LC-MS/MS Analysis to Study the Ubiquitin-Modified Proteome of Recombinant Chinese Hamster Ovary Cells.

Ubiquitination is one of the most important post-translational modifications (PTMs) and involves the covalent attachment of ubiquitin to a lysine residue on a target protein. Despite ubiquitination playing a crucial role in regulating cellular processes, the ubiquitinated proteome has not been studied extensively in recombinant Chinese hamster ovary (CHO) cells. Moreover, ubiquitination modification in CHO cells is likely to have an impact on protein function related to the efficient productivity of biopharmaceuticals. In this chapter, we describe a comprehensive protocol for ubiquitin di-Glycine (diGly) peptide enrichment using an immunoprecipitation method from recombinant CHO cell proteins followed by Liquid chromatography-Mass spectrometry (LC-MS) analysis of the ubiquitinated proteome. The methods described are also applicable to differential ubiquitinated proteomic studies.

VTE rates and risk factors in major trauma patients.

BACKGROUND: Venous thromboembolism (VTE) is a common and in some instances life-threatening complication following severe traumatic injury. Owing to a lack of high-quality evidence in VTE risk prediction and prevention in this cohort, major trauma patients receive variable VTE preventative care. The aim of this systematic review was to determine the reported rates of VTE in major trauma patients, and associated risk factors. METHODS: A comprehensive database search was conducted using EBSCO/MEDLINE, EMBASE, CINAHL, Cochrane and Scopus to identify studies published between 1990 and 2023. Original Studies quantifying the occurrence of and/or evaluating risk factors for VTE, PE and DVT in a defined population were eligible for inclusion. Five reviewers screened, appraised, and extracted data from the selected studies. RESULTS: A total of 22 studies fulfilled the inclusion criteria. Most studies were conducted in Northern America (72 %), followed by Asia (18 %), and Europe (9 %). Of the 22 studies, 17 were retrospective, 4 were prospective and 1 was the control arm of an RCT. The reported rates in included studies ranged from 0.39 % to 32 % (VTE), 0.59 % to 57.60 % (DVT) and 0.35 % to 24.0 % (PE). Operative procedure was the most consistently reported associated variable for DVT followed by delays to prophylaxis and pelvic injury. Lower extremity injury was the most frequently reported associated variable for PE followed by male sex and increased age. Age was the most frequently reported variable for both DVT and PE. CONCLUSION: There exists significant variation in the reported rates of VTE in major trauma patients globally. Operative procedure, delays to prophylaxis and pelvic injury were the most consistently reported associated variables for DVT. Lower extremity injury followed by male sex and increased age were the most frequently reported associated variables for PE. Although studies indicate possible differences in risk factors for DVT and PE, heterogeneity in study characteristics and outcome reporting impedes any meaningful conclusions. Reconciliation of VTE rates in major trauma patients is necessary when comparing populations.

Greenwashed Cigarette Ad Text and Imagery Produce Inaccurate Harm, Addictiveness, and Nicotine Content Perceptions: Results from a Randomized Online Experiment.

INTRODUCTION: The tobacco industry has a long history of circumventing regulations to present their products, inaccurately, as less harmful. Greenwashing (portraying a product as natural/eco-friendly) is increasingly used by tobacco companies and may mislead consumers to believe that certain cigarettes are less harmful than others. This study assesses the effect of some common greenwashing tactics on consumer product perceptions. METHODS: We conducted an online experiment with 1,504 participants ages 18-29, randomized to view a cigarette ad manipulated for presence/absence of a combination of 4 different greenwashing techniques: greenwashed ad text, greenwashed ad imagery, recycled paper ad background, and image of greenwashed cigarette pack. Participants rated perceived absolute harm, relative harm to other cigarettes, absolute addictiveness, relative addictiveness, and relative nicotine content. RESULTS: Participants who viewed ads containing greenwashed text were more likely to have inaccurate perceptions about absolute harm (AOR=1.72), relative harm (AOR=3.92), relative addictiveness (AOR=2.93) and nicotine content (AOR=2.08). Participants who viewed ads containing greenwashed imagery were more likely to have inaccurate perceptions of relative harm (AOR=1.55), absolute addictiveness (AOR=1.72), relative addictiveness (AOR=1.60) and nicotine content (AOR=1.48). Forty-two percent of those who saw an ad with all greenwashed features believed the product was less harmful than other cigarettes vs. 2% of those who saw an ad without greenwashed features. CONCLUSIONS: We found greenwashed text and imagery produced inaccurate risk perceptions. More active U.S. Food & Drug Administration (FDA) enforcement against such greenwashing and new FDA rulemaking to prohibit unnecessary imagery in tobacco advertising and establish plain packaging requirements would help protect consumers and public health. IMPLICATIONS: These findings provide evidence that greenwashing tactics used by the tobacco industry increase inaccurate product risk perceptions. These tactics could be a way for the industry to make implicit modified risk claims, despite applicable U.S. Family Smoking Prevention and Tobacco Control Act prohibitions. Findings from this study support the need for prohibitions on these tactics, and the potential for such prohibitions to help protect public health.

Effects of Immunotherapy on Quality-of-Life Outcomes in Patients with Gastroesophageal Cancers: A Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have revolutionized cancer care, with increasing data demonstrating improved survival outcomes using ICIs among patients with advanced gastroesophageal cancer (GEC). ICIs are also associated with a lower incidence of grade ≥ 3 adverse events (AEs) compared to chemotherapy, suggesting that ICIs may have favorable effects on health-related quality of life (HRQoL). This meta-analysis sought to evaluate the effects of ICIs on the HRQoL of patients with advanced GEC. METHODS: We conducted an online bibliographic search on Medline via PubMed using MeSH-based terms to retrieve randomized controlled trials (RCTs) that evaluated the effects of ICIs on HRQoL in patients with advanced GEC (we searched for all studies between 2018 and 2021). We included RCTs that incorporated ICIs as part of the intervention arm either as monotherapy (first or second line) or as a combination therapy (first-line) with another ICI or chemotherapy. We combined the HRQoL measures into a meta-analysis using standard random effects models, from which estimates of the average mean difference (MD) were obtained with 95% confidence intervals. We assessed the heterogeneity of the study outcomes using the Q and I2 statistics. RESULTS: We identified 11 phase 3 RCTs that met the inclusion criteria, with a mean enrollment of 820 patients. Eight RCTs used an ICI plus chemotherapy combination in the intervention arm, three had ICIs as monotherapy, and one had doublet ICI therapy in the intervention arm. All RCTs used chemotherapy for the control arm. Collectively, the trials reported 37 HRQoL measures using five different HRQoL tools. The pooled analysis favored the intervention over the control arm in terms of the Functional Assessment of Cancer Therapy-Esophageal (FACT-E) scores [MD 2.7 (95% CI 0.1 to 5.3), p < 0.041]. In a subgroup analysis of eight RCTs comparing combination therapy with ICIs plus chemotherapy versus chemotherapy alone, the effect estimates favored the ICI arm regarding the FACT-E [MD 2.7 (95% CI 0.1 to 5.3), p < 0.041] and the EORTC QLQ-OES18 pain scale [MD -2.2 (95% CI -4.3 to -0.2), p < 0.030]. Likewise, the effect estimates favored the ICI monotherapy arm over the chemotherapy arm regarding the QLQ-STO22 hair loss subscale [MD -23.2 (95% CI -29.7 to -16.7), p < 0.001], QLQ-STO22 dysphagia subscale [MD 6.7 (95% CI 1.7 to 11.7), p = 0.009], EQ-5D pain scale [MD 6.9 (95% CI 2.9 to 10.9), p < 0.001], and QLQ-OES18 saliva subscale [MD 5.8 (95% CI 0.1 to 11.6), p = 0.046]. CONCLUSIONS: In this meta-analysis, we found that the inclusion of ICIs as a first-line treatment for advanced GEC yielded better HRQoL outcomes than chemotherapy alone. Further research on the impact of ICIs on HRQoL is needed, with increasing evidence that ICIs improve the survival outcomes in patients with advanced GEC.

An Optimized CT Protocol for Detecting Suspected Cauda Equina Syndrome: A Comparative Analysis with MRI.

BACKGROUND AND PURPOSE: Lumbar disc herniation, potentially leading to nerve root compression and cauda equina syndrome, is typically evaluated using MR imaging. However, the limited availability of MR imaging outside regular hours in certain health care systems poses considerable challenges. This purpose of this study was to prospectively evaluate the diagnostic accuracy of an optimized CT lumbar spine protocol as a potential alternative to MR imaging in assessing suspected neural compression. MATERIALS AND METHODS: Patients presenting to the emergency department with suspected cauda equina syndrome or acute radicular symptoms secondary to lumbar disc herniation referred for MR imaging were prospectively enrolled for an additional CT optimized to assess spinal stenosis. An expert radiologist, blinded to clinical data, graded canal stenosis at each lumbar level on CT. The same grading process was applied to MR imaging after a 4-week interval to maintain blinding. RESULTS: Fifty-nine individuals were included in the final analysis. In 22 (39%) cases, no significant stenosis was identified. In a further 22 (37%) cases, disc pathology was identified that was managed conservatively. Thirteen (22%) individuals proceeded to urgent surgical decompression. In 1 (2%) instance, an alternative diagnosis was identified. Compared with MR imaging, the sensitivity, specificity, and positive and negative predictive values for CT in detecting disc pathology in patients presenting with symptoms suggestive of acute neural compression were 97% (95% CI, 82%-99%), 97% (95% CI, 83%-99%), 97% (95% CI, 92%-99%), and 97% (95% CI, 83%-99%), respectively. CT accurately identified all cases requiring urgent decompression. CONCLUSIONS: CT accurately predicted MR imaging findings in patients with suspected cauda equina and nerve root compression, demonstrating its utility as an adjunct tool for patient triage in emergency settings with limited MR imaging access. This protocol could enhance the allocation of emergency resources by appropriately selecting patients for emergent MR imaging.

Exploring the research needs, barriers and facilitators to the collection of biological data in adolescence for mental health research: a scoping review protocol paper.

INTRODUCTION: While research into adolescent mental health has developed a considerable understanding of environmental and psychosocial risk factors, equivalent biological evidence is lacking and is not representative of economic, social and ethnic diversity in the adolescent population. It is important to understand the possible barriers and facilitators to conduct this research. This will then allow us to improve our understanding of how biology interacts with environmental and psychosocial risk factors during adolescence. The objective of this scoping review is to identify and understand the needs, barriers and facilitators related to the collection of biological data in adolescent mental health research. METHODS AND ANALYSIS: Reviewers will conduct a systematic search of PubMed, Medline, Scopus, Cochrane, ERIC, EMBASE, ProQuest, EBSCO Global Health electronic databases, relevant publications and reference lists to identify studies published in the English language at any time. This scoping review will identify published studies exploring mental health/psychopathology outcomes, with biological measures, in participants between the ages of 11 and 18 and examine the reported methodology used for data collection. Data will be summarised in tabular form with narrative synthesis and will use the methodology of Levac et al, supplemented by subsequent recommendations from the Joanna Briggs Institute Scoping Review Methodology. ETHICS AND DISSEMINATION: Ethical approval is not required for this scoping review. The scoping review will be conducted with input from patient and public involvement, specifically including young people involved in our study ('Co-producing a framework of guiding principles for Engaging representative and diverse cohorts of young peopLE in Biological ReseArch in menTal hEalth'-www.celebrateproject.co.uk) Youth Expert Working Group. Dissemination will include publication in peer-reviewed journals, academic presentations and on the project website.

National survey of patient perspectives on cost discussions among recipients of copay assistance.

BACKGROUND: Individuals with cancer and other medical conditions often experience financial concerns from high costs-of-care and may utilize copay assistance programs (CAP). We sought to describe CAP recipients' experiences/preferences for cost discussions with clinicians. METHODS: We conducted a national, cross-sectional electronic-survey from 10/2022 to 11/2022 of CAP recipients with cancer or autoimmune conditions to assess patient perspectives on cost discussions. We used multivariable logistic regression models to explore associations of patient perspectives on cost discussions with patient characteristics and patient-reported outcomes (eg, financial toxicity, depression/anxiety, and health literacy). RESULTS: Among 1,566 participants, 71% had cancer and 29% had autoimmune conditions. Although 62% of respondents desired cost discussions, only 32% reported discussions took place. Additionally, 52% of respondents wanted their doctor to consider out-of-pocket costs when deciding the best treatment, and 61% of respondents felt doctors should ensure patients can afford treatment prescribed. Participants with depression symptoms were more likely to want doctors to consider out-of-pocket costs (OR = 1.54, P = .005) and to believe doctors should ensure patients can afford treatment (OR = 1.60, P = .005). Those with severe financial toxicity were more likely to desire cost discussions (OR = 1.65, P < .001) and want doctors to consider out-of-pocket costs (OR = 1.52, P = .001). Participants with marginal/inadequate health literacy were more likely to desire cost discussions (OR = 1.37, P = .01) and believe doctors should ensure patients can afford treatment (OR = 1.30, P = .036). CONCLUSIONS: In this large sample of CAP recipients with cancer and autoimmune conditions, most reported a desire for cost discussions, but under one-third reported such discussions took place.

Is Maintenance or Switching Between Freebase and Nicotine Salt Liquid Associated with Electronic Nicotine Delivery Systems Dependence?

BACKGROUND: Electronic nicotine delivery systems (ENDS) use one of two formulations of nicotine-freebase or nicotine salt. This study examines whether maintenance or switching between nicotine formulations is associated with ENDS dependence using longitudinal survey data. METHODS: 543 U.S. adults (21+) using ENDS frequently (5+ days/week) self-reported and uploaded photos of their most used ENDS liquids in wave 3-5 online surveys from September 2021 to April 2023. Nicotine formulation from photo data was used if available; otherwise, self-reported data were used. ENDS dependence was measured in each wave by a 4-item E-cigarette Dependence Scale (EDS: range 0-4, 4 being most dependent). Data were analyzed using ANCOVA. RESULTS: Participants using nicotine salt liquids in three waves reported the highest EDS in wave 5 (49.3%, EDS = 2.59), followed by participants switching from salt to freebase (3.2%, EDS = 2.58), participants switching from freebase to salt (10.1%, EDS = 2.52), participants using freebase in three waves (34.9%, EDS = 2.18), and participants changing back and forth (2.4%, EDS = 2.11). After controlling for smoking status, participants stably using nicotine salt and participants switching from freebase to salt reported significantly higher EDS than those stably using freebase (p < 0.01). CONCLUSIONS: Over an 18-month period, people consistently using nicotine salt liquids and participants switching from freebase to nicotine salt were more likely to have a higher ENDS dependence than those consistently using freebase liquids. Understanding how switching between nicotine formulations relates to ENDS dependence can inform nicotine formulation and concentration regulations that may impact addiction.

Opening the doors of precision medicine: novel tools to assess intestinal barrier in inflammatory bowel disease and colitis-associated neoplasia.

Mounting evidence underscores the pivotal role of the intestinal barrier and its convoluted network with diet and intestinal microbiome in the pathogenesis of inflammatory bowel disease (IBD) and colitis-associated colorectal cancer (CRC). Moreover, the bidirectional association of the intestinal barrier with the liver and brain, known as the gut-brain axis, plays a crucial role in developing complications, including extraintestinal manifestations of IBD and CRC metastasis. Consequently, barrier healing represents a crucial therapeutic target in these inflammatory-dependent disorders, with barrier assessment predicting disease outcomes, response to therapy and extraintestinal manifestations.New advanced technologies are revolutionising our understanding of the barrier paradigm, enabling the accurate assessment of the intestinal barrier and aiding in unravelling the complexity of the gut-brain axis. Cutting-edge endoscopic imaging techniques, such as ultra-high magnification endocytoscopy and probe-based confocal laser endomicroscopy, are new technologies allowing real-time exploration of the 'cellular' intestinal barrier. Additionally, novel advanced spatial imaging technology platforms, including multispectral imaging, upconversion nanoparticles, digital spatial profiling, optical spectroscopy and mass cytometry, enable a deep and comprehensive assessment of the 'molecular' and 'ultrastructural' barrier. In this promising landscape, artificial intelligence plays a pivotal role in standardising and integrating these novel tools, thereby contributing to barrier assessment and prediction of outcomes.Looking ahead, this integrated and comprehensive approach holds the promise of uncovering new therapeutic targets, breaking the therapeutic ceiling in IBD. Novel molecules, dietary interventions and microbiome modulation strategies aim to restore, reinforce, or modulate the gut-brain axis. These advancements have the potential for transformative and personalised approaches to managing IBD.

Comparison of 3T MR arthrography and 3T MRI in intra-articular hip pathology: a cost-analysis.

BACKGROUND: MR arthrography (MRA) has previously been the radiological gold standard for investigating labral and chondral lesions of the hip joint. In recent years, 3T MRI has demonstrated comparable accuracy, being adopted as the first-line imaging investigation in many institutions. AIMS: We compare the associated increased cost and radiation dose of the fluoroscopic component of the MRA compared to MRI. METHODS: In this retrospective review over 2 years, 120 patients (mean age 27.3 years ± 13.2, range 8-67) underwent 3T MRA or non-contrast 3T MRI. Three musculoskeletal radiologists reported the data independently. Primary objectives included cost-comparison between each and radiation dose of the fluoroscopic component of the MRA. Secondary objectives included comparing detection of pathology involving the acetabular labrum, femoral cartilage, and acetabular cartilage. RESULTS: Then, 58 (48%) underwent 3T MRA and 62 (52%) patients underwent 3T MRI. The added cost of the fluoroscopic injection prior to MRA was €116.31/patient, equating to €7211.22 savings/year. MRA was associated with a small radiation dose of 0.003 mSv. CONCLUSIONS: Transitioning from 3T MRA to 3T MRI in the investigation of intra-articular hip pathology increases cost savings and reduces radiation dose.

Examining mental health and autonomic function as putative mediators of the relationship between sleep and trajectories of cognitive function: findings from the Irish longitudinal study on ageing (TILDA).

OBJECTIVES: This study investigates the mediating roles of autonomic function and mental health in the association between sleep and cognitive decline in adults aged 50 and above. METHOD: A total of 2,697 participants with observations on sleep and mediators at baseline and repeated measures of cognitive function (MMSE) were included. Clusters of individuals with similar cognitive trajectories (high-stable, mid-stable and low-declining) were identified. Multinomial logistic regressions were used to estimate the likelihood of membership to each trajectory group based on sleep duration and disturbance. Finally, mediation analysis tested potential mediating effects of autonomic function and mental health underpinning the sleep-cognition relationship. RESULTS: Short (p = .028), long (p =.019), and disturbed sleep (p =.008) increased the likelihood of a low-declining cognitive trajectory. Mental health measures fully attenuated relationships between cognitive decline and short or disturbed sleep but not long sleep. No autonomic function mediation was observed. CONCLUSION: Older adults with short or disturbed sleep are at risk of cognitive decline due to poor mental health. Individuals with long sleep are also at risk, however, the acting pathways remain to be identified. These outcomes have clinical implications, potentially identifying intervention strategies targeting mental health and sleep as prophylactic measures against dementia.

Born in Bradford's Age of Wonder cohort: protocol for adolescent data collection.

Background: Adolescence and transition into adulthood are periods shaping life-long mental health, cardiometabolic risk, and inequalities. However, they are poorly studied and understood. By extending and expanding the Born in Bradford (BiB) cohort study through this period using innovative, co-produced approaches to collect and analyse data, we aim to understand better the interplay of factors that influence health and wellbeing, and inform/evaluate interventions to improve them and reduce inequalities. Protocol: BiB Age of Wonder (AoW) is a large, whole city cohort that will capture the contemporary lived experience amongst multi-ethnic adolescents progressing into young adulthood. We will collect repeated data from existing BiB participants and their peers (N~30,000 adolescents). The protocol for the first phase of the quantitative methods, involving survey measurements and health assessments in mainstream secondary schools is described here. We describe the co-production behind these methods, and lessons learned from the first year of data collection.

Born in Bradford have been following the health and wellbeing of over 13,000 Bradford children since they were born. This group of children are now in their teenage years ­ a time that is crucial for their future mental and physical health. Age of Wonder aims to capture this journey through adolescence and early adulthood with up to 30,000 young people in Bradford over 7 years. In the first phase of this project, data collection is taking part in secondary schools in Bradford. This protocol describes how this data collection is currently being carried out in the schools. Young people aged 12-15 are being asked to complete questionnaires, covering topics such as mental and physical health. These topics have been designed with groups of young people, schools and other partners, to make sure we are capturing data on the things most important to young people. Those in Year 9 (13-14 years old), are also asked to take part in physical health measurements such as height, weight, blood pressure and a blood sample, as well as computer-based assessments of cognition (memory), movement and language. There have been a number of lessons learned from the first full year of data collection, such as how to make the research as easy as possible for schools to take part in when they have so many competing demands on their time.

Hypofractionated Radiotherapy-Related Lymphopenia Is Associated With Worse Survival in Unresectable Intrahepatic Cholangiocarcinoma.

OBJECTIVE: The aim of this study was to evaluate the incidence of radiotherapy (RT)-related lymphopenia, its predictors, and association with survival in unresectable intrahepatic cholangiocarcinoma (ICC) treated with hypofractionated-RT (HF-RT). METHODS: Retrospective analysis of 96 patients with unresectable ICC who underwent HF-RT (median 58.05 Gy in 15 fractions) between 2009 and 2022 was performed. Absolute lymphocyte count (ALC) nadir within 12 weeks of RT was analyzed. Primary variable of interest was severe lymphopenia, defined as Grade 3+ (ALC <0.5 k/µL) per CTCAE v5.0. Primary outcome of interest was overall survival (OS) from RT. RESULTS: Median follow-up was 16 months. Fifty-two percent of patients had chemotherapy pre-RT, 23% during RT, and 40% post-RT. Pre-RT, median ALC was 1.1 k/µL and 5% had severe lymphopenia. Post-RT, 68% developed RT-related severe lymphopenia. Patients who developed severe lymphopenia had a significantly lower pre-RT ALC (median 1.1 vs. 1.5 k/µL, P =0.01) and larger target tumor volume (median 125 vs. 62 cm 3 , P =0.02). In our multivariable Cox model, severe lymphopenia was associated with a 1.7-fold increased risk of death ( P =0.04); 1-year OS rates were 63% vs 77% ( P =0.03). Receipt of photon versus proton-based RT (OR=3.50, P =0.02), higher mean liver dose (OR=1.19, P <0.01), and longer RT duration (OR=1.49, P =0.02) predicted severe lymphopenia. CONCLUSIONS: HF-RT-related lymphopenia is an independent prognostic factor for survival in patients with unresectable ICC. Patients with lower baseline ALC and larger tumor volume may be at increased risk, and use of proton therapy, minimizing mean liver dose, and avoiding treatment breaks may reduce RT-related lymphopenia.

Palliative Care for Patients With Cancer: ASCO Guideline Update.

PURPOSE: To provide evidence-based guidance to oncology clinicians, patients, nonprofessional caregivers, and palliative care clinicians to update the 2016 ASCO guideline on the integration of palliative care into standard oncology for all patients diagnosed with cancer. METHODS: ASCO convened an Expert Panel of medical, radiation, hematology-oncology, oncology nursing, palliative care, social work, ethics, advocacy, and psycho-oncology experts. The Panel conducted a literature search, including systematic reviews, meta-analyses, and randomized controlled trials published from 2015-2023. Outcomes of interest included quality of life (QOL), patient satisfaction, physical and psychological symptoms, survival, and caregiver burden. Expert Panel members used available evidence and informal consensus to develop evidence-based guideline recommendations. RESULTS: The literature search identified 52 relevant studies to inform the evidence base for this guideline. RECOMMENDATIONS: Evidence-based recommendations address the integration of palliative care in oncology. Oncology clinicians should refer patients with advanced solid tumors and hematologic malignancies to specialized interdisciplinary palliative care teams that provide outpatient and inpatient care beginning early in the course of the disease, alongside active treatment of their cancer. For patients with cancer with unaddressed physical, psychosocial, or spiritual distress, cancer care programs should provide dedicated specialist palliative care services complementing existing or emerging supportive care interventions. Oncology clinicians from across the interdisciplinary cancer care team may refer the caregivers (eg, family, chosen family, and friends) of patients with cancer to palliative care teams for additional support. The Expert Panel suggests early palliative care involvement, especially for patients with uncontrolled symptoms and QOL concerns. Clinicians caring for patients with solid tumors on phase I cancer trials may also refer them to specialist palliative care.Additional information is available at www.asco.org/supportive-care-guidelines.

A family-centered approach to social needs awareness in the pediatric emergency department.

Objective: We aimed to understand family preferences around reporting and receiving health-related social needs (HRSN) information by assessment modality during pediatric emergency department (PED) visits. Methods: Families were randomized into paper (control), cell phone, or tablet modality groups by their child's exam room. Nurses alerted families to complete a single HRSN assessment during routine workflow. We used logistic regression and McNemar's test to assess discordance in modality preference. Results: Forty-seven percent of families disclosed at least one HRSN across a total 611 assessments. Disclosure of HRSN was similar by modality. Twenty-three percent of those assigned tablet preferred cell phone (p < 0.001). Two-thirds of families preferred receiving digitally formatted community resources (email or text). There was no difference in preferred timing of HRSN assessment completion. Conclusions: Assessment modality did not appear to influence family HRSN disclosure. Families were generally satisfied with all HRSN assessment modalities but demonstrated a particular preference in using personal cell phones over tablets. Digitally formatted community referrals also pose numerous advantages over conventional paper handouts. Innovation: Use of personal cell phones is a novel, streamlined method of HRSN interventions in the clinical setting, performing similar to more conventional modalities, with a preference among families when compared to tablets.

Application and demonstration of meso-activity exposure factors to advance estimates of incidental soil ingestion among agricultural workers.

BACKGROUND: Soil is an understudied and underregulated pathway of chemical exposure, particularly for agricultural workers who cultivate food in soils. Little is known about how agricultural workers spend their time and how they may contact soil while growing food. Exposure factors are behavioral and environmental variables used in exposure estimation. OBJECTIVES: Our study aimed to derive exposure factors describing how growers engage in different tasks and use those factors to advance the use of time-activity data to estimate soil ingestion exposures among agricultural workers. METHODS: We administered a meso-activity-based, season-specific soil contact activity questionnaire to 38 fruit and vegetable growers. We asked growers to estimate the frequency and duration of six meso-activities and describe how they completed them. We used questionnaire data to derive exposure factors and estimate empirical and simulated exposures to a hypothetical contaminant in soil via incidental ingestion using daily, hourly, and hourly-task-specific ingestion rates. RESULTS: We generated exposure factors characterizing the frequency and duration of six meso-activities by season, and self-reported soil contact, glove use, and handwashing practices by meso-activity and season. Seasonal average daily doses (ADDs) were similar across all three forms of ingestion rates. No consistent patterns regarding task-specific contributions to seasonal or annual ADDs were observed.

Changes in Compliance With Bans on Tobacco Product Display and Advertising at Traditional and Modern Point-of-Sale Retailers in Depok, Indonesia, 2019-2021.

INTRODUCTION: Banning Point-of-Sale (POS) advertising and product display is an important tobacco control strategy. Depok, Indonesia enacted some regional tobacco control policies regulating the POS environment in 2021. This study examined changes in compliance before and after the implementation of these policies as of 2021. METHODS: Data collectors visited 180 modern retailers (hyper/supermarkets/convenience stores) and 147 traditional retailers (warungs) in 2019. The same retailers were revisited in 2021. Data collectors assessed compliance with tobacco product display, and advertising regulations at POS, including if products were displayed in spaces to target minors (near candy or at a child's eye level). Data were analyzed using McNemar and Mann-Whitney U tests. RESULTS: From 2019 to 2021, in modern retailers, tobacco product display (95.6% vs. 52.2%) and product advertising (36.1% vs. 3.9%) were significantly reduced (p < .001). In traditional retailers, tobacco product display (94.6% in 2019, 91.2% in 2021, p > .05) and product advertising (87.1% in 2019, 87.8% in 2021, p > .05) remained common during both data collection periods. Tobacco products were commonly displayed in spaces to target minors in both modern retailers (43.3% in 2019, 34.4% in 2021, p > .05) and traditional retailers (90.5% in 2019, 83.0% in 2021, p > .05). CONCLUSIONS: Compliance with bans on tobacco product advertising and display at modern retailers improved significantly from 2019 to 2021; however, most modern retailers continue to display tobacco products in 2021. Traditional retailers remain largely noncompliant. Tobacco products are commonly displayed in areas that target minors. The enforcement of regional regulations should be strengthened, particularly among traditional retailers. IMPLICATIONS: In Depok, Indonesia, tobacco advertising and product display bans have been implemented; however, more work is needed to support compliance. Enforcement efforts, such as those carried out by civil police, can focus on tobacco product display bans in traditional and modern retailers, and traditional retailers need additional support to remove tobacco product advertising. Retailers may receive money from the tobacco industry for these advertisements. Creative solutions may include supporting retailers in finding alternative advertising revenue.

The Emerging Role and Clinical Applications of Morphomics in Diagnostic Imaging.

Analytic morphomics refers to the accurate measurement of specific biological markers of human body composition in diagnostic medical imaging. The increasing prevalence of disease processes that alter body composition including obesity, cachexia, and sarcopenia has generated interest in specific targeted measurement of these metrics to possibly prevent or reduce negative health outcomes. Typical morphomic measurements include the area and density of muscle, bone, vascular calcification, visceral fat, and subcutaneous fat on a specific validated axial level in the patient's cross-sectional diagnostic imaging. A distinct advantage of these measurements is that they can be made retrospectively and opportunistically with pre-existing datasets. We provide a narrative review of the current state of art in morphomics, but also consider some potential future directions for this exciting field. Imaging based quantitative assessment of body composition has enormous potential across the breadth and scope of modern clinical practice. From risk stratification to treatment planning, and outcome assessment, all can be enhanced with the use of analytic morphomics. Moreover, it is likely that many new opportunities for personalized medicine will emerge as the field evolves. As radiologists, embracing analytic morphomics will enable us to contribute added value in the care of every patient.

Transfer Learning Reveals Cancer-Associated Fibroblasts Are Associated with Epithelial-Mesenchymal Transition and Inflammation in Cancer Cells in Pancreatic Ductal Adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy characterized by an immunosuppressive tumor microenvironment enriched with cancer-associated fibroblasts (CAF). This study used a convergence approach to identify tumor cell and CAF interactions through the integration of single-cell data from human tumors with human organoid coculture experiments. Analysis of a comprehensive atlas of PDAC single-cell RNA sequencing data indicated that CAF density is associated with increased inflammation and epithelial-mesenchymal transition (EMT) in epithelial cells. Transfer learning using transcriptional data from patient-derived organoid and CAF cocultures provided in silico validation of CAF induction of inflammatory and EMT epithelial cell states. Further experimental validation in cocultures demonstrated integrin beta 1 (ITGB1) and vascular endothelial factor A (VEGFA) interactions with neuropilin-1 mediating CAF-epithelial cell cross-talk. Together, this study introduces transfer learning from human single-cell data to organoid coculture analyses for experimental validation of discoveries of cell-cell cross-talk and identifies fibroblast-mediated regulation of EMT and inflammation. SIGNIFICANCE: Adaptation of transfer learning to relate human single-cell RNA sequencing data to organoid-CAF cocultures facilitates discovery of human pancreatic cancer intercellular interactions and uncovers cross-talk between CAFs and tumor cells through VEGFA and ITGB1.

Social Care Education and Training Among US Pediatric Emergency Medicine Fellowship Programs.

OBJECTIVE: The aim of the study is to assess the association of social determinants of health (SDOH) education and social needs training on pediatric emergency medicine (PEM) physician perception and practices of social care. METHODS: Data were derived from the 2021 National Social Care Practices Survey of PEM program directors (PDs) and fellows. Ordinal and binary logistic regression modeling were completed for educational/training factors and social care perspective and practice outcomes. RESULTS: A national sample of 44 PDs (49% response rate) and 109 fellows (28%) participated. A minority of fellows received SDOH education and social needs training during fellowship. Fellows and PDs with SDOH education had a 3.1 odds (95% confidence interval CI, 1.4-6.9) of screening for social needs, with 4.4 odds among fellows (95% CI, 1.2-20.7). Those with social needs training were more comfortable assessing social risk, with 2.4 odds overall (95% CI, 1.2-4.7) and 3.1 odds among fellows (95% CI, 1.4-6.7). They also had 2.4 odds overall (95% CI, 1.1-4.9) of screening for social needs, with a 2.9 odds among fellows (95% CI, 1.3-6.8). CONCLUSIONS: Social care education and training appear to be associated with comfort assessing social risk and social needs screening tendency among both PEM PDs and fellows. Key areas for educational interventions are identified among PEM fellows, who are uniquely positioned as clinical leaders and patient advocates.