Unrelenting pressure and an "always-on" culture can leave no time for genuine rest among young adults. While playing video games has been noted to afford cognitive escapism and relaxation, critical questions remain about the influence of popular video games, such as Super Mario Bros., and their potential effects on young adults' burnout risk. This study examined the extent to which, if at all, popular video games such as Super Mario Bros. and Yoshi could foster childlike wonder. It also investigated the potential of these games to reduce burnout risk among young adults. We used a mixed methods approach. First, qualitative data were collected through 41 exploratory, in-depth interviews (women: n=19, 46.3%; men: n=21, 51.2%; prefer not to disclose sex: n=1, 2.4%; mean age 22.51, SD 1.52 years) with university students who had experience playing Super Mario Bros. or Yoshi. Second, quantitative data were collected in a cross-sectional survey (N=336) of players of Super Mario Bros. and Yoshi to examine the games' affordance of childlike wonder, overall happiness in life, and burnout risk. Insights from in-depth interviews showed that players appreciated the ability of Super Mario Bros. and Yoshi games to instill childlike wonder, enhance happiness in life, and reduce burnout risk. Quantitative analyses showed that the games' affordance of childlike wonder positively affected young adults' happiness (b=0.30, SE=0.04, t=6.80, 95% CI 0.21-0.38; P<.001). In turn, overall happiness significantly reduced the risk of burnout (b=-0.48, SE=0.05, t=-9.55, 95% CI -0.572 to -0.377). Results showed that happiness fully mediated the impact of childlike wonder on burnout, as the direct effect of childlike wonder on burnout risk became insignificant (b=-0.08, SE=0.04, t=-1.88, 95% CI -0.16 to 0.01; P=.06), while the indirect effect of childlike wonder on burnout risk was significant (b=-0.14, bootstrapped SE=0.03, 95% CI -0.20 to -0.09). The findings showed the significant positive effect of popular video games such as Super Mario Bros. and Yoshi on fostering players' childlike wonder, increasing happiness, and reducing burnout risk. This study was among the first to identify childlike wonder as an emotional pathway through which mainstream video games could enhance well-being and reduce burnout. By moving beyond escapism and nostalgia, it offers a new perspective on how well-designed, globally familiar games can function as accessible, resilience-building digital microenvironments. These findings contributed to research bridging gaming and mental health and have practical implications for game designers, educators, and health professionals interested in promoting mental wellness through everyday play.
BRAF mutations occur in 5-10% of metastatic colorectal cancer (mCRC) cases, but their implications for prognosis and optimal treatment remain unclear. This multicenter, prospective observational study analyzed 377 RAS wild-type cases from 511 patients across 32 centers, using PCR-based methods. BRAF mutations were identified in 21% (79/377) of cases, predominantly V600E (89.9%) with a minority of non-V600E (10.1%). Microsatellite instability (MSI) testing revealed MSI-high in 11.3%, exclusively among V600E cases. V600E mutations were linked to right-sided tumors, poor differentiation, and elevated CA19-9 levels. Median survival was significantly lower in V600E cases compared to BRAF wild-type (12.4 vs. 37.5 months, HR 3.25, p < 0.001) and marginally lower non-V600E cases (12.4 vs. 34.7 months, HR 0.61, p = 0.057). Chemotherapy regimens (doublet vs. triplet) and targeted treatments (bevacizumab vs. anti-EGFR) showed no significant survival differences in V600E patients. Similarly, RAS/BRAF wild-type patients had comparable survival with bevacizumab versus anti-EGFR, even for left-sided tumors. These findings highlight distinct clinical and prognostic profiles for BRAF V600E and non-V600E mutations, while treatment choice appears to have limited impact on survival in these subgroups or RAS/BRAF wild-type cases.
This study tracks the use of familiarizer vocatives across the twentieth century in Ontario, Canada from a corpus comprising 11 million words of conversational interviews from individuals in eighteen communities, born between the 1880s and the 2000s. Vocatives are a richly variable grammatical category which are strongly tied to their sociolinguistic context. We focus here on the sub-category of familiarizers for birth years 1950-2004, which in these materials are almost entirely dominated by man, buddy, and dude. We extracted and coded several thousand vocative tokens, yielding 467 familiarizers. Random Forest modeling shows significant effects of birth year, gender, and community; but not education nor occupation. The dominant familiarizer man declines with the rise of buddy (outside Toronto) and dude (especially inside Toronto). Women use these incoming forms more than men do, perhaps as alternatives to the masculine-associated form man. The results show rapid change for familiarizers in patterns which parallel longstanding sociolinguistic principles.
Exposure to orthopaedics has been shown to positively influence medical student perceptions of the field; however, fewer than half of medical schools require or even offer an orthopaedic rotation as part of the core clinical curriculum. We hypothesized that a mandatory rotation during the clerkship year would counteract stereotypes about the field. Therefore, we sought to characterize the perceptions of orthopaedic surgery before and after such a clinical rotation at our institution. Over a 2-year period, we administered an anonymous survey to all 320 medical students completing our mandatory 1-week orthopaedic surgery rotation. We received 267 prerotation and 153 postrotation survey responses. Students were asked for their sex, age, race/ethnicity, and "three words that describe your perception of orthopaedic surgery." These words were categorized according to theme and positive/negative connotation by the study team and evaluated for association with medical student demographics. The most frequent prerotation words were "bones" (10.1% of words), "intense" (6.5% of words), and "bros" (6.4% of words). The most frequent postrotation words were "bones" (6.2% of words), "fun" (5.9% of words), and "intense" (2.9% of words). The percentage of negative and neutral words decreased after the rotation (negative: 27.5% to 14.1%; P < 0.001; neutral: 50.2% to 38.3%; P < 0.001), whereas the percentage of positive words increased (21.3% to 47.4%; P < 0.001). Positive words increased postrotation for both men (23.4% to 54.7%; P < 0.001) and women (20.9% to 40.5%; P < 0.001), whereas negative words decreased for both men (20.1% to 10.4%; P < 0.001) and women (34.2% to 17.6%; P < 0.001). This study demonstrates that initially negative perceptions of orthopaedic surgery, particularly those related to its reputation as a male-dominated "bro" culture, markedly improved following a clinical rotation. This suggests that a mandatory orthopaedic surgery rotation may counteract stereotypes about the field, particularly among women students.
Understanding the molecular architecture of peripheral sensory neurons is critical as we pursue novel drug targets against pain and neuropathy. Sensory neurons in the dorsal root ganglion (DRG) show extensive compartmentalization; thus, understanding each compartment-from the peripheral to central terminals-is key to this effort. To systematically profile this spatial complexity, we generated a TurboIDfl/fl transgenic mouse line (ROSA26em1(TurboID)Bros), enabling targeted proximity labelling and deep proteomic profiling of DRG neuron compartments via Tg(Advillin-Cre)+. Our data reveal distinct proteomic signatures across neuronal compartments that reflect specialized neuronal functions. We provide proteomic insights into previously inaccessible nerve terminals both in the periphery (innervating the skin) and in the spinal cord. Further, using a DRG explant model of chemotherapy-induced peripheral neuropathy, we uncover novel and discrete proteome changes, highlighting neuronal vulnerability. Together, our findings provide a unique proteome atlas of the sensory neuron proteome across anatomical domains and demonstrate the utility of proximity labelling proteomics for detecting compartment-specific molecular alterations in a disease model. This study highlights the potential of TurboID-based proteomics to uncover cell type-specific differences in the peripheral nervous system, serving as a valuable resource for mechanistic studies of sensory neuron function and pathology.
Comorbid rheumatoid arthritis (RA) is known to be associated with excess mortality in patients with bronchiectasis. However, whether excess mortality is affected by RA seropositivity and is altered by using disease-modifying anti-rheumatic drugs (DMARDs) remains unknown. To assess the association between comorbid RA and mortality in participants with bronchiectasis, plus the impacts of seropositivity and DMARDs on this association. A retrospective cohort study. Mortality rates were compared between participants with bronchiectasis-RA overlap syndrome (BROS) (n = 3355; 2632 seropositive RA (SPRA) and 723 seronegative RA (SNRA)) and 1:5 age- and sex-matched participants with bronchiectasis only (n = 16,240) who were enrolled between 2010 and 2017 in the Korean National Health Insurance Service database. The participants were followed up from 1 year after RA diagnosis or the corresponding index date to the date of death, censored date, or 31 December 2020. During a median follow-up of 5.8 years (interquartile range, 4.2-7.8 years), participants with BROS revealed a 2.09-fold higher mortality risk compared with participants with bronchiectasis only, even after adjusting for potential confounders (95% confidence interval (CI), 1.88-2.33). In an analysis of RA serologic status using a fully adjusted model, participants with SPRA and those with SNRA showed 2.34-fold (95% CI, 2.09-2.62) and 1.29-fold (95% CI, 1.01-1.65) increased risks, respectively, than participants with bronchiectasis only. DMARDs use was related to increased mortality. The presence of RA doubles the mortality risk in patients with bronchiectasis. Increased mortality risk was more evident in patients with SPRA and those who use DMARDs. Causality cannot be ascertained, but these data suggest that rheumatic inflammation may affect disease progression and excess mortality in patients with BROS.
To provide recommendations for eco-responsible optimization of choice and use of medicines and medical devices. A committee of 16 experts brought together by CERES and from SPFDM/Euro-Pharmat, SFAR, SFCR, SFED, SF2H, SFPC, SFR, SF2S has been set up. A policy for declaring links of interest was applied and respected throughout the process of creating the reference system. Similarly, it has not provided any funding from a company marketing a health product (drug or medical device). The committee had to respect and follow the GRADE® method (Grading of Recommendations Assessment, Development and Evaluation) to assess the quality of the evidence on which the recommendations were based. The recommendations were formulated by identifying 4 different fields: practice of care (optimization of medicines and medical devices), packaging (reduction of the environmental impact of medical devices), organization of care (integration of environmental criteria) and waste management (reduction, sorting and recovery). Each question was formulated according to the PICO (Patients, Intervention, Comparison, Outcome) format. The analysis of the literature and the recommendations were carried out according to the GRADE® methodology. The experts' synthesis work resulted in 46 recommendations validated after one round of voting. For all questions, since the GRADE grid ® method could not be applied in full, the recommendations were formulated in the form of expert opinions. From a strong agreement between experts, we were able to formulate 46 recommendations for eco-responsible optimization of the choice and use of medicines and medical devices.
Cardiovascular and cerebrovascular diseases are the top global causes of mortality. Internal medicine professionals are vital in educating the public on prevention, yet they themselves may experience the very risk factors they warn against. This study aimed to assess cardiometabolic risk factors among Indonesian internal medicine specialists to raise awareness among health care workers. This cross-sectional study was conducted by the Indonesian Society of Internal Medicine (INASIM). Our study recruited 1,568 internal medicine specialists from 39 INASIM branches in Indonesia using clustered random sampling (December 2023-March 2024). Cardiometabolic risk was calculated using atherosclerotic cardiovascular disease (ASCVD) risk scores and SCORE-2 (Systematic Coronary Risk Evaluation-2) Asia Pacific. The mean age of 1,064 participants who completed the study was 45 ± 10.4 years. The prevalences of dyslipidemia, obesity, hypertension, and diabetes mellitus were 84.6% (95% CI: 82.4%-86.9%), 61.4% (95% CI: 58.5%-64.3%), 20.3% (95% CI: 17.9%-22.7%), and 10.2% (95% CI: 8.4%-12.1%), respectively. Participants' 10-year ASCVD risk scores were 6.0% (95% CI: 4.4%-8.1%) high, 18.5% (95% CI: 15.7%-21.7%) intermediate, 9.6% (95% CI: 7.5%-12.1%) borderline, and 66.0% (95% CI: 62.2%-69.6%) low. Their SCORE-2 Asia Pacific risk scores were 1.2% (95% CI: 0.5%-2.5%) very very high, 10.7% (95% CI: 8.3%-13.7%) very high, 46.5% (95% CI: 42.1%-50.9%) high, and 41.6% (95% CI: 37.3%-46.1%) moderate. The prevalences of dyslipidemia and obesity were high among internal medicine specialists in Indonesia. The prevalences of highest risk category profile were 6.0% (ASCVD) and 1.2% (SCORE-2).
To assess in-hospital and 1-year cause-specific outcomes in the contemporary European Society of Cardiology (ESC) Heart Failure (HF) III Registry. Patients were enrolled in European or ESC affiliated countries and characterized in detail regarding clinical characteristics and cause-specific outcomes. Between 1 November 2018 and 31 December 2020, 10,162 patients were enrolled from 220 centres in 41 countries. Of these, 39% had acute HF ('AHF', age 70 [62-79] years, 36% women) and 61% had out-patient visit for HF ['out-patient HF', age 66 (58-75) years, 33% women]. Overall, 58% had HF with reduced ejection fraction (HFrEF), 17% HF with mildly reduced ejection fraction (HFmrEF), and 25% HF with preserved ejection fraction (HFpEF). In AHF, median [interquartile range (IQR)] duration of hospitalization was 9 (6-14) days, and 5.1% died in hospital (HFrEF 5.2%; HFmrEF 4.8%, HFpEF 3.4%). In AHF discharged alive and in out-patient HF, after a median (IQR) follow-up of 376 (360-432) days, all-cause, cardiovascular (CV), and unknown-cause mortality rates per 100 patient-years were as follows: AHF HFrEF: 19, 13, and 3.0 per 100 patient-years. The corresponding numbers were in AHF HFmrEF: 22, 11, and 6.3; AHF HFpEF: 16, 7.0, and 4.7; out-patient HFrEF: 6.6, 4.3, and 0.9; out-patient HFmrEF: 4.0, 2.6, and 0.8; out-patient HFpEF: 3.9, 1.7, and 1.2. At least one (re-)hospitalization for HF was experienced in 44% AHF HFrEF, 42% AHF HFmrEF, 36% AHF HFpEF, 21% out-patient HFrEF, 14% out-patient HFmrEF, and 18% out-patient HFpEF. In HF in Europe and affiliated countries, in-hospital mortality was 5.1% and greater with lower ejection fraction. Among hospital survivors and out-patients over 1 year of follow-up, event rates per 100 patient-years varied for death, 3.9-22, CV death 1.7-13, and unknown cause of death 0.8-6.3. The percent of patients that were (re-)hospitalized for HF at least once over 1-year follow-up ranged 14-44% and was twice as high post-AHF compared with post-out-patient visit.
Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality, particularly in advanced stages where therapeutic options are limited. Cancer-associated fibroblasts (CAF) within the tumor microenvironment (TME) contribute significantly to tumor progression and represent a promising therapeutic target. In this study, we developed biocompatible and biodegradable polycarbonate nanogels for the improved lipid-free, CAF-targeted delivery of siRNA against microfibrillar-associated protein 5 (MFAP-5), a pro-angiogenic factor expressed by inflammatory CAF (iCAF). Using a cirrhotic murine HCC model (C-HCC), we demonstrated that intravenously injected anti-MFAP-5-siRNA-loaded nanogels (NG:siMFAP5) silenced the MFAP-5 expression, reduced fibroblast activation, and suppressed tumor growth in a dose-dependent manner. In vivo biodistribution studies revealed preferential uptake of nanogels by CAF, followed by dendritic cells and macrophages. Mechanistically, MFAP-5 was shown to promote angiogenesis via NOTCH/Hes1 signaling in fibroblasts. MFAP-5 expression in human HCC samples and conserved signaling pathways between mice and humans underscore the translational relevance of this target. Our findings highlight the therapeutic potential of CAF-targeted siRNA delivery using polycarbonate-based nanogels to inhibit stromal-driven angiogenesis and tumor progression in HCC.
Synchrotron radiation (SR) technology serves as a core tool for the microstructural characterization of fibrous materials. Leveraging its high-resolution imaging and three-dimensional structural analysis capabilities, it enablesin-situand non-destructive characterization of microstructural information. Compared with laboratory light sources, SR sources boast a light intensity of up to 1010-1014photons, which is 6-8 orders of magnitude higher than that of laboratory sources. Their collimation is over 100 times better, and the spatial resolution reaches the nanometer level, capable of resolving the structures of nanoscale micropores, microcrystals, and interfaces, far exceeding the micrometer-submicrometer resolution level of laboratory light sources. This paper constructs a three-dimensional integrated framework that encompasses x-ray energy classification, technical type details, and targeted applications for fibrous materials. Based on the energy dimensions of soft x-rays, medium-energy x-rays, and hard x-rays, the suitable fibrous material characterization scenarios are identified. The principles, advantages, and application cases of scattering techniques, absorption fine-structure techniques, and imaging techniques are systematically integrated to achieve a precise connection between the technical system and material research. Combined within-situand non-destructive characterization examples of fibrous materials, this paper reveals the correlation mechanism between material structure evolution and performance, and looks forward to the development trends and application potential of SR technology, providing references for future research and technological advancements in this field.
The serine/threonine phosphatase-2 (PP2A) controls mitogen-associated signaling and DNA replication. The WEE1 protein tyrosine kinase controls S phase progression and G2/M phase transition. Databases disclose that the levels of PP2A and WEE1 are associated with poor prognosis of leukemic patients (p = 0,0017/0,025; n = 54-163). We applied advanced, clinically used drugs that block PP2A and WEE1 to human cultured leukemia cells, primary pre-leukemic and chronic myeloid leukemia cells, and pancreatic ductal adenocarcinoma cells. Combined application of the drugs depleted cells in all cell cycle phases, synergistically triggered apoptosis, and evoked the induction of DNA stress foci and mitotic catastrophe. In 93 lymphoid, 40 myeloid, and 47 pancreatic cancer cells, genetic depletion of PP2A-Cα and WEE1 stalls the proliferation of most cells. Unlike cancer cells, normal human immune cells are not killed upon inhibition of PP2A and WEE1. This is linked to higher expression of PP2A and WEE1 in chronic myeloid (n = 274), acute myeloid (n = 1858) and acute lymphoblastic leukemia cells (n = 1817) than in normal blood cells. These data suggest that pharmacological modulators of serine/threonine and tyrosine signaling allow targeted chemotherapy.
Small-molecule immunodrugs hold significant promise for immunotherapeutic applications including vaccination and cancer therapy. However, their clinical use is limited by severe side effects resulting from systemic distribution. To address this challenge, a biodegradable, acid-responsive nanocarrier system designed for controlled immunodrug delivery in vivo is presented. It is based on polymeric micelles that disassemble in response to acidic environments, enabling site-specific particle unfolding following endocytosis by antigen-presenting cells. Its core structure features a hydrolysable aliphatic poly(carbonate) backbone, promoting both biocompatibility and biodegradability. The high precision of the applied ring-opening polymerization allows for polymer end group functionalization, including the integration of fluorophores for Förster resonance energy transfer (FRET)-based monitoring of particle integrity and unfolding. The observations reveal a pH-dependent disassembly profile both in vitro and in vivo. Comparative studies with non-responsive poly(carbonate)s demonstrate the superior performance of the acid-responsive design in selectively disassembling under acidic conditions and enhancing polymer backbone degradation. Furthermore, covalent conjugation of a small molecule Toll-like receptor 7/8 agonist promotes its controlled delivery in vitro and in vivo, resulting in improved immune cell uptake and regulated cytokine production. The findings underscore the potential of this biodegradable, acid-responsive micellar nanocarrier system as precision delivery platform for safer and effective immunotherapeutics.
Liver transplantation is a curative treatment for selected patients with hepatocellular carcinoma (HCC). While the Milan criteria remain the established benchmark for transplant eligibility, several expanded selection models have been developed to increase access while maintaining acceptable oncologic outcomes. Reported survival and recurrence outcomes across these criteria vary across institutions and regions. To systematically review published evidence comparing post-transplant survival and recurrence outcomes associated with Milan, UCSF, Kyoto, ASAN (Korean), and Toronto criteria. A systematic search of PubMed, Cochrane Central, and ScienceDirect was conducted for studies published between 2000 and August 2025. Studies evaluating at least one of the predefined selection criteria in adult HCC patients undergoing liver transplantation and reporting 5-year overall survival and/or recurrence outcomes were included. Findings were synthesized descriptively in accordance with PRISMA guidelines. Twenty-three studies comprising 6318 patients met inclusion criteria. Milan criteria consistently demonstrated 5-year survival rates exceeding 70% with low recurrence rates across diverse transplant settings. Expanded criteria, particularly UCSF and Kyoto, reported comparable survival outcomes in selected cohorts, though recurrence rates varied by region, donor type, and institutional practice. Biologically driven approaches incorporating AFP and PIVKA-II showed promising results but demonstrated heterogeneity across centers. Milan criteria remain the most consistently validated framework for liver transplantation in HCC. Expanded criteria may provide acceptable outcomes in carefully selected patients, particularly in experienced centers. Selection strategies should be applied within the context of institutional expertise and regional transplant practice.
Liver transplantation (LT) is the definitive treatment for end-stage liver disease, acute liver failure, and selected cases of hepatocellular carcinoma. Despite global advances, institutional experience remains critical for optimizing outcomes. This study describes LT outcomes at Changwon Hanmaeum Hospital, South Korea, over a 2.5-year period. A retrospective review was conducted of all LTs performed between January 2023 and July 2025. Demographic characteristics, primary diagnoses, model for end-stage liver disease (MELD) scores, Child-Turcotte-Pugh classifications, ischemic times, graft types, surgical details, postoperative complications, and survival outcomes were analyzed. Outcomes were compared between living donor liver transplantation (LDLT) and deceased donor liver transplantation (DDLT), and between early (2023-2024) and recent (2025) cases. A total of 56 LTs were performed, including 29 LDLT and 27 DDLT procedures. The mean recipient age was 45 years in the LDLT group and 52 years in the DDLT group. Alcoholic cirrhosis (39.3%) and hepatitis B-related cirrhosis (26.8%) were the most common indications. MELD scores were higher in DDLT recipients than in LDLT recipients. Mean cold ischemic time was 141.7 minutes in LDLT and 282.2 minutes in DDLT. Laparoscopic donor hepatectomy was attempted in 17 donors (58.6%), with eight conversions (27.6%) to open surgery. Infectious complications predominated, particularly bacterial pneumonia (8.9%). Overall, 46 patients (82.1%) survived to discharge, with improved outcomes observed in 2025 compared with 2023-2024 (90.5% vs. 77.1%). Recipient operative time decreased from 429 to 360 minutes over the study period. LT outcomes improved progressively over the study period, likely reflecting accumulated surgical expertise, adoption of laparoscopic donor techniques, and optimization of perioperative management. Continued training, multidisciplinary collaboration, and systematic program evaluation remain essential for sustainable program development.
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Reservoir computing is a form of machine learning particularly suited for time-series analysis, including forecasting predictions. We take an implementation of quantum reservoir computing that was initially designed to generate variants of musical scores and adapt it to create levels of Super Mario Bros. Motivated by our analysis of these levels, we develop a new Roblox obstacle course game (known as an "obby") where the courses can be generated in real time on superconducting qubit hardware and investigate some of the constraints placed by such real-time generation.
Background: Electroencephalography (EEG) systems based on textile electrodes are increasingly being developed to address the need for more wearable sensor systems for brain function monitoring. Blink-related oscillations (BROs) are a new measure of brain function that corresponds to brainwave responses occurring after spontaneous blinking, and indexes neural processes as the brain evaluates new visual information appearing after eye re-opening. Prior studies have reported BRO utility as both a clinical and non-clinical biomarker of cognition, but no study has demonstrated BRO measurement using textile-based EEG devices that facilitate user comfort for real-world applications. Methods: We investigated BRO measurement using a four-channel EEG system with textile electrodes by extracting BRO responses using existing, publicly available EEG data (n = 9). We compared BRO effects derived from textile-based electrodes with those from standard dry Ag/Ag-Cl electrodes collected at the same locations (i.e., Fp1, Fp2, F7, F8) and using the same EEG amplifier. Results: Results showed that BRO effects measured using textile electrodes exhibited similar features in both time and frequency domains compared to dry Ag/Ag-Cl electrodes. Data from both technologies also showed similar performance in artifact removal and signal capture. Conclusions: These findings provide the first demonstration of successful BRO signal capture using four-channel EEG with textile electrodes, providing compelling evidence toward the development of a comfortable and user-friendly EEG technology that uses the simple activity of blinking for objective brain function assessment in a variety of settings.
Finding the right balance between education and entertainment in science communication has always been a challenge. This essay argues that this balance has often been framed in terms of the correct proportion and use of animation and live-action footage in popular-science media. Clarifying the assumptions behind a century of concerns about animation and science, this historical case study examines the advisory board's complaints about animation in the Bell System Science Series, which aired in the United States between 1956 and 1964. AT&T interrupted the series mid-stream by switching the creative team from Frank Capra and his production company to Owen Crump at Warner Bros. Studio. Capra's use of animation in the series featured prominently in this decision. The historical record - as well as Capra's and Crump's different aesthetic choices about animation - tells us much about the board's objections and how they were resolved in production. This essay examines the differences between the two parts of the series to uncover a course correction steered primarily by the scientific advisory board, which reveals a sometimes-fraught relationship between live-action footage and animation in science education that persists even today.
Asthma is a chronic inflammatory disease characterized by dysregulated cytokine expression. The RNA-binding protein KSRP reduces the expression of several pro-inflammatory mediators. Therefore, we investigated whether KSRP modulates Th2-associated immune responses in vivo in an ovalbumin-induced (OVA) allergic asthma model in C57BL/6 KSRP-deficient mice (KSRP-/-). Asthma severity in OVA-immunized wild type or KSRP-/- mice was determined by airway hyperresponsiveness (AHR), structural changes of lung tissue, and OVA-specific antibody production. Cytokine expression in bronchoalveolar lavage fluid (BALF) was measured by Cytometric Bead Array (CBA) analysis. Cellular signaling pathways involved in KSRP-mediated effects in asthma pathogenesis were analyzed in vitro in cell culture models using specific inhibitors. KSRP deficiency exacerbates OVA-induced allergic asthma compared to wild type mice, as indicated by increased AHR, more severe lung damage, goblet cell hyperplasia and increased OVA-specific antibody production. CBA analyses confirmed, that KSRP deficiency enhances IL-4, IL-5 and IL-13 production in BALF. The effect of KSRP on Th2-associated cytokine expression appears to be mediated by modulation of the STAT6 and NFAT signaling pathway rather than by inhibiting the stability of cytokine-encoding mRNA species. Our data demonstrate that KSRP dampens Th2 immune cell activity and therefore seems to be important for the pathogenesis of Th2-mediated diseases.