Digital Commons Network^™

Identifying Opportunities For Prevention Of Adverse Outcomes Following Female Genital Fistula Repair: Protocol For A Mixed-Methods Study In Uganda, Alison El Ayadi, Susan Obore, Fred Kirya, Suellen Miller, Abner Korn, Hadija Nalubwama, John Neuhaus, Monica Getahun, Patrick Eyul, Robert Twine, Erin Andrew, Justus Barageine

Department of Obstetrics and Gynecology Faculty Papers

BACKGROUND: Female genital fistula is a traumatic debilitating injury, frequently caused by prolonged obstructed labor, affecting between 500,000-2 million women in lower-resource settings. Vesicovaginal fistula causes urinary incontinence, and other morbidity may occur during fistula development. Women with fistula are stigmatized, limit social and economic engagement, and experience psychiatric morbidity. Improved surgical access has reduced fistula consequences yet post-repair risks impacting quality of life and well-being include fistula repair breakdown or recurrence and ongoing or changing urine leakage or incontinence. Limited evidence on risk factors contributing to adverse outcomes hinders interventions to mitigate adverse events. This study aims to quantify …

A Syndromic Neurodevelopmental Disorder Caused By Rare Variants In Ppfia3, Hiuling Chan, Jessica M Pfliger, Jill A Rosenfeld, Vanesa C Lerma, Alyssa Tran, Megan A Longley, Richard A Lewis, Monika Weisz-Hubshman, Mir Reza Bekheirnia, Nasim Bekheirnia, Lauren Massingham, Michael Zech, Matias Wagner, Hartmut Engels, Kirsten Cremer, Elisabeth Mangold, Sophia Peters, Jessica Trautmann, Jessica L Mester, Maria J Guillen Sacoto, Richard Person, Pamela P Mcdonnell, Stacey R Cohen, Laina Lusk, Ana S A Cohen, Jean-Baptiste Le Pichon, Tomi Pastinen, Dihong Zhou, Kendra Engleman, Caroline Racine, Laurence Faivre, Sébastien Moutton, Anne-Sophie Denommé-Pichon, Hyun Yong Koh, Annapurna Poduri, Jeffrey Bolton, Cordula Knopp, Dong Sun Julia Suh, Andrea Maier, Mehran Beiraghi Toosi, Ehsan Ghayoor Karimiani, Reza Maroofian, Gerald Bradley Schaefer, Vijayalakshmi Ramakumaran, Pradeep Vasudevan, Chitra Prasad, Matthew Osmond, Sarah Schuhmann, Georgia Vasileiou, Sophie Russ-Hall, Ingrid E Scheffer, Gemma L Carvill, Heather Mefford, Undiagnosed Diseases Network, Carlos A Bacino, Brendan H Lee, Hsiao-Tuan Chao

Faculty, Staff and Students Publications

PPFIA3 encodes the protein-tyrosine phosphatase, receptor-type, F-polypeptide-interacting-protein-alpha-3 (PPFIA3), which is a member of the LAR-protein-tyrosine phosphatase-interacting-protein (liprin) family involved in synapse formation and function, synaptic vesicle transport, and presynaptic active zone assembly. The protein structure and function are evolutionarily well conserved, but human diseases related to PPFIA3 dysfunction are not yet reported in OMIM. Here, we report 20 individuals with rare PPFIA3 variants (19 heterozygous and 1 compound heterozygous) presenting with developmental delay, intellectual disability, hypotonia, dysmorphisms, microcephaly or macrocephaly, autistic features, and epilepsy with reduced penetrance. Seventeen unique PPFIA3 variants were detected in 18 families. To determine the pathogenicity …

Inhibiting Metabotropic Glutamate Receptor 5 After Stroke Restores Brain Function And Connectivity, Jakob Hakon, Miriana J Quattromani, Carin Sjölund, Daniela Talhada, Byungchan Kim, Slavianka Moyanova, Federica Mastroiacovo, Luisa Di Menna, Roger Olsson, Elisabet Englund, Ferdinando Nicoletti, Karsten Ruscher, Adam Q Bauer, Tadeusz Wieloch

2020-Current year OA Pubs

Stroke results in local neural disconnection and brain-wide neuronal network dysfunction leading to neurological deficits. Beyond the hyper-acute phase of ischaemic stroke, there is no clinically-approved pharmacological treatment that alleviates sensorimotor impairments. Functional recovery after stroke involves the formation of new or alternative neuronal circuits including existing neural connections. The type-5 metabotropic glutamate receptor (mGluR5) has been shown to modulate brain plasticity and function and is a therapeutic target in neurological diseases outside of stroke. We investigated whether mGluR5 influences functional recovery and network reorganization rodent models of focal ischaemia. Using multiple behavioural tests, we observed that treatment with negative …

Effects Of Cooking With Liquefied Petroleum Gas Or Biomass On Stunting In Infants, William Checkley, Lindsay J Underhill, Victor G Dávila-Román, Et Al.

2020-Current year OA Pubs

BACKGROUND: Household air pollution is associated with stunted growth in infants. Whether the replacement of biomass fuel (e.g., wood, dung, or agricultural crop waste) with liquefied petroleum gas (LPG) for cooking can reduce the risk of stunting is unknown.

METHODS: We conducted a randomized trial involving 3200 pregnant women 18 to 34 years of age in four low- and middle-income countries. Women at 9 to less than 20 weeks' gestation were randomly assigned to use a free LPG cookstove with continuous free fuel delivery for 18 months (intervention group) or to continue using a biomass cookstove (control group). The length …

Low Rna Disruption During Neoadjuvant Chemotherapy Predicts Pathologic Complete Response Absence In Patients With Breast Cancer, Marina Elena Cazzaniga, Foluso Ademuyiwa, Et Al.

2020-Current year OA Pubs

In previously reported retrospective studies, high tumor RNA disruption during neoadjuvant chemotherapy predicted for post-treatment pathologic complete response (pCR) and improved disease-free survival at definitive surgery for primary early breast cancer. The BREVITY (Breast Cancer Response Evaluation for Individualized Therapy) prospective clinical trial (NCT03524430) seeks to validate these prior findings. Here we report training set (Phase I) findings, including determination of RNA disruption index (RDI) cut points for outcome prediction in the subsequent validation set (Phase II; 454 patients). In 80 patients of the training set, maximum tumor RDI values for biopsies obtained during neoadjuvant chemotherapy were significantly higher in …

Self-Sampling Tools To Increase Cancer Screening Among Underserved Patients: A Pilot Randomized Controlled Trial, Jennifer L Moss, Juliette Entenman, Kelsey Stoltzfus, Jiangang Liao, Tracy Onega, Paul L Reiter, Lisa M Klesges, George Garrow, Mack T Ruffin

2020-Current year OA Pubs

BACKGROUND: Screening can reduce cancer mortality, but uptake is suboptimal and characterized by disparities. Home-based self-sampling can facilitate screening for colorectal cancer (with stool tests, eg, fecal immunochemical tests) and for cervical cancer (with self-collected human papillomavirus tests), especially among patients who face barriers to accessing health care. Additional data are needed on feasibility and potential effects of self-sampling tools for cancer screening among underserved patients.

METHODS: We conducted a pilot randomized controlled trial with patients (female, ages 50-65 years, out of date with colorectal and cervical cancer screening) recruited from federally qualified health centers in rural and racially segregated …

Experiences Of Family Communication And Cascade Genetic Testing For Hereditary Cancer In Medically Underserved Populations-A Qualitative Study, Erica M Bednar, J Alejandro Rauh-Hain, Jose J Garcia, Norma De Aguinaga, Mary Anne Powell, Roni Nitecki, Natasha L Rudy, Karen H Lu, Charles A Leath, Isabel C Scarinci

Faculty, Staff and Student Publications

UNLABELLED: We sought to explore the intrafamilial communication and cascade genetic testing (CGT) experiences of patients with hereditary cancer from diverse, medically underserved populations and their relatives. Participants included patients receiving oncology care at an urban, safety net hospital in Texas or comprehensive cancer center in Alabama and their first-degree relatives. In-depth semi-structured qualitative interviews were completed wherein patients shared their experiences with genetic counseling (GC), genetic testing (GT), and communicating their results to relatives. Relatives shared their experiences receiving information from the patient and considering CGT. Interviews were transcribed, coded, and themes were identified. Of 25 participating patients, most …

Surveillance And Selective Treatment Of Brugia Malayi Filariasis Eleven Years After Stopping Mass Drug Administration In Belitung District, Indonesia, Taniawati Supali, Yenny Djuardi, Santoso, Lita Renata Sianipar, Nungki Hapsari Suryaningtyas, Rahmat Alfian, Yossi Destani, Elisa Iskandar, Hendri Astuty, Noviani Sugianto, Peter U Fischer

2020-Current year OA Pubs

A key component to achieving the global goal of elimination of lymphatic filariasis (LF) is the availability of appropriate tools for disease mapping, monitoring, and surveillance. However, the development of these tools for a neglected disease such as LF can be a challenge. The lack of a commercial market and low familiarity with these diseases leave little incentive for diagnostic manufacturers to invest in this space. The Filarial Test Strip (FTS) development story provides a case study on how a multi-stakeholder, public-private partnership model facilitated the development, evaluation, and introduction of a new monitoring and surveillance tool for LF. This …

Heat Shock Factor 1 Directly Regulates Transsulfuration Pathway To Promote Prostate Cancer Proliferation And Survival, Mu-En Wang, Yue Zhao, Lingfan Xu, Holly Quang, William Butler, Ming Chen, Everardo Macias, Xia Gao, Yiping He, Jiaoti Huang

Faculty, Staff and Students Publications

There are limited therapeutic options for patients with advanced prostate cancer (PCa). We previously found that heat shock factor 1 (HSF1) expression is increased in PCa and is an actionable target. In this manuscript, we identify that HSF1 regulates the conversion of homocysteine to cystathionine in the transsulfuration pathway by altering levels of cystathionine-β-synthase (CBS). We find that HSF1 directly binds the CBS gene and upregulates CBS mRNA levels. Targeting CBS decreases PCa growth and induces tumor cell death while benign prostate cells are largely unaffected. Combined inhibition of HSF1 and CBS results in more pronounced inhibition of PCa cell …

Features Of Acute Covid-19 Associated With Post-Acute Sequelae Of Sars-Cov-2 Phenotypes: Results From The Impacc Study, Esther Melamed, Carly E Milliren, Jingjing Qi, Linda N Geng, Grace A Mccomsey, Charles B Cairns, Lindsey R Baden, Joanna Schaenman, Albert C Shaw, Hady Samaha, Vicki Seyfert-Margolis, Florian Krammer, Lindsey B Rosen, Hanno Steen, Caitlin Syphurs, Ravi Dandekar, Casey P Shannon, Rafick P Sekaly, Lauren I R Ehrlich, David B Corry, Farrah Kheradmand, Mark A Atkinson, Scott C Brakenridge, Nelson I Agudelo Higuita, Jordan P Metcalf, Catherine L Hough, William B Messer, Bali Pulendran, Kari C Nadeau, Mark M Davis, Ana Fernandez Sesma, Viviana Simon, Harm Van Bakel, Seunghee Kim-Schulze, David A Hafler, Ofer Levy, Monica Kraft, Chris Bime, Elias K Haddad, Carolyn S Calfee, David J Erle, Charles R Langelier, Walter Eckalbar, Steven E Bosinger, Bjoern Peters, Steven H Kleinstein, Elaine F Reed, Alison D Augustine, Joann Diray-Arce, Holden T Maecker, Matthew C Altman, Ruth R Montgomery, Patrice M Becker, Nadine Rouphael

Faculty, Staff and Students Publications

Post-acute sequelae of SARS-CoV-2 (PASC) is a significant public health concern. We describe Patient Reported Outcomes (PROs) on 590 participants prospectively assessed from hospital admission for COVID-19 through one year after discharge. Modeling identified 4 PRO clusters based on reported deficits (minimal, physical, mental/cognitive, and multidomain), supporting heterogenous clinical presentations in PASC, with sub-phenotypes associated with female sex and distinctive comorbidities. During the acute phase of disease, a higher respiratory SARS-CoV-2 viral burden and lower Receptor Binding Domain and Spike antibody titers were associated with both the physical predominant and the multidomain deficit clusters. A lower frequency of circulating B …

Preclinical Repurposing Of Sitagliptin As A Drug Candidate For Colorectal Cancer By Targeting Cd24/Ctnnb1/Sox4-Centered Signaling Hub, Yan-Jiun Huang

Faculty, Staff and Student Publications

Despite significant advances in treatment modalities, colorectal cancer (CRC) remains a poorly understood and highly lethal malignancy worldwide. Cancer stem cells (CSCs) and the tumor microenvironment (TME) have been shown to play critical roles in initiating and promoting CRC progression, metastasis, and treatment resistance. Therefore, a better understanding of the underlying mechanisms contributing to the generation and maintenance of CSCs is crucial to developing CSC-specific therapeutics and improving the current standard of care for CRC patients. To this end, we used a bioinformatics approach to identify increased CD24/SOX4 expression in CRC samples associated with poor prognosis. We also …

Il-12 Reprograms Car-Expressing Natural Killer T Cells To Long-Lived Th1-Polarized Cells With Potent Antitumor Activity, Gabriele Casirati, Vincenzo Cinella, Simone Stucchi, Leah M Flick, Tracy A Withers, Hanna Hudson, Giulia Casorati, Paolo Dellabona, Pietro Genovese, Barbara Savoldo, Leonid S Metelitsa, Gianpietro Dotti

Faculty, Staff and Students Publications

Human natural killer T cells (NKTs) are innate-like T lymphocytes increasingly used for cancer immunotherapy. Here we show that human NKTs expressing the pro-inflammatory cytokine interleukin-12 (IL-12) undergo extensive and sustained molecular and functional reprogramming. Specifically, IL-12 instructs and maintains a Th1-polarization program in NKTs in vivo without causing their functional exhaustion. Furthermore, using CD62L as a marker of memory cells in human NKTs, we observe that IL-12 maintains long-term CD62L-expressing memory NKTs in vivo. Notably, IL-12 initiates a de novo programming of memory NKTs in CD62L-negative NKTs indicating that human NKTs circulating in the peripheral blood possess an intrinsic …

Novel Techniques In Imaging Congenital Heart Disease: Jacc Scientific Statement, Lars Grosse-Wortmann, B Kelly Han, Luc Mertens, Ryan A Moore, Laura J Olivieri, Anitha Parthiban, Andrew J Powell

Faculty, Staff and Students Publications

Recent years have witnessed exponential growth in cardiac imaging technologies, allowing better visualization of complex cardiac anatomy and improved assessment of physiology. These advances have become increasingly important as more complex surgical and catheter-based procedures are evolving to address the needs of a growing congenital heart disease population. This state-of-the-art review presents advances in echocardiography, cardiac magnetic resonance, cardiac computed tomography, invasive angiography, 3-dimensional modeling, and digital twin technology. The paper also highlights the integration of artificial intelligence with imaging technology. While some techniques are in their infancy and need further refinement, others have found their way into clinical workflow …

Patient Priorities-Aligned Care For Older Adults With Multiple Conditions: A Nonrandomized Controlled Trial, Toyomi Goto, Lilian Dindo, Fan Li

Faculty, Staff and Student Publications

IMPORTANCE: Older adults with multiple conditions receive health care that may be burdensome, of uncertain benefit, and not focused on what matters to them. Identifying and aligning care with patients' health priorities may improve outcomes.

OBJECTIVE: to assess the association of receiving patient priorities care (PPC) vs usual care (UC) with relevant clinical outcomes.

DESIGN, SETTING, AND PARTICIPANTS: In this nonrandomized controlled trial with propensity adjustment, enrollment occurred between August 21, 2020, and May 14, 2021, with follow-up continuing through February 26, 2022. Patients who were aged 65 years or older and with 3 or more chronic conditions were enrolled …

Microbial Co-Occurrences On Catheters From Long-Term Catheterized Patients, Erin Lowry, Aleksandra Klim, Karen W Dodson, Ana L Flores-Mireles, Jennifer N Walker, Daniel Garrett Wong, Alana Desai, Michael G Caparon, Scott J Hultgren

Faculty, Staff and Student Publications

Catheter-associated urinary tract infections (CAUTIs), a common cause of healthcare-associated infections, are caused by a diverse array of pathogens that are increasingly becoming antibiotic resistant. We analyze the microbial occurrences in catheter and urine samples from 55 human long-term catheterized patients collected over one year. Although most of these patients were prescribed antibiotics over several collection periods, their catheter samples remain colonized by one or more bacterial species. Examination of a total of 366 catheter and urine samples identify 13 positive and 13 negative genus co-occurrences over 12 collection periods, representing associations that occur more or less frequently than expected …

"Once I Take That One Bite": The Consideration Of Harm Reduction As A Strategy To Support Dietary Change For Patients With Diabetes, Alexzandra Gentsch, Megan Reed, Amy Cunningham, Anna Marie Chang, Stephanie Kahn, Danielle Kovalsky, Amanda Doty, Geoffrey Mills, Judd Hollander, Kristin Rising

College of Population Health Faculty Papers

BACKGROUND: Despite well-established guidelines to treat diabetes, many people with diabetes struggle to manage their disease. For many, this struggle is related to challenges achieving nutrition-related lifestyle changes. We examined how people with diabetes describe barriers to maintaining a healthy diet and considered the benefits of using a harm reduction approach to assist patients to achieve nutrition-related goals.

METHODS: This is a secondary analysis of 89 interviews conducted with adults who had type 1 or type 2 diabetes. Interviews were analyzed using a content analysis approach. Themes regarding food or diet were initially captured in a "food" node. Data in …

Process Evaluation Of A Double-Blind Randomized Controlled Trial To Assess The Efficacy And Safety Of A Quadruple Ultra-Low-Dose Treatment For Hypertension Within A Federally Qualified Health Center Network (Quartet Usa), Olutobi A Sanuade, Tyler A Jacobson, Adriana Quintana, Fallon M Flowers, Hiba Abbasi, My H Vu, Abigail S Baldridge, Jairo Mejia, Danielle Lazar, Jody D Ciolino, Mark D Huffman, Namratha R Kandula

2020-Current year OA Pubs

BACKGROUND: This convergent parallel-design mixed-methods process evaluation of the QUARTET USA (Quadruple Ultra-Low-Dose Treatment for Hypertension USA) clinical trial (NCT03640312) explores patient and health care professional perceptions about the use of low-dose quadruple therapy (LDQT) as a novel strategy for hypertension management.

METHODS AND RESULTS: A survey of all 62 patients enrolled in the QUARTET USA trial was conducted. A subsample of 13 patients and 11 health care professionals, recruited via purposive sampling, took part in semistructured interviews. At enrollment, 68% of participants (mean [SD] age, 51.7 [11.5] years; 56% self-identified as Hispanic: Mexican ethnicity, 16% as Hispanic: other ethnicity, …

A Dataset Of Digital Holograms Of Normal And Thalassemic Cells, Vahid Abbasian, Arash Darafsheh

2020-Current year OA Pubs

Digital holographic microscopy (DHM) is an intriguing medical diagnostic tool due to its label-free and quantitative nature, providing high-contrast images of phase samples. By capturing both intensity and phase information, DHM enables the numerical reconstruction of quantitative phase images. However, the lateral resolution is limited by the diffraction limit, which prompted the recent suggestion of microsphere-assisted DHM to enhance the DHM resolution straightforwardly. The use of such a technique as a medical diagnostic tool requires testing and validation of the proposed assays to prove their feasibility and viability. This paper publishes 760 and 609 microsphere-assisted DHM images of normal and …

Contrast Response Function Estimation With Nonparametric Bayesian Active Learning, Dom C P Marticorena, Quinn Wai Wong, Jake Browning, Ken Wilbur, Samyukta Jayakumar, Pinakin Gunvant Davey, Aaron R Seitz, Jacob R Gardner, Dennis L Barbour

2020-Current year OA Pubs

Multidimensional psychometric functions can typically be estimated nonparametrically for greater accuracy or parametrically for greater efficiency. By recasting the estimation problem from regression to classification, however, powerful machine learning tools can be leveraged to provide an adjustable balance between accuracy and efficiency. Contrast sensitivity functions (CSFs) are behaviorally estimated curves that provide insight into both peripheral and central visual function. Because estimation can be impractically long, current clinical workflows must make compromises such as limited sampling across spatial frequency or strong assumptions on CSF shape. This article describes the development of the machine learning contrast response function (MLCRF) estimator, which …

Fatty Acid Synthesis Suppresses Dietary Polyunsaturated Fatty Acid Use, Anna Worthmann, Sangeeta Adak, Clay F Semenkovich, Et Al.

2020-Current year OA Pubs

Dietary polyunsaturated fatty acids (PUFA) are increasingly recognized for their health benefits, whereas a high production of endogenous fatty acids - a process called de novo lipogenesis (DNL) - is closely linked to metabolic diseases. Determinants of PUFA incorporation into complex lipids are insufficiently understood and may influence the onset and progression of metabolic diseases. Here we show that fatty acid synthase (FASN), the key enzyme of DNL, critically determines the use of dietary PUFA in mice and humans. Moreover, the combination of FASN inhibition and PUFA-supplementation decreases liver triacylglycerols (TAG) in mice fed with high-fat diet. Mechanistically, FASN inhibition …

Microbial Co-Occurrences On Catheters From Long-Term Catheterized Patients, Taylor M Nye, Zongsen Zou, Chloe L P Obernuefemann, Jerome S Pinkner, Erin Lowry, Kent Kleinschmidt, Karla Bergeron, Aleksandra Klim, Karen W Dodson, Ana L Flores-Mireles, Jennifer N Walker, Daniel Garrett Wong, Alana Desai, Michael G Caparon, Scott J Hultgren

2020-Current year OA Pubs

Catheter-associated urinary tract infections (CAUTIs), a common cause of healthcare-associated infections, are caused by a diverse array of pathogens that are increasingly becoming antibiotic resistant. We analyze the microbial occurrences in catheter and urine samples from 55 human long-term catheterized patients collected over one year. Although most of these patients were prescribed antibiotics over several collection periods, their catheter samples remain colonized by one or more bacterial species. Examination of a total of 366 catheter and urine samples identify 13 positive and 13 negative genus co-occurrences over 12 collection periods, representing associations that occur more or less frequently than expected …

Genome-Wide And Targeted Crispr Screens Identify Rnf213 As A Mediator Of Interferon Gamma-Dependent Pathogen Restriction In Human Cells, Sumit K Matta, Hinissan P Kohio, Pallavi Chandra, Adam Brown, John G Doench, Jennifer A Philips, Siyuan Ding, L David Sibley

2020-Current year OA Pubs

To define cellular immunity to the intracellular pathogen

Hat: De Novo Variant Calling For Highly Accurate Short-Read And Long-Read Sequencing Data, Jeffrey K Ng, Tychele N Turner

2020-Current year OA Pubs

MOTIVATION: de novo variants (DNVs) are variants that are present in offspring but not in their parents. DNVs are both important for examining mutation rates as well as in the identification of disease-related variation. While efforts have been made to call DNVs, calling of DNVs is still challenging from parent-child sequenced trio data. We developed Hare And Tortoise (HAT) as an automated DNV detection workflow for highly accurate short-read and long-read sequencing data. Reliable detection of DNVs is important for human genomics and HAT addresses this need.

RESULTS: HAT is a computational workflow that begins with aligned read data (i.e. …

Cell Cycle Arrest Induces Lipid Droplet Formation And Confers Ferroptosis Resistance, Hyemin Lee, Amber Horbath, Lavanya Kondiparthi, Jitendra Kumar Meena, Guang Lei, Xiaoguang Liu, Pranavi Koppula, Mi Li, Iqbal Mahmud, Bo Wei, Philip L Lorenzi, Khandan Keyomarsi, Masha V Poyurovsky, Kellen Olszewski, Boyi Gan

Faculty, Staff and Student Publications

How cells coordinate cell cycling with cell survival and death remains incompletely understood. Here, we show that cell cycle arrest has a potent suppressive effect on ferroptosis, a form of regulated cell death induced by overwhelming lipid peroxidation at cellular membranes. Mechanistically, cell cycle arrest induces diacylglycerol acyltransferase (DGAT)-dependent lipid droplet formation to sequester excessive polyunsaturated fatty acids (PUFAs) that accumulate in arrested cells in triacylglycerols (TAGs), resulting in ferroptosis suppression. Consequently, DGAT inhibition orchestrates a reshuffling of PUFAs from TAGs to phospholipids and re-sensitizes arrested cells to ferroptosis. We show that some slow-cycling antimitotic drug-resistant cancer cells, such as …

Integrated Multi-Omics Analyses Identify Anti-Viral Host Factors And Pathways Controlling Sars-Cov-2 Infection, Jiakai Hou, Yanjun Wei, Jing Zou, Roshni Jaffery, Long Sun, Ningbo Zheng, Nicholas A Egan, Ritu Bohat, Si Chen, Caishang Zheng, Xiaobo Mao, S Stephen Yi, Ken Chen, Daniel J Mcgrail, Nidhi Sahni, Pei-Yong Shi, Yiwen Chen, Xuping Xie, Weiyi Peng

Faculty, Staff and Student Publications

Host anti-viral factors are essential for controlling SARS-CoV-2 infection but remain largely unknown due to the biases of previous large-scale studies toward pro-viral host factors. To fill in this knowledge gap, we perform a genome-wide CRISPR dropout screen and integrate analyses of the multi-omics data of the CRISPR screen, genome-wide association studies, single-cell RNA-Seq, and host-virus proteins or protein/RNA interactome. This study uncovers many host factors that are currently underappreciated, including the components of V-ATPases, ESCRT, and N-glycosylation pathways that modulate viral entry and/or replication. The cohesin complex is also identified as an anti-viral pathway, suggesting an important role of …

Mutant P53 Gains Oncogenic Functions Through A Chromosomal Instability-Induced Cytosolic Dna Response, Mei Zhao, Tianxiao Wang, Frederico O Gleber-Netto, Zhen Chen, Daniel J Mcgrail, Wutong Ju, Wencai Ma, Li Shen, Qi Wang, Ximing Tang, Sen Pathak, Maria Gabriela Raso, Jared K Burks, Shiaw-Yih Lin, Jing Wang, Asha S Multani, Curtis R Pickering, Junjie Chen, Jeffrey N Myers, Ge Zhou

Faculty, Staff and Student Publications

Inactivating TP53 mutations leads to a loss of function of p53, but can also often result in oncogenic gain-of-function (GOF) of mutant p53 (mutp53) proteins which promotes tumor development and progression. The GOF activities of TP53 mutations are well documented, but the mechanisms involved remain poorly understood. Here, we study the mutp53 interactome and find that by targeting minichromosome maintenance complex components (MCMs), GOF mutp53 predisposes cells to replication stress and chromosomal instability (CIN), leading to a tumor cell-autonomous and cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING)-dependent cytosolic DNA response that activates downstream non-canonical nuclear factor kappa light chain …

Effect Of Acupuncture Vs Sham Acupuncture On Patients With Poststroke Motor Aphasia: A Randomized Clinical Trial, Boxuan Li, Shizhe Deng, Bifang Zhuo, Bomo Sang, Junjie Chen, Guang Tian, Yuzheng Du, Peng Zheng, Gonglei Yue, Zhihong Meng

Faculty, Staff and Student Publications

IMPORTANCE: Motor aphasia is common among patients with stroke. Acupuncture is recommended as an alternative therapy for poststroke aphasia, but its efficacy remains uncertain.

OBJECTIVE: To investigate the effects of acupuncture on language function, neurological function, and quality of life in patients with poststroke motor aphasia.

DESIGN, SETTING, AND PARTICIPANTS: This multicenter, sham-controlled, randomized clinical trial was conducted in 3 tertiary hospitals in China from October 21, 2019, to November 13, 2021. Adult patients with poststroke motor aphasia were enrolled. Data analysis was performed from February to April 2023.

INTERVENTIONS: Eligible participants were randomly allocated (1:1) to manual acupuncture (MA) …

Pediatric Medical Subspecialist Use In Outpatient Settings, Ruth Cooper, Lauren E Parlett

Faculty, Staff and Student Publications

Importance

A first step toward understanding whether pediatric medical subspecialists are meeting the needs of the nation’s children is describing rates of use and trends over time.

Objectives

To quantify rates of outpatient pediatric medical subspecialty use.

Design, Setting, and Participants

This repeated cross-sectional study of annual subspecialist use examined 3 complementary data sources: electronic health records from PEDSnet (8 large academic medical centers [January 1, 2010, to December 31, 2021]); administrative data from the Healthcare Integrated Research Database (HIRD) (14 commercial health plans [January 1, 2011, to December 31, 2021]); and administrative data from the Transformed Medicaid Statistical Information …

Unraveling The Intercellular Communication Disruption And Key Pathways In Alzheimer’S Disease: An Integrative Study Of Single-Nucleus Transcriptomes And Genetic Association

Faculty, Staff and Student Publications

BACKGROUND: Recently, single-nucleus RNA-seq (snRNA-seq) analyses have revealed important cellular and functional features of Alzheimer's disease (AD), a prevalent neurodegenerative disease. However, our knowledge regarding intercellular communication mediated by dysregulated ligand-receptor (LR) interactions remains very limited in AD brains.

METHODS: We systematically assessed the intercellular communication networks by using a discovery snRNA-seq dataset comprising 69,499 nuclei from 48 human postmortem prefrontal cortex (PFC) samples. We replicated the findings using an independent snRNA-seq dataset of 56,440 nuclei from 18 PFC samples. By integrating genetic signals from AD genome-wide association studies (GWAS) summary statistics and whole genome sequencing (WGS) data, we prioritized …

Economic Review Of Point-Of-Care Eeg., Adam Green, M Elizabeth Wegman, John P Ney

Cooper Medical School of Rowan University Departmental Research

Aims: Point-of-care electroencephalogram (POC-EEG) is an acute care bedside screening tool for the identification of nonconvulsive seizures (NCS) and nonconvulsive status epilepticus (NCSE). The objective of this narrative review is to describe the economic themes related to POC-EEG in the United States (US).

Materials and methods: We examined peer-reviewed, published manuscripts on the economic findings of POC-EEG for bedside use in US hospitals, which included those found through targeted searches on PubMed and Google Scholar. Conference abstracts, gray literature offerings, frank advertisements, white papers, and studies conducted outside the US were excluded.

Results: Twelve manuscripts were identified and reviewed; results …