Introduction A few studies have identified childhood animal exposure as associated with adiposity, but results are inconsistent and differ in timing. Methods We conducted an observational cohort study of children ages 4–8 in the Environmental Influences on Child Health Outcomes [ECHO] study. The main exposure was having a dog in the home and/or regular contact with farm animals during the first year of life. Outcomes of interest were child BMI percentile (adjusted for gender and age) categorized as normal/underweight (<85th percentile), overweight (85th to <95th), and obese (≥95th), and percent fat mass (continuous). Associations were analyzed using multinomial logistic regression and multivariable linear regression, respectively, with and without multiple imputation. Results First-year animal exposure occurred in 245 of 770 (31.8%) children. Children with early animal exposure had 0.53 (95% CI: 0.28, 0.997) times the odds of being in the obese BMI category compared to those exposed to animals after controlling for covariates: maternal pre-pregnancy BMI, race/ethnicity, reported child activity level, receiving food assistance, age child began daycare (<1 year vs 1+), exclusively breastfed x6 months, and NICU admission (n = 721). Children with early animal exposure had, on average, 1.5% (95% CI: −3.0, −0.1) less fat mass than exposed children after adjustment for maternal BMI, race/ethnicity, activity, food assistance, breastfeeding, and maternal education (n = 548). Multiple imputation did not alter either result. Conclusion These results provide evidence that exposure to dogs or farm animals in the first year of life is associated with lower odds of obesity and lower percent fat mass in childhood.
Background: Glioma is the most common intracranial malignancy with a poor prognosis. Although remarkable advances have been made in the study of diagnostic and prognostic biomarkers, the efficacy of current treatment strategies is still unsatisfactory. Therefore, developing novel and reliable targets is desperately needed for glioma patients. Pyroptosis reshapes tumor immune microenvironment (TME) and promotes the destruction of the tumor by the immune system. Moreover, pyroptosis levels correlate with prognosis and immunotherapy response in many cancer patients. This study performed a comprehensive analysis of pyroptosis in the glioma, unveiling its potential value in glioma prognosis prediction and therapy efficacy. Methods: Firstly, the pyroptosis regulation patterns were comprehensively evaluated on 33 pyroptosis-related genes in 1716 glioma samples. The correlations were analyzed between pyroptosis regulation patterns and TME immune cell infiltration properties. Next, pyroptosis regulation patterns were measured by the PSscore model based on principal component analysis algorithms. The correlations were analyzed between PSscore and tumor mutational burden (TMB), immune checkpoint blockade (ICB) therapeutic advantages. Last, the findings were validated in an independently collected external clinical cohort. Results: We determined two distinct pyroptosis regulation patterns. The cluster-A was high immune cell infiltration with a poor prognosis (p < 0.001), whereas the cluster-B was low immune cell infiltration with a better prognosis (p < 0.001). We developed the PSscore as a measure for pyroptosis regulation patterns. The high PSscore with an inflamed TME phenotype, a high TMB (p < 0.0001), increased innate immune response, and a poor prognosis (p < 0.001). It was in stark contrast to the low PSscore (p < 0.001). Analysis of PSscore with checkpoint therapy indicated high PSscore were correlated with enhanced response to anti-PD-1 immunotherapy (p = 0.0046). For validation, we utilized in vitro experiments on an external clinical cohort. The results demonstrated that GSDMD expression level in the high PSscore group was significantly upregulated compared to the low PSscore group (p < 0.001); the CD3+ T cells and the CD3+PD-1+ cells significantly increased in the high PSscore group compared to the low PSscore group (p < 0.01). Conclusions: The PSscore of pyroptosis regulation pattern is a reliable biomarker, and it is valuable to predict prognosis, TME, and ICB therapeutic efficiency in glioma patients.
Neutrophils are closely involved in the regulation of tumor progression and formation of pre-metastatic niches. However, the mechanisms of their involvement and therapeutic regulation of these processes remain elusive. Here, we report a critical role of neutrophil peptidylarginine deiminase 4 (PAD4) in neutrophil migration in cancer. In several transplantable and genetically engineered mouse models, tumor growth was accompanied by significantly elevated enzymatic activity of neutrophil PAD4. Targeted deletion of PAD4 in neutrophils markedly decreased the intratumoral abundance of neutrophils and led to delayed growth of primary tumors and dramatically reduced lung metastases. PAD4 mediated neutrophil accumulation by regulating the expression of the major chemokine receptor CXCR2. PAD4 expression and activity as well as CXCR2 expression were significantly upregulated in neutrophils from patients with lung and colon cancers compared to healthy donors, and PAD4 and CXCR2 expression were positively correlated in neutrophils from cancer patients. In tumor-bearing mice, pharmacological inhibition of PAD4 with the novel PAD4 isoform-selective small molecule inhibitor JBI-589 resulted in reduced CXCR2 expression and blocked neutrophil chemotaxis. In mouse tumor models, targeted deletion of PAD4 in neutrophils or pharmacological inhibition of PAD4 with JBI-589 reduced both primary tumor growth and lung metastases and substantially enhanced the effect of immune checkpoint inhibitors. Taken together, these results suggest a therapeutic potential of targeting PAD4 in cancer.
Purpose Breast cancer (BC) survivors and their intimate partners face several adverse consequences from the cancer experience, including sleep disturbance, which is a common side effect of BC and its treatment. Sleep has been conceptualized and examined as an individual phenomenon despite most adults sharing a bed/room with a partner. Limited research has examined the associations between daily relationship processes and sleep in couples coping with cancer. Using an intensive longitudinal design, the present study examined the daily, within-person links between attempted and perceived partner responsiveness and subjective sleep. Methods Immediately following adjuvant treatment, 72 early-stage BC survivors and their intimate partners (144 paired individuals) reported on daily attempted and perceived partner responsiveness each evening and subjective sleep each morning for 21 consecutive days. Results Survivor and partner reports of partner responsiveness were associated with their own subjective sleep, such that greater attempted and perceived partner responsiveness were associated with improvements in one’s own subjective sleep. Effects of one participant’s partner responsiveness on their partner’s sleep were not observed. Conclusions Findings suggest that among couples coping with early-stage BC, increased partner responsiveness is associated with subsequent improvements in subjective sleep. Implications for cancer survivors Sleep disturbance is a serious concern for BC survivors and their intimate partners. Future research should assess intimacy processes as a potential method to improve BC survivor and partner sleep.
Introduction: Pheochromocytomas and paragangliomas are rare neuroendocrine tumors that secrete catecholamines. Symptoms of these tumors are related directly to catecholamine excess but can be intermittent and easily misattributed to other, more common pathologies. Identification in the emergency department (ED) is inherently difficult. During the coronavirus 2019 (COVID-19) pandemic, physicians have had to account for both the disease itself as well as associated increased prevalence of cardiac, pulmonary, and vascular complications. Such shifting of disease prevalence arguably makes rarer diseases like pheochromocytoma less likely to be recognized. Case report: We report a case of pheochromocytoma in a patient who presented to the ED in the fall of 2020, at a regional height of the COVID-19 pandemic, with complaints of fatigue, tachycardia, and diaphoresis. The differential diagnosis included pulmonary embolism, cardiomyopathy, congestive heart failure, and infectious causes. A broad workup was begun that included serology, electrocardiogram, computed tomography angiogram (CTA), and COVID-19 testing. Imaging was consistent with COVID-19 infection, and laboratory testing confirmed the diagnosis. A tiny retroperitoneal tumor was reported on CTA as "incidental" in the setting of multifocal pneumonia from severe acute respiratory syndrome coronavirus 2 infection. Additional history-taking revealed many years of intermittent symptoms suggesting that the tumor may have been more contributory to the patient's presentation than originally suspected. Subsequent magnetic resonance imaging and surgical pathology confirmed the dual diagnosis of pheochromocytoma and COVID-19 pneumonia. Conclusion: This case presentation highlights the importance of careful history-taking, keeping a broad differential, and examining incidental findings in the context of the patient's presentation.
Background: There are no guidelines for anesthesia or staff support needed during rigid bronchoscopy (RB). Identifying current practice patterns for RB pertinent to anesthesia, multidisciplinary teams, and algorithms of intra and post-procedural care may inform best practice recommendations. Methods: Thirty-three-question survey created obtaining practice patterns for RB, disseminated via email to the members of the American Association of Bronchology and Interventional Pulmonology and the American College of Chest Physicians Interventional Chest Diagnostic Procedures Network. Results: One hundred seventy-five clinicians participated. Presence of a dedicated interventional pulmonology (IP) suite correlated with having a dedicated multidisciplinary RB team (P=0.0001) and predicted higher likelihood of implementing team-based algorithms for managing complications (39.4% vs. 23.5%, P=0.024). A dedicated anesthesiology team was associated with the increased use of high-frequency jet ventilation (P=0.0033), higher likelihood of laryngeal mask airway use post-RB extubation (P=0.0249), and perceived lower rates of postprocedural anesthesia adverse effects (P=0.0170). Although total intravenous anesthesia was the most used technique during RB (94.29%), significant variability in the modes of ventilation and administration of muscle relaxants was reported. Higher comfort levels in performing RB are reported for both anesthesiologists (P=0.0074) and interventional pulmonologists (P=0.05) with the presence of dedicated anesthesia and RB supportive teams, respectively. Conclusion: Interventional bronchoscopists value dedicated services supporting RB. Multidisciplinary dedicated RB teams are more likely to implement protocols guiding management of intraprocedural complications. There are no preferred modes of ventilation during RB. These findings may guide future research on RB practices.
Evidence from observational studies has become increasingly important for supporting healthcare policy making via cost-effectiveness analyses. Similar as in comparative effectiveness studies, health economic evaluations that consider subject-level heterogeneity produce individualized treatment rules that are often more cost-effective than one-size-fits-all treatment. Thus, it is of great interest to develop statistical tools for learning such a cost-effective individualized treatment rule under the causal inference framework that allows proper handling of potential confounding and can be applied to both trials and observational studies. In this paper, we use the concept of net-monetary-benefit to assess the trade-off between health benefits and related costs. We estimate cost-effective individualized treatment rule as a function of patients’ characteristics that, when implemented, optimizes the allocation of limited healthcare resources by maximizing health gains while minimizing treatment-related costs. We employ the conditional random forest approach and identify the optimal cost-effective individualized treatment rule using net-monetary-benefit-based classification algorithms, where two partitioned estimators are proposed for the subject-specific weights to effectively incorporate information from censored individuals. We conduct simulation studies to evaluate the performance of our proposals. We apply our top-performing algorithm to the NIH-funded Systolic Blood Pressure Intervention Trial to illustrate the cost-effectiveness gains of assigning customized intensive blood pressure therapy.
We introduce a multi-institutional data harvesting (MIDH) method for longitudinal observation of medical imaging utilization and reporting. By tracking both large-scale utilization and clinical imaging results data, the MIDH approach is targeted at measuring surrogates for important disease-related observational quantities over time. To quantitatively investigate its clinical applicability, we performed a retrospective multi-institutional study encompassing 13 healthcare systems throughout the United States before and after the 2020 COVID-19 pandemic. Using repurposed software infrastructure of a commercial AI-based image analysis service, we harvested data on medical imaging service requests and radiology reports for 40,037 computed tomography pulmonary angiograms (CTPA) to evaluate for pulmonary embolism (PE). Specifically, we compared two 70-day observational periods, namely (i) a pre-pandemic control period from 11/25/2019 through 2/2/2020, and (ii) a period during the early COVID-19 pandemic from 3/8/2020 through 5/16/2020. Natural language processing (NLP) on final radiology reports served as the ground truth for identifying positive PE cases, where we found an NLP accuracy of 98% for classifying radiology reports as positive or negative for PE based on a manual review of 2,400 radiology reports. Fewer CTPA exams were performed during the early COVID-19 pandemic than during the pre-pandemic period (9806 vs. 12,106). However, the PE positivity rate was significantly higher (11.6 vs. 9.9%, p < 10−4) with an excess of 92 PE cases during the early COVID-19 outbreak, i.e., ~1.3 daily PE cases more than statistically expected. Our results suggest that MIDH can contribute value as an exploratory tool, aiming at a better understanding of pandemic-related effects on healthcare.
Glioblastoma is the most common aggressive adult brain tumor. Numerous studies have reported results from either private institutional data or publicly available datasets. However, current public datasets are limited in terms of: a) number of subjects, b) lack of consistent acquisition protocol, c) data quality, or d) accompanying clinical, demographic, and molecular information. Toward alleviating these limitations, we contribute the “University of Pennsylvania Glioblastoma Imaging, Genomics, and Radiomics” (UPenn-GBM) dataset, which describes the currently largest publicly available comprehensive collection of 630 patients diagnosed with de novo glioblastoma. The UPenn-GBM dataset includes (a) advanced multi-parametric magnetic resonance imaging scans acquired during routine clinical practice, at the University of Pennsylvania Health System, (b) accompanying clinical, demographic, and molecular information, (d) perfusion and diffusion derivative volumes, (e) computationally-derived and manually-revised expert annotations of tumor sub-regions, as well as (f) quantitative imaging (also known as radiomic) features corresponding to each of these regions. This collection describes our contribution towards repeatable, reproducible, and comparative quantitative studies leading to new predictive, prognostic, and diagnostic assessments.
Background Identity formation is a dynamic process and key developmental task that begins in adolescence. During this time, children look to adults as role models and mentors. These adults can have a significant impact on adolescents' decisions of appropriate or inappropriate behaviors, potentially causing a positive or negative change. Little research has been performed to identify these role models and understand how they affect the development of physical and mental health of children. Objective The goal of this study is to see if there is a relationship between identified role models, mentors, and/or heroes and adolescents' interest in education, participation in risky behavior, confidence level, happiness, safety, violence-related behaviors, and physical activity. Methods In this study, 198 children aged 11-18 years were identified on the scheduling platforms at various Hershey Medical Center sites to take a 10-minute survey via RedCap. The survey identified their role model, mentor, and/or hero and followed up with outcome questions from validated tools. Results The results show that 140 participants (70.7%) identified having a role model compared to 88 (44.4%) having mentors and 61 (30.8%) having heroes, and family members were the most identified figures for each category. There were significant differences between identified categories of role models, mentors, and heroes, and interest in education, happiness, risky behavior, and safety, while no significant differences were found for violence-related behavior, physical activity, and confidence level. Adolescents with family heroes had safer behavior (2.39 ± 0.70) than those with celebrity heroes (3.16 ±1.86, p=0.0277), and those with peer heroes (11.3 ± 2.31) had more risky behavior than those with celebrity heroes (9.16 ± 1.98, p=0.0347). However, children with adult peer heroes had a higher interest in education (2.00 ± 0) compared to those with celebrities (3.79 ± 1.03, p=0.0246) or public figures (3.78 ± 1.09, p=0.0333) as their heroes. Additionally, those with family (3.48 ± 1.05) or adult peers (3.32 ± 1.38) as their mentors had a higher interest in education compared to those with same-age peer mentors (5.80 ± 1.30, p=<0.0001). Adolescents with family mentors also had higher happiness scores (3.25 ± 0.33) than those with same-age peer mentors (2.59 ± 1.47, p=0.0358) and also engaged in safer behavior (2.52 ± 0.80) compared to all other categories (3.03 ±1.59, 0.0462). Conclusion These results point to the idea that who adolescents choose to look up to has effects on various aspects of their life that could affect both their physical and mental health status, with family members having the most impact. Further research could explore differences between which family members are chosen as role models, mentors, and heroes and what effect they might have on adolescent development.
Purpose: There is no consensus on how age and expectations influence planning for total knee arthroplasty (TKA). This study developed and evaluated a new expectation questionnaire and assessed the relationship between preoperative expectations and patient characteristics. Method: The questionnaire evaluated expectations for mobility, pain, participation, and rate of recovery after surgery. Fifty-five participants completed a six-minute walk test and expectation questionnaire prior to TKA; 17 participants repeated the questionnaire one week later for reliability testing. Analysis of the questionnaire included intra-class correlation coefficient (ICC), homoscedasticity, skewness, kurtosis, multicollinearity, and descriptive measures. A four-step hierarchical linear regression was completed to determine the relationship of patient age, BMI, previous contralateral TKA, and six-minute walk scores to expectations. Results: The questionnaire showed good/high test-retest reliability (ICC 0.84, 95% CI of 0.57 to 0.94; p > 0.001). The final model was significant in predicting expectation scores R ² = 0.19 ( p = 0.017). Conclusions: This questionnaire reliably measures patient expectations before TKA; however, further research is needed. Although we anticipated younger age to be related to higher expectations, higher function prior to TKA appears to be more strongly associated with higher expectations.
Objectives: Although the World Health Organization (WHO) Clinical Progression Scale for COVID-19 is useful in prospective clinical trials, it cannot be effectively used with retrospective Electronic Health Record (EHR) datasets. Modifying the existing WHO Clinical Progression Scale, we developed an ordinal severity scale (OS) and assessed its usefulness in the analyses of COVID-19 patient outcomes using retrospective EHR data. Materials and methods: An OS was developed to assign COVID-19 disease severity using the Observational Medical Outcomes Partnership common data model within the National COVID Cohort Collaborative (N3C) data enclave. We then evaluated usefulness of the developed OS using heterogenous EHR data from January 2020 to October 2021 submitted to N3C by 63 healthcare organizations across the United States. Principal component analysis (PCA) was employed to characterize changes in disease severity among patients during the 28-day period following COVID-19 diagnosis. Results: The data set used in this analysis consists of 2 880 456 patients. PCA of the day-to-day variation in OS levels over the totality of the 28-day period revealed contrasting patterns of variation in disease severity within the first and second 14 days and illustrated the importance of evaluation over the full 28-day period. Discussion: An OS with well-defined, robust features, based on discrete EHR data elements, is useful for assessments of COVID-19 patient outcomes, providing insights on the progression of COVID-19 disease severity over time. Conclusions: The OS provides a framework that can facilitate better understanding of the course of acute COVID-19, informing clinical decision-making and resource allocation.
Background The prevalence of food insecurity declined in the United States but paradoxically increased in the large metropolitan area of Philadelphia in the past decade, and compared to the general U.S. population, a greater percentage of households in Philadelphia are affected by food insecurity and dependent on programs such as SNAP. The objective of this study was to determine food insecurity prevalence and demographics of the populations near Philadelphia Federally Qualified Health Center (FQHC) clinics. In line with risk factors on the national level, we hypothesized that food insecure people in a low-income area of Philadelphia would be more likely to be older, female, Hispanic, and overweight or obese. Methods This cross-sectional study took place in North Philadelphia, a populous section of Philadelphia with a high concentration of poverty and many zip codes reporting 30–45% or more of the population below the federal poverty line. Students and clinicians affiliated with a local FQHC conducted surveys on residents (n = 379) within 1-mile radiuses of three FQHC sites using the validated food security tool, the Hunger Vital Sign™. Survey data were collected through door-to-door visits in the summer of 2019. We used multivariate logistic regression models to predict food insecurity with independent variables including age, sex, language preference, and BMI category. Results The percentage of food insecurity in the area surveyed was much higher (36.9%) than previously reported in both Philadelphia and nationwide. Contrary to our hypothesis, food insecure individuals were younger on average and more likely to be English-speaking; these individuals had statistically significant lower mean BMI and lower odds of being overweight or obese vs. normal weight, with no significant difference by sex. Conclusion These North Philadelphia areas had a high prevalence of food insecurity associated with normal and low BMI and demographics of younger, English-speaking individuals. Some of these findings may be related to local confounding factors such as employment or substance abuse status, demonstrating a need for public health and organizations to work together for more locally targeted research and interventions on food insecurity in impoverished urban settings.
Background: Small for gestational age (SGA) infants are likely to have decreased placental transfer of opioids and other substances and lower amounts of fat deposition, hence less severe neonatal abstinence syndrome (NAS). The goal of this study is to correlate SGA status and severity of NAS in infants admitted to the neonatal intensive care unit (NICU). Methods: This is a retrospective analysis of term and late-preterm infants (≥35 weeks gestation) exposed to in-utero substances, born between September 2006 and May 2021, and admitted to an inner-city NICU for medical therapy for NAS. Indicators of the severity of NAS (duration of medical treatment, duration of hospitalization, use of phenobarbital, and use of clonidine) were compared between infants characterized as SGA (birth weight <10th percentile for gestational age) to those not categorized as SGA (non-SGA). Results: A total of 992 infants met the study criteria; 205 (20.7%) in the SGA group and 787 (79.3%) in the non-SGA group. The median duration of medical treatment was significantly lower in infants in the SGA group (22 days vs. 26 days, p = 0.04) and they were less likely to be treated with phenobarbital (19% vs. 26.8%, p = 0.02). Conclusion: SGA infants displayed less severe NAS symptoms as indicated by shorter a duration of medical treatment and decreased need for phenobarbital. Our findings may impact decisions around identifying the optimum treatment protocols catered to SGA infants with NAS.
Background There continues to be controversy regarding the simultaneous encouragement of both breastfeeding and immediate postpartum contraception. Research Aim To explore postpartum women’s perspectives about breastfeeding and their breastfeeding behaviors, while using one of three different hormonally systemic contraceptive methods immediately postpartum over a 6 month period of time. Methods This was a retrospective, longitudinal, three group comparative, secondary analysis of a prospective cohort study ( N = 471) of immediate postpartum contraception. Breastfeeding, for this study, was defined as providing any human milk to the infant. Participants who chose one of three different hormonally systemic forms of contraception immediately postpartum (a long-acting hormonal reversible contraceptive ( n = 200), depot medroxyprogesterone acetate 150 mg ( n = 98), or a non-hormonal method ( n = 173)) were compared at hospital discharge, 6 weeks, 3 months, and 6 months postpartum. The primary outcome was any breastfeeding at 6 months. Secondary outcomes included any and exclusive breastfeeding, concerns about breastfeeding while using contraception, and reasons for breastfeeding discontinuation. Results There was no significant difference in the rate of any breastfeeding between the two hormonal and the non-hormonal contraceptive groups at 6 months postpartum (long-acting hormonal 20.1%, non-hormonal 21.7%, depot medroxyprogesterone acetate 13.9%, p = .77, 0.28, respectively). The number of participants who reported stopping breastfeeding due to decreased milk supply was not significantly different between any groups at all time points (total number who discontinued at 6 months postpartum was long-acting hormonal 24.7%, non-hormonal 25.1%, depot medroxyprogesterone acetate 19.3%, p = .30). Conclusions Breastfeeding perspectives and behavioral outcomes over the first 6 months postpartum were not influenced by participants chosen form of immediate postpartum contraception.
Objective: This study examined the dynamic, real-time associations between partner involvement in diabetes self-care and continuous glucose monitor (CGM) metrics in adults with type 2 diabetes. Methods: Over one week, 63 participants wore Dexcom G4 CGMs and provided momentary reports of partner involvement in diabetes self-care five times per day. Dynamic structural equation models were used to estimate the reciprocal lagged effects of partner involvement on next-hour CGM metrics (and vice versa). Results: Partner involvement predicted improved next-hour glucose control for five of six CGM metrics in analyses adjusted for time-varying covariates. The hour after partner involvement, the model predicted a 26.34 mg/dL-decrease in glucose level (standardized β = -0.19), 30% greater odds of meeting target TIR (β = 0.07), 48% higher odds of target TBR (β = 0.04; the only non-significant effect), 47% greater odds of target TAR (β = 0.11), 4.20-unit decrease in glucose SD (β = -0.19), and 0.01-unit decrease in glucose CV (β = -0.08; all ps < .05). There was less consistent support for the reverse pathway, with only two metrics significantly related to next-hour partner involvement: glucose level (β = 0.15) and TBR (β = 0.21), such that having higher levels and meeting target TBR were significantly predictive of next-hour partner involvement. Conclusions: This is the first study showing that partner involvement in daily diabetes management predicts short-term glucose control. More research is needed to understand how partners influence glycemic control and evaluate interventions that promote their involvement in diabetes care.
Enteral nutrition (EN) is a vital component of nutrition around the world. EN allows for delivery of nutrients to those who cannot maintain adequate nutrition by oral intake alone. Common questions regarding EN are when to initiate and in what scenarios it is safe. The answers to these questions are often complex and require an evidence‐based approach. The Board of Directors of the American Society for Parenteral and Enteral Nutrition (ASPEN) established an Enteral Nutrition Committtee to address the important questions surrounding the indications for EN. Consensus recommendations were established based on eight extremely clinically relevant questions regarding EN indications as deemed by the Enteral Nutrition Committee. These consensus recommendations may act as a guide for clinicians and stakeholders on difficult questions pertaining to indications for EN. This paper was approved by the ASPEN Board of Directors.
There are approximately 500,000 implanted cardiac pacemakers in the United States, and another 100,000 are implanted each year . In the emergency department, a physician may be faced with a pacemaker that is not functioning appropriately. To understand the ways in which a pacemaker can malfunction or lead to medical complications, first it is important to understand how pacemakers work when they do so appropriately.
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