Open Access Policy Articles

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The IUPUI Faculty Council adopted an open access policy on October 7th, 2014 (available from: https://openaccess.indianapolis.iu.edu/). This policy shows IUPUI's commitment to disseminating the fruits of research and scholarship as widely as possible. Open access policies increase authors’ rights, readership and citation rates for scholarly articles. The opt out provision ensures that all faculty authors have the freedom to publish in the journal of their choice.

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Now showing 1 - 10 of 26512

Entinostat plus Pembrolizumab in Patients with Metastatic NSCLC Previously Treated with Anti-PD-(L)1 Therapy
(American Association for Cancer Research, 2021) Hellmann, Matthew D.; Jänne, Pasi A.; Opyrchal, Mateusz; Hafez, Navid; Raez, Luis E.; Gabrilovich, Dmitry; Wang, Fang; Trepel, Jane B.; Lee, Min-Jung; Yuno, Akira; Lee, Sunmin; Brouwer, Susan; Sankoh, Serap; Wang, Lei; Tamang, David; Schmidt, Emmett; Meyers, Michael L.; Ramalingam, Suresh S.; Shum, Elaine; Ordentlich, Peter; Medicine, School of Medicine
Purpose: New therapies are needed to treat immune checkpoint inhibitor-resistant non-small cell lung cancer (NSCLC) and identify biomarkers to personalize treatment. Epigenetic therapies, including histone deacetylase inhibitors, may synergize with programmed cell death-1 (PD-1) blockade to overcome resistance. We report outcomes in patients with anti-programmed cell death ligand-1 [PD-(L)1]-resistant/refractory NSCLC treated with pembrolizumab plus entinostat in ENCORE 601. Patients and methods: The expansion cohort of ENCORE 601 included patients with NSCLC who previously experienced disease progression with immune checkpoint inhibitors. The primary endpoint for the phase II expansion cohort is overall response rate (ORR); safety, tolerability, and exploratory endpoints are described. Results: Of 76 treated patients, 71 were evaluable for efficacy. immune-regulated RECIST-assessed ORR was 9.2% [95% confidence interval (CI): 3.8-18.1], which did not meet the prespecified threshold for positivity. Median duration of response was 10.1 months (95% CI: 3.9-not estimable), progression-free survival (PFS) at 6 months was 22%, median PFS was 2.8 months (95% CI: 1.5-4.1), and median overall survival was 11.7 months (95% CI: 7.6-13.4). Benefit was enriched among patients with high levels of circulating classical monocytes at baseline. Baseline tumor PD-L1 expression and IFNγ gene expression were not associated with benefit. Treatment-related grade ≥3 adverse events occurred in 41% of patients. Conclusions: In anti-PD-(L)1-experienced patients with NSCLC, entinostat plus pembrolizumab did not achieve the primary response rate endpoint but provided a clinically meaningful benefit, with objective response in 9% of patients. No new toxicities, including immune-related adverse events, were seen for either drug. Future studies will continue to evaluate the association of monocyte levels and response.
The cost of elective nodal coverage in prostate cancer: Late quality of life outcomes and dosimetric analysis with 0, 45 or 54 Gy to the pelvis
(Elsevier, 2022-06-27) Jensen, Garrett L.; Jhavar, Sameer G.; Ha, Chul S.; Hammonds, Kendall P.; Swanson, Gregory P.; Radiation Oncology, School of Medicine
Purpose: Elective pelvic lymph node radiotherapy (PLNRT) in prostate cancer is often omitted from definitive (n = 267) and post prostatectomy (n = 160) radiotherapy (RT) due to concerns regarding toxicity and efficacy. Data comparing patient-reported outcome measures (PROMs) with or without PLNRT is limited. Our long-term supposition is that PLNRT, particularly to higher doses afforded by IMRT, will decrease pelvic failure rate in select patients. We aim to establish the impact of two different PLNRT doses on long term quality of life (QOL). Methods and materials: Prostate cancer patients (n = 428) recorded baseline scores using the Expanded Prostate Cancer Index Composite (EPIC), prior to definitive or post-prostatectomy RT. PLNRT, if given, was prescribed to 45 or 54 Gy at 1.8 Gy per fraction. New EPIC scores were recorded 20-36 months after radiotherapy. Absolute change in each domain subscale and summary score was recorded, along with if these changes met minimally important difference (MID) criteria. A separate multivariate analysis (MVA) was performed for each measure. Subsequent dosimetric analysis was performed. Results: Frequency of a MID decline was significantly greater with PLNRT to 54 Gy for urinary function, incontinence, and overall. No urinary decline was correlated with PLNRT to 45 Gy. PLNRT to 54 Gy was significant for decline in urinary function, bother, irritative, incontinence, and overall score in one or both MVA models while 45 Gy was not. Postoperative status was significant for decline in urinary function, incontinence, and overall. Amongst postoperative patients, there was significantly greater decline in urinary function score in the salvage setting. Neither 54 nor 45 Gy significantly affected bowel subscale or overall score decline. Conclusions: Using conventional fractionation, adding PLNRT to 54 Gy, but not 45 Gy, correlates with worse urinary QOL, with postoperative patients experiencing a steeper decline. PLNRT had no significant impact on bowel QOL with either dose.
Genetic Testing for Heritable Cardiovascular Diseases in Pediatric Patients: A Scientific Statement From the American Heart Association
(American Heart Association, 2021) Landstrom, Andrew P.; Kim, Jeffrey J.; Gelb, Bruce D.; Helm, Benjamin M.; Kannankeril, Prince J.; Semsarian, Christopher; Sturm, Amy C.; Tristani-Firouzi, Martin; Ware, Stephanie M.; Medical and Molecular Genetics, School of Medicine
Genetic diseases that affect the cardiovascular system are relatively common and include cardiac channelopathies, cardiomyopathies, aortopathies, hypercholesterolemias, and structural diseases of the heart and great vessels. The rapidly expanding availability of clinical genetic testing leverages decades of research into the genetic origins of these diseases, helping inform diagnosis, clinical management, and prognosis. Although a number of guidelines and statements detail best practices for cardiovascular genetic testing, there is a paucity of pediatric-focused statements addressing the unique challenges in testing in this vulnerable population. In this scientific statement, we seek to coalesce the existing literature around the use of genetic testing for cardiovascular disease in infants, children, and adolescents.
Deep learning analysis of single‐cell data in empowering clinical implementation
(Wiley, 2022) Ma, Anjun; Wang, Juexin; Xu, Dong; Ma, Qin; Medical and Molecular Genetics, School of Medicine
The impact of COVID‐19 on clinical outcomes among acute myocardial infarction patients undergoing early invasive treatment strategy
(Wiley, 2022) Sharma, Prerna; Shah, Kajal; Loomba, Johanna; Patel, Arti; Mallawaarachchi, Indika; Blazek, Olivia; Ratcliffe, Sarah; Breathett, Khadijah; Johnson, Amber E.; Taylor, Angela M.; Salerno, Michael; Ragosta, Michael; Sodhi, Nishtha; Addison, Daniel; Mohammed, Selma; Bilchick, Kenneth C.; Mazimba, Sula; Graduate Medical Education, School of Medicine
Background: The implications of coronavirus disease 2019 (COVID-19) infection on outcomes after invasive therapeutic strategies among patients presenting with acute myocardial infarction (AMI) are not well studied. Hypothesis: To assess the outcomes of COVID-19 patients presenting with AMI undergoing an early invasive treatment strategy. Methods: This study was a cross-sectional, retrospective analysis of the National COVID Cohort Collaborative database including all patients presenting with a recorded diagnosis of AMI (ST-elevation myocardial infarction (MI) and non-ST elevation MI). COVID-19 positive patients with AMI were stratified into one of four groups: (1a) patients who had a coronary angiogram with percutaneous coronary intervention (PCI) within 3 days of their AMI; (1b) PCI within 3 days of AMI with coronary artery bypass graft (CABG) within 30 days; (2a) coronary angiogram without PCI and without CABG within 30 days; and (2b) coronary angiogram with CABG within 30 days. The main outcomes were respiratory failure, cardiogenic shock, prolonged length of stay, rehospitalization, and death. Results: There were 10 506 COVID-19 positive patients with a diagnosis of AMI. COVID-19 positive patients with PCI had 8.2 times higher odds of respiratory failure than COVID-19 negative patients (p = .001). The odds of prolonged length of stay were 1.7 times higher in COVID-19 patients who underwent PCI (p = .024) and 1.9 times higher in patients who underwent coronary angiogram followed by CABG (p = .001). Conclusion: These data demonstrate that COVID-19 positive patients with AMI undergoing early invasive coronary angiography had worse outcomes than COVID-19 negative patients.
Electroacupuncture Alleviates Anxiety-like Behavior in Pain Aversion Rats by Attenuating the Expression of Neuropeptide Y in Anterior Cingulate Cortex
(Elsevier, 2022) Shao, Fangbing; Du, Junying; Wang, Sisi; Cerne, Rok; Fang, Junfan; Shao, Xiaomei; Jin, Xiaoming; Fang, Jianqiao; Anatomy, Cell Biology and Physiology, School of Medicine
Background: Pain is considered as a multidimensional conscious experience that includes a sensory component and a negative affective-motivational component. Electroacupuncture (EA) is widely used to treat pain and pain-induced negative emotions, however, little is known about the mechanisms underlying the effect of EA. Objective: This study investigated the effect of EA on alleviating the anxiety-like behaviors in pain aversion rats and its anterior cingulate cortex (ACC) regulation mechanism. Methods: After a Freund's complete adjuvant (CFA)-conditioned place aversion (C-CPA) model was established in rats, EA treatment (2/100 Hz, 30 min, once/day, 4 days totally) was applied at bilateral Zusanli (ST36) and Kunlun (BL60) acupoints. Von Frey filaments were used to measure changes of pain withdrawal threshold (PWT) at indicated time points. Elevated zero maze (EZM) was used to investigate the changes of pain-related anxiety and CPA was used to investigate the changes of pain aversion. The protein expression levels of GAD67, PV, and NPY in ACC were detected by Western blotting. Results: Compared with the control group, the staying time in the "CFA-paired compartment" was significantly reduced, and the PWT was decreased in model group. In the EZM assessment, the distance and the time in open arm, as well as the number of open arm entries of model group were significantly lower than those in the control group. In the CPA assessment, the time spent in the "CFA-paired compartment" was significantly decreased in model group compared with control group, and EA reversed the changes in pain sensation and in pain-related emotions. Western blotting showed that the NPY level, but not the levels of GAD67 and PV, was significantly increased in the ACC of the model group compared to that of the control group. The increased expression of NPY in the ACC was significantly downregulated by EA, while sham EA produced no such effect. Conclusion: EA can effectively relieve the pain and pain-related emotions, and its mechanism may be achieved by down-regulating the expression of NPY in the ACC.
The protection conferred by HSD17B13 rs72613567 on hepatic fibrosis is likely mediated by lowering ballooning and portal inflammation
(Elsevier, 2023) Vilar-Gomez, Eduardo; Liang, Tiebing; Yates, Katherine; Wilson, Laura; Loomba, Rohit; Chalasani, Naga; Medicine, School of Medicine
Clinical Characterization of Juvenile Fibromyalgia in a Multicenter Cohort of Adolescents Enrolled in a Randomized Clinical Trial
(Wiley, 2023) Lynch-Jordan, Anne M.; Connelly, Mark; Guite, Jessica W.; King, Christopher; Goldstein-Leever, Alana; Logan, Deirdre E.; Nelson, Sarah; Stinson, Jennifer N.; Ting, Tracy V.; Wakefield, Emily O.; Williams, Amy E.; Williams, Sara E.; Kashikar-Zuck, Susmita; Fibromyalgia Integrative Training for Teens Clinical Trial Study Group; Childhood Arthritis and Rheumatology Research Alliance Pain Workgroup Investigators; Psychiatry, School of Medicine
Objective: Juvenile fibromyalgia (JFM) is a complex chronic pain condition that remains poorly understood. The study aimed to expand the clinical characterization of JFM in a large representative sample of adolescents with JFM and identify psychological factors that predict pain interference. Methods: Participants were 203 adolescents (ages 12-17 years) who completed baseline assessments for the multisite Fibromyalgia Integrative Training for Teens (FIT Teens) randomized control trial. Participants completed the Pain and Symptom Assessment Tool, which includes a Widespread Pain Index (WPI; 0-18 pain locations) and Symptom Severity checklist of associated somatic symptoms (SS; 0-12) based on the 2010 American College of Rheumatology criteria for fibromyalgia. Participants also completed self-report measures of pain intensity, functional impairment, and psychological functioning. Results: Participants endorsed a median of 11 painful body sites (WPI score) and had a median SS score of 9. Fatigue and nonrestorative sleep were prominent features and rated as moderate to severe by 85% of participants. Additionally, neurologic, autonomic, gastroenterologic, and psychological symptoms were frequently endorsed. The WPI score was significantly correlated with pain intensity and catastrophizing, while SS scores were associated with pain intensity and all domains of physical and psychological functioning. Depressive symptoms, fatigue, and pain catastrophizing predicted severity of pain impairment. Conclusion: JFM is characterized by chronic widespread pain with fatigue, nonrestorative sleep, and other somatic symptoms. However, how diffusely pain is distributed appears less important to clinical outcomes and impairment than other somatic and psychological factors, highlighting the need for a broader approach to the assessment and treatment of JFM.
Risk Stratification of Pancreatic Cysts With Confocal Laser Endomicroscopy
(Elsevier, 2022-02-03) Singh, Ritu R.; Perisetti, Abhilash; Pallav, Kumar; Chandan, Saurabh; De Leon, Mariajose Rose; Sharma, Neil R.; Medicine, School of Medicine
In the modern era of high-quality cross-sectional imaging, pancreatic cysts (PCs) are a common finding. The prevalence of incidental PCs detected on cross-sectional abdominal imaging (such as CT scan) is 3%-14% which increases with age, up to 8% in those 70 years or older. Although PCs can be precursors of future pancreatic adenocarcinoma, imaging modalities such as CT scan, MRI, or endoscopic ultrasound with fine-needle aspiration (EUS-FNA) are suboptimal at risk stratifying the malignant potential of individual cysts. An inaccurate diagnosis could potentially overlook premalignant lesions, which can lead to missed lesions, lead to unnecessary surveillance, or cause significant long-term surgical morbidity from unwarranted removal of benign lesions. Although current guidelines recommend an EUS or MRI for surveillance, they lack the sensitivity to risk stratify and guide management decisions. Needle-based confocal laser endomicroscopy (nCLE) with EUS-FNA can be a superior diagnostic modality for PCs with sensitivity and accuracy exceeding 90%. Despite this, a significant challenge to the widespread use of nCLE is the lack of adequate exposure and training among gastroenterologists for the real-time interpretation of images. Better understanding, training, and familiarization with this novel technique and the imaging characteristics can overcome the limitations of nCLE use, improving clinical care of patients with PCs. Here, we aim to review the types of CLE in luminal and nonluminal gastrointestinal disorders with particular attention to the evaluation of PCs. Furthermore, we discuss the adverse events and safety of CLE.
Anti-cytomegalovirus antibody levels stratify human immune profiles across the lifespan
(Springer, 2024) Watanabe, Makiko; Davidson, Lisa; Smith, Patricia; Castellucio, Peter F.; Jergovic, Mladen; Uhrlaub, Jennifer L.; Smithey, Megan J.; Fantry, Lori E.; Dechambre, Brett; Wilson, Rachel C.; Knox, Kenneth C.; Stowe, Raymond P.; Weinstock, George; Twigg, Homer, III; Nikolich, Janko Ž.; Biostatistics and Health Data Science, School of Medicine
Human cytomegalovirus (hCMV) is a ubiquitous latent persistent herpesvirus infecting 60-90% of the population worldwide. hCMV carriage in immunocompetent people is asymptomatic; thus, hCMV can be considered a component of normative aging. However, hCMV powerfully modulates many features of the immune, and likely other, systems and organs. Questions remain as to how hCMV carriage affects the human host. We used anti-CMV antibody titers as a stratifying criterion to examine the impact of "intensity" of hCMV infection as a potential biomarker of aging, inflammation, and immune homeostasis in a cohort of 247 participants stratified into younger (21-40 years) and older (> 65 years of age) groups. We showed that anti-CMV antibody titers increased with age and directly correlated to increased levels of soluble tumor necrosis factor (sTNFR) I in younger but not older participants. CD8 + cell numbers were reduced in the older group due to the loss in CD8 + T naïve (Tn) cells. In CMV carriers and, in particular, in anti-CMV Ab-high participants, this loss was mitigated or reversed by an increase in the numbers of CD8 + T effector memory (Tem) and T effector memory reexpressing CD45RA (Temra) cells. Analysis of CD38, HLA-DR, and CD57 expression revealed subset (CD4 or CD8)-specific changes that correlated with anti-CMV Ab levels. In addition, anti-CMV Ab levels predicted anti-CMV CD8 T cell responsiveness to different CMV open reading frames (ORFs) selectively in older participants, which correlated to the transcriptional order of expression of specific CMV ORFs. Implications of these results for the potential predictive value of anti-CMV Ab titers during aging are discussed.

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