The biodistribution of polystyrene nanoparticles administered intravenously in the chicken embryo.

Nanoplastics can cause severe malformations in chicken embryos. To improve our understanding of the toxicity of nanoplastics to embryos, we have studied their biodistribution in living chicken embryos. We injected the embryos in the vitelline vein at stages 18-19. We injected polystyrene nanoparticles (PS-NPs) tagged with europium- or fluorescence. Their biodistribution was tracked using inductively-coupled plasma mass spectrometry on tissue lysates, paraffin histology, and vibratome sections analysed by machine learning algorithms. PS-NPs were found at high levels in the heart, liver and kidneys. Furthermore, PS-NPs crossed the endocardium of the heart at sites of epithelial-mesenchymal transformation; they also crossed the liver endothelium. Finally, we detected PS-NPs in the allantoic fluid, consistent with their being excreted by the kidneys. Our study shows the power of the chicken embryo model for analysing the biodistribution of nanoplastics in embryos. Such experiments are difficult or impossible in mammalian embryos. These findings are a major advance in our understanding of the biodistribution and tissue-specific accumulation of PS-NPs in developing animals.

Disease progression, survival, and molecular disparities in Black and White patients with endometrioid endometrial carcinoma in real-world registries and GOG/NRG oncology randomized phase III clinical trials.

OBJECTIVE: Investigate racial disparities in outcomes and molecular features in Black and White patients with endometrioid endometrial carcinoma (EEC). METHODS: Black and White patients diagnosed with EEC who underwent hysterectomy ± adjuvant treatment in SEER, National Cancer Database (NCDB), the Genomics Evidence Neoplasia Information Exchange (GENIE) project (v.13.0), and eight NCI-sponsored randomized phase III clinical trials (RCTs) were studied. Hazard ratio (HR) and 95% confidence interval (CI) were estimated for cancer-related death (CRD), non-cancer death (NCD), and all-cause death. RESULTS: Black (n = 4397) vs. White (n = 47,959) patients in SEER had a HR (95% CI) of 2.04 (1.87-2.23) for CRD and 1.22 (1.09-1.36) for NCD. In NCDB, the HR (95% CI) for death in Black (n = 13,468) vs. White (n = 155,706) patients was 1.52 (1.46-1.58) dropping to 1.29 (1.23-1.36) after propensity-score matching for age, comorbidity, income, insurance, grade, stage, LVSI, and treatment. In GENIE, Black (n = 109) vs. White (n = 1780) patients had fewer PTEN, PIK3R1, FBXW7, NF1, mTOR, CCND1, and PI3K-pathway-related gene mutations. In contrast, TP53 and DNA-repair-related gene mutation frequency as well as tumor mutational burden-high status were similar in Black and White patients. In RCTs, Black (n = 187) vs. White (n = 2877) patients were more likely to have advanced or recurrent disease, higher grade, worse performance status and progressive disease. Risk of death in Black vs. White patients in RCTs was 2.19 (1.77-2.71) persisting to 1.32 (1.09-1.61) after matching for grade, stage, and treatment arm while balancing age and performance status. CONCLUSIONS: Differences exist in clinical presentation, outcomes, and molecular features in Black vs. White patients with EEC in real-world registries and RCTs. Targeted-drug development, strategies to modify social determinants, and diverse inclusion in RCTs are approaches to reduce disparities.

Immuno-Molecular Targeted Therapy Use and Survival Benefit in Patients with Stage IVB Cervical Carcinoma in Commission on Cancer®-Accredited Facilities in the United States.

PURPOSE: To investigate IMT use and survival in real-world stage IVB cervical cancer patients outside randomized clinical trials. METHODS: Patients diagnosed with stage IVB cervical cancer during 2013-2019 in the National Cancer Database and treated with chemotherapy (CT) ± external beam radiation (EBRT) ± intracavitary brachytherapy (ICBT) ± IMT were studied. The adjusted hazard ratio (AHR) and 95% confidence interval (CI) for risk of death were estimated in patients treated with vs. without IMT after applying propensity score analysis to balance the clinical covariates. RESULTS: There were 3164 evaluable patients, including 969 (31%) who were treated with IMT. The use of IMT increased from 11% in 2013 to 46% in 2019. Age, insurance, facility type, sites of distant metastasis, and type of first-line treatment were independently associated with using IMT. In propensity-score-balanced patients, the median survival was 18.6 vs. 13.1 months for with vs. without IMT (p < 0.001). The AHR was 0.72 (95% CI = 0.64-0.80) for adding IMT overall, 0.72 for IMT + CT, 0.66 for IMT + CT + EBRT, and 0.69 for IMT + CT + EBRT + ICBT. IMT-associated survival improvements were suggested in all subgroups by age, race/ethnicity, comorbidity score, facility type, tumor grade, tumor size, and site of metastasis. CONCLUSIONS: IMT was associated with a consistent survival benefit in real-world patients with stage IVB cervical cancer.

Survival disparities in non-Hispanic Black and White cervical cancer patients vary by histology and are largely explained by modifiable factors.

PURPOSE: We investigated racial disparities in survival by histology in cervical cancer and examined the factors contributing to these disparities. METHODS: Non-Hispanic Black and non-Hispanic White (hereafter known as Black and White) patients with stage I-IV cervical carcinoma diagnosed between 2004 and 2017 in the National Cancer Database were studied. Survival differences were compared using Cox modeling to estimate hazard ratio (HR) or adjusted HR (AHR) and 95% confidence interval (CI). The contribution of demographic, socioeconomic and clinical factors to the Black vs White differences in survival was estimated after applying propensity score weighting in patients with squamous cell carcinoma (SCC) or adenocarcinoma (AC). RESULTS: This study included 10,111 Black and 43,252 White patients with cervical cancer. Black patients had worse survival than White cervical cancer patients (HR = 1.40, 95% CI = 1.35-1.45). Survival disparities between Black and White patients varied significantly by histology (HR = 1.20, 95% CI = 1.15-1.24 for SCC; HR = 2.32, 95% CI = 2.12-2.54 for AC, interaction p < 0.0001). After balancing the selected demographic, socioeconomic and clinical factors, survival in Black vs. White patients was no longer different in those with SCC (AHR = 1.01, 95% CI 0.97-1.06) or AC (AHR = 1.09, 95% CI = 0.96-1.24). In SCC, the largest contributors to survival disparities were neighborhood income and insurance. In AC, age was the most significant contributor followed by neighborhood income, insurance, and stage. Diagnosis of AC (but not SCC) at ≥65 years old was more common in Black vs. White patients (26% vs. 13%, respectively). CONCLUSIONS: Histology matters in survival disparities and diagnosis at ≥65 years old between Black and White cervical cancer patients. These disparities were largely explained by modifiable factors.

Parasitic fish embryos do a "front-flip" on the yolk to resist expulsion from the host.

Embryonic development is often considered shielded from the effects of natural selection, being selected primarily for reliable development. However, embryos sometimes represent virulent parasites, triggering a coevolutionary "arms race" with their host. We have examined embryonic adaptations to a parasitic lifestyle in the bitterling fish. Bitterlings are brood parasites that lay their eggs in the gill chamber of host mussels. Bitterling eggs and embryos have adaptations to resist being flushed out by the mussel. These include a pair of projections from the yolk sac that act as an anchor. Furthermore, bitterling eggs all adopt a head-down position in the mussel gills which further increases their chances of survival. To examine these adaptations in detail, we have studied development in the rosy bitterling (Rhodeus ocellatus) using molecular markers, X-ray tomography, and time-lapse imaging. We describe a suite of developmental adaptations to brood parasitism in this species. We show that the mechanism underlying these adaptions is a modified pattern of blastokinesis-a process unique, among fish, to bitterlings. Tissue movements during blastokinesis cause the embryo to do an extraordinary "front-flip" on the yolk. We suggest that this movement determines the spatial orientation of the other developmental adaptations to parasitism, ensuring that they are optimally positioned to help resist the ejection of the embryo from the mussel. Our study supports the notion that natural selection can drive the evolution of a suite of adaptations, both embryonic and extra-embryonic, via modifications in early development.

Racial, ethnic and country of origin disparities in aggressive endometrial cancer histologic subtypes.

OBJECTIVE: This study investigated the risk of an aggressive endometrial cancer (EC) diagnosis by race, ethnicity, and country of origin to further elucidate histologic disparities in non-Hispanic Black (NHB), Hispanic, Asian/Pacific Islander (API), American Indian/Alaskan Native (AIAN) vs. non-Hispanic White (NHW) patients, particularly in Hispanic or API subgroups. METHODS: Patient diagnosed between 2004 and 2020 with low grade (LG)-endometrioid endometrial cancer (ECC) or an aggressive EC including grade 3 EEC, serous carcinoma, clear cell carcinoma, mixed epithelial carcinoma, or carcinosarcoma in the National Cancer Database were studied. The odds ratio (OR) and 95% confidence interval (CI) for diagnosis of an aggressive EC histology was estimated using logistic modeling. RESULTS: There were 343,868 NHW, 48,897 NHB, 30,013 Hispanic, 15,015 API and 1646 AIAN patients. The OR (95% CI) for an aggressive EC diagnosis was 3.07 (3.01-3.13) for NHB, 1.08 (1.06-1.11) for Hispanic, 1.17 (1.13-1.21) for API and 1.07 (0.96-1.19) for AIAN, relative to NHW patients. Subset analyses by country of origin illustrated the diversity in the OR for an aggressive EC diagnosis among Hispanic (1.18 for Mexican to 1.87 for Dominican), Asian (1.14 Asian Indian-Pakistani to 1.48 Korean) and Pacific Islander (1.00 for Hawaiian to 1.33 for Samoan) descendants. Hispanic, API and AIAN patients were diagnosed 5-years younger that NHW patients, and the risk for an aggressive EC histology were all significantly higher than NHW patients after correcting for age. Insurance status was another independent risk factor for aggressive histology. CONCLUSIONS: Risk of an aggressive EC diagnosis varied by race, ethnicity, and country of origin. NHB patients had the highest risk, followed by Dominican, South/Central American, Cuban, Korean, Thai, Vietnamese, and Filipino descendants.

Uterine cancer among Asian Americans - Disparities & clinical characteristics.

OBJECTIVE: To evaluate the patterns and trends of uterine cancer among Asian subgroups living in the U.S. METHODS: Data were obtained from United States Cancer Statistics (2001-2017), National Cancer Database (2004-2015), and World Population Review (2023). SEER*Stat version 8.3.9.2, Joinpoint regression program 4.9.0.0, and SAS v 9.4 were employed for statistical analysis. RESULTS: Based on data from 778,891 women in the United States Cancer Statistics database, Asians had a 3.4-fold higher rate of incident uterine cancer compared to White populations (2.14% vs. 0.63%; p < 0.001). Using the National Cancer Database, 7,641 Asian women from six subgroups were analyzed: Filipino, Korean, Indian/Pakistani, Vietnamese, Chinese, and Japanese. Indian and Pakistani women had the greatest increase in the proportion of cancer diagnoses (5.0% to 14.4%; p = 0.0003). Additionally, Indian and Pakistani patients had higher comorbidity scores while Koreans had the lowest (22.7% vs. 10.7%, p < 0.0001). Regarding stage of disease, 25.3% of Filipinos presented with advanced stage disease compared to 19.2% of Indians and Pakistanis (p = 0.0001). Furthermore, Filipinos had the highest proportion of non-endometrioid cancers at 18.4% compared to other subgroups (p = 0.0003). Using the World Population Review, female obesity was highest in Pakistan (8.6%) and the Philippines (7.5%) and lowest in Vietnam (2.6%). CONCLUSION: Uterine cancer incidence increased at higher rates among Asians compared to White populations. Specifically, Indian and Pakistani uterine cancer patients were more likely to have higher comorbidity rates and Filipino patients had more advanced stage cancer with non-endometrioid histologies than other Asian subgroups. Further research is warranted to better understand these trends.

Latest advances in immuno-oncology for endometrial cancer: single-agent and combination regimens.

PURPOSE OF REVIEW: The scope of immuno-oncology in endometrial cancer has changed rapidly in the last several years, requiring up-to-date knowledge for those who treat these patients. RECENT FINDINGS: This article will focus on molecular profiling, recent trials, and FDA approvals of targeted immuno-oncology medications in endometrial cancer. These include immune checkpoint inhibitors alone or with combination treatment. SUMMARY: The publication of the TCGA has led to significant focus on molecular subgroupings into POLEm, MMRd, NSMP, and p53m groups. For those patients with MMRd vs. MMRp tumors, there are indications for single agent immune checkpoint inhibitors with dostarlimab or pembrolizumab. For those with MMRp tumors, the addition of lenvatinib to pembrolizumab has proven clinical benefit. The recent publication of the RUBY and NRG-GY018 trials have shown clinical benefit in both subgroups with addition of immune checkpoint inhibitor to platinum-based chemotherapy. Now there is approval for use of dostarlimab in frontline chemotherapy and maintenance for advanced stage or recurrent endometrial cancer. Several upcoming trials investigating molecular subgroups from the TCGA are eagerly anticipated.

Sox9 is associated with two distinct patterning events during snake lung morphogenesis.

The evolutionary forces that allowed species adaptation to different terrestrial environments and led to great diversity in body shape and size required acquisition of innovative strategies of pattern formation during organogenesis. An extreme example is the formation of highly elongated viscera in snakes. What developmental patterning strategies allowed to overcome the space constraints of the snake's body to meet physiological demands? Here we show that the corn snake uses a Sox2-Sox9 developmental tool kit common to other species to generate and shape the lung in two phases. Initially Sox9 was found at low levels at the tip of the primary lung bud during outgrowth and elongation of the bronchial bud, without driving branching programs characteristic of mammalian lungs. Later, Sox9 induction is recapitulated in the formation of an extensive network of radial septae emerging along the elongated bronchial bud that generates the respiratory region. We propose that altogether these represent key patterning events for formation of both the respiratory faveolar and non-respiratory posterior compartments of the snake's lung.

Preoperative and pre-chemotherapy CA-125 levels in high-risk early-stage ovarian cancer - An NRG/GOG study.

OBJECTIVES: To determine clinical significance of preoperative and pre-chemotherapy CA-125 in high-risk early-stage epithelial ovarian cancer patients. METHODS: All patients with stage IA/IB and grade 3, stage IC, clear cell, or completed resected stage II cancer were enrolled in a phase III trial and treated with chemotherapy. Kaplan-Meier method and Cox proportional hazards model were used for statistical analyses. RESULTS: 427 patients with high-risk early-stage ovarian cancer were enrolled. Of 213 patients with preoperative CA-125 data, 79% had elevated CA-125. Median preoperative CA-125 level was 103 U/mL. Patients with ≤10, 11-15, and > 15 cm tumors had median preoperative CA-125 levels of 62, 131 and 158 U/mL, respectively (p = 0.002). For the 350 patients with data for pre-chemotherapy CA-125 level, 69% had elevated pre-chemotherapy CA-125 above 35 U/mL with median value of 65 U/mL. However, age, race, stage, cell type and grade of disease were not correlated with CA-125 levels before and after surgery. On multivariate analysis, elevated pre-chemotherapy CA-125 independently predicted worse recurrence-free survival (HR = 2.13, 95% CI: 1.23-3.69; p = 0.007) and overall survival (HR = 1.99, 95% CI: 1.10-3.59; p = 0.022) after adjusting for age, stage, cell type and grade of disease. Compared to those with normal CA-125, patients with elevated pre-chemotherapy CA-125 had lower recurrence-free survival (RFS, 87% vs. 75%; p = 0.007) and overall survival (OS, 88% vs. 82%; p = 0.02). However, preoperative CA-125 was not prognostic of RFS (p = 0.699) or OS (p = 0.701). CONCLUSIONS: Preoperative CA-125 was elevated in nearly 80% of high-risk early-stage ovarian cancer patients. Pre-chemotherapy CA-125 was associated with recurrence-free and overall survival; however, preoperative CA-125 was not prognostic.

Underrepresentation of racial and ethnic minority groups in gynecologic oncology: An analysis of over 250 trials.

OBJECTIVE: To describe the participation of racial and ethnic minority groups (REMGs) in gynecologic oncology trials. METHODS: Gynecologic oncology studies registered on ClinicalTrials.gov between 2007 and 2020 were identified. Trials with published results were analyzed based on reporting of race/ethnicity in relation to disease site and trial characteristics. Expected enrollment by race/ethnicity was calculated and compared to actual enrollment, adjusted for 2010 US Census population data. RESULTS: 2146 gynecologic oncology trials were identified. Of published trials (n = 252), 99 (39.3%) reported race/ethnicity data. Recent trials were more likely to report these data (36% from 2007 to 2009; 51% 2013-2015; and 53% from 2016 to 2018, p = 0.01). Of all trials, ovarian cancer trials were least likely to report race/ethnicity data (32.1% vs 39.3%, p = 0.011). Population-adjusted under-enrollment for Blacks was 7-fold in ovarian cancer, Latinx 10-fold for ovarian and 6-fold in uterine cancer trials, Asians 2.5-fold in uterine cancer trials, and American Indian and Alaska Native individuals 6-fold in ovarian trials. Trials for most disease sites have enrolled more REMGs in recent years - REMGs made up 19.6% of trial participants in 2007-2009 compared to 38.1% in 2016-2018 (p < 0.0001). CONCLUSION: Less than half of trials that published results reported race/ethnicity data. Available data reveals that enrollment of REMGs is significantly below expected rates based on national census data. These disparities persisted even after additionally adjusting for population size. Despite improvement in recent years, additional recruitment of REMGs is needed to achieve more representative and equitable participation in gynecologic cancer clinical trials.

Autistic young people adaptively use gaze to facilitate joint attention during multi-gestural dyadic interactions.

LAY ABSTRACT: Autistic people have been said to have 'problems' with joint attention, that is, looking where someone else is looking. Past studies of joint attention have used tasks that require autistic people to continuously look at and respond to eye-gaze cues. But joint attention can also be done using other social cues, like pointing. This study looked at whether autistic and non-autistic young people use another person's eye gaze during joint attention in a task that did not require them to look at their partner's face. In the task, each participant worked together with their partner to find a computer-generated object in virtual reality. Sometimes the participant had to help guide their partner to the object, and other times, they followed their partner's lead. Participants were told to point to guide one another but were not told to use eye gaze. Both autistic and non-autistic participants often looked at their partner's face during joint attention interactions and were faster to respond to their partner's hand-pointing when the partner also looked at the object before pointing. This shows that autistic people can and do use information from another person's eyes, even when they don't have to. It is possible that, by not forcing autistic young people to look at their partner's face and eyes, they were better able to gather information from their partner's face when needed, without being overwhelmed. This shows how important it is to design tasks that provide autistic people with opportunities to show what they can do.

Behavioral dynamics of conversation, (mis)communication and coordination in noisy environments.

During conversations people coordinate simultaneous channels of verbal and nonverbal information to hear and be heard. But the presence of background noise levels such as those found in cafes and restaurants can be a barrier to conversational success. Here, we used speech and motion-tracking to reveal the reciprocal processes people use to communicate in noisy environments. Conversations between twenty-two pairs of typical-hearing adults were elicited under different conditions of background noise, while standing or sitting around a table. With the onset of background noise, pairs rapidly adjusted their interpersonal distance and speech level, with the degree of initial change dependent on noise level and talker configuration. Following this transient phase, pairs settled into a sustaining phase in which reciprocal speech and movement-based coordination processes synergistically maintained effective communication, again with the magnitude of stability of these coordination processes covarying with noise level and talker configuration. Finally, as communication breakdowns increased at high noise levels, pairs exhibited resetting behaviors to help restore communication-decreasing interpersonal distance and/or increasing speech levels in response to communication breakdowns. Approximately 78 dB SPL defined a threshold where behavioral processes were no longer sufficient for maintaining effective conversation and communication breakdowns rapidly increased.

Development of a decision support tool to prevent community acquired pressure injuries for use in the spinal cord injury clinic using the delphi technique.

STUDY DESIGN: Delphi Technique. OBJECTIVES: Describe the development of a decision support tool to prevent community-acquired pressure injuries (CAPrIs) in individuals with spinal cord injury (SCI) for use in SCI clinics, called the Community-Acquired Pressure Injury Prevention-Field Implementation Tool (CAPP-FIT). SETTING: Veteran Health Administration Hospital, Chicago, Illinois, USA. METHODS: Concept mapping of current pressure injury (PrI) guidelines and qualitative research describing risks, actions, and resources needed to prevent CAPrIs associated with SCI were used to develop 40 veteran checklist items (Items) along with 37 associated provider actions (Actions) for the tool. The Delphi technique was used to refine Items and Actions with a panel of interprofessional SCI providers (n = 15), veterans with SCI (n = 4), and caregivers (n = 3) to determine consensus on a 4-point Likert scale (strongly agree-strongly disagree) for each Item and Action. A 75% agreement was set for responses rated as strongly agree or agree. RESULTS: Panelists were 60% female, 62% White, 33% veterans with SCI or caregivers, 33% wound care certified with a mean age of 59 years. Two survey rounds were required for consensus for 41 Item and 38 Action CAPP-FIT. Response rate was 95% for both rounds. Delphi round 1 showed all but two Actions affirming agreement above 75%. Substantive comments from panelists required revision to 5 Items and 9 Actions and one additional Item/Actions related to coping, meeting threshold percent agreement in Round 2. CONCLUSIONS: The CAPP-FIT could become a useful tool for Veterans living with SCI, caregivers, and SCI providers.

Comparing Ultrasound with Magnetic Resonance Imaging in the Evaluation of Subungual Glomus Tumors and Subungual Myxoid Cysts.

Introduction: Subungual myxoid cysts and subungual glomus tumors demonstrate characteristic features on magnetic resonance imaging (MRI) and ultrasound (US). It is not yet well-established whether US is congruent to MRI in diagnostic evaluation of these subungual lesions. Methods: Participants with clinical suspicion for subungual glomus tumors or subungual myxoid cysts were recruited. After clinical evaluation, participants underwent radiography, MRI, and US plus biopsy, aspiration, or excision where possible. Differential diagnoses were revised after review of imaging, and imaging findings were compared to definitive diagnosis by pathology, aspiration, or clinical course. Results: All lesions were visible on both US and MRI and size estimates agreed between the two modalities. US and MRI findings of subungual glomus tumors and subungual myxoid cysts agreed with their known respective imaging characteristics. Conclusions: Diagnosis of subungual myxoid cysts and subungual glomus tumors agreed between US and MRI. We provide sample MRI and US imaging parameters for optimal evaluation of subungual myxoid cysts and glomus tumors. We demonstrate that subungual MRI evaluation can be performed without special equipment, allowing for evaluation by most radiology departments. Lastly, US is user-dependent and may be non-inferior for a sonographer familiar with subungual US.

Sequential Targeted Therapy for Advanced, Metastatic, and Recurrent Cervical Cancer: A Cost-Effectiveness Analysis of the Patient Journey.

OBJECTIVES: To evaluate outcomes and cost-effectiveness of targeted therapy sequencing for metastatic and recurrent cervical cancer. METHOD: Models were simulated based on phase II and III trials on bevacizumab (bev) from GOG-240, cemiplimab (cemi) from GOG 3016, pembrolizumab (pembro) from KEYNOTE-826, and tisotumab vedotin (tiso) from GOG 3023. Costs were based on IBM Micromedex RED BOOK™ and company listed costs. RESULTS: For [chemo + bev → chemo], total cost was $125,918.04, with median overall survival (mOS) of 21.8 months, and cost-effectiveness ratio (CER) of $119,835.79. For [chemo + bev → cemi], total cost was $187,562.99 with mOS of 28.5 months and CER of $162,039.16. For [chemo + bev + pembro → chemo], total cost was $319,963.78 with mOS 32.9 months and CER of $249,930.10. For [chemo + bev + pembro → tiso], total cost was $455,204.45, with mOS 36.5 months and CER of $320,072.99. CONCLUSION: The combination of immunotherapies and biologics have significantly increased overall survival, but with associated higher costs, primarily related to drug costs.

Dynamical biomarkers in teams and other multiagent systems.

Effective team behavior in high-performance environments such as in sport and the military requires individual team members to efficiently perceive the unfolding task events, predict the actions and action intents of the other team members, and plan and execute their own actions to simultaneously accomplish individual and collective goals. To enhance team performance through effective cooperation, it is crucial to measure the situation awareness and dynamics of each team member and how they collectively impact the team's functioning. Further, to be practically useful for real-life settings, such measures must be easily obtainable from existing sensors. This paper presents several methodologies that can be used on positional and movement acceleration data of team members to quantify and/or predict team performance, assess situation awareness, and to help identify task-relevant information to support individual decision-making. Given the limited reporting of these methods within military cohorts, these methodologies are described using examples from team sports and teams training in virtual environments, with discussion as to how they can be applied to real-world military teams.

Initial phase and frequency modulations of pumping a playground swing.

The playground swing is a dynamic, coupled oscillator system consisting of the swing as an object and a human as the swinger. Here, we propose a model for capturing the effect of the initial phase of natural upper body motion on the continuous pumping of a swing and validate this model from the motion data of ten participants pumping swings of three different swing chain lengths. Our model predicts that the swing pumps the most if the phase of maximum lean back, which we call the initial phase, occurs when the swing is at a vertical (midpoint) position and moving forward when the amplitude is small. As the amplitude grows, the optimal initial phase gradually shifts towards an earlier phase of the cycle, the back extreme of the swing's trajectory. As predicted by our model, all participants shifted the initial phase of their upper body movements earlier as swing amplitude increased. This indicated that swingers adjust both the frequency and initial phase of their upper body movements to successfully pump a playground swing.

Predicting and understanding human action decisions during skillful joint-action using supervised machine learning and explainable-AI.

This study investigated the utility of supervised machine learning (SML) and explainable artificial intelligence (AI) techniques for modeling and understanding human decision-making during multiagent task performance. Long short-term memory (LSTM) networks were trained to predict the target selection decisions of expert and novice players completing a multiagent herding task. The results revealed that the trained LSTM models could not only accurately predict the target selection decisions of expert and novice players but that these predictions could be made at timescales that preceded a player's conscious intent. Importantly, the models were also expertise specific, in that models trained to predict the target selection decisions of experts could not accurately predict the target selection decisions of novices (and vice versa). To understand what differentiated expert and novice target selection decisions, we employed the explainable-AI technique, SHapley Additive explanation (SHAP), to identify what informational features (variables) most influenced modelpredictions. The SHAP analysis revealed that experts were more reliant on information about target direction of heading and the location of coherders (i.e., other players) compared to novices. The implications and assumptions underlying the use of SML and explainable-AI techniques for investigating and understanding human decision-making are discussed.

Nanoplastics causes extensive congenital malformations during embryonic development by passively targeting neural crest cells.

Nanomaterials are widespread in the human environment as pollutants, and are being actively developed for use in human medicine. We have investigated how the size and dose of polystyrene nanoparticles affects malformations in chicken embryos, and have characterized the mechanisms by which they interfere with normal development. We find that nanoplastics can cross the embryonic gut wall. When injected into the vitelline vein, nanoplastics become distributed in the circulation to multiple organs. We find that the exposure of embryos to polystyrene nanoparticles produces malformations that are far more serious and extensive than has been previously reported. These malformations include major congenital heart defects that impair cardiac function. We show that the mechanism of toxicity is the selective binding of polystyrene nanoplastics nanoparticles to neural crest cells, leading to the death and impaired migration of those cells. Consistent with our new model, most of the malformations seen in this study are in organs that depend for their normal development on neural crest cells. These results are a matter of concern given the large and growing burden of nanoplastics in the environment. Our findings suggest that nanoplastics may pose a health risk to the developing embryo.