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Amyloid-related default mode network hyperconnectivity and longitudinal decline in network distinctiveness in preclinical Alzheimer's disease
No full textIntroduction: We investigated stage-specific alterations in functional connectivity (FC) of the default mode network (DMN) across the Alzheimer's disease (AD) continuum and tested whether early amyloid beta (Aβ)-related changes in within-DMN FC (DMN-FCwithin) predicted longitudinal alterations in DMN between-network connectivity (DMN-FCbetween).
Methods: Resting-state functional magnetic resonance imaging (fMRI) data were analyzed from 396 older adults: Aβ-negative cognitively normal (CN-, n = 213), Aβ-positive CN (CN+, n = 37), Aβ-positive mild cognitive impairment (MCI+, n = 72), and Aβ-positive dementia (dementia+, n = 74). Cross-sectional analyses compared DMN-FC across groups and examined associations with continuous Aβ burden at baseline. Longitudinal analyses in 171 CN participants with 2-year follow-up (CN-, n = 147; CN+, n = 24) tested whether baseline DMN-FCwithin predicted changes in DMN-FCbetween.
Results: CN+ individuals showed elevated DMN-FCwithin and reduced DMN-FCbetween relative to other groups. In CN, Aβ burden was associated with FC, and baseline DMN-FCwithin predicted longitudinal increases in DMN-FCbetween only in CN+.
Discussion: Aβ-related hyperconnectivity characterizes preclinical AD and may drive progressive network-level vulnerability.
Highlights: Cognitively normal amyloid beta (Aβ)-positive (CN+) individuals showed stronger connectivity within the default mode network (DMN). CN+ individuals also showed weaker links between the DMN and other brain networks. Amyloid was not linked to connectivity changes in cognitively impaired adults. Higher DMN connectivity predicted broader network changes in CN+ individuals
Characterization of Spirometric Response to Standard-of-care Treatment in Lung Allograft Recipients With Bronchiolitis Obliterans and the Utility of Spirometric Criteria for Rescue Therapy: Implications for the Design of Risk-stratified Clinical Trials
No full textBackground: The spirometric response to standard-of-care (SOC) immunosuppressive therapy for the management of bronchiolitis obliterans syndrome (BOS) has been sparsely reported in the literature. Data from a Medicare-approved Registry were analyzed to characterize the effectiveness/durability of a wide range of SOC interventions to manage the decline of lung function and to validate the study spirometric criteria for initiation of rescue therapy.
Methods: Lung transplant recipients with refractory BOS at 21 US collaborating centers were enrolled in the Registry. Data included both nonspirometric (eg, demographic, Immunosuppressive Regimens for management of BOS) and spirometric parameters (ie, forced expiratory volume in 1 s [FEV 1 ] measurements and derived indices). The utility of study FEV 1 criteria for treatment (ie, statistically significant rate of FEV 1 decline >30 mL/mo) was evaluated by comparing the spirometric course between participants who met or did not meet this criterion.
Results: Only 21% of participants treated with SOC therapy had >50% decrease (76 ± 25% decrease) in the rate of FEV 1 decline. Although 51% of participants had a partial response (rate of FEV 1 decline decreased on average 71%), 49% of participants had a substantial increase (mean increase 224%). The FEV 1 criterion for treatment was able to identify 19% of participants (48/258) who achieved durable stabilization (ie, nonsignificant rate of FEV 1 <30 mL/mo) with SOC therapy.
Conclusions: Patients with BOS have a widely variable response to SOC therapy. Our findings support the use of FEV 1 rate of decline to assess response to SOC therapy and to ensure appropriate assignment of participants with refractory BOS to rescue therapy treatment cohorts
The Price of Dedication: An Analysis of Wage Trajectories in State and Local Public Health From 2017 to 2024
No full textContext: Salary plays a crucial role in recruiting and retaining employees in public health; however, information about trends in compensation is limited.
Objective: To analyze trends in earnings among state and local governmental public health workers between 2017 and 2024.
Methods: Data used are from the Public Health Workforce Interests and Needs Survey for the years 2017, 2021, and 2024. The analytic sample comprised 34 379 full-time permanent employees with complete salary data in 2017, 32 862 in 2021, and 45 241 in 2024, representing state health agency (SHA) and local health department (LHD) public health workers in each respective year. We performed a multi-cross-sectional analysis using descriptive and bivariate analyses and interval-based regression techniques to explore relationships between annualized earnings and key individual and agency-level characteristics.
Results: Earning patterns in 2024 were largely consistent with historical patterns. Individual and agency-level characteristics continued to play a significant role in shaping salary. Higher salaries remained associated with higher supervisory status, longer tenure, higher educational attainment, salaried (versus hourly) employment, union/bargaining unit representation, and employment setting within SHAs versus LHDs. Between 2017 and 2024, annual earnings for full-time permanent employees increased from 73 299 in 2024, representing a 27% average increase of $15 482. However, when adjusted for inflation, annual wages showed no real growth, indicating that earnings remained largely stable in terms of purchasing power during this timeframe. Subgroups that experienced declines in inflation-adjusted salaries between 2017 and 2024 include executives, employees with longer tenures, employees with doctoral degrees, and employees with public health degrees versus degrees in other fields.
Conclusions: The continued decline in inflation-adjusted earnings for certain groups and persistent gender and racial pay gaps indicate that without targeted interventions, public health agencies may face challenges in retaining experienced professionals, attracting new talent, and ensuring workforce stability
2026 IUSM Plastic Surgery Research Day Program
No full textOfficial programs for the third annual Indiana University School of Medicine Plastic Surgery Research Day held at Sidney & Lois Eskenazi Hospital on February 4, 2026
Optimizing Control Definitions in Opioid Use Disorder Genetic Research Using Electronic Health Records
No full textAmidst the opioid crisis, understanding the genetic basis of opioid use disorder (OUD) is crucial for identifying biological mechanisms and intervention points. However, genome-wide association studies (GWASs) have been hampered by inadequate sample sizes and often the use of control populations not assessed for prior opioid exposure. Because opioid exposure is a prerequisite for the development of OUD, consideration of exposure history in controls is important. Electronic health record data (EHR) paired with genomic information allow a broader sampling of patients with OUD and exposed controls. We leveraged data across two healthcare systems to evaluate the impact of using controls not screened for opioid exposure ('generic') versus minimally opioid-exposed control ('exposed'). First, at the phenotypic level, we conducted phenome-wide association studies (PheWAS) to compare the medical comorbidity profiles of OUD cases when using generic versus exposed controls. While PheWAS results for OUD-related comorbidities were more pronounced when using the generic group, 83% of the disease associations were overlapping and of similar effect sizes. Second, at the genetic level, we conducted GWAS (cases vs. generic; cases vs. exposed) and assessed differences in genetic correlations and degrees of phenotypic misclassification. Genetic results were concordant across control groups based on heritability (generic: 0.16 ± 0.07 vs. 0.10 ± 0.07), associations with the coding OPRM1 variant rs1799971 (pgeneric = 8.83E-03 vs. pexposed = 1.83E-02) and genetic correlations with prior OUD GWAS (rg-generic = 0.83 ± 0.26 vs. rg-exposed = 0.78 ± 0.27). Although GWASs were limited by sample size (Ngeneric = 6269, Nexposed = 6365), compared to an independent OUD GWAS (N = 425 944), the dilution value for the two GWAS was not different from 1, suggesting no major impact of phenotypic misclassification. This study represents the first effort to enhance OUD genetic research through optimization of control definitions using EHR data. Generic controls ascertained within the US health systems, where exposure to prescription opioids is high, offer a practical alternative for genetic studies of OUD
Fulfilling the Promise: A Mixed-Methods, Deweyan Analysis of the 21st Century Scholars Program at Ivy Tech
No full textIUIThis dissertation examines the structural fit between the 21st Century Scholars (TFCS) program’s eligibility requirements and the lived realities of student Scholars at Ivy Tech Community College in Muncie, Indiana. Drawing on John Dewey’s pragmatist philosophy, particularly his concepts of education, democracy, and vocational development, the study explores how program rules intersect with students’ work obligations, family responsibilities, and community involvement.
Employing an explanatory sequential mixed-methods design, the research begins with a student experience survey administered to all 21st Century Scholars who attended Ivy Tech Muncie between 2016 and 2024. The survey identifies statistical relationships between eligibility compliance and key variables such as employment hours, caregiving duties, and access to campus resources. Qualitative interviews with a subset of respondents follow, offering narrative insights into how students experience, interpret, and navigate those structural tensions.
Findings reveal significant misalignments between policy expectations, particularly the 30-credit annual requirement, and students’ lived experiences, often shaped by economic precarity and competing obligations. These misalignments not only threaten eligibility but also undermine the broader goals of higher education as defined by Dewey: to cultivate democratic participation, personal growth, and vocational purpose. Ultimately, the study shows that while the TFCS program aims to expand access to college for low-income students, its increasingly restrictive compliance model creates barriers that disproportionately affect the very students it intends to support. The dissertation concludes by recommending targeted policy changes and institutional interventions—grounded in Deweyan educational theory—that promise to better support student success, foster shared interests, and realign the program with its democratic ideals
The concurrence of lung malignancies and organizing pneumonia
No full textIntroduction: Organizing pneumonia (OP) is often considered a benign finding, but in some cases, it may be associated with underlying malignancy. With the increasing use of minimally invasive biopsy techniques, understanding the relationship between OP and lung cancer is critical to avoid delayed or missed diagnoses. This study aims to evaluate the prevalence of OP and lung malignancy and report characteristics of these cases.
Material and methods: A retrospective review was conducted of all lung pathology reports at Indiana University from January 1, 2010, to January 1, 2023, encompassing over 8,000 cases. Cases with histopathologic diagnoses of OP with and without lung malignancy were identified; relevant clinical, radiologic, and follow-up data were extracted. Using language extraction, we identified pathology cases showing both organizing pneumonia and carcinoma (Cohort 1) and transbronchial biopsies identified as "organizing pneumonia" (Cohort 2). Cohort 2 was selected to reflect current clinical practice.
Results: In Cohort 1 (n=57), 88% of samples demonstrating both organizing pneumonia and malignancy were obtained via surgical resection. Among these, squamous cell carcinoma accounted for 46% and adenocarcinoma for 37% of cases, with all T-stages represented (44% T1, 29% T2, 16% T3, and 11% T4). In this cohort, thirty-eight prior biopsy samples prior to surgery were reviewed; 76% revealed malignancy, but none showed definitive organizing pneumonia likely due to focal nature of OP. Cohort 2 (n=40), 7.5% of patients in whom organizing pneumonia was identified through minimally invasive bronchoscopic sampling were ultimately diagnosed with concurrent lung cancer. All required repeat tissue sampling for cancer diagnosis.
Conclusion: Lung malignancy is known to be associated with OP. A high degree of suspicion should be maintained if OP is found on minimally invasive techniques, particularly if malignancy is strongly suspected
Low‐grade glial neoplasms of germ cell origin may represent maturation of embryonic‐type neuroectodermal elements
No full textAims: Glial tumours of germ cell origin are relatively rare in men, occurring predominantly after chemotherapy. Many exhibit low-grade histological features within a spectrum that includes teratomas with mature glial/ganglioglial elements and pure low-grade tumours with glial/ganglioglial phenotype (LGGT) that resemble gliomas/gangliogliomas of the central nervous system. Because foci of glial differentiation are very often seen in association with embryonic-type neuroectodermal tumour (ENT), we hypothesise that LGGTs may represent differentiation of embryonic-type neuroectodermal elements of teratoma and/or ENT.
Methods and results: To address this hypothesis, we compared LGGTs, ENT, non-teratomas, and teratomas using microRNA and DNA methylation analyses. Seven LGGTs underwent microRNA-371~373 analysis and genomic methylation profiling. Evidence of a prior or concurrent germ cell tumour component containing embryonic neuroectoderm (including overt ENT) was present in 4 LGGTs. None of the tested LGGTs were positive for miR-371a-3p, with three cases demonstrating low levels of expression within the so-called "grey zone". Unsupervised clustering based on microRNA-371~373 showed two clusters, one comprising non-teratomas and another including teratomas, ENTs, and LGGTs. Clustering according to top-differentially methylated probes did not demonstrate a clear separation according to histology. Genome-wide assessment of mean methylation levels using violin plots demonstrated that LGGT show a methylation profile "intermediate" between ENT and teratoma.
Conclusions: These results suggest that LGGTs of germ cell origin result from the maturation of ENT components
P-15 Peptide Enhanced Bone Graft in Transforaminal Lumbar Interbody Fusion: A Randomized, Controlled, Investigational Device Exemption Study Demonstrating Improved Composite Clinical Success
No full textStudy design: Prospective, multicenter, single-blind, randomized, controlled pivotal study.
Objective: To evaluate whether P-15L (PearlMatrix P-15 Peptide Enhanced Bone Graft) is noninferior in effectiveness to local autograft when applied in single-level instrumented transforaminal lumbar interbody fusion (TLIF).
Summary of background data: P-15L, an FDA-designated Breakthrough Drug-Device, is a composite drug-device combination bone graft containing P-15, a 15-amino acid polypeptide, which enhances cell binding, proliferation, and differentiation, resulting in bone formation.
Materials and methods: Skeletally mature patients, aged 22 to 80 years, with degenerative disc disease (DDD) were randomized 1:1 to P-15L (investigational) or to the local autograft (control) during single-level TLIF with a polyetheretherketone (PEEK) cage and supplemental pedicle screw fixation. The primary outcome was composite clinical success (CCS) at 24 months, defined as: no index level secondary surgical procedures; achievement of fusion; ≥15-point improvement in Oswestry low back pain disability questionnaire (ODI) from baseline; no new or worsening persistent neurological deficit relative to baseline; and no device-related serious adverse events (SAEs).
Results: A total of 290 patients were enrolled at 33 sites: 141 (48.6%) received P-15L, and 149 (51.3%) received local autograft. P-15L was noninferior ( P <0.0001) and superior ( P =0.002) to autograft with respect to CCS, with 55.5% of the investigational group achieving composite clinical success compared with 37.5% of the control group. P-15L had a 25.8% higher fusion rate as compared with autograft for the CCS at 24 months (84.3% vs. 58.5%, respectively). Device-related SAE rates were similar in both groups.
Conclusion: P-15L was superior to local autograft in achieving clinical success at 24 months. Furthermore, P-15L produced a significantly higher fusion rate as compared with autograft. No meaningful clinical differences were found in the incidence of device-related SAEs. P-15L appears to be a safe and effective option for TLIF