OBJECTIVES/GOALS: Using a community-based participatory research (CBPR) approach, the All of Us (AoU) Wisconsin Froedtert & the Medical College of Wisconsin (MCW) site aimed to improve public understanding of science by creating a Special Interest Group (SIG) of community members and scientists and driving healthcare research relevant to Southeastern Wisconsin. METHODS/STUDY POPULATION: We recruited community members from the AoU advisory boards and scientists from Froedtert & MCW. These SIG participants will converge on a hypothesis that aligns with community priorities and conduct research using the national AoU database, which combines EHR, survey, and whole genome sequencing data. A year of monthly SIG meetings from 2022-2023 will serve as focus group sessions that will be recorded and transcribed. In addition to descriptive statistics on participant demographics and affiliations, we plan to qualitatively characterize transcripts, field notes, and feedback, such as participation satisfaction or reflection on self- and group-driven impact. We will publish alongside all SIG members on both the research outcomes and the SIG-driven process to inform future similar endeavors. RESULTS/ANTICIPATED RESULTS: To date, we held three SIG meetings, which together formed the discover and define stages in the human-centered design framework. We narrowed down SIG membership to 15 consistent participants. Our coalition building conversations emphasized group priorities and future payoffs for independent research and community partnerships. Realizing a crucial need for bioinformaticians to prosecute SIG-driven research questions, we created a data subgroup of trainees and scientists to familiarize themselves with the AoU Researcher Workbench. Through shared decision making during this community engaged process, we are converging on a research direction centering on specific diseases or adverse outcomes with relevance to Southeastern Wisconsin communities and with implications for personalized medicine. DISCUSSION/SIGNIFICANCE: SIG scientists will learn about CBPR and access the AoU database. SIG community members will better understand the research process and share their lessons with local communities. The AoU Wisconsin research team will disseminate findings on the collective research process and empower scientist use of this nationally curated AoU database.

The objective was to evaluate the association between serum carotenoid levels and respiratory morbidity and mortality in a nationally representative sample of US adults. We assessed the association of serum carotenoid levels with respiratory morbidity and mortality using logistic regression and proportional hazards regression models. Meanwhile, a series of confounders were controlled in regression models and restricted cubic spline, which included age, sex, race, marriage, education, income, drinking, smoking, regular exercise, BMI, daily energy intake, vitamin E, vitamin C, fruit intake, vegetable intake, diabetes, hypertension, asthma, emphysema and chronic bronchitis. Compared with participants in the lowest tertiles, participants in the highest tertiles of serum total carotenoids, β-cryptoxanthin and lutein/zeaxanthin levels had a significantly lower prevalence of emphysema (ORtotal carotenoids = 0·61, 95% CI: 0·41–0·89, OR β-cryptoxanthin = 0·67, 95% CI: 0·49–0·92), chronic bronchitis (OR β-cryptoxanthin = 0·66, 95% CI: 0·50–0·87) and asthma (Q2: ORlutein/zeaxanthin = 0·78, 95% CI: 0·62–0·97); participants in the highest tertiles of total carotenoids, α-carotene, lutein/zeaxanthin and lycopene had a lower risk of respiratory mortality (hazard ratio (HR)total carotenoids = 0·62, 95% CI: 0·42–0·90, HR α-carotene = 0·54, 95% CI: 0·36–0·82, HRlutein/zeaxanthin = 0·48, 95% CI: 0·33–0·71, HRlycopene = 0·66, 95% CI: 0·45–0·96) than those in the lowest tertiles. Higher serum total carotenoids and β-cryptoxanthin levels is associated with decreased prevalence of emphysema and chronic bronchitis, and higher serum total carotenoids, α-carotene, lutein/zeaxanthin and lycopene levels had a lower mortality of respiratory disease.

The phase summation effect in sum-frequency mixing process is utilized to avoid a nonlinearity obstacle in the power scaling of single-frequency visible or ultraviolet lasers. Two single-frequency fundamental lasers are spectrally broadened by phase modulation to suppress stimulated Brillouin scattering in fiber amplifier and achieve higher power. After sum-frequency mixing in a nonlinear optical crystal, the upconverted laser returns to single frequency due to phase summation, when the phase modulations on two fundamental lasers have a similar amplitude but opposite sign. The method was experimentally proved in a Raman fiber amplifier-based laser system, which generated a power-scalable sideband-free single-frequency 590 nm laser. The proposal manifests the importance of phase operation in wave-mixing processes for precision laser technology.

Coastal eutrophication and hypoxia remain a persistent environmental crisis despite the great efforts to reduce nutrient loading and mitigate associated environmental damages. Symptoms of this crisis have appeared to spread rapidly, reaching developing countries in Asia with emergences in Southern America and Africa. The pace of changes and the underlying drivers remain not so clear. To address the gap, we review the up-to-date status and mechanisms of eutrophication and hypoxia in global coastal oceans, upon which we examine the trajectories of changes over the 40 years or longer in six model coastal systems with varying socio-economic development statuses and different levels and histories of eutrophication. Although these coastal systems share common features of eutrophication, site-specific characteristics are also substantial, depending on the regional environmental setting and level of social-economic development along with policy implementation and management. Nevertheless, ecosystem recovery generally needs greater reduction in pressures compared to that initiated degradation and becomes less feasible to achieve past norms with a longer time anthropogenic pressures on the ecosystems. While the qualitative causality between drivers and consequences is well established, quantitative attribution of these drivers to eutrophication and hypoxia remains difficult especially when we consider the social economic drivers because the changes in coastal ecosystems are subject to multiple influences and the cause–effect relationship is often non-linear. Such relationships are further complicated by climate changes that have been accelerating over the past few decades. The knowledge gaps that limit our quantitative and mechanistic understanding of the human-coastal ocean nexus are identified, which is essential for science-based policy making. Recognizing lessons from past management practices, we advocate for a better, more efficient indexing system of coastal eutrophication and an advanced regional earth system modeling framework with optimal modules of human dimensions to facilitate the development and evaluation of effective policy and restoration actions.

In recent years, the incidence of teratospermia has been increasing, and it has become a very important factor leading to male infertility. The research on the molecular mechanism of teratospermia is also progressing rapidly. This article briefly summarizes the clinical incidence of teratozoospermia, and makes a retrospective summary of related studies reported in recent years. Specifically discussing the relationship between gene status and spermatozoa, the review aims to provide the basis for the genetic diagnosis and gene therapy of teratozoospermia.

High-power continuous-wave single-frequency Er-doped fiber amplifiers at 1560 nm by in-band and core pumping of a 1480 nm Raman fiber laser are investigated in detail. Both co- and counter-pumping configurations are studied experimentally. Up to 59.1 W output and 90% efficiency were obtained in the fundamental mode and linear polarization in the co-pumped case, while less power and efficiency were achieved in the counter-pumped setup for additional loss. The amplifier performs indistinguishably in terms of laser linewidth and relative intensity noise in the frequency range up to 10 MHz for both configurations. However, the spectral pedestal is raised in co-pumping, caused by cross-phase modulation between the pump and signal laser, which is observed and analyzed for the first time. Nevertheless, the spectral pedestal is 34.9 dB below the peak, which has a negligible effect for most applications.

Homeostasis of gut microbiota is a critical contributor to growth and health in weaned piglets. Fish oil is widely reported to benefit health of mammals including preventing intestinal dysfunction, yet its protective effect during suckling-to-weaning transition in piglets remains undetermined. Low (30 g/d) and high (60 g/d) doses of n-3-rich fish oil were supplemented in sows from late gestation to lactation. Serum indicators and gut microbiota were determined to evaluate the effects of maternal fish oil on growth performance, immunity and diarrhea of piglets. DHA and EPA in the colostrum as well as serum of suckling and 1-week post-wean piglets were significantly and linearly increased by maternal supplementation of fish oil (P < 0.05). IGF1 and T3 in nursing and weaned piglets were significantly elevated by maternal fish oil (P < 0.05), and the increase of IGF1 was concerning the dosage of fish oil. Colostrum IgG, plasma IgG, IgM in suckling piglets, IgG, IgM and IgA in weaned piglets were significantly increase as maternal replenishment of fish oil increased (P < 0.05). Additionally, cortisol was significantly reduced in weaned pigs (P < 0.05), regardless of dosage. 16S rRNA sequencing revealed that α-diversity of fecal microbiota in nursery piglets, and fecal Lactobacillus genus, positively correlated with post-weaning IgA, was significantly increased by high dosage. Collectively, maternal fish oil during late pregnancy and lactation significantly promoted growth, enhanced immunity, and reduced post-weaning diarrhea in piglets, therefore facilitated suckling-to-weaning transition in piglets, which may be partially due to the altered gut microbial community.

Many protected areas worldwide have been established to protect the last natural refuges of flagship animal species. However, long-established protected areas do not always match the current distributions of target species under changing environmental conditions. Here we present a case study of the Asian elephant Elephas maximus in Xishuangbanna, south-west China, to evaluate whether the established protected areas match the species’ current distribution and to identify key habitat patches for Asian elephant conservation. Our results show that currently only 24.5% of the predicted Asian elephant distribution in Xishuangbanna is located within Xishuangbanna National Nature Reserve, which was established for elephant conservation. Based on the predicted Asian elephant distribution, we identified the most important habitat patches for elephant conservation in Xishuangbanna. The three most important patches were outside Xishuangbanna National Nature Reserve and together they contained 43.3% of the estimated food resources for Asian elephants in all patches in Xishuangbanna. Thus, we identified a spatial mismatch between immobile protected areas and mobile animals. We recommend the inclusion of the three identified key habitat patches in a new national park currently being planned by the Chinese authorities for the conservation of the Asian elephant.

Corrosion is an important problem that engineers and scientists must overcome to avoid the collapse of structures, chemical processing plants, and metallic objects, which can lead to not only economic loss but also environmental and human losses. One of the simplest and most widely used methods to quantify corrosion rates (CRs) is the immersion test. The usual approach that has been used to date, to quantify the CR by this method, is to assume that the initial surface area of the corroding object remains constant over time. It is shown that such approximations underestimate the true CR and that they may lead to significant errors. A formula to calculate the CR considering changes in the area is presented in this work. The formula herein can be used to accurately quantify the CR by the immersion test and improve the quality of experimental data and the analysis and modeling of corrosion phenomena.

Lower-crust-derived adakitic rocks in the Gangdese belt provide important constraints on the timing of Tibetan crustal thickening and on the relative contributions of magmatic and tectonic processes. Here we present geochronological and geochemical data for the Wangdui porphyritic monzogranites in the western Gangdese belt. Zircon U–Pb dating yields emplacement ages of 46–44 Ma. All samples have high Sr (321–599 ppm), low Yb (0.76–1.33 ppm) and Y (10.6–18.3 ppm) contents, with high La/Yb (51.1–72.3) and Sr/Y (21.0–51.4) ratios, indicating adakitic affinities. The low MgO (0.97–1.76 wt %), Cr (7.49–53.6 ppm) and Ni (4.75–29.1 ppm) contents, as well as high 87Sr/86Sr(i) (0.7143–0.7145), low ϵNd(t) (−10.4 to −9.8) and zircon ϵHf(t) (−17.7 to 0.4) values, suggest that the Wangdui pluton most likely originated from partial melting of the thickened ancient lower crust. In combination with previously published data, despite the east–west-trending heterogeneity of crustal composition in the Gangdese belt, the La/Yb ratios of magmatic rocks reveal that both western and eastern segments experienced remarkable crustal thickening in the Eocene. However, in contrast to the thickened juvenile lower crust in the eastern segment formed by the underplating of mantle-derived magmas, tectonic shortening plays a more crucial role in thickening of the ancient basement in western Gangdese. In fact, such Eocene-thickened ancient lower-crust-derived adakitic rocks are widely distributed in the central Himalayan–Tibetan orogen. This, together with the extensive development of fold–thrust belts, suggests that tectonic shortening might be the main mechanism accounting for the crustal thickening associated with the India–Asia collision.

Demodex infestation and density changes remain one of the main challenges in some clinical settings. Tumour necrosis factor-α (TNF-α) inhibitors have been recommended as a first-line treatment for ankylosing spondylitis (AS). However, there have been no studies investigating the impact of TNF-α inhibitor adalimumab on changes in the Demodex density in patients with AS. The aim of this study was to investigate Demodex density changes before and after adalimumab treatment and analyse the relationship between the Demodex density and clinical characteristics in AS. It was found that the Demodex density was positively correlated with age and C-reactive protein levels and the number of Demodex mites could increase after adalimumab treatment in AS.

Insulin-like growth factor 1 receptor (IGF1R) is a cell surface receptor, belonging to the tyrosine kinase receptor superfamily. IGF1R plays a role not only in normal cell development but also in malignant transformation, which has become a candidate therapeutic target for the treatment of human cancer. This study aimed to explore insertions and deletions (indels) in IGF1R gene and investigate their association with growth traits in four Chinese cattle breeds (Xianan cattle, Jinnan cattle, Qinchuan cattle and Nanyang cattle). The current paper identified a 28-bp indel by polymerase chain reaction within IGF1R gene. The analysis showed that there was a significant correlation between the locus and the hucklebone width of Nanyang cattle in four periods, in which it was highly correlated at 6, 12 and 18 months. At the age of 6 months, it was also significantly correlated with body height, body weight and body length. Association analysis showed that the locus in Jinnan cattle was extremely significantly correlated with body slanting length and body weight, and significantly correlated with chest circumference. There was no significant correlation between this locus and growth traits of Xianan cattle and Qinchuan cattle. The detected indel in the IGF1R gene was significantly associated with growth traits in Jinnan and Nanyang cattle, and could be used as a molecular marker for growth trait selection.

This study investigates the dynamics of low-viscosity nanodroplets impacting surfaces with static contact angles from θ = 73° to 180° via molecular dynamics (MD) simulations. Two typical morphologies of impacting nanodroplets are observed at the maximum spreading state, a Hertz-ball-like in a low-Weber-number range and a thin-film-like in a high-Weber-number range. Only inertial and capillary forces dominate the impact for the former, whereas viscous force also becomes dominant for the latter. Regardless of morphologies at the maximum spreading state, the ratio of spreading time to contact time always remains constant on an ideal superhydrophobic surface with θ = 180°. With the help of different kinematic approximations of the spreading time and scaling laws of the contact time, scaling laws of the maximum spreading factor ${\beta _{max}}\sim W{e^{1/5}}$ in the low-Weber-number range (capillary regime) and ${\beta _{max}}\sim W{e^{2/3}}R{e^{ - 1/3}}$ (or ${\beta _{max}}\sim W{e^{1/2}}O{h^{1/3}}$) in the high-Weber-number range (cross-over regime) are obtained. Here, We, Re, and Oh are the Weber number, Reynolds number, and Ohnesorge number, respectively. Although the scaling laws are proposed only for the ideal superhydrophobic surface, they are tested valid for θ over 73° owing to the ignorable zero-velocity spreading effect. Furthermore, combining the two scaling laws leads to an impact number, $W{e^{3/10}}O{h^{1/3}} = 2.1$. This impact number can be used to determine whether viscous force is ignorable for impacting nanodroplets, thereby distinguishing the capillary regime from the cross-over regime.

This retrospective study investigated the predictive value of the Controlling Nutritional Status (CONUT) score in patients with intermediate-stage hepatocellular carcinoma (HCC) who received transarterial chemoembolization (TACE). Nomograms were developed to predict progression-free and overall survival (PFS, OS). The medical data of 228 patients with HCC and treated with TACE were collected. The patients were apportioned to 2 groups according to CONUT score: low or high (<4, ≥4). Univariate and multivariate analyses were performed using Cox regression for OS and PFS. OS and PFS were estimated by the Kaplan-Meier curve and compared with the log-rank test. Nomograms were constructed to predict patient OS and PFS. The nomograms were evaluated for accuracy, discrimination, and efficiency. The cut-off value of CONUT score was 4. The higher the CONUT score, the worse the survival; Kaplan-Meier curves showed significant differences in OS and PFS between the low and high CONUT score groups (P = 0·033, 0·047). The nomograms including CONUT, based on the prognostic factors determined by the univariate and multivariate analyses, to predict survival in HCC after TACE were generated. The CONUT score is an important prognostic factor for both OS and PFS for patients with intermediate HCC who underwent TACE. The cut-off value of the CONUT score was 4. A high CONUT score suggests poor survival outcomes. Nomograms generated based on the CONUT score were good models to predict patient OS and PFS.