Machine Learning Models for Parkinson Disease: Systematic Review.

Background: With the increasing availability of data, computing resources, and easier-to-use software libraries, machine learning (ML) is increasingly used in disease detection and prediction, including for Parkinson disease (PD). Despite the large number of studies published every year, very few ML systems have been adopted for real-world use. In particular, a lack of external validity may result in poor performance of these systems in clinical practice. Additional methodological issues in ML design and reporting can also hinder clinical adoption, even for applications that would benefit from such data-driven systems. Objective: To sample the current ML practices in PD applications, we conducted a systematic review of studies published in 2020 and 2021 that used ML models to diagnose PD or track PD progression. Methods: We conducted a systematic literature review in accordance with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines in PubMed between January 2020 and April 2021, using the following exact string: "Parkinson's" AND ("ML" OR "prediction" OR "classification" OR "detection" or "artificial intelligence" OR "AI"). The search resulted in 1085 publications. After a search query and review, we found 113 publications that used ML for the classification or regression-based prediction of PD or PD-related symptoms. Results: Only 65.5% (74/113) of studies used a holdout test set to avoid potentially inflated accuracies, and approximately half (25/46, 54%) of the studies without a holdout test set did not state this as a potential concern. Surprisingly, 38.9% (44/113) of studies did not report on how or if models were tuned, and an additional 27.4% (31/113) used ad hoc model tuning, which is generally frowned upon in ML model optimization. Only 15% (17/113) of studies performed direct comparisons of results with other models, severely limiting the interpretation of results. Conclusions: This review highlights the notable limitations of current ML systems and techniques that may contribute to a gap between reported performance in research and the real-life applicability of ML models aiming to detect and predict diseases such as PD.

Early Prediction of Poststroke Rehabilitation Outcomes Using Wearable Sensors.

OBJECTIVE: Inpatient rehabilitation represents a critical setting for stroke treatment, providing intensive, targeted therapy and task-specific practice to minimize a patient's functional deficits and facilitate their reintegration into the community. However, impairment and recovery vary greatly after stroke, making it difficult to predict a patient's future outcomes or response to treatment. In this study, the authors examined the value of early-stage wearable sensor data to predict 3 functional outcomes (ambulation, independence, and risk of falling) at rehabilitation discharge. METHODS: Fifty-five individuals undergoing inpatient stroke rehabilitation participated in this study. Supervised machine learning classifiers were retrospectively trained to predict discharge outcomes using data collected at hospital admission, including patient information, functional assessment scores, and inertial sensor data from the lower limbs during gait and/or balance tasks. Model performance was compared across different data combinations and was benchmarked against a traditional model trained without sensor data. RESULTS: For patients who were ambulatory at admission, sensor data improved the predictions of ambulation and risk of falling (with weighted F1 scores increasing by 19.6% and 23.4%, respectively) and maintained similar performance for predictions of independence, compared to a benchmark model without sensor data. The best-performing sensor-based models predicted discharge ambulation (community vs household), independence (high vs low), and risk of falling (normal vs high) with accuracies of 84.4%, 68.8%, and 65.9%, respectively. Most misclassifications occurred with admission or discharge scores near the classification boundary. For patients who were nonambulatory at admission, sensor data recorded during simple balance tasks did not offer predictive value over the benchmark models. CONCLUSION: These findings support the continued investigation of wearable sensors as an accessible, easy-to-use tool to predict the functional recovery after stroke. IMPACT: Accurate, early prediction of poststroke rehabilitation outcomes from wearable sensors would improve our ability to deliver personalized, effective care and discharge planning in the inpatient setting and beyond.

Influences of 23 different equations used to calculate gene copies of SARS-CoV-2 during wastewater-based epidemiology.

Following the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in late 2019, the use of wastewater-based surveillance (WBS) has increased dramatically along with associated infrastructure globally. However, due to the global nature of its application, and various workflow adaptations (e.g., sample collection, water concentration, RNA extraction kits), numerous methods for back-calculation of gene copies per volume (gc/L) of sewage have also emerged. Many studies have considered the comparability of processing methods (e.g., water concentration, RNA extraction); however, for equations used to calculate gene copies in a wastewater sample and subsequent influences on monitoring viral trends in a community and its association with epidemiological data, less is known. Due to limited information on how many formulas exist for the calculation of SARS-CoV-2 gene copies in wastewater, we initially attempted to quantify how many equations existed in the referred literature. We identified 23 unique equations, which were subsequently applied to an existing wastewater dataset. We observed a range of gene copies based on use of different equations, along with variability of AUC curve values, and results from correlation and regression analyses. Though a number of individual laboratories appear to have independently converged on a similar formula for back-calculation of viral load in wastewater, and share similar relationships with epidemiological data, differential influences of various equations were observed for variation in PCR volumes, RNA extraction volumes, or PCR assay parameters. Such observations highlight challenges when performing comparisons among WBS studies when numerous methodologies and back-calculation methods exist. To facilitate reproducibility among studies, the different gc/L equations were packaged as an R Shiny app, which provides end users the ability to investigate variability within their datasets and support comparisons among studies.

Validation of Proprietary and Novel Step-counting Algorithms for Individuals Ambulating With a Lower Limb Prosthesis.

OBJECTIVE: To compare the accuracy and reliability of 10 different accelerometer-based step-counting algorithms for individuals with lower limb loss, accounting for different clinical characteristics and real-world activities. DESIGN: Cross-sectional study. SETTING: General community setting (ie, institutional research laboratory and community free-living). PARTICIPANTS: Forty-eight individuals with a lower limb amputation (N=48) wore an ActiGraph (AG) wGT3x-BT accelerometer proximal to the foot of their prosthetic limb during labeled indoor/outdoor activities and community free-living. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Intraclass correlation coefficient (ICC), absolute and root mean square error (RMSE), and Bland Altman plots were used to compare true (manual) step counts to estimated step counts from the proprietary AG Default algorithm and low frequency extension filter, as well as from 8 novel algorithms based on continuous wavelet transforms, fast Fourier transforms (FFTs), and peak detection. RESULTS: All algorithms had excellent agreement with manual step counts (ICC>0.9). The AG Default and FFT algorithms had the highest overall error (RMSE=17.81 and 19.91 steps, respectively), widest limits of agreement, and highest error during outdoor and ramp ambulation. The AG Default algorithm also had among the highest error during indoor ambulation and stairs, while a FFT algorithm had the highest error during stationary tasks. Peak detection algorithms, especially those using pre-set parameters with a trial-specific component, had among the lowest error across all activities (RMSE=4.07-8.99 steps). CONCLUSIONS: Because of its simplicity and accuracy across activities and clinical characteristics, we recommend the peak detection algorithm with set parameters to count steps using a prosthetic-worn AG among individuals with lower limb loss for clinical and research applications.

AI in Rehabilitation Medicine: Opportunities and Challenges.

Artificial intelligence (AI) tools are increasingly able to learn from larger and more complex data, thus allowing clinicians and scientists to gain new insights from the information they collect about their patients every day. In rehabilitation medicine, AI can be used to find patterns in huge amounts of healthcare data. These patterns can then be leveraged at the individual level, to design personalized care strategies and interventions to optimize each patient's outcomes. However, building effective AI tools requires many careful considerations about how we collect and handle data, how we train the models, and how we interpret results. In this perspective, we discuss some of the current opportunities and challenges for AI in rehabilitation. We first review recent trends in AI for the screening, diagnosis, treatment, and continuous monitoring of disease or injury, with a special focus on the different types of healthcare data used for these applications. We then examine potential barriers to designing and integrating AI into the clinical workflow, and we propose an end-to-end framework to address these barriers and guide the development of effective AI for rehabilitation. Finally, we present ideas for future work to pave the way for AI implementation in real-world rehabilitation practices.

Protocol for a randomized controlled trial to evaluate a year-long (NICU-to-home) evidence-based, high dose physical therapy intervention in infants at risk of neuromotor delay.

INTRODUCTION: Developmental disabilities and neuromotor delay adversely affect long-term neuromuscular function and quality of life. Current evidence suggests that early therapeutic intervention reduces the severity of motor delay by harnessing neuroplastic potential during infancy. To date, most early therapeutic intervention trials are of limited duration and do not begin soon after birth and thus do not take full advantage of early neuroplasticity. The Corbett Ryan-Northwestern-Shirley Ryan AbilityLab-Lurie Children's Infant Early Detection, Intervention and Prevention Project (Project Corbett Ryan) is a multi-site longitudinal randomized controlled trial to evaluate the efficacy of an evidence-based physical therapy intervention initiated in the neonatal intensive care unit (NICU) and continuing to 12 months of age (corrected when applicable). The study integrates five key principles: active learning, environmental enrichment, caregiver engagement, a strengths-based approach, and high dosage (ClinicalTrials.gov identifier NCT05568264). METHODS: We will recruit 192 infants at risk for neuromotor delay who were admitted to the NICU. Infants will be randomized to either a standard-of-care group or an intervention group; infants in both groups will have access to standard-of-care services. The intervention is initiated in the NICU and continues in the infant's home until 12 months of age. Participants will receive twice-weekly physical therapy sessions and caregiver-guided daily activities, assigned by the therapist, targeting collaboratively identified goals. We will use various standardized clinical assessments (General Movement Assessment; Bayley Scales of Infant and Toddler Development, 4th Edition (Bayley-4); Test of Infant Motor Performance; Pediatric Quality of Life Inventory Family Impact Module; Alberta Infant Motor Scale; Neurological, Sensory, Motor, Developmental Assessment; Hammersmith Infant Neurological Examination) as well as novel technology-based tools (wearable sensors, video-based pose estimation) to evaluate neuromotor status and development throughout the course of the study. The primary outcome is the Bayley-4 motor score at 12 months; we will compare scores in infants receiving the intervention vs. standard-of-care therapy.

Applying machine learning to consumer wearable data for the early detection of complications after pediatric appendectomy.

When children are discharged from the hospital after surgery, their caregivers often rely on subjective assessments (e.g., appetite, fatigue) to monitor postoperative recovery as objective assessment tools are scarce at home. Such imprecise and one-dimensional evaluations can result in unwarranted emergency department visits or delayed care. To address this gap in postoperative monitoring, we evaluated the ability of a consumer-grade wearable device, Fitbit, which records multimodal data about daily physical activity, heart rate, and sleep, in detecting abnormal recovery early in children recovering after appendectomy. One hundred and sixty-two children, ages 3-17 years old, who underwent an appendectomy (86 complicated and 76 simple cases of appendicitis) wore a Fitbit device on their wrist for 21 days postoperatively. Abnormal recovery events (i.e., abnormal symptoms or confirmed postoperative complications) that arose during this period were gathered from medical records and patient reports. Fitbit-derived measures, as well as demographic and clinical characteristics, were used to train machine learning models to retrospectively detect abnormal recovery in the two days leading up to the event for patients with complicated and simple appendicitis. A balanced random forest classifier accurately detected 83% of these abnormal recovery days in complicated appendicitis and 70% of abnormal recovery days in simple appendicitis prior to the true report of a symptom/complication. These results support the development of machine learning algorithms to predict onset of abnormal symptoms and complications in children undergoing surgery, and the use of consumer wearables as monitoring tools for early detection of postoperative events.

Experiences of transgender and gender diverse patients in emergency psychiatric settings: A scoping review.

Objective: This scoping review aims to characterize what is known about transgender and gender diverse (TGD) individuals in emergency psychiatric settings and identify what gaps persist in this literature. Methods: A search of 4 electronic databases (PubMed, Web of Science, GenderWatch, and PsycINFO) was used for data collection. Included were studies that looked at TGD individuals presenting to a psychiatric emergency department (ED) or ED with a primary mental health concern. Study screening progress was documented in a Preferred Reporting Items for Systematic reviews and Meta-Analyses flow chart. A total of 232 titles and abstracts were screened, 38 full texts were evaluated for eligibility, and 10 studies were included. Results: The studies reviewed identified mental health vulnerabilities unique to the TGD population, including service denial in health care settings, gender dysphoria, increased rates of non-suicidal self-injury, and in some studies an increase in suicidality. Societal inequities, including the risk of discrimination and residential instability, were also revealed. A subset of the studies identified best practices in caring for this population, including the use of non-judgmental, affirmative, and inclusive language, and on a structural level creating emergency environments that are confidential, inclusive, and therapeutic for these individuals. Conclusions: There is limited information on TGD individuals in emergency psychiatric settings, and thus it is difficult to form strong conclusions. However, the current evidence available suggests possible inequities in this population. Three major themes with regards to TGD individuals in emergency psychiatric settings were identified: mental health vulnerabilities, societal inequities, and best practices in caring for this population. Overall, there is a scarcity of literature in this field, and further research on the experiences of this population is needed to inform clinical practice.

Validity and reliability of a commercial wearable sensor system for measuring spatiotemporal gait parameters in a post-stroke population: the effects of walking speed and asymmetry.

Objective.Commercial wearable sensor systems are a promising alternative to costly laboratory equipment for clinical gait evaluation, but their accuracy for individuals with gait impairments is not well established. Therefore, we investigated the validity and reliability of the APDM Opal wearable sensor system to measure spatiotemporal gait parameters for healthy controls and individuals with chronic stroke.Approach.Participants completed the 10 m walk test over an instrumented mat three times in different speed conditions. We compared performance of Opal sensors to the mat across different walking speeds and levels of step length asymmetry in the two populations.Main results. Gait speed and stride length measures achieved excellent reliability, though they were systematically underestimated by 0.11 m s-1and 0.12 m, respectively. The stride and step time measures also achieved excellent reliability, with no significant errors (median absolute percentage error <6.00%,p> 0.05). Gait phase duration measures achieved moderate-to-excellent reliability, with relative errors ranging from 4.13%-21.59%. Across gait parameters, the relative error decreased by 0.57%-9.66% when walking faster than 1.30 m s-1; similar reductions occurred for step length symmetry indices lower than 0.10.Significance. This study supports the general use of Opal wearable sensors to obtain quantitative measures of post-stroke gait impairment. These measures should be interpreted cautiously for individuals with moderate-severe asymmetry or walking speeds slower than 0.80 m s-1.

Assessing the impact and resource implications of contrast-enhanced ultrasound on workflow of patients with incidental focal liver lesions on the UK national health service.

Background: Focal liver lesions (FLL) are abnormal growths that require timely identification. Contrast-enhanced ultrasound (CEUS) is a cost-effective imaging modality for characterising FLL with similar sensitivity to computed tomography (CT) and magnetic resonance imaging (MRI). Despite being recommended by NICE, its adoption within the national health service (NHS) is limited due to low clinical demand, limited referral, and lack of knowledge. Purpose: To evaluate the impact of CEUS on patients with incidental FLL and assess the resource implications of introducing CEUS as a diagnostic service within the NHS. Material and methods: A patient flow review and cost-minimisation analysis were conducted. This involved a targeted literature review, NHS Trust stakeholder consultations, and development of a Microsoft Excel cost-minimisation model to explore potential value of CEUS use versus CT and MRI by episode. A scenario analysis of the base-case explored increasing CEUS use to 50% and 90%. A sensitivity analysis was performed to assess how changes in assumptions impacted the model and the resulting cost estimates. Results: The model, comparing a world with and without CEUS, showed that current use (base-case: 5%) resulted in cost savings of £224,790/year. The sensitivity analysis indicated that regardless of changes to the assumptions, CEUS still resulted in cost savings to the NHS. By increasing CEUS use to 50% and 90%, cost savings of up to £2,247,894/year and £4,046,208/year could be achieved, respectively. Conclusion: By standardising CEUS use for characterising FLL, substantial cost savings could be realised, whilst reducing wait times and expanding diagnostic capacity, thus preserving limited CT and MRI capacity for high-priority cases.

Unmet needs in uncomplicated urinary tract infection in the United States and Germany: a physician survey.

BACKGROUND: Uncomplicated urinary tract infections (uUTIs/acute cystitis) are among the most common infections in women worldwide. There are differences in uUTI treatment guidelines between countries and understanding the needs of physicians in diverse healthcare systems is important for developing new treatments. We performed a survey of physicians in the United States (US) and Germany to understand their perceptions of, and management approaches to uUTI. METHODS: This was a cross-sectional online survey of physicians in the US and Germany who were actively treating patients with uUTI (≥ 10 patients/month). Physicians were recruited via a specialist panel and the survey was piloted with 2 physicians (1 US, 1 Germany) prior to study commencement. Data were analyzed with descriptive statistics. RESULTS: A total of 300 physicians were surveyed (n = 200 US, n = 100 Germany). Across countries and specialties, physicians estimated 16-43% of patients did not receive complete relief from initial therapy and 33-37% had recurrent infections. Urine culture and susceptibility testing was more common in the US and among urologists. The most commonly selected first-line therapy was trimethoprim-sulfamethoxazole in the US (76%) and fosfomycin in Germany (61%). Ciprofloxacin was the most selected following multiple treatment failures (51% US, 45% Germany). Overall, 35% of US and 45% of German physicians agreed with the statement "I feel there is a good selection of treatment options" and ≥ 50% felt that current treatments provided good symptom relief. More than 90% of physicians included symptom relief amongst their top 3 treatment goals. The overall impact of symptoms on patients' lives was rated "a great deal" by 51% of US and 38% of German physicians, increasing with each treatment failure. Most physicians (> 80%) agreed that antimicrobial resistance (AMR) is serious, but fewer (56% US, 46% Germany) had a high level of confidence in their knowledge of AMR. CONCLUSIONS: Treatment goals for uUTI were similar in the US and Germany, although with nuances to disease management approaches. Physicians recognized that treatment failures have a significant impact on patients' lives and that AMR is a serious problem, though many did not have confidence in their own knowledge of AMR.

Examination of physical activity development in early childhood: protocol for a longitudinal cohort study of mother-toddler dyads.

BACKGROUND: Physical activity (PA) development in toddlers (age 1 and 2 years) is not well understood, partly because of a lack of analytic tools for accelerometer-based data processing that can accurately evaluate PA among toddlers. This has led to a knowledge gap regarding how parenting practices around PA, mothers' PA level, mothers' parenting stress, and child developmental and behavioral problems influence PA development in early childhood. METHODS: The Child and Mother Physical Activity Study is a longitudinal study to observe PA development in toddlerhood and examine the influence of personal and parental characteristics on PA development. The study is designed to refine and validate an accelerometer-based machine learning algorithm for toddler activity recognition (Aim 1), apply the algorithm to compare the trajectories of toddler PA levels in males and females age 1-3 years (Aim 2), and explore the association between gross motor development and PA development in toddlerhood, as well as how parenting practices around PA, mothers' PA, mothers' parenting stress, and child developmental and behavioral problems are associated with toddlerhood PA development (Exploratory Aims 3a-c). DISCUSSION: This study will be one of the first to use longitudinal data to validate a machine learning activity recognition algorithm and apply the algorithm to quantify free-living ambulatory movement in toddlers. The study findings will help fill a significant methodological gap in toddler PA measurement and expand the body of knowledge on the factors influencing early childhood PA development.

Effect of Transcranial Direct Current Stimulation versus Virtual Reality on Gait for Children with Bilateral Spastic Cerebral Palsy: A Randomized Clinical Trial.

Impaired gait is a common sequela in bilateral spastic cerebral palsy. We compared the effects of two novel research interventions-transcranial direct current stimulation and virtual reality-on spatiotemporal and kinetic gait impairments in children with bilateral spastic CP. Forty participants were randomized to receive either transcranial direct current stimulation or virtual reality training. Both groups received standard-of-care gait therapy during the assigned intervention and for the subsequent 10 weeks afterward. Spatiotemporal and kinetic gait parameters were evaluated at three different times: (i) before starting the intervention, (ii) after two weeks of intervention, and (iii) 10 weeks after intervention completion. Both groups exhibited higher velocity and cadence, as well as longer stance time, step length, and stride length after intervention (p < 0.001). Only the transcranial direct current stimulation group exhibited increased maximum force and maximum peak pressure after intervention (p's ≤ 0.001), with continued improvements in spatiotemporal parameters at follow-up. The transcranial direct current stimulation group had higher gait velocities, stride length, and step length at follow-up compared to the virtual reality group (p ≤ 0.02). These findings suggest that transcranial direct current stimulation has a broader and longer-lasting effect on gait than virtual reality training for children with bilateral spastic cerebral palsy.

An intrasplenic injection model of pancreatic cancer metastasis to the liver in mice.

Here, we provide a protocol for an intrasplenic injection model to establish pancreatic tumors in the mouse liver. We describe the steps to inject tumor cells into mouse spleen and to perform a splenectomy, followed by animal recovery and end point analysis of tumors in the liver. This model allows rapid and reproducible tumor growth in a clinically relevant metastatic site, providing a platform to evaluate the efficacy of anti-cancer drugs. This technique can be expanded to other cancer cell lines. For complete details on the use and execution of this protocol, please refer to Poh et al. (2022).1.

A Cross-Sectional Examination of Educational Expectation Among Welfare Users in an Asset Building Program.

The Children's Savings Accounts (CSAs) program, an asset-building intervention, has gained increasing attention for its potential to elevate low-in families' education expectations, college enrollment, and completion. Variations in program enrollment policy can lead to different levels of program participation among vulnerable populations. This paper examines the enrollment policy of one of the oldest CSA programs and explores program participation among a financially vulnerable group-welfare users. While welfare users were 43% less likely to expect their children to attend college, those who enrolled in the CSA program were about two times more likely to expect their children to go to college than welfare users who did not participate in the program. Findings shed light on research and policies that facilitate asset-building efforts among vulnerable populations and encourage visioning CSAs a potential drive for better financial inclusion.

Rationalising pre-operative trauma bloods can lead to significant cost savings.

BACKGROUND: A full set of pre-operative bloods is being done on nearly all trauma patients who are admitted to our institute for surgery-regardless of variables such as patient age, injury sustained, or co-morbidities. This leads to unnecessary bloods being taken. AIMS: The primary aims are (1) to calculate the costs associated with routine pre-operative bloods and (2) to examine how much money could be saved by retrospectively applying a more pragmatic pre-operative bloods policy. METHODS: Trauma theatre cases over a 5-week period were identified with their pre-operative bloods and post-operative transfusions. Labour, material, and processing costs were estimated for each test. An updated pre-operative blood schedule was proposed and applied retrospectively to see if cost savings could be found. RESULTS: Of the 173 orthopaedic procedures performed, 109 (63%) had a group and screen or crossmatch pre-operatively. Fifteen (8.6%) required a post-operative blood transfusion. One hundred and twenty-eight (74%) patients had a full blood count, and renal profile taken pre-operatively. A full set of bloods costs approximately €51.23 to take and process. When the updated pre-operative blood guidelines were retrospectively applied, it would have led to cost savings of €2496 over the 5-week period of this audit, and if extrapolated up to 1 year, could lead to potential annual savings of €25,960. CONCLUSIONS: We have demonstrated that an excessive amount of unnecessary pre-operative bloods have been taken using the current blood schedule. A pragmatic pre-operative blood schedule can lead to significant actual cost savings.

Tumor Growth Remains Refractory to Myc Ablation in Host Macrophages.

Aberrant expression of the oncoprotein c-Myc (Myc) is frequently observed in solid tumors and is associated with reduced overall survival. In addition to well-recognized cancer cell-intrinsic roles of Myc, studies have also suggested tumor-promoting roles for Myc in cells of the tumor microenvironment, including macrophages and other myeloid cells. Here, we benchmark Myc inactivation in tumor cells against the contribution of its expression in myeloid cells of murine hosts that harbor endogenous or allograft tumors. Surprisingly, we observe that LysMCre-mediated Myc ablation in host macrophages does not attenuate tumor growth regardless of immunogenicity, the cellular origin of the tumor, the site it develops, or the stage along the tumor progression cascade. Likewise, we find no evidence for Myc ablation to revert or antagonize the polarization of alternatively activated immunosuppressive macrophages. Thus, we surmise that systemic targeting of Myc activity may confer therapeutic benefits primarily through limiting Myc activity in tumor cells rather than reinvigorating the anti-tumor activity of macrophages.

Inhibition of HCK in myeloid cells restricts pancreatic tumor growth and metastasis.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with a low 5-year survival rate and is associated with poor response to therapy. Elevated expression of the myeloid-specific hematopoietic cell kinase (HCK) is observed in PDAC and correlates with reduced patient survival. To determine whether aberrant HCK signaling in myeloid cells is involved in PDAC growth and metastasis, we established orthotopic and intrasplenic PDAC tumors in wild-type and HCK knockout mice. Genetic ablation of HCK impaired PDAC growth and metastasis by inducing an immune-stimulatory endotype in myeloid cells, which in turn reduced the desmoplastic microenvironment and enhanced cytotoxic effector cell infiltration. Consequently, genetic ablation or therapeutic inhibition of HCK minimized metastatic spread, enhanced the efficacy of chemotherapy, and overcame resistance to anti-PD1, anti-CTLA4, or stimulatory anti-CD40 immunotherapy. Our results provide strong rationale for HCK to be developed as a therapeutic target to improve the response of PDAC to chemo- and immunotherapy.

Physical Activity among U.S. Preschool-Aged Children: Application of Machine Learning Physical Activity Classification to the 2012 National Health and Nutrition Examination Survey National Youth Fitness Survey.

Early childhood is an important development period for establishing healthy physical activity (PA) habits. The objective of this study was to evaluate PA levels in a representative sample of U.S. preschool-aged children. The study sample included 301 participants (149 girls, 3-5 years of age) in the 2012 U.S. National Health and Examination Survey National Youth Fitness Survey. Participants were asked to wear an ActiGraph accelerometer on their wrist for 7 days. A machine learning random forest classification algorithm was applied to accelerometer data to estimate daily time spent in moderate- and vigorous-intensity PA (MVPA; the sum of minutes spent in running, walking, and other moderate- and vigorous-intensity PA) and total PA (the sum of MVPA and light-intensity PA). We estimated that U.S. preschool-aged children engaged in 28 min/day of MVPA and 361 min/day of total PA, on average. MVPA and total PA levels were not significantly different between males and females. This study revealed that U.S. preschool-aged children engage in lower levels of MVPA and higher levels of total PA than the minimum recommended by the World Health Organization.