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Computational Modeling of Patient-Specific Healing and Deformation Outcomes Following Breast-Conserving Surgery Based on MRI Data
No full textPurpose: Breast-conserving surgery (BCS) is the standard of care for early-stage breast cancer, offering recurrence and survival rates comparable to mastectomy while preserving healthy breast tissue. However, surgical cavity healing post-BCS often leads to highly variable tissue remodeling, including scar tissue formation and contracture, leading to visible breast deformation or asymmetry. These outcomes significantly impact patient quality of life but are difficult to predict due to the complex interplay between biologic healing processes and individual patient variability. To address this challenge, we extended our calibrated computational mechanobiological model of post-BCS healing by incorporating diagnostic imaging data to evaluate how patient-specific breast and tumor characteristics influence healing trajectories and deformation.
Methods: The model captured multi-scale biologic and biomechanical processes, including fibroblast activity, collagen remodeling, and nonlinear tissue mechanics, to simulate time-dependent tissue remodeling. Patient-specific breast and tumor geometries from preoperative magnetic resonance imaging (MRI) were integrated into finite element simulations of cavity healing, whose outputs trained Gaussian process surrogate models for rapid prediction of healing dynamics and breast surface deformation across diverse patient profiles.
Results: These models revealed how factors including breast density, cavity volume, breast volume, and cavity depth influence post-surgical cavity contraction and measures of breast surface deformation.
Conclusion: This framework has the potential to provide a personalized, predictive tool for surgical planning and decision-making, enabling clinicians and patients to anticipate healing trajectories and cosmetic outcomes, with the goal of optimizing surgical results and enhancing patient quality of life
Next-generation precision medicine for pain
No full textChronic pain remains a massive problem in society in general, and in mental health patients in particular, being strongly bi-directionally connected to mental health. Lack of widespread use of objective information has hampered treatment and prevention efforts. Pain is a spectrum of severity, from transient vague discomfort to chronic excruciating incapacitation. Blood biomarkers that track pain severity can provide a window into the biology of pain, as well as could help with assessment and treatment. A previous study by us was positive. Here we describe new studies we conducted trans-diagnostically in psychiatric patients, starting with the whole genome, to expand the identification, prioritization, validation and testing of blood gene expression biomarkers for pain. We carried out two separate studies, on two different platforms, microarrays and RNA sequencing, using for each study a multiple independent cohorts design. This ensured biological and technical reproducibility. We then focused at the end on biomarkers that were convergent and reproducible between the two studies. We found new as well as previously known biomarkers that were predictive of high pain states, and of future emergency department visits related to them, using cross-sectional and longitudinal approaches. Using a polyevidence score, the overall top decreased in expression biomarker ("pain-suppressor gene") was CD55, a gene that suppresses the complement cascade and cell damage. The top increased biomarker ("algogene") was ANXA1, a gene that is an effector of glucocorticoid-mediated responses and regulator of the inflammatory processes. The top biological pathways were related to cellular response to TNF and to neuroinflammation. The top upstream regulator was TNF. Top therapeutic matches overall were the medications lithium and ketamine, as well as the nutraceuticals omega-3 fatty acids and magnesium. Drug repurposing bioinformatic analyses also identified the potential of carvedilol, sirolimus, budesonide, berbamine, and quetiapine, as well as of medications already used to treat pain such as amyleine, sulindac, sufentanil, carbamazepine, and meclofenamic acid, that serve as de facto positive controls. Additionally, we show how personalized patient reports for doctors would look like based on blood biomarkers testing, to aid with objective assessment of severity and risk, as well with individualized matching to medications and nutraceuticals. Given the fact that pain disorders are highly prevalent, can severely affect quality of life, and even lifespan, there is an urgent need for insights and tools such as the ones we have developed to be applied to and improve clinical diagnosis, treatment, and prevention options
Sex, hormones, and lung health
No full textSex plays an essential role as a biological variable in lung health, leading to observed differences in lung disease susceptibility. Some respiratory conditions are more common in women than men, especially after puberty, indicating the influence of ovarian hormones on disease mechanisms. Other conditions display sex disparities that begin in utero and progress throughout the life span. Preclinical and clinical studies have indicated that both sex chromosomes and hormones can influence lung disease outcomes, immune responses, susceptibility to viral and bacterial infection, and responses to environmental challenges. This review summarizes the latest research on how sex affects lung physiology and health, drawing on a wide range of studies in respiratory physiology and anatomy, genetics, molecular and cellular biology, environmental health, and immunity. We emphasize how biological sex, gonadal hormones, and occupational and environmental exposures can impact disease mechanisms and outcomes. As clinical outcomes among women have not improved at the same rate as men over the past few decades, it is crucial to understand the role played by the sex variable in designing strategies to prevent and mitigate disease. The collective research indicates that sex-induced differences in the respiratory system are essential determinants of physiological responses and clinical outcomes
P-35. Long-Term Healthcare Utilization and Expenditures for Infants with Invasive Bacterial Infections During Birth Hospitalizations
No full textBackground:
Invasive bacterial infections among newborns are associated with significant morbidity, mortality, and economic costs. While most newborns fully recover following the acute phase of illness, some develop long-term complications that require additional medical care. The objective of this real-world study was to estimate long-term healthcare utilization and expenditures among infants with bacterial meningitis or sepsis during their birth hospitalizations.
Methods:
A retrospective cohort design and the PharMetrics Plus Healthcare Claims Database (01/01/16-04/30/24) were employed. Study population comprised infants who, during their birth hospitalizations, had diagnosis codes for meningitis or sepsis due to bacterial pathogens as well as comparison infants without evidence of these conditions matched (1:1) on birth gestational age, birth weight, sex, high-risk conditions, and an estimated propensity score. Infants with evidence of meningitis and sepsis were included in the former subgroup. Study measures—including numbers of, and expenditures (2023 USD) for, all-cause hospitalizations, ambulatory encounters, and outpatient prescriptions—were ascertained during the 1-year period following discharge from the birth hospitalization and were annualized to adjust for differential follow-up.
Results:
Among infants with bacterial meningitis and matched comparators (N [pairs] = 678), 61% were born prematurely, 27% had birthweight < 1500 grams, and 56% had ≥1 high-risk condition; among those with sepsis (N [pairs] = 33,478), corresponding values were 48%, 20%, and 33%. Mean levels of healthcare utilization and expenditures during the 1-year follow-up period were markedly higher among infants with meningitis (total expenditures: by 39,257) versus matched comparison infants; differences were largely attributable to acute-care hospitalizations (Table).
Conclusion:
Invasive bacterial infections among infants place a substantial burden on the US healthcare system, including treatment of acute illness as well as associated long-term complications. Interventions targeting the prevention of infant bacterial infections have the potential to yield significant cost offsets
Bridging Mammography and Lung Cancer Screening: Eligibility, Uptake and Potential Impact
No full textIntroduction: Lung cancer (LC) is the top cancer killer in women, yet lung cancer screening (LCS) uptake is substantially lower than mammography. Leveraging the reach of mammography programs may improve LCS uptake, but the potential gain in LC detection from this approach is unknown. This study aimed to determine the proportion of women with LC eligible for both screenings, potential LC detection via integrated screening, and factors influencing each screening uptake among those dually eligible.
Methods: This retrospective cross-sectional study included 345 women newly diagnosed with LC presenting at a Midwestern Comprehensive Cancer Center (2019-2020). Pre-diagnosis LCS-eligibility was determined per 2013 and 2021 USPSTF criteria, LCS-uptake per 2013 criteria, and mammography-eligibility per 2016 criteria. We assessed sociodemographic variables associated with screening uptake among dually eligible women.
Results: Among 345 women (mean [SD] age 64.8 [11.35] years), 73.3% were eligible for mammography, while 43.5% were eligible for LCS (2013), increasing to 49.3% (2021). Mammography uptake (41.5%) substantially exceeded LCS uptake (13.9%). Overall, 45.2% were eligible for both screenings, representing 92.4% (157/170) of all LCS-eligible (2021) cases. Notably, 20.3% were LCS-eligible (2021) and received mammography, that is, 41.2% (70/170) of LCS-eligible cases. Among dually eligible women, rural residency correlated with lower LCS uptake (odds ratio [OR], 0.42; 95% CI = 0.19-0.94; p = 0.031), whereas receiving mammography correlated with higher LCS uptake (OR, 2.67; 95% CI = 1.21-5.87; p = 0.013).
Conclusion: A substantial proportion of women with LC who are LCS-eligible underwent mammography, representing a missed opportunity for earlier LC detection. Integrating these screenings could enhance LC detection, especially for rural residents who experience disparities in LCS but not mammography uptake
WHO classification of skin tumours: key updates in the fifth edition
No full textThe 5th edition of the World Health Organization Classification of Tumours (WCT) serves as a foundation for global diagnostic standards in tumour pathology. Similar to other volumes in this series, the Skin Tumours (Skin5) edition follows a standardized approach. This edition introduces two new chapters: 'Tumours of the nail unit' and 'Metastases to skin', along with new entities across relevant chapters. This review article provides an overview of the updates in Skin5 based on currently published evidence, with emphasis on newly introduced chapters and newly described entities that involve the skin, in particular, epidermal, melanocytic and appendageal tumours
Sex differences in the physiological response to acute anterior cruciate ligament overuse
No full textYoung female athletes are at least two times more likely to suffer a non-contact anterior cruciate ligament (ACL) injury than males, and one and a half times more likely to have a recurrent injury. Primary factors contributing to this disparity are less stiff and weaker ACLs, and greater knee laxity than males. Also, some evidence suggests females may exhibit a muted response to repetitive, high-intensity activity compared to males. Here, we test the hypothesis that female ACLs would accumulate more extracellular matrix (ECM) damage and show a delayed reparative response compared to males under equivalent submaximal fatigue loading. Using an adolescent mouse model (C57BL/6J), ACLs were cyclically loaded to induce an acute submaximal overuse injury (n = 20 per sex). ECM damage was assessed via immunofluorescence, apoptotic activity via immunohistochemistry, and gene expression changes through RNA-sequencing at 24 and 72 h post-injury. Female ACLs showed significantly greater collagen denaturation than males (P = 0.05), with no significant difference in apoptosis. Transcriptomic analyses suggest sex-specific healing strategies. Females followed a slower, more regulated reparative response, whereas males exhibited a more aggressive repair approach emphasizing mitosis, cell proliferation and migration. These findings may explain higher female ACL failure rates as greater matrix damage combined with a slower repair response could lead to injury propagation if reloading occurs prematurely. By contrast, the faster male response might reduce recurrence risk but increase fibrosis potential. If confirmed further, these potential physiological differences may require the implementation of sex-specific strategies for training and recovery regimens to prevent overuse injuries and optimize healing outcomes in young athletes. KEY POINTS: Females are at least twice as likely to suffer an anterior cruciate ligament injury (ACL) relative to males when participating in the same, or comparable sport. Sex differences in ACL structure and function are primary factors for increased female injury risk. Here, we show that the female mouse ACL accrues more collagen matrix damage than males under comparable fatigue loads. Additionally, female mice demonstrated a slower, more regulated ACL reparative response, while male mice exhibited a more aggressive repair approach emphasizing mitosis, cell proliferation and migration. These results, if translatable, may in part explain the sex-disparity in ACL failure rates with greater matrix damage and a slower repair response increasing the risk of reinjury, and a faster male response potentially reducing injury recurrence risk with further physical activity
Plasma inflammatory biomarkers lack strong association with cognitive outcomes among young adults with perinatal HIV exposure and/or acquisition
No full textBackground: Our objective was to evaluate the association between inflammatory biomarkers and NIH Toolbox cognitive outcomes in young adults with perinatal HIV exposure but uninfected (YAPHEU) and those with perinatal HIV (YAPHIV), with or without prior HIV disease progression.
Setting: We analyzed participants with plasma samples and NIH Toolbox cognitive scores at entry into a multisite longitudinal cohort in the United States.
Methods: Participants were subdivided into groups by HIV status: YAPHIV who experienced a stage 3 event (YAPHIV-W3, indicating history of HIV disease progression), YAPHIV who had not (YAPHIV-WO3), and YAPHEU. Fifteen biomarkers were measured. Principal component analysis was used to derive biomarker principal component (PC) scores, with 4 PCs retained, accounting for 67% of the variance within biomarker correlations. We computed Pearson correlations of individual log-transformed biomarkers and PCs with NIH Toolbox Total, Fluid, and Crystallized Cognition Composite Scores, separately by HIV status.
Results: A total of 638 participants (135 YAPHIV-W3, 383 YAPHIV-WO3, 117 YAPHEU, and 3 YAPHIV without stage 3 information) met eligibility criteria. The median age was 20.6 years (Interquartile Range 18.6-24.6), and 60% (n = 381) were female. In both YAPHIV-WO3 and YAPHIV-W3, PC3 was weakly negatively correlated with Fluid and Total Cognition Composite Scores. In YAPHIV-W3, PC2 was also weakly negatively associated with Fluid Cognition. In YAPHEU, PC1 was weakly positively correlated with Fluid Cognition and weakly negatively correlated with Crystallized Cognition.
Conclusions: No inflammatory biomarkers or summary score measures showed meaningful associations with worse cognitive outcomes in a population with long-term perinatal HIV acquisition or exposure
Indiana's 2024 Behavioral Health and Human Services Workforce Snapshot: All Associate-Level Professionals
No full textThis document is a 2024 data snapshot of Indiana’s actively practicing associate-level Behavioral Health and Human Services (BHHS) professionals (including LMHCA, LMFTA, LCACA, and LACA). It presents aggregate workforce statistics, notably the total number of active professionals (783), their primary practice settings (with private practice being the largest category), and the types of services most commonly provided, such as mental health services, family and children services, addictions treatment, and general counseling. The document also highlights key client populations served, with a strong focus on adults, individuals in recovery, and general mental health populations, and includes limited information on geographic distribution and training locations (Indiana, neighboring states, other U.S. states, and other countries)
Cross‐Sectional Analysis of Plasma GFAP Across Alzheimer's Disease Stages
No full textBackground:
Alzheimer's Disease (AD) is the leading cause of dementia worldwide, with Late‐Onset Alzheimer's Disease (LOAD) comprising over 90% of cases. Multiple biomarkers are being investigated for their association with pathologies associated with AD including glial acidic fibrillary protein (GFAP). GFAP levels have been observed to increase in plasma and cerebrospinal fluid of AD patients, particularly in response to amyloid‐β, before behavioral symptoms appear. This indicates GFAP's utility as an early‐AD biomarker. However, GFAP levels vary significantly between subjects due to various factors, such as demographics or medical comorbidities. To use plasma GFAP levels as an accurate biomarker in AD studies, it is essential to fully understand and identify all potential reasons for variation in its levels.
Method:
The uniform data set (UDS), which contains longitudinal subject data from AD Centers (ADC) was obtained from the National Alzheimer's Coordinating Center (NACC). Total GFAP levels from 23 ADC's were measured by the National Centralized Repository for Alzheimer's Disease and Related Dementias (NCRAD) using Quanterix Simoa‐HDx (N4PE and N2PB). Results were log10‐transformed and z‐scored for analysis. A total of 3,456 unique subjects at a single visit, aged 60+, were included in this cross‐sectional analysis. T‐tests, one‐way ANOVAs, Tukey's‐ HSD Post‐Hoc and linear regression were used to examine the association of GFAP levels with diagnosis, pathology, demographics and comorbid conditions.
Result:
Analysis showed that GFAP levels varied significantly (p‐value < 0.05) with age in addition to sex, APOE genotype, elevated amyloid PET, hippocampal atrophy, and cognitive status. The non‐demographic associations were not significantly modified when adjusting for the subjects' age despite a significant association of GFAP levels with age overall.
Conclusion:
Plasma GFAP levels differed significantly between males and females, emphasizing the need to account for sex differences in biomarker research. Plasma GFAP levels show strong associations with risk alleles, elevated amyloid PET levels, hippocampal atrophy, and cognitive status, supporting its potential as a biomarker for AD diagnosis. Future efforts will focus on exploring the impact of changes in GFAP on changes in atrophy, cognitive decline, and how these relationships are modified by comorbid conditions