morbidity, costs-mortality, and costs-efficacy were the primary outcomes assessed, with postoperative overall morbidity, mortality, and length of stay associated with total costs for open, laparoscopic, and robotic liver resection. Laparoscopic liver resection incurred the lowest total costs (laparoscopic liver resection versus open liver resection: mean difference −2,529.84, 95% credible intervals −4,192.69 to −884.83; laparoscopic liver resection versus robotic liver resection: mean difference −3,363.37, 95% credible intervals −5,629.24 to −1,119.38). Open liver resection had the lowest procedural costs but incurred the highest hospitalization costs compared to laparoscopic liver resection and robotic liver resection. Conversely, robotic liver resection had the highest total and procedural costs but the lowest hospitalization costs. Robotic liver resection and laparoscopic liver resection had a significantly reduced length of stay than open liver resection and showed less postoperative morbidity. Laparoscopic liver resection resulted in the lowest readmission and liver-specific complication rates. Laparoscopic liver resection and robotic liver resection demonstrated advantages in costs-morbidity efficiency. While robotic liver resection offered notable benefits in mortality and length of stay, these were balanced against its highest total costs, presenting a nuanced trade-off in the costs-mortality and costs-efficacy analyses. Laparoscopic liver resection represents a more cost-effective option for hepatectomy with superior postoperative outcomes and shorter length of stay than open liver resection. Robotic liver resection, though costlier than laparoscopic liver resection, along with laparoscopic liver resection, consistently exceeds open liver resection in surgical performance. [ABSTRACT FROM AUTHOR]