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Yiwang Zhou,1 Madeline R Horan,2 Samira Deshpande,1 Kirsten K Ness,2 Melissa M Hudson,3 I-Chan Huang,2,* Deokumar Srivastava1,* 1Department of Biostatistics, St. Jude Children’s Research Hospital, Memphis, TN, USA; 2Department of Epidemiology and Cancer Control, St. Jude Children’s Research Hospital, Memphis, TN, USA; 3Department of Oncology, St. Jude Children’s Research Hospital, Memphis, TN, USA*These authors contributed equally to this workCorrespondence: Yiwang Zhou, Department of Biostatistics, St. Jude Children’s Research Hospital, 262 Danny Thomas Place, Mail Stop 768, Memphis, Tennessee, TN 38105, USA, Tel +1 901-595-6736, Email yiwang.zhou@stjude.orgPurpose: Childhood cancer survivors experience interconnected symptoms, patterns of which can be elucidated by network analysis. However, current symptom networks are constructed based on the average survivors without considering individual heterogeneities. We propose to evaluate personal symptom network estimation using the Ising model with covariates through simulations and estimate personal symptom network for adult childhood cancer survivors.Patients and Methods: We adopted the Ising model with covariates to construct networks by employing logistic regressions for estimating associations between binary symptoms. Simulation experiments assessed the robustness of this method in constructing personal symptom network. Real-world data illustration included 1708 adult childhood cancer survivors from the St. Jude Lifetime Cohort Study (SJLIFE), a retrospective cohort study with prospective follow-up to characterize the etiology and late effects for childhood cancer survivors. Patients’ baseline symptoms in 10 domains (cardiac, pulmonary, sensation, nausea, movement, pain, memory, fatigue, anxiety, depression) and individual characteristics (age, sex, race/ethnicity, attained education, personal income, and marital status) were self-reported using survey. Treatment variables (any chemo or radiation therapy) were obtained from medical records. Personal symptom network of 10 domains was estimated using the Ising model, incorporating individual characteristics and treatment data.Results: Simulations confirmed the robustness of the Ising model with covariates in constructing personal symptom networks. Real-world data analysis identified age, sex, race/ethnicity, education, marital status, and treatment (any chemo and radiation therapy) as major factors influencing symptom co-occurrence. Older childhood cancer survivors showed stronger cardiac-fatigue associations. Survivors of racial/ethnic minorities had stronger pain-fatigue associations. Female survivors with above-college education demonstrated stronger pain-anxiety associations. Unmarried survivors who received radiation had stronger association between movement and memory problems.Conclusion: The Ising model with covariates accurately estimates personal symptom networks. Individual heterogeneities exist in symptom co-occurrence patterns for childhood cancer survivors. The estimated personal symptom network offers insights into interconnected symptom experiences.Keywords: bootstrap testing, individual heterogeneity, Ising model, network analysis, sociodemographic

The respective roles of aligned collagen fiber morphology found in the extracellular matrix (ECM) of pancreatic cancer patients and cellular migration dynamics have been gaining attention because of their connection with increased aggressive phenotypes and poor prognosis. To better understand how collagen fiber morphology influences cell-matrix interactions associated with metastasis, we used Second Harmonic Generation (SHG) images from patient biopsies with Pancreatic ductal adenocarcinoma (PDAC) as models to fabricate collagen scaffolds to investigate processes associated with motility. Using the PDAC BxPC-3 metastatic cell line, we investigated single and collective cell dynamics on scaffolds of varying collagen alignment. Collective or clustered cells grown on the scaffolds with the highest collagen fiber alignment had increased E-cadherin expression and larger focal adhesion sites compared to single cells, consistent with metastatic behavior. Analysis of single cell motility revealed that the dynamics were characterized by random walk on all substrates. However, examining collective motility over different time points showed that the migration was super-diffusive and enhanced on highly aligned fibers, whereas it was hindered and sub-diffusive on un-patterned substrates. This was further supported by the more elongated morphology observed in collectively migrating cells on aligned collagen fibers. Overall, this approach allows the decoupling of single and collective cell behavior as a function of collagen alignment and shows the relative importance of collective cell behavior as well as fiber morphology in PDAC metastasis. We suggest these scaffolds can be used for further investigations of PDAC cell biology. STATEMENT OF SIGNIFICANCE: Pancreatic ductal adenocarcinoma (PDAC) has a high mortality rate, where aligned collagen has been associated with poor prognosis. Biomimetic models representing this architecture are needed to understand complex cellular interactions. The SHG image-based models based on stromal collagen from human biopsies afford the measurements of cell morphology, cadherin and focal adhesion expression as well as detailed motility dynamics. Using a metastatic cell line, we decoupled the roles of single cell and collective cell behavior as well as that arising from aligned collagen. Our data suggests that metastatic characteristics are enhanced by increased collagen alignment and that collective cell behavior is more relevant to metastatic processes. These scaffolds provide new insight in this disease and can be a platform for further experiments such as testing drug efficacy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

We argue that the type of meta-learning proposed by Binz et al. generates models with low interpretability and falsifiability that have limited usefulness for neuroscience research. An alternative approach to meta-learning based on hyperparameter optimization obviates these concerns and can generate empirically testable hypotheses of biological computations.

Study Design: Retrospective chart review., Objective: To determine the effect of conservative measures on radiographic outcomes in those with isolated spondylolysis., Summary of Background Data: Spondylolysis is a common cause of low back pain in pediatric patients, affecting between 4.4% and 4.7% of all pediatric patients. This rate is even higher in high-level athletes, with recent studies suggesting a rate of 47% in this population. Conservative measures are recommended for treating symptomatic spondylolysis and are effective in controlling symptoms, but there is little evidence regarding their effect on radiographic outcomes., Methods: A retrospective review was conducted of patients diagnosed with spondylolysis who were treated at a single academic institution between January 1, 2012, and January 1, 2022. Data collected included demographics, presentation characteristics, pretreatment and post-treatment radiologic findings, types of treatments employed, and final symptomatic status at follow-up. The Student t test and the Wilcoxon rank sum test were used to compare continuous variables. The χ 2 test was used to compare categorical variables., Results: A total of 119 patients were included in the study. There was an 81.5% rate of healing on advanced imaging for those treated with conservative measures. When comparing those with healing on advanced imaging to those without, those with healing were more likely to have an acute fracture ( P= 0.04), have symptomatic improvement ( P <0.01), and return-to-play ( P= 0.02) compared with those without. Those with healing also had an odds ratio of 6.9 ( P <0.01) and 4.5 ( P =0.02) to achieve symptomatic improvement and return to their sport, respectively, compared with those who did not., Conclusion: Our study found those with isolated spondylolysis who were treated with conservative measures had a high healing rate on advanced imaging and those with healing had significantly higher odds of having symptomatic improvement and returning to play compared with those without., Level of Evidence: 4., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction and Importance: Adrenal Lipoma (LA) is a benign very rare tumor that accounts for 0.7 % of primary adrenal tumors and 4 % of adrenal fatty tumors. They are asymptomatic and discovered accidentally by a CT scan or the US., Case Presentation: This case report describes an incidentally discovered giant adrenal lipoma in a 45-year-old Asian woman with no prior medical history, presenting with episodic blood pressure fluctuations and abdominal pain attributed to coexisting gallstones. Imaging revealed a heterogeneous, well-demarcated adrenal mass measuring 17 × 14 × 11 cm with a 2 × 3 cm nodular density. Histopathological examination confirmed a 15 cm lipoma with ischemic changes, devoid of atypical features. This case underscores the importance of thorough investigation for adrenal masses, even in asymptomatic individuals., Discussion: This case report details a rare instance of a giant adrenal lipoma (17 × 14 × 11 cm, 870 g) co-occurring with gallstones in a 45-year-old woman experiencing chronic abdominal pain. Computed tomography revealed a characteristic homogenous fatty lesion, prompting open surgical resection due to the tumor's size. Hormonal evaluation confirmed a non-functioning tumor. This case emphasizes the challenges in diagnosing and managing giant adrenal lipomas, advocating for comprehensive investigation of adrenal masses, particularly with concurrent hypertension., Conclusion: Giant adrenal lipomas (LAs) are rare, benign tumors often presenting asymptomatically. This report documents the fifth largest and third heaviest LA reported, notably co-occurring with gallstones. While laparoscopic resection is ideal, delayed diagnosis due to insidious presentation can lead to increased tumor size, potentially precluding minimally invasive approaches., Competing Interests: Conflict of interest statement All authors declared no conflict of interest., (Copyright © 2024. Published by Elsevier Ltd.)

Background: The 10 Warning Signs of Primary Immunodeficiency were created 30 years ago to advance recognition of inborn errors of immunity (IEI). However, no population-level assessment of their utility applied to electronic health record (EHR) data has been conducted., Objective: We sought to quantify the value of having ≥2 warning signs (WS) toward diagnosing IEI using a highly representative real-world US cohort. A secondary goal was estimating the US prevalence of IEI., Methods: In this cohort study, we accessed normalized and de-identified EHR data on 152 million US patients. An IEI cohort (n = 41,080), in which patients were defined by having at least 1 verifiable IEI diagnosis placed ≥2 times in their record, was compared with a matched set of controls (n = 250,262). WS were encoded along with relevant diagnoses, relative weights were calculated, and the proportion of IEI cases versus controls with ≥2 WS was compared., Results: The proportion of IEI cases with ≥2 WS significantly differed from controls (0.33 vs 0.031; P < .0005, χ 2 test). We also estimated a US IEI prevalence of 6 per 10,000 individuals (41,080/73,165,655; 0.056%). WS 9 (≥2 deep-seated infections), 7 (fungal infections), 5 (failure to thrive) and 4 (≥2 pneumonias in 1 year) were the most heavily weighted among the IEI cohort., Conclusions: This nationally representative US-based cohort study demonstrates that presence of WS and associated clinical diagnoses can facilitate identification of patients with IEI from EHR data. In addition, we estimate that 6 in 10,000, or approximately 150,000 to 200,000 individuals are affected by IEI across the United States., (Copyright © 2024 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Introduction and Importance: Urothelial carcinoma of the bladder predominantly affects adults with rare cases in young patients. This manuscript presents a rare case of urothelial carcinoma highlighting clinical characteristics, diagnosis, treatment, and prognosis in this age group. Our aim is to raise awareness among healthcare professionals for improved outcomes in children and adolescents with bladder urothelial carcinoma., Case Presentation: A 17-year-old male presented with hematuria and urinary symptoms. No history of smoking, alcohol, surgeries, family conditions, or medications. The patient had environmental chemical exposure near an oil refinery. An initial ultrasound and Cystoscopy showed a sizable bladder tumor. A complete TURBT was done, followed by cauterization and catheter placement. The tumor was diagnosed as low-grade urothelial carcinoma (pT1). Follow-up cystoscopies after 3 and 9 months showed no recurrence., Clinical Discussion: Urothelial bladder carcinoma (UBC) is linked to occupational exposure and smoking. Limited research exists on UBC in young patients, but genetic factors and environmental exposure may play a role. In young individuals, UBC typically presents as low-grade, non-muscle invasive tumors (NMIBC). Transurethral resection may be sufficient for low-grade tumors, and postoperative follow-up with ultrasound is important. Larger tumors have a higher risk of recurrence and progression., Conclusion: The present case emphasizes the need to consider urothelial bladder carcinoma as a potential cause of hematuria in young patients and conduct a thorough evaluation of all risk factors. Future research is needed to establish evidence-based guidelines for managing this condition in pediatric and adolescent patients., Competing Interests: Declaration of competing interest All authors declared no conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The purpose of this study was to perform a systematic review of the psychometric properties of the Sibling Perception Questionnaire (SPQ) in children with a sibling with a chronic illness. Full-text journal articles were located in APA PsycInfo and PubMed databases and by searching the reference lists of studies. Studies included reported on the psychometric properties of at least one domain of the SPQ in children under 18 years who had a sibling with a chronic health condition. Twenty-three studies met inclusion criteria. The quality of the evidence was assessed with the COSMIN Risk of Bias Checklist. None of the included studies reported on all 10 properties recommended by COSMIN and there was extensive variability in the quality of methods used to assess the psychometric properties of the SPQ across studies. The negative adjustment scale demonstrated the strongest internal consistency reliability across the studies included in the review. Eight studies assessed convergent validity, with all but one demonstrating the SPQ total score to be adequately correlated with like constructs. The studies included in the review provided preliminary support for the responsive of the SPQ in detecting clinically significant changes due to an intervention. Taken as a whole, findings from this review provide preliminary evidence for the SPQ as a reliable, valid, and responsive measure in children who have a chronically ill sibling. Future studies with stronger methodological quality and that assess test re-test reliability, known groups validity, and the factor structure of the SPQ are needed. This work did not receive any funding and the authors have no competing interests to declare.

Competing Interests: None declared

Competing Interests: None declared

Gathering information is crucial for maximizing fitness, but requires diverting resources from searching directly for primary rewards to actively exploring the environment. Optimal decision-making thus maximizes information while reducing effort costs, but little is known about the neuro-computational implementation of this tradeoff. We present a Reinforcement Meta-Learning (RML) computational model that solves the trade-off between the value and costs of gathering information. We implement the RML in a biologically plausible architecture that links catecholaminergic neuromodulators, the medial prefrontal cortex and topographically organized visual maps and show that it accounts for neural and behavioral findings on information demand motivated by instrumental incentives and intrinsic utility. Moreover, the utility function used by the RML, encoded by dopamine, is an approximation of variational free energy. Thus, the RML presents a biologically plausible mechanism for coordinating motivational, executive and sensory systems generate visual information gathering policies that minimize free energy., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background/aims: To assess the association between placental morphology and neonatal and infant anthropometry, including analysis by sex., Study Design: Data from the ROLO Kids [Randomized COntrol Trial of LOw Glycaemic Index in Pregnancy] study were analyzed including placental weight and morphology. Placental, anthropometric and skinfold measurements were recorded as markers of adiposity in 196 neonates and 215 infants at 6 months of age. Ratios including subscapular-to-triceps skinfold ratio and waist-to-height ratio were used as markers of central adiposity, while the sum of all skinfolds and subscapular plus triceps skinfolds were used as markers of general adiposity. Analysis was performed for total groups and by sex., Results: On simple linear regression placental weight was associated with neonatal and infant anthropometric measurements. On multiple regression, the placental weight was associated with birth weight. In the neonatal period placental weight was associated with general adiposity in males only (sum of skinfolds ( B 0.007, p  < .001) and subscapular + triceps skinfolds a marker of general adiposity ( B 0.004 p  < .001)). At 6 months of age placental length was positively associated with central adiposity in the total group ( B 0.006, p .036) and maximum cord diameter was inversely associated with infant central adiposity ( B  - 0.309 p .043) in males only., Conclusion: The placental phenotype is associated with anthropometry at birth and this association persists to early infancy with a stronger relationship noted in this cohort amongst males. This suggests sexual dimorphism may play a role in the impact of the placenta on infant anthropometry.

Animals are intrinsically motivated to obtain information independently of instrumental incentives. This motivation depends on two factors: a desire to resolve uncertainty by gathering accurate information and a desire to obtain positively-valenced observations, which predict favorable rather than unfavorable outcomes. To understand the neural mechanisms, we recorded parietal cortical activity implicated in prioritizing stimuli for spatial attention and gaze, in a task in which monkeys were free (but not trained) to obtain information about probabilistic non-contingent rewards. We show that valence and uncertainty independently modulated parietal neuronal activity, and uncertainty but not reward-related enhancement consistently correlated with behavioral sensitivity. The findings suggest uncertainty-driven and valence-driven information demand depend on partially distinct pathways, with the former being consistently related to parietal responses and the latter depending on additional mechanisms implemented in downstream structures., (© 2022. The Author(s).)

The management of endometriomas in women wishing to preserve their fertility is complex. While surgery can help to achieve pregnancy in some, it may also have a detrimental effect on a woman's ovarian reserve. The present article reviews the impact of endometriomas on fertility and the different management approaches that should be considered in women who wish to preserve their fertility. This study also reviews the role of assisted reproduction in the setting of endometriomas, and the evolving role of oocyte cryopreservation for this benign but progressive disease. Using evidence from the latest guidelines and major publications, we emphasize the need to consider the woman's future fertility when navigating the diverse range of management strategies available, and outline an evidence-based framework to help facilitate fertility-friendly discussion, counseling and management of this complex disease., (© 2021 International Federation of Gynecology and Obstetrics.)

Background: The aim of this review was to discuss the current and newly emerging antiresorptive medications and their potential implications for dental surgeries., Types of Studies Reviewed: The authors searched PubMed (MEDLINE), Cochrane, Embase, and other electronic databases for articles related to osteonecrosis of the jaw and medication-related osteonecrosis of the jaw (MRONJ). In addition, the authors hand searched the bibliographies of all relevant articles, the gray literature, textbooks, and guidelines in association position statements., Results: The following information for MRONJ risk should be evaluated before any invasive dental procedure: metastatic carcinoma has a higher risk than osteoporosis; parenterally administered bisphosphonates and denosumab have a higher risk than orally administered bisphosphonates or antiangiogenic agents; dose and duration of medication received; adjunctive medications or combination of antiresorptive agents also may increase the risk of MRONJ; additive factors and comorbidities such as diabetes, autoimmune disease, immunosuppression, or any condition that might affect healing negatively would result in potentially higher risk of developing MRONJ; angiogenic inhibitors as part of a cancer treatment regimen, with or without antiresorptive medication, are considered high risk., Practical Implications: Patients who received antiresorptive therapy for malignancy were at higher risk of developing MRONJ than those who received the therapy for osteoporosis, regardless of the route of administration and type of drug. Antiangiogenic agents, bevacizumab, aflibercept, and tyrosine kinase inhibitors such as sunitinib were implicated most commonly in the development of MRONJ. Patients who are taking multiple doses of angiogenic inhibitors should be monitored closely for early diagnosis of possible MRONJ., (Copyright © 2022 American Dental Association. Published by Elsevier Inc. All rights reserved.)