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Full-Text Articles in Data Science

Siglec15, Negatively Correlated With Pd-L1 In Hcc, Could Induce Cd8+ T Cell Apoptosis To Promote Immune Evasion, Zheng Chen, Mincheng Yu, Bo Zhang, Lei Jin, Qiang Yu, Shuang Liu, Binghai Zhou, Jiuliang Yan, Wentao Zhang, Xiaoqiang Li, Yongfeng Xu, Yongsheng Xiao, Jian Zhou, Jia Fan, Mien-Chie Hung, Qinghai Ye, Hui Li, Lei Guo Jan 2024

Siglec15, Negatively Correlated With Pd-L1 In Hcc, Could Induce Cd8+ T Cell Apoptosis To Promote Immune Evasion, Zheng Chen, Mincheng Yu, Bo Zhang, Lei Jin, Qiang Yu, Shuang Liu, Binghai Zhou, Jiuliang Yan, Wentao Zhang, Xiaoqiang Li, Yongfeng Xu, Yongsheng Xiao, Jian Zhou, Jia Fan, Mien-Chie Hung, Qinghai Ye, Hui Li, Lei Guo

Faculty, Staff and Student Publications

Functional roles of SIGLEC15 in hepatocellular carcinoma (HCC) were not clear, which was recently found to be an immune inhibitor with similar structure of inhibitory B7 family members. SIGLEC15 expression in HCC was explored in public databases and further examined by PCR analysis. SIGLEC15 and PD-L1 expression patterns were examined in HCC samples through immunohistochemistry. SIGLEC15 expression was knocked-down or over-expressed in HCC cell lines, and CCK8 tests were used to examine cell proliferative ability in vitro. Influences of SIGLEC15 expression on tumor growth were examined in immune deficient and immunocompetent mice respectively. Co-culture system of HCC cell lines and …


Modernizing And Harmonizing Regulatory Data Requirements For Genetically Modified Crops-Perspectives From A Workshop, Nicholas P Storer, Abigail R Simmons, Jordan Sottosanto, Jennifer A Anderson, Ming Hua Huang, Debbie Mahadeo, Carey A Mathesius, Mitscheli Sanches Da Rocha, Shuang Song, Ewa Urbanczyk-Wochniak Jan 2024

Modernizing And Harmonizing Regulatory Data Requirements For Genetically Modified Crops-Perspectives From A Workshop, Nicholas P Storer, Abigail R Simmons, Jordan Sottosanto, Jennifer A Anderson, Ming Hua Huang, Debbie Mahadeo, Carey A Mathesius, Mitscheli Sanches Da Rocha, Shuang Song, Ewa Urbanczyk-Wochniak

Faculty, Staff and Student Publications

Genetically modified (GM) crops that have been engineered to express transgenes have been in commercial use since 1995 and are annually grown on 200 million hectares globally. These crops have provided documented benefits to food security, rural economies, and the environment, with no substantiated case of food, feed, or environmental harm attributable to cultivation or consumption. Despite this extensive history of advantages and safety, the level of regulatory scrutiny has continually increased, placing undue burdens on regulators, developers, and society, while reinforcing consumer distrust of the technology. CropLife International held a workshop at the 16th International Society of Biosafety Research …


Vagus Nerve Stimulation For The Therapy Of Dravet Syndrome: A Systematic Review And Meta-Analysis, Shuang Chen, Man Li, Ming Huang Jan 2024

Vagus Nerve Stimulation For The Therapy Of Dravet Syndrome: A Systematic Review And Meta-Analysis, Shuang Chen, Man Li, Ming Huang

Faculty, Staff and Student Publications

OBJECTIVE: Dravet syndrome (DS) is a refractory developmental and epileptic encephalopathy characterized by seizures, developmental delay and cognitive impairment with a variety of comorbidities, including autism-like behavior, speech dysfunction, and ataxia. Vagus nerve stimulation (VNS) is one of the common therapies for DS. Here, we aim to perform a meta-analysis and systematic review of the efficacy of VNS in DS patients.

METHODS: We systematically searched four databases (PubMed, Embase, Cochrane and CNKI) to identify potentially eligible studies from their inception to January 2024. These studies provided the effective rate of VNS in treating patients with DS. The proportions of DS …


Combination Chemotherapy Optimization With Discrete Dosing, Temitayo Ajayi, Seyedmohammadhossein Hosseinian, Andrew J Schaefer, Clifton D Fuller Jan 2024

Combination Chemotherapy Optimization With Discrete Dosing, Temitayo Ajayi, Seyedmohammadhossein Hosseinian, Andrew J Schaefer, Clifton D Fuller

Faculty, Staff and Student Publications

Chemotherapy drug administration is a complex problem that often requires expensive clinical trials to evaluate potential regimens; one way to alleviate this burden and better inform future trials is to build reliable models for drug administration. This paper presents a mixed-integer program for combination chemotherapy (utilization of multiple drugs) optimization that incorporates various important operational constraints and, besides dose and concentration limits, controls treatment toxicity based on its effect on the count of white blood cells. To address the uncertainty of tumor heterogeneity, we also propose chance constraints that guarantee reaching an operable tumor size with a high probability in …


Reducing Food Scarcity: The Benefits Of Urban Farming, S.A. Claudell, Emilio Mejia Dec 2023

Reducing Food Scarcity: The Benefits Of Urban Farming, S.A. Claudell, Emilio Mejia

Journal of Nonprofit Innovation

Urban farming can enhance the lives of communities and help reduce food scarcity. This paper presents a conceptual prototype of an efficient urban farming community that can be scaled for a single apartment building or an entire community across all global geoeconomics regions, including densely populated cities and rural, developing towns and communities. When deployed in coordination with smart crop choices, local farm support, and efficient transportation then the result isn’t just sustainability, but also increasing fresh produce accessibility, optimizing nutritional value, eliminating the use of ‘forever chemicals’, reducing transportation costs, and fostering global environmental benefits.

Imagine Doris, who is …


Lesion Detection In Women Breast’S Dynamic Contrast-Enhanced Magnetic Resonance Imaging Using Deep Learning, Sudarshan Saikia, Tapas Si, Darpan Deb, Kangkana Bora, Saurav Mallik, Ujjwal Maulik, Zhongming Zhao Dec 2023

Lesion Detection In Women Breast’S Dynamic Contrast-Enhanced Magnetic Resonance Imaging Using Deep Learning, Sudarshan Saikia, Tapas Si, Darpan Deb, Kangkana Bora, Saurav Mallik, Ujjwal Maulik, Zhongming Zhao

Faculty, Staff and Student Publications

Breast cancer is one of the most common cancers in women and the second foremost cause of cancer death in women after lung cancer. Recent technological advances in breast cancer treatment offer hope to millions of women in the world. Segmentation of the breast's Dynamic Contrast-Enhanced Magnetic Resonance Imaging (DCE-MRI) is one of the necessary tasks in the diagnosis and detection of breast cancer. Currently, a popular deep learning model, U-Net is extensively used in biomedical image segmentation. This article aims to advance the state of the art and conduct a more in-depth analysis with a focus on the use …


Mitochondrial Dna Variants At Low-Level Heteroplasmy And Decreased Copy Numbers In Chronic Kidney Disease (Ckd) Tissues With Kidney Cancer, Yuki Kanazashi, Kazuhiro Maejima, Todd A Johnson, Shota Sasagawa, Ryosuke Jikuya, Hisashi Hasumi, Naomichi Matsumoto, Shigekatsu Maekawa, Wataru Obara, Hidewaki Nakagawa Dec 2023

Mitochondrial Dna Variants At Low-Level Heteroplasmy And Decreased Copy Numbers In Chronic Kidney Disease (Ckd) Tissues With Kidney Cancer, Yuki Kanazashi, Kazuhiro Maejima, Todd A Johnson, Shota Sasagawa, Ryosuke Jikuya, Hisashi Hasumi, Naomichi Matsumoto, Shigekatsu Maekawa, Wataru Obara, Hidewaki Nakagawa

Faculty, Staff and Student Publications

The human mitochondrial genome (mtDNA) is a circular DNA molecule with a length of 16.6 kb, which contains a total of 37 genes. Somatic mtDNA mutations accumulate with age and environmental exposure, and some types of mtDNA variants may play a role in carcinogenesis. Recent studies observed mtDNA variants not only in kidney tumors but also in adjacent kidney tissues, and mtDNA dysfunction results in kidney injury, including chronic kidney disease (CKD). To investigate whether a relationship exists between heteroplasmic mtDNA variants and kidney function, we performed ultra-deep sequencing (30,000×) based on long-range PCR of DNA from 77 non-tumor kidney …


Association Between Viral Infections And Glioma Risk: A Two-Sample Bidirectional Mendelian Randomization Analysis, Sheng Zhong, Wenzhuo Yang, Zhiyun Zhang, Yangyiran Xie, Lin Pan, Jiaxin Ren, Fei Ren, Yifan Li, Haoqun Xie, Hongyu Chen, Davy Deng, Jie Lu, Hui Li, Bo Wu, Youqi Chen, Fei Peng, Vinay K Puduvalli, Ke Sai, Yunqian Li, Ye Cheng, Yonggao Mou Dec 2023

Association Between Viral Infections And Glioma Risk: A Two-Sample Bidirectional Mendelian Randomization Analysis, Sheng Zhong, Wenzhuo Yang, Zhiyun Zhang, Yangyiran Xie, Lin Pan, Jiaxin Ren, Fei Ren, Yifan Li, Haoqun Xie, Hongyu Chen, Davy Deng, Jie Lu, Hui Li, Bo Wu, Youqi Chen, Fei Peng, Vinay K Puduvalli, Ke Sai, Yunqian Li, Ye Cheng, Yonggao Mou

Faculty, Staff and Student Publications

Background: Glioma is one of the leading types of brain tumor, but few etiologic factors of primary glioma have been identified. Previous observational research has shown an association between viral infection and glioma risk. In this study, we used Mendelian randomization (MR) analysis to explore the direction and magnitude of the causal relationship between viral infection and glioma.

Methods: We conducted a two-sample bidirectional MR analysis using genome-wide association study (GWAS) data. Summary statistics data of glioma were collected from the largest meta-analysis GWAS, involving 12,488 cases and 18,169 controls. Single-nucleotide polymorphisms (SNPs) associated with exposures were used as instrumental …


Applications Of Causal Inference Methods For The Estimation Of Effects Of Bone Marrow Transplant And Prescription Drugs On Survival Of Aplastic Anemia Patients, Yesha M. Patel Dec 2023

Applications Of Causal Inference Methods For The Estimation Of Effects Of Bone Marrow Transplant And Prescription Drugs On Survival Of Aplastic Anemia Patients, Yesha M. Patel

Computational and Data Sciences (PhD) Dissertations

This dissertation provides an in-depth exploration into the treatment effectiveness for aplastic anemia using causal inference methods, structured around three pivotal research papers. Each paper contributes to a nuanced understanding of treatment impacts, specifically focusing on bone marrow transplantation (BMT) and prescription drugs, and the identification of optimal treatment strategies.

The first paper, "Causal Inference Analysis for Assessing the Effect of Bone Marrow Transplantation on the One-Year Survival of Adult and Pediatric Aplastic Anemia Patients," sets the foundation. It examines the short-term effectiveness of BMT in both adult and pediatric patients, providing crucial insights into how this treatment affects survival …


Brain-Wide Correspondence Of Neuronal Epigenomics And Distant Projections, Jingtian Zhou, Zhuzhu Zhang, May Wu, Hanqing Liu, Yan Pang, Anna Bartlett, Zihao Peng, Wubin Ding, Angeline Rivkin, Will N Lagos, Elora Williams, Cheng-Ta Lee, Paula Assakura Miyazaki, Andrew Aldridge, Qiurui Zeng, J L Angelo Salinda, Naomi Claffey, Michelle Liem, Conor Fitzpatrick, Lara Boggeman, Zizhen Yao, Kimberly A Smith, Bosiljka Tasic, Jordan Altshul, Mia A Kenworthy, Cynthia Valadon, Joseph R Nery, Rosa G Castanon, Neelakshi S Patne, Minh Vu, Mohammad Rashid, Matthew Jacobs, Tony Ito, Julia Osteen, Nora Emerson, Jasper Lee, Silvia Cho, Jon Rink, Hsiang-Hsuan Huang, António Pinto-Duartec, Bertha Dominguez, Jared B Smith, Carolyn O'Connor, Hongkui Zeng, Shengbo Chen, Kuo-Fen Lee, Eran A Mukamel, Xin Jin, M Margarita Behrens, Joseph R Ecker, Edward M Callaway Dec 2023

Brain-Wide Correspondence Of Neuronal Epigenomics And Distant Projections, Jingtian Zhou, Zhuzhu Zhang, May Wu, Hanqing Liu, Yan Pang, Anna Bartlett, Zihao Peng, Wubin Ding, Angeline Rivkin, Will N Lagos, Elora Williams, Cheng-Ta Lee, Paula Assakura Miyazaki, Andrew Aldridge, Qiurui Zeng, J L Angelo Salinda, Naomi Claffey, Michelle Liem, Conor Fitzpatrick, Lara Boggeman, Zizhen Yao, Kimberly A Smith, Bosiljka Tasic, Jordan Altshul, Mia A Kenworthy, Cynthia Valadon, Joseph R Nery, Rosa G Castanon, Neelakshi S Patne, Minh Vu, Mohammad Rashid, Matthew Jacobs, Tony Ito, Julia Osteen, Nora Emerson, Jasper Lee, Silvia Cho, Jon Rink, Hsiang-Hsuan Huang, António Pinto-Duartec, Bertha Dominguez, Jared B Smith, Carolyn O'Connor, Hongkui Zeng, Shengbo Chen, Kuo-Fen Lee, Eran A Mukamel, Xin Jin, M Margarita Behrens, Joseph R Ecker, Edward M Callaway

Faculty, Staff and Student Publications

Single-cell analyses parse the brain’s billions of neurons into thousands of ‘cell-type’ clusters residing in different brain structures1. Many cell types mediate their functions through targeted long-distance projections allowing interactions between specific cell types. Here we used epi-retro-seq2 to link single-cell epigenomes and cell types to long-distance projections for 33,034 neurons dissected from 32 different regions projecting to 24 different targets (225 source-to-target combinations) across the whole mouse brain. We highlight uses of these data for interrogating principles relating projection types to transcriptomics and epigenomics, and for addressing hypotheses about cell types and connections related to genetics. …


Selecting Patient-Reported Outcome Measures For A Patient-Facing Technology, Priyank Raj, Youmin Cho, Yun Jiang, Yang Gong Dec 2023

Selecting Patient-Reported Outcome Measures For A Patient-Facing Technology, Priyank Raj, Youmin Cho, Yun Jiang, Yang Gong

Faculty, Staff and Student Publications

OBJECTIVE: This article provides insight into our process and considerations for selecting patient-reported outcome measures (PROMs) designed for self-reporting symptoms and quality-of-life among breast cancer (BCA) patients undergoing oral anticancer agent treatment via a patient-facing technology (PFT) platform.

METHODS: Following established guidelines, we conducted a thorough assessment of a specific set of PROMs, comparing their content to identify the most suitable options for studying BCA patients.

RESULTS: We recommend utilizing the combination of EORTC QLQ-C30 + EORTC QLQ-BR45 as the preferred instrument, especially when developing a dedicated "breast cancer-only" application.

DISCUSSION: When developing and maintaining a dashboard for a PFT …


Discovery Of Novel 2-Aminopyridine Derivatives As Ros1 And Alk Dual Inhibitors To Combat Drug-Resistant Mutants Including Ros1g2032r And Alkg1202r, Siming Liu, Chuan Huang, Chunhui Huang, Yaqi Huang, Yonghuan Yu, Guowu Wu, Fengqiu Guo, Ying Jiang, Shanhe Wan, Zhengguang Zhu, Yuanxin Tian, Jianghua Zhu, Jiajie Zhang Dec 2023

Discovery Of Novel 2-Aminopyridine Derivatives As Ros1 And Alk Dual Inhibitors To Combat Drug-Resistant Mutants Including Ros1g2032r And Alkg1202r, Siming Liu, Chuan Huang, Chunhui Huang, Yaqi Huang, Yonghuan Yu, Guowu Wu, Fengqiu Guo, Ying Jiang, Shanhe Wan, Zhengguang Zhu, Yuanxin Tian, Jianghua Zhu, Jiajie Zhang

Faculty, Staff and Student Publications

Clinical treatment by FDA-approved ROS1/ALK inhibitor Crizotinib significantly improved the therapeutic outcomes. However, the emergence of drug resistance, especially driven by acquired mutations, have become an inevitable problem and worsened the clinical effects of Crizotinib. To combat drug resistance, some novel 2-aminopyridine derivatives were designed rationally based on molecular simulation, then synthesised and subjected to biological test. The preferred spiro derivative C01 exhibited remarkable activity against CD74-ROS1G2032R cell with an IC50 value of 42.3 nM, which was about 30-fold more potent than Crizotinib. Moreover, C01 also potently inhibited enzymatic activity against clinically Crizotinib-resistant ALKG1202R, harbouring a 10-fold potency superior to …


Targeted Gene Expression Profiling Predicts Meningioma Outcomes And Radiotherapy Responses, William C Chen, Abrar Choudhury, Mark W Youngblood, Mei-Yin C Polley, Calixto-Hope G Lucas, Kanish Mirchia, Sybren L N Maas, Abigail K Suwala, Minhee Won, James C Bayley, Akdes S Harmanci, Arif O Harmanci, Tiemo J Klisch, Minh P Nguyen, Harish N Vasudevan, Kathleen Mccortney, Theresa J Yu, Varun Bhave, Tai-Chung Lam, Jenny Kan-Suen Pu, Lai-Fung Li, Gilberto Ka-Kit Leung, Jason W Chan, Haley K Perlow, Joshua D Palmer, Christine Haberler, Anna S Berghoff, Matthias Preusser, Theodore P Nicolaides, Christian Mawrin, Sameer Agnihotri, Adam Resnick, Brian R Rood, Jessica Chew, Jacob S Young, Lauren Boreta, Steve E Braunstein, Jessica Schulte, Nicholas Butowski, Sandro Santagata, David Spetzler, Nancy Ann Oberheim Bush, Javier E Villanueva-Meyer, James P Chandler, David A Solomon, C Leland Rogers, Stephanie L Pugh, Minesh P Mehta, Penny K Sneed, Mitchel S Berger, Craig M Horbinski, Michael W Mcdermott, Arie Perry, Wenya Linda Bi, Akash J Patel, Felix Sahm, Stephen T Magill, David R Raleigh Dec 2023

Targeted Gene Expression Profiling Predicts Meningioma Outcomes And Radiotherapy Responses, William C Chen, Abrar Choudhury, Mark W Youngblood, Mei-Yin C Polley, Calixto-Hope G Lucas, Kanish Mirchia, Sybren L N Maas, Abigail K Suwala, Minhee Won, James C Bayley, Akdes S Harmanci, Arif O Harmanci, Tiemo J Klisch, Minh P Nguyen, Harish N Vasudevan, Kathleen Mccortney, Theresa J Yu, Varun Bhave, Tai-Chung Lam, Jenny Kan-Suen Pu, Lai-Fung Li, Gilberto Ka-Kit Leung, Jason W Chan, Haley K Perlow, Joshua D Palmer, Christine Haberler, Anna S Berghoff, Matthias Preusser, Theodore P Nicolaides, Christian Mawrin, Sameer Agnihotri, Adam Resnick, Brian R Rood, Jessica Chew, Jacob S Young, Lauren Boreta, Steve E Braunstein, Jessica Schulte, Nicholas Butowski, Sandro Santagata, David Spetzler, Nancy Ann Oberheim Bush, Javier E Villanueva-Meyer, James P Chandler, David A Solomon, C Leland Rogers, Stephanie L Pugh, Minesh P Mehta, Penny K Sneed, Mitchel S Berger, Craig M Horbinski, Michael W Mcdermott, Arie Perry, Wenya Linda Bi, Akash J Patel, Felix Sahm, Stephen T Magill, David R Raleigh

Faculty, Staff and Student Publications

Surgery is the mainstay of treatment for meningioma, the most common primary intracranial tumor, but improvements in meningioma risk stratification are needed and indications for postoperative radiotherapy are controversial. Here we develop a targeted gene expression biomarker that predicts meningioma outcomes and radiotherapy responses. Using a discovery cohort of 173 meningiomas, we developed a 34-gene expression risk score and performed clinical and analytical validation of this biomarker on independent meningiomas from 12 institutions across 3 continents (N = 1,856), including 103 meningiomas from a prospective clinical trial. The gene expression biomarker improved discrimination of outcomes compared with all other systems …


Fimap A Fast Identity-By-Descent Mapping Test For Biobank-Scale Cohorts, Han Chen, Ardalan Naseri, Degui Zhi Dec 2023

Fimap A Fast Identity-By-Descent Mapping Test For Biobank-Scale Cohorts, Han Chen, Ardalan Naseri, Degui Zhi

Faculty, Staff and Student Publications

Although genome-wide association studies (GWAS) have identified tens of thousands of genetic loci, the genetic architecture is still not fully understood for many complex traits. Most GWAS and sequencing association studies have focused on single nucleotide polymorphisms or copy number variations, including common and rare genetic variants. However, phased haplotype information is often ignored in GWAS or variant set tests for rare variants. Here we leverage the identity-by-descent (IBD) segments inferred from a random projection-based IBD detection algorithm in the mapping of genetic associations with complex traits, to develop a computationally efficient statistical test for IBD mapping in biobank-scale cohorts. …


A Transcriptomic Taxonomy Of Mouse Brain-Wide Spinal Projecting Neurons, Carla C Winter, Anne Jacobi, Junfeng Su, Leeyup Chung, Cindy T J Van Velthoven, Zizhen Yao, Changkyu Lee, Zicong Zhang, Shuguang Yu, Kun Gao, Geraldine Duque Salazar, Evgenii Kegeles, Yu Zhang, Makenzie C Tomihiro, Yiming Zhang, Zhiyun Yang, Junjie Zhu, Jing Tang, Xuan Song, Ryan J Donahue, Qing Wang, Delissa Mcmillen, Michael Kunst, Ning Wang, Kimberly A Smith, Gabriel E Romero, Michelle M Frank, Alexandra Krol, Riki Kawaguchi, Daniel H Geschwind, Guoping Feng, Lisa V Goodrich, Yuanyuan Liu, Bosiljka Tasic, Hongkui Zeng, Zhigang He Dec 2023

A Transcriptomic Taxonomy Of Mouse Brain-Wide Spinal Projecting Neurons, Carla C Winter, Anne Jacobi, Junfeng Su, Leeyup Chung, Cindy T J Van Velthoven, Zizhen Yao, Changkyu Lee, Zicong Zhang, Shuguang Yu, Kun Gao, Geraldine Duque Salazar, Evgenii Kegeles, Yu Zhang, Makenzie C Tomihiro, Yiming Zhang, Zhiyun Yang, Junjie Zhu, Jing Tang, Xuan Song, Ryan J Donahue, Qing Wang, Delissa Mcmillen, Michael Kunst, Ning Wang, Kimberly A Smith, Gabriel E Romero, Michelle M Frank, Alexandra Krol, Riki Kawaguchi, Daniel H Geschwind, Guoping Feng, Lisa V Goodrich, Yuanyuan Liu, Bosiljka Tasic, Hongkui Zeng, Zhigang He

Faculty, Staff and Student Publications

The brain controls nearly all bodily functions via spinal projecting neurons (SPNs) that carry command signals from the brain to the spinal cord. However, a comprehensive molecular characterization of brain-wide SPNs is still lacking. Here we transcriptionally profiled a total of 65,002 SPNs, identified 76 region-specific SPN types, and mapped these types into a companion atlas of the whole mouse brain1. This taxonomy reveals a three-component organization of SPNs: (1) molecularly homogeneous excitatory SPNs from the cortex, red nucleus and cerebellum with somatotopic spinal terminations suitable for point-to-point communication; (2) heterogeneous populations in the reticular formation with broad …


Single-Cell Analysis Of Chromatin Accessibility In The Adult Mouse Brain, Songpeng Zu, Yang Eric Li, Kangli Wang, Ethan J Armand, Sainath Mamde, Maria Luisa Amaral, Yuelai Wang, Andre Chu, Yang Xie, Michael Miller, Jie Xu, Zhaoning Wang, Kai Zhang, Bojing Jia, Xiaomeng Hou, Lin Lin, Qian Yang, Seoyeon Lee, Bin Li, Samantha Kuan, Hanqing Liu, Jingtian Zhou, Antonio Pinto-Duarte, Jacinta Lucero, Julia Osteen, Michael Nunn, Kimberly A Smith, Bosiljka Tasic, Zizhen Yao, Hongkui Zeng, Zihan Wang, Jingbo Shang, M Margarita Behrens, Joseph R Ecker, Allen Wang, Sebastian Preissl, Bing Ren Dec 2023

Single-Cell Analysis Of Chromatin Accessibility In The Adult Mouse Brain, Songpeng Zu, Yang Eric Li, Kangli Wang, Ethan J Armand, Sainath Mamde, Maria Luisa Amaral, Yuelai Wang, Andre Chu, Yang Xie, Michael Miller, Jie Xu, Zhaoning Wang, Kai Zhang, Bojing Jia, Xiaomeng Hou, Lin Lin, Qian Yang, Seoyeon Lee, Bin Li, Samantha Kuan, Hanqing Liu, Jingtian Zhou, Antonio Pinto-Duarte, Jacinta Lucero, Julia Osteen, Michael Nunn, Kimberly A Smith, Bosiljka Tasic, Zizhen Yao, Hongkui Zeng, Zihan Wang, Jingbo Shang, M Margarita Behrens, Joseph R Ecker, Allen Wang, Sebastian Preissl, Bing Ren

Faculty, Staff and Student Publications

Recent advances in single-cell technologies have led to the discovery of thousands of brain cell types; however, our understanding of the gene regulatory programs in these cell types is far from complete1-4. Here we report a comprehensive atlas of candidate cis-regulatory DNA elements (cCREs) in the adult mouse brain, generated by analysing chromatin accessibility in 2.3 million individual brain cells from 117 anatomical dissections. The atlas includes approximately 1 million cCREs and their chromatin accessibility across 1,482 distinct brain cell populations, adding over 446,000 cCREs to the most recent such annotation in the mouse genome. The mouse brain cCREs are …


Molecularly Defined And Spatially Resolved Cell Atlas Of The Whole Mouse Brain, Meng Zhang, Xingjie Pan, Won Jung, Aaron R Halpern, Stephen W Eichhorn, Zhiyun Lei, Limor Cohen, Kimberly A Smith, Bosiljka Tasic, Zizhen Yao, Hongkui Zeng, Xiaowei Zhuang Dec 2023

Molecularly Defined And Spatially Resolved Cell Atlas Of The Whole Mouse Brain, Meng Zhang, Xingjie Pan, Won Jung, Aaron R Halpern, Stephen W Eichhorn, Zhiyun Lei, Limor Cohen, Kimberly A Smith, Bosiljka Tasic, Zizhen Yao, Hongkui Zeng, Xiaowei Zhuang

Faculty, Staff and Student Publications

In mammalian brains, millions to billions of cells form complex interaction networks to enable a wide range of functions. The enormous diversity and intricate organization of cells have impeded our understanding of the molecular and cellular basis of brain function. Recent advances in spatially resolved single-cell transcriptomics have enabled systematic mapping of the spatial organization of molecularly defined cell types in complex tissues1-3, including several brain regions (for example, refs. 1-11). However, a comprehensive cell atlas of the whole brain is still missing. Here we imaged a panel of more than 1,100 genes in approximately 10 million cells across the …


Single-Cell Dna Methylome And 3d Multi-Omic Atlas Of The Adult Mouse Brain, Hanqing Liu, Qiurui Zeng, Jingtian Zhou, Anna Bartlett, Bang-An Wang, Peter Berube, Wei Tian, Mia Kenworthy, Jordan Altshul, Joseph R Nery, Huaming Chen, Rosa G Castanon, Songpeng Zu, Yang Eric Li, Jacinta Lucero, Julia K Osteen, Antonio Pinto-Duarte, Jasper Lee, Jon Rink, Silvia Cho, Nora Emerson, Michael Nunn, Carolyn O'Connor, Zhanghao Wu, Ion Stoica, Zizhen Yao, Kimberly A Smith, Bosiljka Tasic, Chongyuan Luo, Jesse R Dixon, Hongkui Zeng, Bing Ren, M Margarita Behrens, Joseph R Ecker Dec 2023

Single-Cell Dna Methylome And 3d Multi-Omic Atlas Of The Adult Mouse Brain, Hanqing Liu, Qiurui Zeng, Jingtian Zhou, Anna Bartlett, Bang-An Wang, Peter Berube, Wei Tian, Mia Kenworthy, Jordan Altshul, Joseph R Nery, Huaming Chen, Rosa G Castanon, Songpeng Zu, Yang Eric Li, Jacinta Lucero, Julia K Osteen, Antonio Pinto-Duarte, Jasper Lee, Jon Rink, Silvia Cho, Nora Emerson, Michael Nunn, Carolyn O'Connor, Zhanghao Wu, Ion Stoica, Zizhen Yao, Kimberly A Smith, Bosiljka Tasic, Chongyuan Luo, Jesse R Dixon, Hongkui Zeng, Bing Ren, M Margarita Behrens, Joseph R Ecker

Faculty, Staff and Student Publications

Cytosine DNA methylation is essential in brain development and is implicated in various neurological disorders. Understanding DNA methylation diversity across the entire brain in a spatial context is fundamental for a complete molecular atlas of brain cell types and their gene regulatory landscapes. Here we used single-nucleus methylome sequencing (snmC-seq3) and multi-omic sequencing (snm3C-seq)1 technologies to generate 301,626 methylomes and 176,003 chromatin conformation–methylome joint profiles from 117 dissected regions throughout the adult mouse brain. Using iterative clustering and integrating with companion whole-brain transcriptome and chromatin accessibility datasets, we constructed a methylation-based cell taxonomy with 4,673 cell groups and 274 …


Virtual Reality In Simulation-Based Emergency Skills Training: A Systematic Review With A Narrative Synthesis, Jonathan R Abbas, Michael M H Chu, Ceyon Jeyarajah, Rachel Isba, Antony Payton, Brendan Mcgrath, Neil Tolley, Iain Bruce Dec 2023

Virtual Reality In Simulation-Based Emergency Skills Training: A Systematic Review With A Narrative Synthesis, Jonathan R Abbas, Michael M H Chu, Ceyon Jeyarajah, Rachel Isba, Antony Payton, Brendan Mcgrath, Neil Tolley, Iain Bruce

Faculty, Staff and Student Publications

OBJECTIVE: An important role is predicted for virtual reality (VR) in the future of medical education. We performed a systematic review of the literature with a narrative synthesis, to examine the current evidence for VR in simulation-based emergency skills training. We broadly define emergency skills as any clinical skill used in the emergency care of patients across all clinical settings.

METHODS: This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta Analyses (PRISMA) guidelines. The data sources accessed during this study included: PubMed, CINAHL, EMBASE, AMED, EMCARE, HMIC, BNI, PsychINFO, Medline, CENTRAL, SCOPUS, Web of Science, BIOSIS …


Innovation Process And Industrial System Of Us Food And Drug Administration-Approved Software As A Medical Device: Review And Content Analysis, Jiakan Yu, Jiajie Zhang, Shintaro Sengoku Nov 2023

Innovation Process And Industrial System Of Us Food And Drug Administration-Approved Software As A Medical Device: Review And Content Analysis, Jiakan Yu, Jiajie Zhang, Shintaro Sengoku

Faculty, Staff and Student Publications

BACKGROUND: There has been a surge in academic and business interest in software as a medical device (SaMD). SaMD enables medical professionals to streamline existing medical practices and make innovative medical processes such as digital therapeutics a reality. Furthermore, SaMD is a billion-dollar market. However, SaMD is not clearly understood as a technological change and emerging industry.

OBJECTIVE: This study aims to review the landscape of SaMD in response to increasing interest in SaMD within health systems and regulation. The objectives of the study are to (1) clarify the innovation process of SaMD, (2) identify the prevailing typology of such …


The Transcription Factor Irf4 Determines The Anti-Tumor Immunity Of Cd8+ T Cells, Hui Yan, Yulin Dai, Xiaolong Zhang, Hedong Zhang, Xiang Xiao, Jinfei Fu, Dawei Zou, Anze Yu, Tao Jiang, Xian C Li, Zhongming Zhao, Wenhao Chen Nov 2023

The Transcription Factor Irf4 Determines The Anti-Tumor Immunity Of Cd8+ T Cells, Hui Yan, Yulin Dai, Xiaolong Zhang, Hedong Zhang, Xiang Xiao, Jinfei Fu, Dawei Zou, Anze Yu, Tao Jiang, Xian C Li, Zhongming Zhao, Wenhao Chen

Faculty, Staff and Student Publications

Understanding the factors that regulate T cell infiltration and functional states in solid tumors is crucial for advancing cancer immunotherapies. Here, we discovered that the expression of interferon regulatory factor 4 (IRF4) was a critical T cell intrinsic requirement for effective anti-tumor immunity. Mice with T-cell-specific ablation of IRF4 showed significantly reduced T cell tumor infiltration and function, resulting in accelerated growth of subcutaneous syngeneic tumors and allowing the growth of allogeneic tumors. Additionally, engineered overexpression of IRF4 in anti-tumor CD8+ T cells that were adoptively transferred significantly promoted their tumor infiltration and transition from a naive/memory-like cell state into …


An Open Natural Language Processing (Nlp) Framework For Ehr-Based Clinical Research: A Case Demonstration Using The National Covid Cohort Collaborative (N3c), Sijia Liu, Andrew Wen, Liwei Wang, Huan He, Sunyang Fu, Robert Miller, Andrew Williams, Daniel Harris, Ramakanth Kavuluru, Mei Liu, Noor Abu-El-Rub, Dalton Schutte, Rui Zhang, Masoud Rouhizadeh, John D Osborne, Yongqun He, Umit Topaloglu, Stephanie S Hong, Joel H Saltz, Thomas Schaffter, Emily Pfaff, Christopher G Chute, Tim Duong, Melissa A Haendel, Rafael Fuentes, Peter Szolovits, Hua Xu, Hongfang Liu Nov 2023

An Open Natural Language Processing (Nlp) Framework For Ehr-Based Clinical Research: A Case Demonstration Using The National Covid Cohort Collaborative (N3c), Sijia Liu, Andrew Wen, Liwei Wang, Huan He, Sunyang Fu, Robert Miller, Andrew Williams, Daniel Harris, Ramakanth Kavuluru, Mei Liu, Noor Abu-El-Rub, Dalton Schutte, Rui Zhang, Masoud Rouhizadeh, John D Osborne, Yongqun He, Umit Topaloglu, Stephanie S Hong, Joel H Saltz, Thomas Schaffter, Emily Pfaff, Christopher G Chute, Tim Duong, Melissa A Haendel, Rafael Fuentes, Peter Szolovits, Hua Xu, Hongfang Liu

Faculty, Staff and Student Publications

Despite recent methodology advancements in clinical natural language processing (NLP), the adoption of clinical NLP models within the translational research community remains hindered by process heterogeneity and human factor variations. Concurrently, these factors also dramatically increase the difficulty in developing NLP models in multi-site settings, which is necessary for algorithm robustness and generalizability. Here, we reported on our experience developing an NLP solution for Coronavirus Disease 2019 (COVID-19) signs and symptom extraction in an open NLP framework from a subset of sites participating in the National COVID Cohort (N3C). We then empirically highlight the benefits of multi-site data for both …


Usp38 Exacerbates Atrial Inflammation, Fibrosis, And Susceptibility To Atrial Fibrillation After Myocardial Infarction In Mice, Yang Gong, Tingting Yu, Wei Shuai, Tao Chen, Jingjing Zhang, He Huang Nov 2023

Usp38 Exacerbates Atrial Inflammation, Fibrosis, And Susceptibility To Atrial Fibrillation After Myocardial Infarction In Mice, Yang Gong, Tingting Yu, Wei Shuai, Tao Chen, Jingjing Zhang, He Huang

Faculty, Staff and Student Publications

BACKGROUND: Inflammation plays an important role in the pathogenesis of atrial fibrillation (AF) after myocardial infarction (MI). The role of USP38, a member of the ubiquitin-specific protease family, on MI-induced atrial inflammation, fibrosis, and associated AF is unclear.

METHODS: In this study, we surgically constructed a mouse MI model using USP38 cardiac conditional knockout (USP38-CKO) and cardiac-specific overexpression (USP38-TG) mice and applied biochemical, histological, electrophysiological characterization and molecular biology to investigate the effects of USP38 on atrial inflammation, fibrosis, and AF and its mechanisms.

RESULTS: Our results revealed that USP38-CKO attenuates atrial inflammation, thereby ameliorating fibrosis, and abnormal electrophysiologic properties, …


Rotational Symmetry Breaking In Superconducting Nickelate Nd08sr02nio2 Films, Haoran Ji, Yi Liu, Yanan Li, Xiang Ding, Zheyuan Xie, Chengcheng Ji, Shichao Qi, Xiaoyue Gao, Minghui Xu, Peng Gao, Liang Qiao, Yi-Feng Yang, Guang-Ming Zhang, Jian Wang Nov 2023

Rotational Symmetry Breaking In Superconducting Nickelate Nd08sr02nio2 Films, Haoran Ji, Yi Liu, Yanan Li, Xiang Ding, Zheyuan Xie, Chengcheng Ji, Shichao Qi, Xiaoyue Gao, Minghui Xu, Peng Gao, Liang Qiao, Yi-Feng Yang, Guang-Ming Zhang, Jian Wang

Faculty, Staff and Student Publications

The infinite-layer nickelates, isostructural to the high-Tc cuprate superconductors, have emerged as a promising platform to host unconventional superconductivity and stimulated growing interest in the condensed matter community. Despite considerable attention, the superconducting pairing symmetry of the nickelate superconductors, the fundamental characteristic of a superconducting state, is still under debate. Moreover, the strong electronic correlation in the nickelates may give rise to a rich phase diagram, where the underlying interplay between the superconductivity and other emerging quantum states with broken symmetry is awaiting exploration. Here, we study the angular dependence of the transport properties of the infinite-layer nickelate Nd0.8Sr0.2NiO2 superconducting …


Economic Equity And People With Disabilities: Development And Characterization Of A Novel Index, Bhavneet Walia, Katherine Mcdonald, Joy Hammel, Lex Frieden, Michael Morris, Barry Whaley, Vinh Nguyen Nov 2023

Economic Equity And People With Disabilities: Development And Characterization Of A Novel Index, Bhavneet Walia, Katherine Mcdonald, Joy Hammel, Lex Frieden, Michael Morris, Barry Whaley, Vinh Nguyen

Faculty, Staff and Student Publications

Here we develop two new social indices: The ADA PARC Absolute Economic Opportunity Index and the ADA PARC Relative Economic Opportunity Index. These indices allow us novel examinations of economic equity between people with and without disabilities within a U.S. State and between people with disabilities in different states using aggregations of multiple component economic indicators. These represent the first efforts to offer U.S. indices of this focus, an important development given the distinct economic needs of people with disabilities and the value in accounting for distinct national policies. The indices rely on U.S. Census and other data on economic …


Ensuring Trust In Genomics Research, Erman Ayday, Jaideep Vaidya, Xiaoqian Jiang, Amalio Telenti Nov 2023

Ensuring Trust In Genomics Research, Erman Ayday, Jaideep Vaidya, Xiaoqian Jiang, Amalio Telenti

Faculty, Staff and Student Publications

Reproducibility, transparency, representation, and privacy underpin the trust on genomics research in general and genome-wide association studies (GWAS) in particular. Concerns about these issues can be mitigated by technologies that address privacy protection, quality control, and verifiability of GWAS. However, many of the existing technological solutions have been developed in isolation and may address one aspect of reproducibility, transparency, representation, and privacy of GWAS while unknowingly impacting other aspects. As a consequence, the current patchwork of technological tools only partially and in an overlapping manner address issues with GWAS, sometimes even creating more problems. This paper addresses the progress in …


Effect Of Ultrasound On The Stability Of Partial Nitrification: Under The Interference Of Aeration Rate, Ying Xie, Yichun Zhu, Jieyuan Yang, Guangming Zhang, Shuai Tian, Junfeng Lian, Shanyan Dong Nov 2023

Effect Of Ultrasound On The Stability Of Partial Nitrification: Under The Interference Of Aeration Rate, Ying Xie, Yichun Zhu, Jieyuan Yang, Guangming Zhang, Shuai Tian, Junfeng Lian, Shanyan Dong

Faculty, Staff and Student Publications

The fluctuation of dissolved oxygen is one of the primary cause of disruptions to the consistent operation of partial nitrification, and the level of dissolved oxygen is mainly controlled by the aeration rate. This study investigated the influence of ultrasonic treatment on the stability of partial nitrification of activated sludge under different aeration conditions. After being treated with ultrasound (energy density = 0.20 W·mL−1, treatment time = 10 min), partial nitrification process operated stably for 67 days, with the nitrite accumulation rate above 83.89 %. The effluent contained 42.50 mg·L−1 of nitrite, much higher than the control reactor (0.30 mg·L−1). …


Surface Premelting Of Ice Far Below The Triple Point, Yulin Lin, Tao Zhou, Nathan D Rosenmann, Lei Yu, Thomas E Gage, Suvo Banik, Arnab Neogi, Henry Chan, Aiwen Lei, Xiao-Min Lin, Martin Holt, Ilke Arslan, Jianguo Wen Oct 2023

Surface Premelting Of Ice Far Below The Triple Point, Yulin Lin, Tao Zhou, Nathan D Rosenmann, Lei Yu, Thomas E Gage, Suvo Banik, Arnab Neogi, Henry Chan, Aiwen Lei, Xiao-Min Lin, Martin Holt, Ilke Arslan, Jianguo Wen

Faculty, Staff and Student Publications

Premelting of ice, a quasi-liquid layer (QLL) at the surface below the melting temperature, was first postulated by Michael Faraday 160 y ago. Since then, it has been extensively studied theoretically and experimentally through many techniques. Existing work has been performed predominantly on hexagonal ice, at conditions close to the triple point. Whether the same phenomenon can persist at much lower pressure and temperature, where stacking disordered ice sublimates directly into water vapor, remains unclear. Herein, we report direct observations of surface premelting on ice nanocrystals below the sublimation temperature using transmission electron microscopy (TEM). Similar to what has been …


Evaluating The Impact Of An Mhealth Platform For Managing Acute Postoperative Dental Pain: Randomized Controlled Trial, Bunmi Tokede, Alfa Yansane, Ana Ibarra-Noriega, Joanna Mullins, Kristen Simmons, Nicholas Skourtes, Urvi Mehta, Sayali Tungare, David Holmes, Joel White, Muhammad Walji, Elsbeth Kalenderian Oct 2023

Evaluating The Impact Of An Mhealth Platform For Managing Acute Postoperative Dental Pain: Randomized Controlled Trial, Bunmi Tokede, Alfa Yansane, Ana Ibarra-Noriega, Joanna Mullins, Kristen Simmons, Nicholas Skourtes, Urvi Mehta, Sayali Tungare, David Holmes, Joel White, Muhammad Walji, Elsbeth Kalenderian

Faculty, Staff and Student Publications

BACKGROUND: Postoperative dental pain is pervasive and can affect a patient's quality of life. Adopting a patient-centric approach to pain management involves having contemporaneous information about the patient's experience of pain and using it to personalize care.

OBJECTIVE: In this study, we evaluated the use of a mobile health (mHealth) platform to collect pain-related patient-reported outcomes over 7 days after the patients underwent pain-inducing dental procedures; we then relayed the information to the dentist and determined its impact on the patient's pain experience.

METHODS: The study used a cluster-randomized experimental study design with an intervention arm where patients were prompted …


Braf D594a Mutation Defines A Unique Biological And Immuno-Modulatory Subgroup Associated With Functional Cd8+ T Cell Infiltration In Colorectal Cancer, Wenjing Li, Chenyi Zhao, Wenhui Li, Yang Gong, Kaili Ma, Yujie Lu, Xiaowei Liu, Lianjun Zhang, Feng Guo Oct 2023

Braf D594a Mutation Defines A Unique Biological And Immuno-Modulatory Subgroup Associated With Functional Cd8+ T Cell Infiltration In Colorectal Cancer, Wenjing Li, Chenyi Zhao, Wenhui Li, Yang Gong, Kaili Ma, Yujie Lu, Xiaowei Liu, Lianjun Zhang, Feng Guo

Faculty, Staff and Student Publications

BACKGROUND: BRAF non-V600 mutation occupies a relatively small but critical subset in colorectal cancer (CRC). However, little is known about the biological functions and impacts of BRAF class III mutation in CRC. Here, we aim to explore how D594A mutation impacts on biological behaviors and immune related signatures in murine CRC cells.

METHODS: BRAF V600E (class I), G469V (class II) and D594A (class III) mutant cell lines were established based on MC38 cells. The biological behaviors of cells were evaluated in respect of cell growth, cell proliferation, cell apoptosis, cell migration and invasion by the methods of colony-forming assay, CCK-8 …