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Over the past two decades, family structures have diversified. International migration has led to a rise in the number of families in which at least one parent is foreign-born. Increases have also been observed in both the rate of partnership separation, leading to a greater number of single-parent households and an increase in the number of families where grandparents have assumed caring responsibilities for their grandchildren. Evidence indicates a strong relationship between family structure and children's educational outcomes. Parental involvement is well documented as a key ingredient for the educational success of children. Drawing on Taiwanese multi-wave survey data (Taiwan Assessment of Student Achievement) and a machine-learning-based propensity score algorithm for multiple treatments, this paper aims to determine the various relationships between children from different household structures (two-parent households, skipped generation households, single-parent households, and immigrant households) and their cognitive knowledge (measured by test scores). Key findings reveal that children from skipped generation households achieve the lowest performance scores and that those from immigrant households tend to perform even better than children from traditional two-parent households in certain disciplines. Our results suggest that policy interventions targeted at providing remedial education and/or financial assistance are needed to support children from skipped generation families to redress existing educational disadvantages in Taiwan.

Abstract Efforts to develop disease-modifying treatments for Parkinson’s disease (PD) have been hindered by the lack of animal models replicating all hallmarks of PD and the insufficient attention to extra-nigrostriatal regions pathologically critical for the prodromal appearance of non-motor symptoms. Among PD models, 6-hydroxydopamine (6-OHDA) infusion in mice has gained prominence since 2012, primarily focusing on the nigrostriatal region. This study characterized tyrosine hydroxylase-positive neuron and fiber loss across the brain following a unilateral 6-OHDA (20 µg) infusion into the dorsal striatum. Our analysis integrates immunolabeling, brain clearing (iDISCO+), light sheet microscopy, and computational methods, including fMRI and machine learning tools. We also examined sex differences, disease progression, neuroinflammatory responses, and pro-apoptotic signaling in nigrostriatal regions of C57BL/6 mice exposed to varying 6-OHDA dosages (5, 10, or 20 µg) followed by 1, 7, and 14 days of recovery. This comprehensive, spatiotemporal analysis of 6-OHDA-induced pathology was used to map the time course of neuronal degeneration and the onset of neuroinflammation.

Tonsillitis, the inflammation of the palatine tonsils, is a common cause of throat pain. It is most often due to viruses but can also be related to bacteria. Necrotizing tonsillitis is a rare complication of acute tonsillitis with relatively few cases reported in the literature. We present a case of necrotizing tonsillitis in a patient with mononucleosis related to infection by Epstein-Barr virus, with superinfection with Streptococcus pyogenes, or group A streptococcus. To our knowledge, this is the first case of this nature to be reported in the medical literature. While the role of radiologic imaging is generally of limited diagnostic utility in cases of uncomplicated tonsillitis, its use was invaluable in ascertaining the nature and scope of necrotizing tonsillitis in this case. Further research remains to determine whether viral or bacterial superinfection can be used to further stratify patients who present with sore throat.

Centrifugal separation is a highly efficient technique for accelerating the sedimentation of blood constituents in a cylindrical container through high-speed spin-up rotation. Few studies have reported on the separation of different blood constituents from homogeneous mixture of whole blood. In this study, the process through which blood constituent sedimentation occurs in a spin-up rotating cylindrical container is numerically investigated. Whole blood is considered a homogeneous mixture of red blood cells (RBC) and plasma, which are both considered incompressible viscous liquids. The Euler multi-fluid VOF (volume of fluid) model is introduced to simulate the separation of RBCs and plasma. The effects of the rotation speed and the geometric construction of the cylindrical container on the sedimentation and stratification of different blood constituents are studied. A stable interface between the RBC layer and plasma layer forms earlier in a high position. With an increase in the rotation speed, the interface between the RBCs and plasma layers forms more quickly. In the cylindrical container with a helical groove on the outer wall, a stable vortex occurs near the groove, which forces red blood cells to move toward the lower location of the groove, resulting in a conical distribution of the RBC layer and a larger volume fraction of plasma near the exit at the top. This allows for sufficient precipitation of the plasma, improving the separation efficiency.

Abstract Background Recovery from SARS CoV-2 infection is expected within 3 months. Long COVID occurs after SARS-CoV-2 when symptoms are present for more than 3 months that are continuous, relapsing and remitting, or progressive. Better understanding of Long COVID illness trajectories could strengthen patient care and support. Methods We characterized functional impairments, quality of life (QoL), and cognition among patients who recovered from SARS-CoV-2 infection within 3 months (without Long COVID), after 3 months (Recovered Long COVID), or remained symptomatic (Long COVID). Among 7305 patients identified with previous SARS-CoV-2 infection between March 2020 and December 2021, confirmed in the medical record with laboratory test or physician diagnosis, 435 (6%) completed a single self-administered survey between March 2022 and September 2022. Multi-domain QoL and cognitive concerns were evaluated using PROMIS-29 and the Cognitive Change Index-12. Results Nearly half the participants (47.7%) were surveyed more than 2 years from initial infection (median = 23.3 months; IQR = 18.6, 26.7) and 86.7% were surveyed more than 1 year from infection. A significantly greater proportion of the Long COVID (n = 215) group, (Current and Recovered combined), had moderate-to-severe impairment in all health domains assessed compared to those Without Long COVID (n = 220; all p

Abstract Background Chronic overlapping pain conditions (COPCs), pain-related conditions that frequently occur together, may occur in patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and could impact illness severity. This study aimed to identify comorbid COPCs in patients with ME/CFS and evaluate their impact on illness severity. Methods We used data from 923 participants in the Multi-Site Clinical Assessment of ME/CFS study, conducted in seven U.S. specialty clinics between 2012 and 2020, who completed the baseline assessment (595 ME/CFS and 328 healthy controls (HC)). COPCs included chronic low back pain (cLBP), chronic migraine/headache (cMHA), fibromyalgia (FM), interstitial cystitis/irritable bladder (IC/IB), irritable bowel syndrome (IBS), temporomandibular disorder (TMD). Illness severity was assessed through questionnaires measuring symptoms and functioning. Multivariate analysis of variance and analysis of covariance models were used for analyses. Log-binomial regression analyses were used to compute prevalence of COPCs and prevalence ratios (PR) between groups with 95% confidence intervals. Both unadjusted and adjusted results with age and sex are presented. Results 76% of participants with ME/CFS had at least one COPCs compared to 17.4% of HC. Among ME/CFS participants, cMHA was most prevalent (48.1%), followed by FM (45.0%), cLBP (33.1%), and IBS (31.6%). All individual COPCs, except TMD, were significantly more frequent in females than males. The unadjusted PR (ME/CFS compared to HC) was highest for FM [147.74 (95% confidence interval (CI) = 20.83-1047.75], followed by cLBP [39.45 (12.73-122.27)], and IC/IB [13.78 (1.88-101.24)]. The significance and order did not change after age and sex adjustment. The COPC comorbidities of cLBP and FM each had a significant impact on most health measures, particularly in pain attributes (Cohen’s d effect size 0.8 or larger). While the impact of COPC comorbidities on non-pain attributes and quality of life measures was less pronounced than that on pain, statistically significant differences between ME/CFS participants with and without COPCs were still evident. Conclusions More than 75% of ME/CFS participants had one or more COPCs. Multiple COPCs further exacerbated illness severity, especially among females with ME/CFS. Assessment and management of COPCs may help improve the health and quality of life for patients with ME/CFS.

Abstract The electron-positron pair (EPP) creation under Gaussian and super-Gaussian pulse trains are studied by the computational quantum field theory (CQFT) in the single-photon regime. The details of the EPP creation are studied from the time evolution of the EPP number, energy spectra and spatial distribution of the electrons. The results indicate that the final created EPPs is the non-linear accumulation of the multi-pulses, which depends on the time interval, pulse shape and pulse number. The optimal time interval can be chosen based on the pulse resonance condition, which is derived by the perturbation method. Besides, steeper super-Gaussian pulses and adding more pulses facilitate the EPP creation as well. The results indicate that, under optimal multi-pulse parameters, the number of the EPPs obtained is much larger than the sum of the EPPs created under the same number of single pulses. This finding not only can enhance the EPP creation, but also can improve the multi-pulse utilization and guide future experimental research on the EPP creation.

Compliant bistable mechanisms are specialized mechanisms that have specific self-locking characteristics in two positions. They are widely used in aerospace, micro-electromechanical systems, and high-precision manufacturing. The coupling of kinematic with elastomechanical behaviors of compliant mechanisms, known as kinetostatics, increases the difficulty of synthesizing compliant mechanisms. Currently, most research relies on optimization approaches to find compliant mechanisms that meet motion requirements. To address this challenge, this paper proposes a geometric synthesis method for compliant bistable mechanisms to solve the rigid guidance problem. The pole similarity transformation characteristics of planar beams and the static equilibrium characteristic of bistable mechanisms at stable positions are utilized to decouple the kinematic synthesis and static analysis. The proposed method introduces a task-driven synthesis process, where the critical structural parameters in compliant mechanisms are determined based on the desired guidance positions of motion tasks. This approach eliminates the need for a tedious and time-consuming iterative optimization process. The resulting bistable mechanisms have two stable positions that correspond to the desired guidance positions of the motion task. To illustrate the effectiveness of the geometric synthesis method, a two-position problem of a compliant bistable mechanism is provided as an example.

Interdisciplinary education has become increasingly prominent as a core instrument to prepare the next generation workforce. Yet, little is known about the impacts of long-term degree-oriented interdisciplinary education on post-graduation outcomes. This paper aims to investigate the influence of long-term degree-oriented interdisciplinary education on graduates' post-graduation plan choices and labour market outcomes using unique administrative micro-data and career-tracking data from a comprehensive research university. Our results indicate that higher levels of engagement in interdisciplinary learning increase the probability of pursuing future study and employment in a field that differs from a graduate's college degree, and are also associated with a higher probability to enter the workforce. Yet, this positive association between interdisciplinary learning and the probability of entering the workforce is specific to graduates from traditional disciplinary programmes. Additionally, our findings suggest that the impact of long-term degree-oriented interdisciplinary education on early labour market outcomes is overall beneficial but varies across degree fields. The findings of our study provided partial evidence in support of the influence of long-term degree-oriented interdisciplinary education on post-graduation plan choices and early labour market outcomes. We suggest that given resource constraints, higher education institutions could consider relaxing module choice restrictions in traditional disciplinary programmes to promote interdisciplinary education. However, it is important to note that higher education institutions should carefully consider the potential trade-off between the breadth of interdisciplinary content and the depth of specialist content, in order to strike a balance.

Immune checkpoint inhibitor (ICI) therapy is a cornerstone treatment for many cancers, but it can induce severe immunotoxicity, including acute interstitial nephritis (AIN). Currently, kidney biopsy is required to differentiate ICI-AIN from other causes of acute kidney injury (AKI). However, this invasive approach can lead to morbidity, delayed glucocorticoid treatment for patients with AIN, and unnecessarily prolonged suspension of ICI therapy in non-AIN patients. Delayed or incorrect diagnosis of ICI-AIN is particularly detrimental, as over 50% of patients are at risk of permanent renal damage. Thus, there is an urgent need for non-invasive biomarkers that can rapidly and accurately distinguish ICI-AIN from other causes of AKI.The urine and plasma proteome contain actively secreted proteins that provide real-time insights into dynamic physiological processes. However, identification of effective biomarkers of disease using established technologies such as proximity ligation assays (PLA) and bead-based immunoassays is challenging due to their limited sensitivity and loss of precision in multiplex analysis.To address this, we employed cutting-edge NUcleic acid Linked Immuno-Sandwich Assay (NULISA) technology to measure protein expression in urine and plasma samples from AKI patients undergoing ICI therapy. NULISA offers 10,000-fold greater precision than PLA, enabling quantification of over 200 inflammatory proteins with unprecedented precision. Our analysis revealed that urine was more sensitive and specific than plasma in distinguishing ICI-AIN from non-AIN cases. Pathway analyses highlighted the involvement of JAK-STAT and tumor necrosis factor (TNF) signaling in ICI-AIN pathogenesis. We identified several novel urine biomarkers, including IL-5, Fas, TNFSF4, CD274, IL-20, TNFSF15, TSLP, TREM1 and CCL1 while confirming previously reported markers such as CXCL9 and TNF-α. Using statistical and machine learning methods, we constructed a novel urine biomarker signature—IL-5+Fas—that achieved an area under the curve of 0.94 for diagnosing ICI-AIN.By leveraging high-sensitivity proteomics, we developed a non-invasive strategy for diagnosing ICI-AIN. This approach will enable earlier intervention to mitigate immunotoxicity, preservation of antitumor efficacy of ICI therapy in non-AIN patients, and safe rechallenge of ICI therapy in patients previously treated for ICI-AIN.

Abstract Influenza is an acute respiratory infection that spreads rapidly and widely in densely populated areas with low vaccination coverage. The trends and drivers of the spatial and temporal dynamics of influenza incidence among residents of mainland China have not been systematically studied. This study comprehensively analyses the dynamics and spatial correlation of influenza using long‐term scale data and spatial panel data. It then identifies the interactive process of socio‐economic and natural elements on the incidence of influenza. The highest prevalence of influenza was found in the 0–4 years age group in mainland China (mean prevalence, 67.56/100,000). In addition, influenza in mainland China shows seasonality, with fall and winter being the periods of high incidence. Between 2014 and 2017, influenza incidence was clustered in Hubei and Anhui provinces, and the spatial clustering was statistically significant (Z value > 1.96, P

Background: The introduction of direct-acting antivirals (DAA) has revolutionized hepatitis C virus (HCV) treatment but has not translated into an appreciable decline in HCV prevalence, which is estimated to be 2.4 million in the United States. Efforts are thought to be limited by the lack of experience among nonspecialist providers in managing HCV. However, there have been no comprehensive surveys assessing HCV knowledge among medical trainees to determine if trends have shifted since the discovery of DAAs. Methods: We performed a retrospective observational study of internal medicine (IM) residents in the United States (n = 1763) who completed the Physician Education and Assessment Center HCV learning module between 2021 and 2022. Participant pre- and post-test performance was compared with further stratified analysis by training year, geography, training program type, and local HCV prevalence using ANOVA and Chi-squared tests of proportions, respectively. Results: IM residents universally lacked baseline HCV knowledge (average score ± standard deviation, 43% ± 19%); less than 50% of participants answered correctly in the majority of tested domains. There were no consistent trends in performance regardless of resident characteristic used to stratify the participants. Knowledge gaps improved after completing an online educational training module (P < .001). Conclusions: HCV knowledge remains limited among IM residents despite expansion of treatment options. Addressing these gaps during clinical training may substantially increase the availability of HCV treatment in the community, and online modules may be one means by which to integrate these efforts into medical training.

Abstract Paradoxically, cigarette smoking is associated with a reduced risk of Parkinson’s Disease (PD). This led us to hypothesize that carbon monoxide (CO) levels, which are constitutively but modestly elevated in smokers, might contribute to neuroprotection. Using rodent models of PD based on α-synuclein (αSyn) accumulation and oxidative stress, we show that low-dose CO mitigates neurodegeneration and reduces αSyn pathology. Oral CO administration activated signaling cascades mediated by heme oxygenase-1 (HO-1), which have been implicated in limiting oxidative stress, and in promoting αSyn degradation, thereby conferring neuroprotection. Consistent with the neuroprotective effect of smoking, HO-1 levels in cerebrospinal fluid were higher in human smokers compared to nonsmokers. Moreover, in PD brain samples, HO-1 levels were higher in neurons without αSyn pathology. Thus, CO in rodent PD models reduces pathology and increases oxidative stress responses, phenocopying possible protective effects of smoking evident in PD patients. These data highlight the potential for low-dose CO-modulated pathways to slow symptom onset and limit pathology in PD patients.

Abstract The rise of drug resistance has become a global crisis, with >1 million deaths due to resistant bacterial infections each year. Pseudomonas aeruginosa, in particular, remains a serious problem with limited solutions due to complex resistance mechanisms that now lead to more than 32,000 multidrug-resistant (MDR) infections and over 2000 deaths in the U.S. annually. While the emergence of resistant bacteria has become ominously common, identification of useful new drug classes has been limited over the past over 40 years. We found that a potential novel therapeutic, the peptide-mimetic TM5, is effective at killing P. aeruginosa and displays sufficiently low toxicity in mammalian cells to allow for use in treatment of infections. Interestingly, TM5 kills P. aeruginosa more rapidly than traditional antibiotics, within 30–60 min in vitro, and is effective against a range of clinical isolates, including extensively drug resistant strains. In vivo, TM5 significantly reduced bacterial load in the lungs within 24 h compared to untreated mice and demonstrated few adverse effects. Taken together, these observations suggest that TM5 shows promise as an alternative therapy for MDR P. aeruginosa respiratory infections.

Abstract The randomized, phase 2 GRIFFIN study (NCT02874742) evaluated daratumumab plus lenalidomide/bortezomib/dexamethasone (D-RVd) in transplant-eligible newly diagnosed multiple myeloma (NDMM). We present final post hoc analyses (median follow-up, 49.6 months) of clinically relevant subgroups, including patients with high-risk cytogenetic abnormalities (HRCAs) per revised definition (del[17p], t[4;14], t[14;16], t[14;20], and/or gain/amp[1q21]). Patients received 4 induction cycles (D-RVd/RVd), high-dose therapy/transplant, 2 consolidation cycles (D-RVd/RVd), and lenalidomide±daratumumab maintenance (≤ 2 years). Minimal residual disease–negativity (10−5) rates were higher for D-RVd versus RVd in patients ≥ 65 years (67.9% vs 17.9%), with HRCAs (54.8% vs 32.4%), and with gain/amp(1q21) (61.8% vs 28.6%). D-RVd showed a trend toward improved progression-free survival versus RVd (hazard ratio [95% confidence interval]) in patients ≥ 65 years (0.29 [0.06–1.48]), with HRCAs (0.38 [0.14–1.01]), and with gain/amp(1q21) (0.42 [0.14–1.27]). In the functional high-risk subgroup (not MRD negative at the end of consolidation), the hazard ratio was 0.82 (0.35–1.89). Among patients ≥ 65 years, grade 3/4 treatment-emergent adverse event (TEAE) rates were higher for D-RVd versus RVd (88.9% vs 77.8%), as were TEAEs leading to discontinuation of ≥ 1 treatment component (37.0% vs 25.9%). One D-RVd patient died due to an unrelated TEAE. These results support the addition of daratumumab to RVd in transplant-eligible patients with high-risk NDMM. Video Abstract

The Okmok volcanic eruption in Alaska has recently been discovered and is precisely dated to have occurred in 43 BCE. Some Chinese climate records of 43–33 BCE have been found in historical documents that provide descriptions of observed environmental abnormities that appear to be consistent with the anticipated changes due to volcanic climate forcing. In this paper, we provide a full translation with discussions of the Chinese climate records that may be related to the Okmok eruption. We have converted ancient Chinese calendar dates to modern Gregorian dates and provided the latitudes and longitudes of the geographical locations mentioned in the records. Relevant climate information in similar areas of China in the decades after the 1783 Laki eruption is also briefly summarized for comparison. We believe the detailed information contained in these records will be useful for further research on the climate impact of volcanic eruptions.

Introduction: Clinical preventive services, such as screening tests, vaccinations, behavioral counseling, or preventive medication, are offered to most people on the basis of age, sex, health behaviors, or clinical risk factors, with goals of detecting early disease, preventing future disease, or mitigating the impact of unhealthy behaviors on future health. However, many people do not receive all the recommended services for which they are eligible. Methods: The Agency for Healthcare Research and Quality identified 4 topics for gathering stakeholder input on evidence and implementation for the equitable delivery of clinical preventive services. These included technology, innovative delivery models, public health linkages, and disparities. For each topic, the authors conducted an environmental scan to identify existing programs or interventions to promote the delivery of clinical preventive services, a technical expert panel meeting, and key informant interviews. The authors synthesized input from each topic's technical expert panel and key informant interviews and used inductive reasoning to identify themes. Within each overarching theme, the authors identified subthemes supported by specific statements, examples, and illustrative quotes. Results: A total of 90 individuals participated on stakeholder panels, technical expert panels, or key informant interviews; some individuals participated in multiple roles. Across the topics, the authors identified 3 overarching themes from synthesis of the technical expert panel and key informant interview comments across topics: (1) transitioning to holistic healthcare delivery and financing models, (2) including community and patient voice in healthcare system design, and (3) leveraging technology to improve clinical preventive services delivery. Conclusions: Promoting the equitable delivery of clinical preventive services requires improving access to primary care but also expanding efforts beyond clinical settings to encompass public health and community infrastructure and engagement. Experts recommended that person-centered preventive care should empower patients to make informed decisions about clinical preventive services on the basis of their values, risks, and preferences. This more individualized approach tailored to needs and context may reduce barriers to receipt of clinical preventive services.

Introduction: The elbow is prone to wound complications due to its subcutaneous location with limited overlying connective tissue. Elbow instability may place patients at risk for wound complications, though this relationship is not well described. We present a series of four case reports from our institution to gain insight into the association of elbow instability and wound healing. Methods: Four patients who presented to our institution with elbow instability between January 2019 and September 2022 were identified by the senior author, and chart review was performed. Results: Patients A and B presented to our clinic with synovial cutaneous fistulas (SCFs) after undergoing elbow surgery. It was only after their underlying elbow instability was addressed that their wounds fully healed. Patients C and D presented with open injuries and grossly unstable elbows placing them at high risk for wound complications. In patients C and D, preventive stabilization of their elbow instability was performed, and wound complications never occurred. Conclusion: Each of these cases emphasizes the importance of achieving elbow stability to prevent SCFs and further wound complications, though further rigorous studies are required to definitively establish a causal relationship.

IntroductionPatients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) experience cognitive problems with attention, information processing speed, working memory, learning efficiency, and executive function. Commonly, patients report worsening of cognitive symptoms over time after physical and/or cognitive challenges. To determine, monitor, and manage longitudinal decrements in cognitive function after such exposures, it is important to be able to screen for cognitive dysfunction and changes over time in clinic and also remotely at home. The primary objectives of this paper were: (1) to determine whether a brief computerized cognitive screening battery will detect differences in cognitive function between ME/CFS and Healthy Controls (HC), (2) to monitor the impact of a full-day study visit on cognitive function over time, and (3) to evaluate the impact of exercise testing on cognitive dysfunction.MethodsThis cognitive sub-study was conducted between 2013 and 2019 across seven U.S. ME/CFS clinics as part of the Multi-Site Clinical Assessment of ME/CFS (MCAM) study. The analysis included 426 participants (261 ME/CFS and 165 HC), who completed cognitive assessments including a computerized CogState Brief Screening Battery (CBSB) administered across five timepoints (T0-T4) at the start of and following a full day in-clinic visit that included exercise testing for a subset of participants (182 ME/CFS and 160 HC). Exercise testing consisted of ramped cycle ergometry to volitional exhaustion. The primary outcomes are performance accuracy and latency (performance speed) on the computerized CBSB administered online in clinic (T0 and T1) and at home (T2-T4).ResultsNo difference was found in performance accuracy between ME/CFS and HCs whereas information processing speed was significantly slower for ME/CFS at most timepoints with Cohen’s d effect sizes ranging from 0.3–0.5 (p < 0.01). The cognitive decline over time on all CBSB tasks was similar for patients with ME/CFS independent of whether exercise testing was included in the clinic visit.ConclusionThe challenges of a clinic visit (including cognitive testing) can lead to further cognitive deficits. A single short session of intense exercise does not further reduce speed of performance on any CBSB tasks.

Abstract The detection and quantification of protein biomarkers in bodily fluids is important for many clinical applications, including disease diagnosis and health monitoring. Current techniques for ultrasensitive protein detection, such as enzyme‐linked immunosorbent assay (ELISA) and electrochemical sensing, involve long incubation times (1.5–3 h) and rely on single‐use sensing electrodes which can be costly and generate excessive waste. This work demonstrates a reusable electrochemical immunosensor employing magnetic nanoparticles (MNPs) and dually labeled gold nanoparticles (AuNPs) for ultrasensitive measurements of protein biomarkers. As proof of concept, this platform is used to detect C‐X‐C motif chemokine ligand 9 (CXCL9), a biomarker associated with kidney transplant rejection, immune nephritis from checkpoint inhibitor therapy, and drug‐associated acute interstitial nephritis, in human urine. The sensor successfully detects CXCL9 at concentrations as low as 27 pg mL−1 within ≈1 h. This immunosensor was also adapted onto a handheld smartphone‐based diagnostic device and used for measurements of CXCL9, which exhibited a lower limit of detection of 65 pg mL−1. Lastly, this work demonstrates that the sensing electrodes can be reused for at least 100 measurements with a negligible loss in analytical performance, reducing the costs and waste associated with electrochemical sensing.

Abstract Objective Youth-onset type 2 diabetes (T2D) is physiologically distinct from adult-onset, but it is not clear how the two diseases differ at a molecular level. In utero exposure to maternal type 2 diabetes (T2D) is known to be a specific risk factor for youth-onset T2D. DNA methylation (DNAm) changes associated with T2D but which differ between youth- and adult-onset might delineate the impacts of T2D development at different ages and could also determine the contribution of exposure to in utero diabetes. Methods We performed an epigenome-wide analysis of DNAm on whole blood from 218 youth with T2D and 77 normoglycemic controls from the iCARE (improving renal Complications in Adolescents with type 2 diabetes through REsearch) cohort. Associations were tested using multiple linear regression models while adjusting for maternal diabetes, sex, age, BMI, smoking status, second-hand smoking exposure, cell-type proportions and genetic ancestry. Results We identified 3830 differentially methylated sites associated with youth T2D onset, of which 3794 were moderately (adjusted p-value 0.01) associated and 36 were strongly (adjusted p-value 0.05) associated. A total of 3725 of these sites were not previously reported in the EWAS Atlas as associated with T2D, adult obesity or youth obesity. Moreover, three CpGs associated with youth-onset T2D in the PFKFB3 gene were also associated with maternal T2D exposure (FDR 0.01). This is the first study to link PFKFB3 and T2D in youth. Conclusion Our findings support that T2D in youth has different impacts on DNAm than adult-onset, and suggests that changes in DNAm could provide an important link between in utero exposure to maternal diabetes and the onset of T2D.

Abstract Unenhanced CT scans exhibit high specificity in detecting moderate-to-severe hepatic steatosis. Even though many CTs are scanned from health screening and various diagnostic contexts, their potential for hepatic steatosis detection has largely remained unexplored. The accuracy of previous methodologies has been limited by the inclusion of non-parenchymal liver regions. To overcome this limitation, we present a novel deep-learning (DL) based method tailored for the automatic selection of parenchymal portions in CT images. This innovative method automatically delineates circular regions for effectively detecting hepatic steatosis. We use 1,014 multinational CT images to develop a DL model for segmenting liver and selecting the parenchymal regions. The results demonstrate outstanding performance in both tasks. By excluding non-parenchymal portions, our DL-based method surpasses previous limitations, achieving radiologist-level accuracy in liver attenuation measurements and hepatic steatosis detection. To ensure the reproducibility, we have openly shared 1014 annotated CT images and the DL system codes. Our novel research contributes to the refinement the automated detection methodologies of hepatic steatosis on CT images, enhancing the accuracy and efficiency of healthcare screening processes.

Abstract The full data set of the Daya Bay reactor neutrino experiment is used to probe the effect of the charged current non-standard interactions (CC-NSI) on neutrino oscillation experiments. Two different approaches are applied and constraints on the corresponding CC-NSI parameters are obtained with the neutrino flux taken from the Huber-Mueller model with a 5% uncertainty. For the quantum mechanics-based approach (QM-NSI), the constraints on the CC-NSI parameters ϵ eα and ϵ eα s $$ {\epsilon}_{e\alpha}^s $$ are extracted with and without the assumption that the effects of the new physics are the same in the production and detection processes, respectively. The approach based on the weak effective field theory (WEFT-NSI) deals with four types of CC-NSI represented by the parameters [ε X ] eα . For both approaches, the results for the CC-NSI parameters are shown for cases with various fixed values of the CC-NSI and the Dirac CP-violating phases, and when they are allowed to vary freely. We find that constraints on the QM-NSI parameters ϵ eα and ϵ eα s $$ {\epsilon}_{e\alpha}^s $$ from the Daya Bay experiment alone can reach the order O $$ \mathcal{O} $$ (0.01) for the former and O $$ \mathcal{O} $$ (0.1) for the latter, while for WEFT-NSI parameters [ε X ] eα , we obtain O $$ \mathcal{O} $$ (0.1) for both cases.

The Gaoping Submarine Canyon (GPSC) off southwest Taiwan has been extensively studied due to its unique geology, its role in transferring terrestrial material to the deep sea, and its diverse biological communities. However, there is a lack of understanding of carbon cycling across the sediment–water interface in the canyon. This study aims to fill the gap by utilizing the field data collected between 2014 and 2020 and a linear inverse model (LIM) to reconstruct the benthic food web (i.e., carbon flows through different stocks) in the head of GPSC and the upper Gaoping slope (GS). The biotic and abiotic organic carbon (OC) stocks were significantly higher on the slope than in the canyon, except for the bacteria stock. The sediment oxygen utilization was similar between the two habitats, but the magnitude and distribution of the OC flow in the food web were distinctively different. Despite a significant input flux of ∼ 2020 mg C m−2 d−1 in the canyon, 84 % of the carbon flux exited the system, while 12 % was buried. On the slope, 84 % of the OC input (∼ 109 mg C m−2 d−1) was buried, and only 7 % exited the system. Bacteria processes play a major role in the carbon fluxes within the canyon. In contrast, the food web in the upper slope exhibited stronger interactions among metazoans, indicated by higher fluxes between meiofauna and macrofauna compartments. Network indices based on the LIM outputs showed that the canyon head had higher total system throughput (T..) and total system throughflow (TST), indicating greater energy flowing through the system. In contrast, the slope had a significantly higher Finn cycling index (FCI), average mutual information (AMI), and longer OC turnover time, suggesting a relatively more stable ecosystem with higher energy recycling. Due to sampling limitations, the present study only represents the benthic food web during the “dry” period. By integrating the field data into a food web model, this study provides valuable insight into the fates of OC cycling in an active submarine canyon, focusing on the often overlooked benthic communities. Future studies should include “wet” period sampling to reveal the effects of typhoons and monsoon rainfalls on OC cycling.

Abstract In the MASTER study (NCT03224507), daratumumab+carfilzomib/lenalidomide/dexamethasone (D-KRd) demonstrated promising efficacy in transplant-eligible newly diagnosed multiple myeloma (NDMM). In GRIFFIN (NCT02874742), daratumumab+lenalidomide/bortezomib/dexamethasone (D-RVd) improved outcomes for transplant-eligible NDMM. Here, we present a post hoc analysis of patients with high-risk cytogenetic abnormalities (HRCAs; del[17p], t[4;14], t[14;16], t[14;20], or gain/amp[1q21]). Among 123 D-KRd patients, 43.1%, 37.4%, and 19.5% had 0, 1, or ≥2 HRCAs. Among 120 D-RVd patients, 55.8%, 28.3%, and 10.8% had 0, 1, or ≥2 HRCAs. Rates of complete response or better (best on study) for 0, 1, or ≥2 HRCAs were 90.6%, 89.1%, and 70.8% for D-KRd, and 90.9%, 78.8%, and 61.5% for D-RVd. At median follow-up (MASTER, 31.1 months; GRIFFIN, 49.6 months for randomized patients/59.5 months for safety run-in patients), MRD-negativity rates as assessed by next-generation sequencing (10–5) were 80.0%, 86.4%, and 83.3% for 0, 1, or ≥2 HRCAs for D-KRd, and 76.1%, 55.9%, and 61.5% for D-RVd. PFS was similar between studies and superior for 0 or 1 versus ≥2 HRCAs: 36-month PFS rates for D-KRd were 89.9%, 86.2%, and 52.4%, and 96.7%, 90.5%, and 53.5% for D-RVd. These data support the use of daratumumab-containing regimens for transplant-eligible NDMM with HCRAs; however, additional strategies are needed for ultra-high–risk disease (≥2 HRCAs). Video Abstract

Bifurcated vessels represent a typical vascular unit of the cardiovascular system. In this study, the blood flow in symmetric and asymmetric bifurcated vessels are simulated based on computational fluid dynamics method. The blood is modeled as non-Newtonian fluid, and the pulsatile flow velocity is applied on the inlet. The effects of the fluid model, bifurcation angle and symmetry of the geometry of the vessel are investigated. The results show that the wall shear stress (WSS) on the outer wall of daughter branches for the non-Newtonian fluid flow is greater than that for Newtonian fluid flow, and the discrepancy between the flow of two fluid models is obvious at relatively low flow rates. With the bifurcation angle increases, the peak axial velocity of the cross-section of daughter branch decreases, so the WSS increases. For the non-Newtonian fluid flow in the asymmetric bifurcated vessels, more flow passes through the daughter vessel with a lower angle, and the WSS along the outer wall of which is lower. Furthermore, the region with a low time-averaged wall stress (TAWSS) and high oscillating shear index(OSI) distributed on the outer wall of bifurcation vessels are larger for the flow in the vessel with smaller bifurcation angle. In conclusion, the effects of the blood viscosity cannot be neglected at low flow rates and the geometry of the bifurcated vessel plays a key role with regards to the blood flow.

As campuses become increasingly diverse, it is important that faculties maintain inclusive classrooms. Students of underrepresented ethnic/racial groups are more likely to experience disengagement in an academic setting (Nagasawa & Wong, 1999), which can lead to underperformance (Major et al., 1998). Students with LGBTQA+ (lesbian, gay, bisexual, transgender, queer, or asexual) identities are at higher risk of poor mental health and lower academic performance compared to cisgender and heterosexual students (Aragon et al., 2014). These detrimental experiences can lead to even more harm in a remote learning environment, where students have fewer opportunities to feel a sense of belonging and connect with their peers and/or instructors. This paper will consider strategies of inclusiveness in the online classroom and in-person learning environment within a social psychology framework to better support underprivileged students to improve academic performance and the overall educational experience. The suggestions and discussions provided apply to both in-person learning as well as remote delivery.

Background: Total ankle arthroplasty (TAA) has primarily been performed in the inpatient setting. However, with the advent of fast-tracked joint arthroplasty protocols, TAA has slowly been shifting to the outpatient setting. Therefore, this systematic review aims to evaluate outcomes of outpatient TAA and compare them to inpatient TAA. Methods: A literature search was performed on October 23, 2023, in the PubMed, Embase, and CENTRAL databases using the PRISMA guidelines. Studies were included if they reported on outcomes of outpatient TAA or compared outcomes between outpatient and inpatient TAA. Pooled odds ratios (ORs) and mean differences were calculated using a random effects model. Quality assessment was performed using the MINORS criteria. Results: 12 studies were included, with 4 outpatient-only and 8 outpatient-inpatient comparative studies. Patients in the outpatient group were relatively younger, had a lower body mass index, and had fewer comorbidities relative to the inpatient group. For outpatient vs inpatient TAA, the pooled complication rate was 2.6% vs 3.6%, readmission rate was 2.5% vs 4%, and reoperation rate was 3.6% vs 5.5%. We found significantly lower odds of complications (OR = 0.47, CI: 0.26-0.85; P = .01), readmissions (OR = 0.63, CI: 0.54-0.74; P

Extrachromosomal DNA is a common cause of oncogene amplification in cancer. The non-chromosomal inheritance of ecDNA enables tumors to rapidly evolve, contributing to treatment resistance and poor outcome for patients. The transcriptional context in which ecDNAs arise and progress, including chromosomally-driven transcription, is incompletely understood. We examined gene expression patterns of 870 tumors of varied histological types, to identify transcriptional correlates of ecDNA. Here, we show that ecDNA-containing tumors impact four major biological processes. Specifically, ecDNA-containing tumors up-regulate DNA damage and repair, cell cycle control, and mitotic processes, but down-regulate global immune regulation pathways. Taken together, these results suggest profound alterations in gene regulation in ecDNA-containing tumors, shedding light on molecular processes that give rise to their development and progression.

Mobile mapping technologies, for example multi-sensor integration and multi-platform mapping technology, have developed and improved over recent decades, various applications such as conventional mapping scenarios, rapid disaster response, smart city, and autonomous vehicle application arise synchronously. Especially, autonomous driving vehicles have made enormous progress. High-definition (HD) maps are key for autonomous driving because of their high accuracy and rich information of road scenes. However, how to make sure that HD maps are suitable for autonomous vehicle requirement is an important topic. The HD maps guidelines and standards in Taiwan are released since 2018 and mainly focus on point cloud and shape file format. In this paper, a procedure for the verification and validation of HD maps for OpenDRIVE and Autoware (Lanelet2) is proposed. It discusses about the verification strategies, suggestion review item, recommendation tools, and process. As shown by our preliminary results, the proposed process can conform not only in closed area but also public road. These issues can help reducing HD maps production costs. When the foundation of HD maps accomplishes, the autonomous driving techniques can naturally complement. The vision of full automation vehicle will come true rapidly in the future.

Abstract Hyaluronic acid is a major component of extracellular matrix which plays an important role in development, cellular response to injury and inflammation, cell migration, and cancer. The naked mole-rat (Heterocephalus glaber) contains abundant high-molecular-mass hyaluronic acid in its tissues, which contributes to this species’ cancer resistance and possibly to its longevity. Here we report that abundant high-molecular-mass hyaluronic acid is found in a wide range of subterranean mammalian species, but not in phylogenetically related aboveground species. These subterranean mammalian species accumulate abundant high-molecular-mass hyaluronic acid by regulating the expression of genes involved in hyaluronic acid degradation and synthesis and contain unique mutations in these genes. The abundant high-molecular-mass hyaluronic acid may benefit the adaptation to subterranean environment by increasing skin elasticity and protecting from oxidative stress due to hypoxic conditions. Our work suggests that high-molecular-mass hyaluronic acid has evolved with subterranean lifestyle.

In Taiwan, map companies have to referenced the HD Maps guideline and standard which published in TAICS, Taiwan to make ensure the quality of data. The procedure costs lots of times and resources. In order to increase the capability and mileage of HD Maps, this study try to use diverse surveying method and different kinds of sources for ground control points to produce the maps. The test field is National expressway No.8 in Taiwan. With different ground control points sources issue, we measure the features as ground control points and check points from UAS orthophoto. The preliminary results show that the absolute accuracy is suitable the requirement of HD Maps guidelines. With the diverse surveying method topic, we use sensor data from autonomous vehicle and SLAM algorithms to make HD Maps. The preliminary map results can be used as a base map to accomplish the concept of ground control point cloud. It can be used as ground control point to establishment, update, and overlay other point cloud data. On the other hand, these point clouds can be provided for application of SAE Level 3 autonomous vehicle to achieve the positioning accuracy of where in lane (0.5 meter). The flexible producing methods are helpful for formulating and renewing our HD Maps guideline and standard. These experiences will improve the efficiency and integrity for making map.

The refined identification of urban functional zones can provide important basic data and decision-making basis for the formulation of urban spatial development planning, effective relaxation of urban spatial development planning, effective relaxation of urban functions, and optimal allocation of resource space. The multi-source spatiotemporal data represented by multi-source geographic data, social perception data, and thematic data have been widely used in various fields, providing new data sources for the refined identification of urban functional areas. However, there are significant differences in the data generation sources, collection methods, and storage organization formats of multi-source data. In this paper, we propose a method for exploring urban functional zones based on Multi-source Semantic knowledge and deep Coupling Model (MSCM). Our approach integrates information from multiple sources and incorporates the semantics of urban functional zones into a knowledge graph, enabling effective fusion and mining of multi-source data.This method can improve the credibility and precision of the results, providing a richer research perspective for refined urban functional zoning. The results of this paper have important theoretical value and practical significance for the construction of identification, labelling, and monitoring tools for engineering smart cities.

The Module-0 Demonstrator is a single-phase 600 kg liquid argon time projection chamber operated as a prototype for the DUNE liquid argon near detector. Based on the ArgonCube design concept, Module-0 features a novel 80k-channel pixelated charge readout and advanced high-coverage photon detection system. In this paper, we present an analysis of an eight-day data set consisting of 25 million cosmic ray events collected in the spring of 2021. We use this sample to demonstrate the imaging performance of the charge and light readout systems as well as the signal correlations between the two. We also report argon purity and detector uniformity measurements and provide comparisons to detector simulations.

Abstract Background By analyzing how health care leaders in the United States view mobile health programs and their impact on the organization’s bottom line, this study equips those who currently operate or plan to deploy mobile clinics with a business case framework. Our aim is to understand health care leaders’ perspectives about business-related incentives and disincentives for mobile healthcare. Methods We conducted 25 semi-structured key informant interviews with U.S. health care leaders to explore their views and experiences related to mobile health care. We used deductive and inductive thematic analysis to identify patterns in the data. An advisory group with expertise in mobile health, health management, and health care finance informed data collection and analysis. Results In addition to improving health outcomes, mobile clinics can bolster business objectives of health care organizations including those related to budget, business strategy, organizational culture, and health equity. We created a conceptual framework that demonstrates how these factors, supported by community engagement and data, come together to form a business case for mobile health care. Discussion Our study demonstrates that mobile clinics can contribute to health care organizations’ business goals by aligning with broader organizational strategies. The conceptual model provides a guide for aligning mobile clinics’ work with business priorities of organizations and funders. Conclusions By understanding how health care leaders reconcile the business pressures they face with opportunities to advance health equity using mobile clinics, we can better support the strategic and sustainable expansion of the mobile health sector.

Owing to the development issues of the Guangdong-Hong Kong-Macao Greater Bay Area in the new domestic and international situation, the content, challenges, and paths of innovation and development of the Greater Bay Area are explored from multiple dimensions, including economic, social, cultural, and institutional. The innovation and development of the Greater Bay Area should strengthen technological and industrial innovation capabilities, improve regional resilience to cope with external shocks, increase the mobility of intraregional factors, improve the well-being of the people's livelihood, enhance the capacity of spatial governance, promote integrated urban-rural development, and optimize the regional pattern of ecological security. The conclusion is that considering the innovation and development of the Greater Bay Area from a systemic and interconnected perspective is crucial for seeking innovations in various development fields and promoting coupling and coordination among them. Therefore, the region may acquire the agency that can continuously break through bottlenecks, resolve external shocks, and unlock new paths of development. We call for the strengthening of cross-field and cross-disciplinary collaborative research to contribute the power of geography to the realization of the development goals of the Guangdong-Hong Kong-Macao Greater Bay Area.

Abstract Background The clinical burden of Long COVID, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and other post-infectious fatiguing illnesses (PIFI) is increasing. There is a critical need to advance understanding of the effectiveness and sustainability of innovative approaches to clinical care of patients having these conditions. Methods We aim to assess the effectiveness of a Long COVID and Fatiguing Illness Recovery Program (LC&FIRP) in a two-arm, single-blind, pragmatic, quality improvement, professional cluster, randomized controlled trial in which 20 consenting clinicians across primary care clinics in a Federally Qualified Health Center system in San Diego, CA, will be randomized at a ratio of 1:1 to either participate in (1) weekly multi-disciplinary team-based case consultation and peer-to-peer sharing of emerging best practices (i.e., teleECHO (Extension for Community Healthcare Outcomes)) with monthly interactive webinars and quarterly short courses or (2) monthly interactive webinars and quarterly short courses alone (a control group); 856 patients will be assigned to participating clinicians (42 patients per clinician). Patient outcomes will be evaluated according to the study arm of their respective clinicians. Quantitative and qualitative outcomes will be measured at 3- and 6-months post-baseline for clinicians and every 3-months post assignment to a participating clinician for patients. The primary patient outcome is change in physical function measured using the Patient-Reported Outcomes Measurement Information System (PROMIS)-29. Analyses of differences in outcomes at both the patient and clinician levels will include a linear mixed model to compare change in outcomes from baseline to each post-baseline assessment between the randomized study arms. A concurrent prospective cohort study will compare the LC&FIRP patient population to the population enrolled in a university health system. Longitudinal data analysis approaches will allow us to examine differences in outcomes between cohorts. Discussion We hypothesize that weekly teleECHO sessions with monthly interactive webinars and quarterly short courses will significantly improve clinician- and patient-level outcomes compared to the control group. This study will provide much needed evidence on the effectiveness of a technology-enabled multi-disciplinary team-based care model for the management of Long COVID, ME/CFS, and other PIFI within a federally qualified health center. Trial registration ClinicalTrials.gov, NCT05167227 . Registered on December 22, 2021.

Abstract Background Definitions for massive transfusion (MT) vary widely between studies, contributing to challenges in interpretation of research findings and practice evaluation. In this first systematic review, we aimed to identify all MT definitions used in randomised controlled trials (RCTs) to date to inform the development of consensus definitions for MT. Methods We systematically searched the following databases for RCTs from inception until 11 August 2022: MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Cumulative Index to Nursing and Allied Health Literature, and Transfusion Evidence Library. Ongoing trials were sought from CENTRAL, ClinicalTrials.gov, and World Health Organisation International Clinical Trials Registry Platform. To be eligible for inclusion, studies had to fulfil all the following three criteria: (1) be an RCT; (2) include an adult patient population with major bleeding who had received, or were anticipated to receive, an MT in any clinical setting; and (3) specify a definition for MT as an inclusion criterion or outcome measure. Results Of the 8,458 distinct references identified, 30 trials were included for analysis (19 published, 11 ongoing). Trauma was the most common clinical setting in published trials, while for ongoing trials, it was obstetrics. A total of 15 different definitions of MT were identified across published and ongoing trials, varying greatly in cut-offs for volume transfused and time period. Almost all definitions specified the number of red blood cells (RBCs) within a set time period, with none including plasma, platelets or other haemostatic agents that are part of contemporary transfusion resuscitation. For completed trials, the most commonly used definition was transfusion of ≥ 10 RBC units in 24 h (9/19, all in trauma), while for ongoing trials it was 3–5 RBC units (n = 7), with the timing for transfusion being poorly defined, or in some trials not provided at all (n = 5). Conclusions Transfusion of ≥ 10 RBC units within 24 h was the most commonly used definition in published RCTs, while lower RBC volumes are being used in ongoing RCTs. Any consensus definitions should reflect the need to incorporate different blood components/products for MT and agree on whether a ‘one-size-fits-all’ approach should be used across different clinical settings.

Abstract Background High-grade serous ovarian cancers (HGSCs) display a high degree of complex genetic alterations. In this study, we identified germline and somatic genetic alterations in HGSC and their association with relapse-free and overall survival. Using a targeted capture of 557 genes involved in DNA damage response and PI3K/AKT/mTOR pathways, we conducted next-generation sequencing of DNA from matched blood and tumor tissue from 71 HGSC participants. In addition, we performed the OncoScan assay on tumor DNA from 61 participants to examine somatic copy number alterations (SCNA). Results Approximately one-third of tumors had loss-of-function (LOF) germline (18/71, 25.4%) or somatic (7/71, 9.9%) variants in the DNA homologous recombination repair pathway genes BRCA1, BRCA2, CHEK2, MRE11A, BLM, and PALB2. LOF germline variants also were identified in other Fanconi anemia genes and in MAPK and PI3K/AKT/mTOR pathway genes. Most tumors harbored somatic TP53 variants (65/71, 91.5%). Using the OncoScan assay on tumor DNA from 61 participants, we identified focal homozygous deletions in BRCA1, BRCA2, MAP2K4, PTEN, RB1, SLX4, STK11, CREBBP, and NF1. In total, 38% (27/71) of HGSC patients harbored pathogenic variants in DNA homologous recombination repair genes. For patients with multiple tissues from the primary debulking or from multiple surgeries, the somatic mutations were maintained with few newly acquired point mutations suggesting that tumor evolution was not through somatic mutations. There was a significant association of LOF variants in homologous recombination repair pathway genes and high-amplitude somatic copy number alterations. Using GISTIC analysis, we identified NOTCH3, ZNF536, and PIK3R2 in these regions that were significantly associated with an increase in cancer recurrence and a reduction in overall survival. Conclusions From 71 patients with HGCS, we performed targeted germline and tumor sequencing and provided a comprehensive analysis of these 557 genes. We identified germline and somatic genetic alterations including somatic copy number alterations and analyzed their associations with relapse-free and overall survival. This single-site long-term follow-up study provides additional information on genetic alterations related to occurrence and outcome of HGSC. Our findings suggest that targeted treatments based on both variant and SCNA profile potentially could improve relapse-free and overall survival.

Abstract The Pandora Software Development Kit and algorithm libraries provide pattern-recognition logic essential to the reconstruction of particle interactions in liquid argon time projection chamber detectors. Pandora is the primary event reconstruction software used at ProtoDUNE-SP, a prototype for the Deep Underground Neutrino Experiment far detector. ProtoDUNE-SP, located at CERN, is exposed to a charged-particle test beam. This paper gives an overview of the Pandora reconstruction algorithms and how they have been tailored for use at ProtoDUNE-SP. In complex events with numerous cosmic-ray and beam background particles, the simulated reconstruction and identification efficiency for triggered test-beam particles is above 80% for the majority of particle type and beam momentum combinations. Specifically, simulated 1 GeV/c charged pions and protons are correctly reconstructed and identified with efficiencies of 86.1 $$\pm 0.6$$ ± 0.6 % and 84.1 $$\pm 0.6$$ ± 0.6 %, respectively. The efficiencies measured for test-beam data are shown to be within 5% of those predicted by the simulation.

Objective: In robot-assisted minimally invasive surgery, proper port positioning ensures that surgical tools have adequate access to the surgical site and avoids mid-surgery collisions of robotic arms. To date, several guidelines have been proposed for more accurate port placement. However, challenges remain due to variations in patient morphology, anatomy, and, in particular, organ displacement due to insufflation in certain laparoscopic procedures. The objective of this study was to design and develop a decision aid for optimal port placement in robot-assisted hysterectomy that accounts for patient variability and organ displacement due to insufflation. Methods: Three components were constructed: a robot model, a patient-specific model, and an optimization algorithm. The three components were integrated, and the system was verified using four different patients who underwent robotic hysterectomy. Once verified, two expert surgeons were asked to evaluate the decision aid for face and construct validity. A usability test was conducted using a torso phantom with target organs located in three different locations. Two expert surgeons performed a simulated hysterectomy task with and without the decision aid to evaluate performance and satisfaction. Results: The optimization algorithm was sensitive to individual differences in anatomy in the four patients. Expert surgeons successfully established face and construct validity. Usability test results showed a 28%–40% reduction in time to task completion with the optimized ports compared to expert-determined port locations without using the decision aid. Conclusions: The decision aid, based on an individualized patient-specific model, robot model, and optimization algorithm, was shown to be effective at addressing the challenges of displaced organs due to insufflation in robot-assisted hysterectomy. The face and construct validity of the decision aid was established by expert surgeons, while efficiency gains in task performance were demonstrated experimentally.

Translational science is the cornerstone of biomedicine that transfers laboratory and clinical research to the hospital bedside in various forms of therapeutic interventions. This scientific branch influences public health decisions, the economy, and ongoing research endeavors. The purpose of this study was to develop a youth-friendly Translational Science course that introduced students to translational science concepts, then examine course outcomes and effects on career choices. The seminar course involved 18-contact hours with 20 high-school juniors (n=10 / Summer 2016 & Summer 2017). The curriculum encompassed the fundamentals of the five translational science phases as well as how to understand scientific readings and conduct efficient research database searches. A concluding student-presentation on a topic of the student's choosing ensured each student had a sufficient understanding of translational science, use of PubMed for original research articles, and demonstrated the student's ability to apply the concepts individually. Analysis of end-of-course and follow-up surveys showed that the majority of students understood the material, felt the course met their expectations and influenced long-term professional goals. These data suggest that exposing students earlier in their career (pre-collegiate) to the importance and structure of translational science could have long-term benefits towards influencing career choices in STEM.