How different face mask types affect interpersonal distance perception and threat feeling in social interaction.

Due to the easing of the pandemic, public policies no longer mandated people to wear masks. People can choose to no wear or wear different types of masks based on personal preferences and safety perceptions during daily interaction. Available information about the influence of face mask type on interpersonal distance (IPD) by different aging populations is still lacking. Thus, this study aimed to investigate the face mask type (no wear, cloth, medical and N95 mask) and age group effect of avatars (children, adults and older adults) on IPD perception, threat feeling and physiological skin conductance response under active and passive approaching. One hundred participants with a range from 20 to 35 years old were recruited for this study. Twelve avatars (three age groups*four face mask conditions) were created and applied in a virtual reality environment. The results showed that age group, mask type and approach mode had significant effects on IPD and subjective threat feeling. A non-significant effect was found on skin conductance responses. Participants maintained a significantly longer IPD when facing the older adults, followed by adults and then children. In the passive approach condition, people tended to maintain a significantly greater comfort distance than during the active approach. For the mask type effect, people kept a significantly largest and shortest IPD when facing an avatar with no mask or the N95 mask, respectively. A non-significant IPD difference was found between the N95 and medical mask. Additionally, based on the subjective threat feeling, facing an avatar wearing a medical mask generated the lowest threat feeling compared to the others. The findings of this study indicated that wearing medical masks provided a benefit in bringing people closer for interaction during specific situations. Understanding that mask-wearing, especially medical one, brought to shortest IPD when compared to the unmasked condition can be utilized to enhance safety measures in crowded public spaces and health-care settings. This information could guide the development of physical distancing recommendations, taking into account both the type of mask and the age groups involved, to ensure the maintenance of appropriate distances.

Modulations of ocean-atmosphere interactions on squid abundance over Southwest Atlantic.

Anthropogenic shifts in seas are reshaping fishing trends, with significant implications for aquatic food sources throughout this century. Examining a 21-year abundance dataset of Argentine shortfin squids Illex argentinus paired with a regional oceanic analysis, we noted strong correlations between squid annual abundance and sea surface temperature (SST) in January and February and eddy kinetic energy (EKE) from March to May in the Southwest Atlantic. A deeper analysis revealed combined ocean-atmosphere interactions, pinpointed as the primary mode in a rotated empirical orthogonal function analysis of SST. This pattern produced colder SST and amplified EKE in the surrounding seas, factors crucial for the unique life stages of squids. Future projections from the CMIP6 archive indicated that this ocean-atmosphere pattern, referred to as the Atlantic symmetric pattern, would persist in its cold SST phase, promoting increased squid abundance. However, rising SSTs due to global warming might counteract the abundance gains. Our findings uncover a previously unrecognized link between squids and specific environmental conditions governed by broader ocean-atmosphere interactions in the Southwest Atlantic. Integrating these insights with seasonal and decadal projections can offer invaluable information to stakeholders in squid fisheries and marine conservation under a changing climate.

Perceived interpersonal distance changes in young Taiwanese pre and post SARS-CoV-2 pandemic.

The persistent SARS-CoV-2 pandemic, spanning over three years, has profoundly impacted daily life worldwide. Crucial measures like interpersonal distance (IPD) and mask-wearing have become paramount in preventing infection. With SARS-CoV-2 now resembling an endemic condition similar to influenza, it is vital to assess the changes in IPD influenced by relevant factors during and after the pandemic. This study concentrated on two specific stages (the pandemic stage and the post-pandemic era) and investigated variations in IPD with different test combinations. Variables taken into account encompassed the pandemic stage, participant gender, target gender, and mask-wearing status. We examined IPD data from 100 young individuals (50 males and 50 females) at each stage, with a one-year interval between tests. The results highlighted the substantial impact of all variables on perceived IPD during the pandemic phase (all p < 0.001). However, in the post-pandemic stage, only mask-wearing demonstrated a notable effect on IPD (p < 0.001). As the SARS-CoV-2 epidemic subsides, the enduring influence of mask usage on IPD persists. Nevertheless, the gap between the two mask-wearing scenarios diminishes, contracting from around 50 cm during the epidemic phase to 20 cm in the post-epidemic phase. Across these two pandemic stages, there was an overall reduction of approximately 90 cm in IPD, indicating a noteworthy decrease in perceived personal space and a consequential shortening of social proximity during the post-pandemic stage. This decrease in IPD may suggest the successful socio-cultural adaptation of the young Taiwanese individuals in our study during the post-pandemic era.

Dysregulation of mitochondrial dynamics mediated aortic perivascular adipose tissue-associated vascular reactivity impairment under excessive fructose intake.

Excessive fructose intake presents the major risk factor for metabolic cardiovascular disease. Perivascular adipose tissue (PVAT) is a metabolic tissue and possesses a paracrine function in regulating aortic reactivity. However, whether and how PVAT alters vascular function under fructose overconsumption remains largely unknown. In this study, male Sprague-Dawley rats (8 weeks old) were fed a 60% high fructose diet (HFD) for 12 weeks. Fasting blood sugar, insulin, and triglycerides were significantly increased by HFD intake. Plasma adiponectin was significantly enhanced in the HFD group. The expression of uncoupling protein 1 (UCP1) and mitochondrial mass were reduced in the aortic PVAT of the HFD group. Concurrently, the expression of peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α) and mitochondrial transcription factor A (TFAM) were suppressed. Furthermore, decreased fusion proteins (OPA1, MFN1, and MFN2) were accompanied by increased fission proteins (FIS1 and phospho-DRP1). Notably, the upregulated α-smooth muscle actin (α-SMA) and osteocalcin in the PVAT were concurrent with the impaired reactivity of aortic contraction and relaxation. Coenzyme Q10 (Q, 10 mg/100 mL, 4 weeks) effectively reversed the aforementioned events induced by HFD. Together, these results suggested that the dysregulation of mitochondrial dynamics mediated HFD-triggered PVAT whitening to impair aortic reactivity. Fortunately, coenzyme Q10 treatment reversed HFD-induced PVAT whitening and aortic reactivity.

Correlation between Psychosomatic Assessment, Heart Rate Variability, and Refractory GERD: A Prospective Study in Patients with Acid Reflux Esophagitis.

BACKGROUND: Gastroesophageal reflux disease (GERD) affects a significant proportion of individuals, with life stress being a contributing factor. This study aimed to investigate the correlation between psychosomatic evaluations, heart rate variability (HRV), and GERD in a cohort of individuals. Additionally, the study aimed to analyze the sequencing changes following proton pump inhibitor (PPI) treatment and identify predictive factors associated with refractory GERD. METHODS: A prospective cohort of 105 individuals with reflux esophagitis and a control group of 50 participants without acid reflux symptoms were enrolled. Psychosomatic evaluations, including GERDQ, GERDQLQ, RSI, BAI, BDI, and SSS-8, were assessed at baseline and during treatment. HRV parameters were also evaluated. Multivariate analysis was used to identify predictive factors for refractory GERD. PPIs were administered regularly for the initial 2 months and then used on-demand. Refractory GERD was defined as less than 50% improvement in symptom relief or GERDQLQ score ≥ 20 after 8 weeks of PPI treatment. RESULTS: The GERD group had higher scores in all psychosomatic evaluations compared to the control group (all p-values < 0.001). There were no significant changes in any parameters of HRV before and after treatment in the GERD group. Strong and consistent correlations were observed between GERD symptoms and psychological scores (BAI, BDI, and SSS-8) across all time points (W0, W4, and W8). Sequential reductions in GERD symptom scores and psychosomatic evaluations were observed during the initial eight weeks of treatment. Higher GERDQ (≥10) and SSS-8 (≥12) scores were predictive of refractory GERD (p = 0.004 and p = 0.009, respectively). CONCLUSIONS: This study emphasizes the importance of considering physiological and psychological factors in the management of GERD. Psychosomatic evaluations provide valuable insights for assessing and treating GERD patients. Integrating stress management and comprehensive assessments into personalized treatment strategies is crucial.

Correction: First-principles modeling of the highly dynamical surface structure of a MoS2 catalyst with S-vacancies.

Correction for 'First-principles modeling of the highly dynamical surface structure of a MoS2 catalyst with S-vacancies' by Po-Yuan Wang et al., Phys. Chem. Chem. Phys., 2022, 24, 24166-24172, https://doi.org/10.1039/D2CP03384D.

Protective Renalase Deficiency in ß-Cells Shapes Immune Metabolism and Function in Autoimmune Diabetes.

Type 1 diabetes (T1D) is caused by the immune-mediated loss of pancreatic ß-cells that produce insulin. The latest advances in stem cell (SC) ß-cell differentiation methods have made a cell replacement therapy for T1D feasible. However, recurring autoimmunity would rapidly destroy transplanted SC ß-cells. A promising strategy to overcome immune rejection is to genetically engineer SC ß-cells. We previously identified Renalase (Rnls) as a novel target for ß-cell protection. Here we show that Rnls deletion endows ß-cells with the capacity to modulate the metabolism and function of immune cells within the local graft microenvironment. We used flow cytometry and single-cell RNA sequencing to characterize ß-cell graft-infiltrating immune cells in a mouse model for T1D. Loss of Rnls within transplanted ß-cells affected both the composition and the transcriptional profile of infiltrating immune cells in favor of an anti-inflammatory profile with decreased antigen-presenting capacity. We propose that changes in ß-cell metabolism mediate local immune regulation and that this feature could be exploited for therapeutic goals. ARTICLE HIGHLIGHTS: Protective Renalase (Rnls) deficiency impacts ß-cell metabolism. Rnls-deficient ß-cell grafts do not exclude immune infiltration. Rnls deficiency in transplanted ß-cells broadly modifies local immune function. Immune cell in Rnls mutant ß-cell grafts adopt a noninflammatory phenotype.

The impact of alcoholic drinks and dietary factors on epigenetic markers associated with triglyceride levels.

Background: Many epigenetic loci have been associated with plasma triglyceride (TG) levels, but epigenetic connections between those loci and dietary exposures are largely unknown. This study aimed to characterize the epigenetic links between diet, lifestyle, and TG. Methods: We first conducted an epigenome-wide association study (EWAS) for TG in the Framingham Heart Study Offspring population (FHS, n = 2,264). We then examined relationships between dietary and lifestyle-related variables, collected four times in 13 years, and differential DNA methylation sites (DMSs) associated with the last TG measures. Third, we conducted a mediation analysis to evaluate the causal relationships between diet-related variables and TG. Finally, we replicated three steps to validate identified DMSs associated with alcohol and carbohydrate intake in the Genetics of Lipid-Lowering Drugs and Diet Network (GOLDN) study (n = 993). Results: In the FHS, the EWAS revealed 28 TG-associated DMSs at 19 gene regions. We identified 102 unique associations between these DMSs and one or more dietary and lifestyle-related variables. Alcohol and carbohydrate intake showed the most significant and consistent associations with 11 TG-associated DMSs. Mediation analyses demonstrated that alcohol and carbohydrate intake independently affect TG via DMSs as mediators. Higher alcohol intake was associated with lower methylation at seven DMSs and higher TG. In contrast, increased carbohydrate intake was associated with higher DNA methylation at two DMSs (CPT1A and SLC7A11) and lower TG. Validation in the GOLDN further supports the findings. Conclusion: Our findings imply that TG-associated DMSs reflect dietary intakes, particularly alcoholic drinks, which could affect the current cardiometabolic risk via epigenetic changes. This study illustrates a new method to map epigenetic signatures of environmental factors for disease risk. Identification of epigenetic markers of dietary intake can provide insight into an individual's risk of cardiovascular disease and support the application of precision nutrition. Clinical Trial Registration: www.ClinicalTrials.gov, the Framingham Heart Study (FHS), NCT00005121; the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN), NCT01023750.

Prevalence and Associated Factors of Work-Related Musculoskeletal Disorders Symptoms among Construction Workers: A Cross-Sectional Study in South China.

Statistics showed that work-related musculoskeletal disorders (WMSDs) are the leading cause of productivity loss in the construction industry. This study aimed to investigate the prevalence of WMSDs and associated factors among construction workers. A cross-sectional study was conducted among 380 construction workers in Guangdong Province, China. A demographic, work-related survey and the Nordic musculoskeletal questionnaire were used to collect the workers' data. Descriptive statists and logistic regression were used for the data analysis. The results showed that the overall prevalence of WMSDs symptoms among the participants in any body region during the last 12 months was 57.9%. Neck (24.7%), shoulder (22.1%), upper back (13.4%), and lower back (12.6%) showed the highest prevalence of WMSDs. Age, exercise, work experience, work position, and level of fatigue after work were significantly associated with the prevalence of WMSDs symptoms in different body regions. The findings of this study showed that the prevalence of WMSDs symptoms among construction workers in south China is still high and is associated with different body areas compared to previous studies. The prevalence of WMSDs and risk-associated factors vary by country and region. This indicates that further local investigations are needed to propose specific solutions to improve the occupational health of construction workers.

Protocol for genome-scale in vivo CRISPR screening to study protection of beta cells under autoimmunity in a type 1 diabetes mouse model.

Autoimmunity-induced pancreatic beta cell failure is the main characteristic of type 1 diabetes (T1D). Here, we describe a protocol for genome-scale in vivo CRISPR-Cas9 screening for use in a mouse model of T1D. Using a non-obese-diabetic-derived mouse beta cell line, NIT-1, and a genome-wide CRISPR-Cas9 knockout library (GeCKO-v2), we describe how to identify genes that confer resistance to autoimmune killing. This protocol can be applied in other mouse models of autoimmunity. For complete details on the use and execution of this protocol, please refer to Cai et al. (2020).1.

Cationic surfactants influencing the enhancement of energy efficiency for perfluorooctanoic acid (PFOA) removal in the electrocoagulation-flotation (ECF) system.

From an environmental perspective, approaching sustainability requires a fundamental conceptual shift from the wastewater treatment process toward integrated treatment systems that consider efficient and effective utilization. This study aims to investigate the effects of different surfactants on the removal of perfluorooctanoic acid (PFOA). We used cationic surfactants as both frothers and collectors in the electrocoagulation-flotation (ECF) method to improve the removal efficiency of PFOA. The results showed that, under a monopolar aluminum electrode and with an initial PFOA concentration of 0.25 mM, the ECF method with decyl-trimethyl-ammonium bromide (DTAB) was able to remove over 98% of PFOA within 10 min. Cationic surfactants with a similar linear alkyl chain shape to PFOA, but a longer chain length, are more effective at removing PFOA through the ECF process. The removal mechanism is thought to involve co-precipitation with aluminum hydroxides through Al-F bonding, co-flotation with cationic surfactants, and mixed micelle formation with cationic surfactants. The optimal conditions were tested in both synthetic and realistic wastewater matrices and produced similar results. It has the potential for real wastewater application. The energy yield (G50) of ECF with 5 mM DTAB is 497 g·kWh-1, superior to other treatments, and is an extremely energy-effective method for separating PFOA from wastewater.

Perceived Interpersonal Distances: A Cross-Cultural Analysis of Young Taiwanese and Young Southeast Asians during the COVID-19 Pandemic.

Prior research on interpersonal distance (IPD) has predominantly concentrated on specific nationalities or population groups within their respective regions. There is a dearth of studies investigating IPD differences among individuals of distinct nationalities coexisting in the same geographical location. This study aimed to examine the variances in IPD between 100 young Taiwanese participants (comprising 50 males and 50 females) and 100 Southeast Asian individuals (including 50 males and 50 females). This study also considered factors affecting IPD, including target genders and mask-wearing conditions. The results of the four-way ANOVA indicate that target gender and mask-wearing conditions had a significant impact on IPD (p < 0.001). While there were no significant main effects for region and participant gender, there was a noteworthy interactive effect between these two variables on IPD. In general, Southeast Asian participants exhibited lower sensitivity to changes in IPD in response to the independent variables in comparison to their Taiwanese counterparts; in certain instances, their IPD did not notably increase when confronted with targets not wearing masks. While prior research typically indicated that women tend to maintain larger IPD than men, the current study observed this gender difference only among young Taiwanese participants. However, such a gender gap was absent among young individuals from Southeast Asia.

Early and Direct Endoscopic Stone Removal in the Moderate Grade of Acute Cholangitis with Choledocholithiasis Was Safe and Effective: A Prospective Study.

BACKGROUND: Evidence supporting the feasibility of single-stage stone removal in patients with a moderate grade of acute cholangitis remains insufficient. The maximal size of a common bile-duct stone suitable for removal during a single-stage ERCP in a moderate grade of acute cholangitis is unknown. METHODS: We prospectively enrolled 196 endoscopic retrograde cholangiopancreatography (ERCP)-naïve patients diagnosed with acute cholangitis and choledocholithiasis. For eligible patients, single-stage treatment involved stone removal at initial ERCP. RESULTS: A total of 123 patients were included in the final analysis. The success rate of complete stone extraction was similar between patients with mild and moderate grades of acute cholangitis (89.2% vs. 95.9%; p = 0. 181). Complication rates were comparable between the two groups. In the moderate grade of the cholangitis group, among patients who underwent early single-stage ERCP, the length of hospitalization declined as short as the patients in the mild grade of cholangitis (10.6 ± 6.2 vs. 10.1 ± 5.1 days; p = 0.408). In the multivariate analysis, early ERCP indicated shorter hospitalization times (≤10 days) (odds ratio (OR), 3.981; p = 0.001). A stone size less than 1.5 cm presented a high success rate (98.0%) for complete stone removal. CONCLUSIONS: Single-stage retrograde endoscopic stone removal in mild and moderate grades of acute cholangitis may be safe and effective, which can obviate the requirement for a second session, thus reducing medical expenses. CLINICALTRIALS: gov: NCT03754491.

Establishment of open web platform based on 3D head model for product adaptability analysis and evaluation.

With improved living conditions, the demand for wearable products has increased, particularly for headwear. Traditionally, the dimensions of headwear products are designed according to 1D anthropometric data, such as head length, width, and eye width. However, this design method, applied to fit the 3D human head, results in differences in adaptability, which affect the wearing comfort of the user. Hence, this study aimed to develop an aided design platform based on a three-dimensional standard head shape to evaluate the virtual wearing of headwear products and adaptability testing. Specifically, a WebGL-based service, named the Chinese Headwear Adaptability Testing (CHAT) platform, was established. Validation and user studies were then conducted using an eye massager device. After the product was redesigned according to evaluation by the proposed system, the results show that the comfort and adaptability of the redesigned eye massager were significantly improved. The findings suggest that using the CHAT platform to design headwear products can help achieve a better wearing fit for the products.

Lipopolysaccharide-induced Autophagy Increases SOX2-positive Astrocytes While Decreasing Neuronal Differentiation in the Adult Hippocampus.

Inflammation alters the neural stem cell (NSC) lineage from neuronal to astrogliogenesis. However, the underlying mechanism is elusive. Autophagy contributes to the decline in adult hippocampal neurogenesis under E. coli lipopolysaccharide (LPS) stimulation. SRY-box transcription Factor 2 (SOX2) is critical for NSC self-renewal and proliferation. In this study, we investigated the role of SOX2 in induced autophagy and hippocampal adult neurogenesis under LPS stimulation. LPS (5 ng•100 g-1•hour-1 for 7 days) was intraperitoneally infused into male Sprague-Dawley rats (8 weeks old) to induce mild systemic inflammation. Beclin 1 and autophagy protein 12 (Atg12) were significantly upregulated concurrent with decreased numbers of Ki67- and doublecortin (DCX)-positive cells in the dentate gyrus. Synchronically, the levels of phospho(p)-mTOR, the p-mTOR/mTOR ratio, p-P85s6k, and the p-P85s6k/P85s6k ratio were suppressed. In contrast, SOX2 expression was increased. The fluorescence micrographs indicated that the colocalization of Beclin 1 and SOX2 was increased in the subgranular zone (SGZ) of the dentate gyrus. Moreover, increased S100ß-positive astrocytes were colocalized with SOX2 in the SGZ. Intracerebroventricular infusion of 3-methyladenine (an autophagy inhibitor) effectively prevented the increases in Beclin 1, Atg12, and SOX2. The SOX2+-Beclin 1+ and SOX2+-S100ß+ cells were reduced. The levels of p-mTOR and p-P85s6k were enhanced. Most importantly, the number of DCX-positive cells was preserved. Altogether, these data suggest that LPS induced autophagy to inactivate the mTOR/P85s6k pathway, resulting in a decline in neural differentiation. SOX2 was upregulated to facilitate the NSC lineage, while the autophagy milieu could switch the SOX2-induced NSC lineage from neurogenesis to astrogliogenesis.

A Simulation-Based Study of the Effect of Brake Light Flashing Frequency on Driver Brake Behavior from the Perspective of Response Time.

To prevent vehicle crashes, studies have proposed the use of flashing signals (brake lights or other light indicators) to improve the driver's response time when the leading vehicle is braking. However, there are no consistent results on the ideal flashing frequency of the brake lights. This study aimed to investigate different brake light flashing frequencies to assess their impact on braking response time. Twenty-four participants aged 25 to 30 were recruited. Two driving speed environments (50 and 80 km/h), three deceleration rates (0.25, 0.6, and 1 g), and four brake light flashing frequencies (0, 2, 4, and 7 Hz) were examined. Braking response time, average braking force, and braking response time ratio were used to evaluate the driving behavior. The results showed that the braking response time and average braking force were affected by the deceleration rate in the 50 km/h driving environment. In the 50 and 80 km/h driving environments, although there were no significant differences among the three deceleration rates, the braking response time decreased by 3-7% under the flashing brake light condition. These findings can be used as a reference for safety designs as well as future studies on driving behavior.

Intratumoral delivery of TransCon™ TLR7/8 Agonist promotes sustained anti-tumor activity and local immune cell activation while minimizing systemic cytokine induction.

BACKGROUND: Intratumoral (IT) delivery of toll-like receptor (TLR) agonists has shown encouraging anti-tumor benefit in preclinical and early clinical studies. However, IT delivery of TLR agonists may lead to rapid effusion from the tumor microenvironment (TME), potentially limiting the duration of local inflammation and increasing the risk of systemic adverse events. METHODS: To address these limitations, TransCon™ TLR7/8 Agonist-an investigational sustained-release prodrug of resiquimod that uses a TransCon linker and hydrogel technology to achieve sustained and predictable IT release of resiquimod-was developed. TransCon TLR7/8 Agonist was characterized for resiquimod release in vitro and in vivo, in mice and rats, and was assessed for anti-tumor efficacy and pharmacodynamic activity in mice. RESULTS: Following a single IT dose, TransCon TLR7/8 Agonist mediated potent tumor growth inhibition which was associated with sustained resiquimod release over several weeks with minimal induction of systemic cytokines. TransCon TLR7/8 Agonist monotherapy promoted activation of antigen-presenting cells in the TME and tumor-draining lymph nodes, with evidence of activation and expansion of CD8+ T cells in the tumor-draining lymph node and TME. Combination of TransCon TLR7/8 Agonist with systemic immunotherapy further promoted anti-tumor activity in TransCon TLR7/8 Agonist-treated tumors. In a bilateral tumor setting, combination of TransCon TLR7/8 Agonist with systemic IL-2 potentiated tumor growth inhibition in both injected and non-injected tumors and conferred protection against tumor rechallenge following complete regressions. CONCLUSIONS: Our findings show that a single dose of TransCon TLR7/8 Agonist can mediate sustained local release of resiquimod in the TME and promote potent anti-tumor effects as monotherapy and in combination with systemic immunotherapy, supporting TransCon TLR7/8 Agonist as a novel intratumoral TLR agonist for cancer therapy. A clinical trial to evaluate the safety and efficacy of TransCon TLR7/8 Agonist, as monotherapy and in combination with pembrolizumab, in cancer patients is currently ongoing (transcendIT-101; NCT04799054).

First-principles modeling of the highly dynamical surface structure of a MoS2 catalyst with S-vacancies.

Vacancy sites, e.g., S-vacancies, are essential for the performance of MoS2 catalysts. As earlier studies have revealed that the size and shape of the S-vacancies may affect the catalytic activity, we have studied the behavior and mobility of such vacancies on MoS2 using DFT calculations and kinetic Monte-Carlo (kMC) simulations. The diffusion barriers for the S-vacancies are highly dependent on the immediate environment: isolated single S-vacancies are found to be immobile. In contrast, small nS-vacancies formed from n = 2 to 5 neighboring S-vacancies are often highly dynamic systems that can move within a confined area. Large extended nS-vacancies are generally unstable and transform quickly into alternating patterns of S-atoms and vacancy sites. These results illustrate the importance of recognizing MoS2 (but also other catalysts) as dynamic structures when trying to tune their catalytic performances by introducing specific defect structures.

Comparative Analysis of Male Cyclist Population in Four Asia Countries for Anthropometric Measurements.

This study aimed to compare the anthropometric variables of male cyclist samples from India, China, Singapore, and Taiwan. The cyclist's body dimensions were measured among 413 randomly chosen males (aged between 18 to 60), which included 104 Indians, 106 Taiwanese, 100 Singaporeans, and 103 Chinese. Based on the previous research articles, the considered 17 anthropometric variables were weight, stature, BMI, buttock extension, shoulder height (sitting), shoulder-elbow length, elbow height (sitting), lower leg length, knee height, acromion-grip length, hand length, elbow-hand length, buttock-popliteal length, buttock-knee length, elbow-to-elbow breadth, hip breadth (sitting), and foot breadth. Using statistical techniques (descriptive statistics, the Mann-Whitney U test, and Kruskal-Wallis H test), the data were analysed in SPSS, version 25.0. The results of the statistical analyses showed significant differences among the cyclists across selected anthropometric characteristics, except for the weight and sitting-related anthropometric measurements. The outcome of the descriptive statistics (percentile values), such as the percentile range (5th to 95th percentile), could be applied to the seat-height adjustment system to cover 95% of the bicyclist population. These types of implantation could enhance the ergonomic benefits for the bicyclist.

TransCon IL-2 ß/γ: a novel long-acting prodrug with sustained release of an IL-2Rß/γ-selective IL-2 variant with improved pharmacokinetics and potent activation of cytotoxic immune cells for the treatment of cancer.

BACKGROUND: Recombinant interleukin-2 (IL-2, aldesleukin) is an approved cancer immunotherapy but causes severe toxicities including cytokine storm and vascular leak syndrome (VLS). IL-2 promotes antitumor function of IL-2Rß/γ+ natural killer (NK) cells and CD8+, CD4+ and gamma delta (γδ) T cells. However, IL-2 also potently activates immunosuppressive IL-2Rα+ regulatory T cells (Tregs) and IL-2Rα+ eosinophils and endothelial cells, which may promote VLS. Aldesleukin is rapidly cleared requiring frequent dosing, resulting in high Cmax likely potentiating toxicity. Thus, IL-2 cancer immunotherapy has two critical drawbacks: potent activation of undesired IL-2Rα+ cells and suboptimal pharmacokinetics with high Cmax and short half-life. METHODS: TransCon IL-2 ß/γ was designed to optimally address these drawbacks. To abolish IL-2Rα binding yet retain strong IL-2Rß/γ activity, IL-2 ß/γ was created by permanently attaching a small methoxy polyethylene glycol (mPEG) moiety in the IL-2Rα binding site. To improve pharmacokinetics, IL-2 ß/γ was transiently attached to a 40 kDa mPEG carrier via a TransCon (transient conjugation) linker creating a prodrug, TransCon IL-2 ß/γ, with sustained release of IL-2 ß/γ. IL-2 ß/γ was characterized in binding and primary cell assays while TransCon IL-2 ß/γ was studied in tumor-bearing mice and cynomolgus monkeys. RESULTS: IL-2 ß/γ demonstrated selective and potent human IL-2Rß/γ binding and activation without IL-2Rα interactions. TransCon IL-2 ß/γ showed slow-release pharmacokinetics with a low Cmax and a long (>30 hours) effective half-life for IL-2 ß/γ in monkeys. In mouse tumor models, TransCon IL-2 ß/γ promoted CD8+ T cell and NK cell activation and antitumor activity. In monkeys, TransCon IL-2 ß/γ induced robust activation and expansion of CD8+ T cells, NK cells and γδ T cells, relative to CD4+ T cells, Tregs and eosinophils, with no evidence of cytokine storm or VLS. Similarly, IL-2 ß/γ enhanced proliferation and cytotoxicity of primary human CD8+ T cells, NK cells and γδ T cells. SUMMARY: TransCon IL-2 ß/γ is a novel long-acting prodrug with sustained release of an IL-2Rß/γ-selective IL-2. It has remarkable and durable pharmacodynamic effects in monkeys and potential for improved clinical efficacy and tolerability compared with aldesleukin. TransCon IL-2 ß/γ is currently being evaluated in a Phase 1/2 clinical trial (NCT05081609).