Browsing by Author "Xu, Jing"

Now showing 1 - 8 of 8
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    A theoretical model for detecting drug interaction with awareness of timing of exposure
    (Springer Nature, 2025-04-21) Shi, Yi; Sun, Anna; Yang, Yuedi; Xu, Jing; Li, Justin; Eadon, Michael; Su, Jing; Zhang, Pengyue; Biostatistics and Health Data Science, Richard M. Fairbanks School of Public Health
    Drug-drug interaction-induced (DDI-induced) adverse drug event (ADE) is a significant public health burden. Risk of ADE can be related to timing of exposure (TOE) such as initiating two drugs concurrently or adding one drug to an existing drug. Thus, real-world data based DDI detection shall be expanded to investigate precise adverse DDI with a special awareness on TOE. We developed a Sensitive and Timing-awarE Model (STEM), which was able to optimize the probability of detection and control false positive rate for mining all two-drug combinations under case-crossover design, in particular for DDIs with TOE-dependent risk. We analyzed a large-scale US administrative claims data and conducted performance evaluation analyses. We identified signals of DDIs by using STEM, in particular for DDIs with TOE-dependent risk. We also observed that STEM identified significantly more signals than the conditional logistic regression model-based (CLRM-based) methods and the Benjamini-Hochberg procedure. In the performance evaluation, we found that STEM demonstrated proper false positive control and achieved a higher probability of detection compared to CLRM-based methods and the Benjamini-Hochberg procedure. STEM has a high probability to identify signals of DDIs in high-throughput DDI mining while controlling false positive rate, in particular for detecting signals of DDI with TOE-dependent risk.
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    Associations Between Neuroinflammation-Related Conditions and Alzheimer’s Disease: A Study of US Insurance Claims Data
    (Sage, 2024) Xu, Jing; Chen, Yao; Shi, Yi; Sun, Anna; Yang, Yuedi; Boustani, Malaz; Su, Jing; Zhang, Pengyue; Biostatistics and Health Data Science, Richard M. Fairbanks School of Public Health
    Background: Early detection of Alzheimer's disease (AD) is a key component for the success of the recently approved lecanemab and aducanumab. Patients with neuroinflammation-related conditions are associated with a higher risk for developing AD. Objective: Investigate the incidence of AD among patients with neuroinflammation-related conditions including epilepsy, hemorrhage stroke, multiple sclerosis (MS), and traumatic brain injury (TBI). Methods: We used Optum's de-identified Clinformatics Data Mart Database (CDM). We derived covariate-matched cohorts including patients with neuroinflammation-related conditions and controls without the corresponding condition. The matched cohorts were: 1) patients with epilepsy and controls (N = 67,825 matched pairs); 2) patients with hemorrhage stroke and controls (N = 81,510 matched pairs); 3) patients with MS and controls (N = 9,853 matched pairs); and 4) patients TBI and controls (N = 104,637 matched pairs). We used the Cox model to investigate the associations between neuroinflammation-related conditions and AD. Results: We identified that epilepsy, hemorrhage stroke, and TBI were associated with increased risks of AD in both males and females (hazard ratios [HRs]≥1.74, p < 0.001), as well as in gender- and race-conscious subpopulations (HRs≥1.64, p < 0.001). We identified that MS was associated with increased risks of AD in both males and females (HRs≥1.47, p≤0.004), while gender- and race-conscious subgroup analysis shown mixed associations. Conclusions: Patients with epilepsy, hemorrhage stroke, MS, and/or TBI are associated with a higher risk of developing AD. More attention on cognitive status should be given to older patients with these conditions.
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    Enhanced amygdala-cingulate connectivity associates with better mood in both healthy and depressive individuals after sleep deprivation
    (National Academy of Science, 2023) Chai, Ya; Gehrman, Philip; Yu, Meichen; Mao, Tianxin; Deng, Yao; Rao, Joy; Shi, Hui; Quan, Peng; Xu, Jing; Zhang, Xiaocui; Lei, Hui; Fang, Zhuo; Xu, Sihua; Boland, Elaine; Goldschmied, Jennifer R.; Barilla, Holly; Goel, Namni; Basner, Mathias; Thase, Michael E.; Sheline, Yvette I.; Dinges, David F.; Detre, John A.; Zhang, Xiaochu; Rao, Hengyi; Radiology and Imaging Sciences, School of Medicine
    Sleep loss robustly disrupts mood and emotion regulation in healthy individuals but can have a transient antidepressant effect in a subset of patients with depression. The neural mechanisms underlying this paradoxical effect remain unclear. Previous studies suggest that the amygdala and dorsal nexus (DN) play key roles in depressive mood regulation. Here, we used functional MRI to examine associations between amygdala- and DN-related resting-state connectivity alterations and mood changes after one night of total sleep deprivation (TSD) in both healthy adults and patients with major depressive disorder using strictly controlled in-laboratory studies. Behavioral data showed that TSD increased negative mood in healthy participants but reduced depressive symptoms in 43% of patients. Imaging data showed that TSD enhanced both amygdala- and DN-related connectivity in healthy participants. Moreover, enhanced amygdala connectivity to the anterior cingulate cortex (ACC) after TSD associated with better mood in healthy participants and antidepressant effects in depressed patients. These findings support the key role of the amygdala-cingulate circuit in mood regulation in both healthy and depressed populations and suggest that rapid antidepressant treatment may target the enhancement of amygdala-ACC connectivity.
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    HOXA9 Reprograms the Enhancer Landscape to Promote Leukemogenesis
    (Elsevier, 2018-10-08) Sun, Yuqing; Zhou, Bo; Mao, Fengbiao; Xu, Jing; Miao, Hongzhi; Zou, Zhenhua; Khoa, Le Tran Phuc; Jang, Younghoon; Cai, Sheng; Witkin, Matthew; Koche, Richard; Ge, Kai; Dressler, Gregory; Levine, Ross L.; Armstrong, Scott A.; Dou, Yali; Hess, Jay L.; Pathology and Laboratory Medicine, School of Medicine
    Aberrant expression of HOXA9 is a prominent feature of acute leukemia driven by diverse oncogenes. Here we show that HOXA9 overexpression in myeloid and B progenitor cells leads to significant enhancer reorganizations with prominent emergence of leukemia-specific de novo enhancers. Alterations in the enhancer landscape lead to activation of an ectopic embryonic gene program. We show that HOXA9 functions as a pioneer factor at de novo enhancers and recruits CEBPα and the MLL3/MLL4 complex. Genetic deletion of MLL3/MLL4 blocks histone H3K4 methylation at de novo enhancers and inhibits HOXA9/MEIS1-mediated leukemogenesis in vivo. These results suggest that therapeutic targeting of HOXA9-dependent enhancer reorganization can be an effective therapeutic strategy in acute leukemia with HOXA9 overexpression
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    Increased Mast Cell Counts and Degranulation in Microscopic Colitis
    (Hindawi, 2020) Chi, Zhikai; Xu, Jing; Saxena, Romil; Pathology and Laboratory Medicine, School of Medicine
    Objectives: Microscopic colitis (MC) is characterized by chronic diarrhea, normal colonoscopy findings, and mucosal inflammation in colonic biopsies and can be classified as collagenous colitis (CC) or lymphocytic colitis (LC). However, the pathogenesis of MC is largely unknown. In this study, we aimed to study mast cell counts and activation in MC. Methods: We investigated 64 biopsy samples from the surgical pathology database of Indiana University Health, which met the diagnostic criteria for CC or LC along with 20 control samples collected from 2014 to 2015. The specimens were used for the quantification of mast cells by examining the presence of intracellular and extracellular tryptase by immunohistochemistry. Results: In the lamina propria, the mast cell count was higher in both CC and LC groups than the control (mean highest count, 39/high-power field (HPF) vs. 30/HPF vs. 23/HPF; P < 0.01). Extracellular tryptase was present in 10% of control subjects as compared to 41% of CC (P < 0.01). Extracellular tryptase was present in 10% of control subjects as compared to 41% of CC (P < 0.01). Extracellular tryptase was present in 10% of control subjects as compared to 41% of CC (. Conclusions: The increased mast cell count and degranulation are identified in MC, suggesting that mast cell activation might be involved in the pathogenesis of MC.
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    A patient-oriented clinical decision support system for CRC risk assessment and preventative care
    (BioMed Central, 2018-12-07) Liu, Jiannan; Li, Chenyang; Xu, Jing; Wu, Huanmei; Biohealth Informatics, School of Informatics and Computing
    Colorectal Cancer (CRC) is the third leading cause of cancer death among men and women in the United States. Research has shown that the risk of CRC associates with genetic and lifestyle factors. It is possible to prevent or minimize certain CRC risks by adopting a healthy lifestyle. Existing Clinical Decision Support Systems (CDSS) mainly targeted physicians as the CDSS users. As a result, the availability of patient-oriented CDSS is limited. Our project is to develop patient-oriented CDSS for active CRC management.
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    Targeting MLL1 H3K4 methyltransferase activity in mixed-lineage leukemia
    (Elsevier, 2014-01-23) Cao, Fang; Townsend, Elizabeth C.; Karatas, Hacer; Xu, Jing; Li, Li; Lee, Shirley; Liu, Liu; Chen, Yong; Ouillette, Peter; Zhu, Jidong; Hess, Jay L.; Atadja, Peter; Lei, Ming; Qin, Zhaohui; Malek, Sami; Wang, Shaomeng; Dou, Yali; IU School of Medicine
    Here we report a comprehensive characterization of our recently developed inhibitor MM-401 that targets the MLL1 H3K4 methyltransferase activity. MM-401 is able to specifically inhibit MLL1 activity by blocking MLL1-WDR5 interaction and thus the complex assembly. This targeting strategy does not affect other mixed-lineage leukemia (MLL) family histone methyltransferases (HMTs), revealing a unique regulatory feature for the MLL1 complex. Using MM-401 and its enantiomer control MM-NC-401, we show that inhibiting MLL1 methyltransferase activity specifically blocks proliferation of MLL cells by inducing cell-cycle arrest, apoptosis, and myeloid differentiation without general toxicity to normal bone marrow cells or non-MLL cells. More importantly, transcriptome analyses show that MM-401 induces changes in gene expression similar to those of MLL1 deletion, supporting a predominant role of MLL1 activity in regulating MLL1-dependent leukemia transcription program. We envision broad applications for MM-401 in basic and translational research.
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    A View from the past into our collective future: the oncofertility consortium vision statement
    (Springer, 2021-01) Woodruff, Teresa K.; Ataman-Millhouse, Lauren; Acharya, Kelly S.; Almeida-Santos, Teresa; Anazodo, Antoinette; Anderson, Richard A.; Appiah, Leslie; Bader, Joy; Becktell, Kerri; Brannigan, Robert E.; Breech, Lesley; Bourlon, Maria T.; Bumbuliene, Žana; Burns, Karen; Campo-Engelstein, Lisa; Campos, Jacira R.; Centola, Grace M.; Chehin, Mauricio Barbour; Chen, Diane; De Vos, Michel; Duncan, Francesca E.; El-Damen, Ahmed; Fair, Douglas; Famuyiwa, Yemi; Fechner, Patricia Y.; Fontoura, Paula; Frias, Olivia; Gerkowicz, Sabrina A.; Ginsberg, Jill; Gracia, Clarisa R.; Goldman, Kara; Gomez-Lobo, Veronica; Hazelrigg, Brent; Hsieh, Michael H.; Hoyos, Luis R.; Hoyos-Martinez, Alfonso; Jach, Robert; Jassem, Jacek; Javed, Murid; Jayasinghe, Yasmin; Jeelani, Roohi; Jeruss, Jacqueline S.; Kaul-Mahajan, Nalini; Keim-Malpass, Jessica; Ketterl, Tyler G.; Khrouf, Mohamed; Kimelman, Dana; Kusuhara, Atsuko; Kutteh, William H.; Laronda, Monica M.; Lee, Jung Ryeol; Lehmann, Vicky; Letourneau, Joseph M.; McGinnis, Lynda K.; McMahon, Eileen; Meacham, Lillian R.; Velez Mijangos, Monserrat Fabiola; Moravek, Molly; Nahata, Leena; Ogweno, George Moses; Orwig, Kyle E.; Pavone, Mary Ellen; Peccatori, Fedro Alessandro; Pesce, Romina Ileana; Pulaski, Hanna; Quinn, Gwendolyn; Quintana, Ramiro; Quintana, Tomas; de Carvalho, Bruno Ramalho; Ramsey-Goldman, Rosalind; Reinecke, Joyce; Reis, Fernando M.; Rios, Julie; Rhoton-Vlasak, Alice S.; Rodriguez-Wallberg, Kenny A.; Roeca, Cassandra; Rotz, Seth J.; Rowell, Erin; Salama, Mahmoud; Saraf, Amanda J.; Scarella, Anibal; Schafer-Kalkhoff, Tara; Schmidt, Deb; Senapati, Suneeta; Shah, Divya; Shikanov, Ariella; Shnorhavorian, Margarett; Skiles, Jodi L.; Smith, James F.; Smith, Kristin; Sobral, Fabio; Stimpert, Kyle; Su, H. Irene; Sugimoto, Kouhei; Suzuki, Nao; Thakur, Mili; Victorson, David; Viale, Luz; Vitek, Wendy; Wallace, W. Hamish; Wartella, Ellen A.; Westphal, Lynn M.; Whiteside, Stacy; Wilcox, Lea H.; Wyns, Christine; Xiao, Shuo; Xu, Jing; Zelinski, Mary; Pediatrics, School of Medicine
    Purpose: Today, male and female adult and pediatric cancer patients, individuals transitioning between gender identities, and other individuals facing health extending but fertility limiting treatments can look forward to a fertile future. This is, in part, due to the work of members associated with the Oncofertility Consortium. Methods: The Oncofertility Consortium is an international, interdisciplinary initiative originally designed to explore the urgent unmet need associated with the reproductive future of cancer survivors. As the strategies for fertility management were invented, developed or applied, the individuals for who the program offered hope, similarly expanded. As a community of practice, Consortium participants share information in an open and rapid manner to addresses the complex health care and quality-of-life issues of cancer, transgender and other patients. To ensure that the organization remains contemporary to the needs of the community, the field designed a fully inclusive mechanism for strategic planning and here present the findings of this process. Results: This interprofessional network of medical specialists, scientists, and scholars in the law, medical ethics, religious studies and other disciplines associated with human interventions, explore the relationships between health, disease, survivorship, treatment, gender and reproductive longevity. Conclusion: The goals are to continually integrate the best science in the service of the needs of patients and build a community of care that is ready for the challenges of the field in the future.