Digital Commons Network^™

Efficacy And Adverse Effects Of Ketamine Versus Electroconvulsive Therapy For Major Depressive Disorder: A Systematic Review And Meta-Analysis, Debora De A Simoes Moreira, Luís Eduardo Gauer, Guilherme Teixeira, Amanda Carolina Fonseca Da Silva, Stefanie Cavalcanti, João Quevedo

Faculty, Staff and Student Publications

Background: ECT is considered the fastest and most effective treatment for TRD. Ketamine seems to be an attractive alternative due to its rapid-onset antidepressant effects and impact on suicidal thoughts. This study aimed to compare efficacy and tolerability of ECT and ketamine for different depression outcomes (PROSPERO/CRD42022349220).

Methods: We searched MEDLINE, Web of Science, Embase, PsycINFO, Google Scholar, Cochrane Library and trial registries, which were the ClinicalTrials.gov and the World Health Organization's International Clinical Trials Registry Platform, without restrictions on publication date.

Selection criteria: randomized controlled trials or cohorts comparing ketamine versus ECT in patients with TRD.

Results: Eight studies …

Enhancement Of Immunotherapies In Head And Neck Cancers Using Biomaterial-Based Treatment Strategies, Gemalene M Sunga, Jeffrey Hartgerink, Andrew G Sikora, Simon Young

Faculty, Staff and Student Publications

Head and neck squamous cell carcinoma (HNSCC) is a challenging disease to treat because of typically late-stage diagnoses and tumor formation in difficult-to-treat areas, sensitive to aggressive or invasive treatments. To date, HNSCC treatments have been limited to surgery, radiotherapy, and chemotherapy, which may have significant morbidity and often lead to long-lasting side effects. The development of immunotherapies has revolutionized cancer treatment by providing a promising alternative to standard-of-care therapies. However, single-agent immunotherapy has been only modestly effective in the treatment of various cancers, including HNSCC, with most patients receiving no overall benefit or increased survival. In addition, single-agent immunotherapy's …

Facial Analytics Based On A Coordinate Extrapolation System (Zface) For Morphometric Phenotyping Of Developing Zebrafish, Lorena Maili, Oscar E Ruiz, Philip H Kahan, Frankie Chiu, Stephen T Larson, S Shahrukh Hashmi, Jacqueline T Hecht, George T Eisenhoffer

Faculty, Staff and Student Publications

Facial development requires a complex and coordinated series of cellular events that, when perturbed, can lead to structural birth defects. A quantitative approach to quickly assess morphological changes could address how genetic or environmental inputs lead to differences in facial shape and promote malformations. Here, we report on a method to rapidly analyze craniofacial development in zebrafish embryos using facial analytics based on a coordinate extrapolation system, termed zFACE. Confocal images capture facial structures and morphometric data are quantified based on anatomical landmarks present during development. The quantitative morphometric data can detect phenotypic variation and inform on changes in facial …

Aibp Regulates Trpv1 Activation In Chemotherapy-Induced Peripheral Neuropathy By Controlling Lipid Raft Dynamics And Proximity To Tlr4 In Dorsal Root Ganglion Neurons, Juliana M Navia-Pelaez, Julia Borges Paes Lemes, Leonardo Gonzalez, Lauriane Delay, Luciano Dos Santos Aggum Capettini, Jenny W Lu, Gilson Gonçalves Dos Santos, Ann M Gregus, Patrick M Dougherty, Tony L Yaksh, Yury I Miller

Faculty, Staff and Student Publications

Nociceptive afferent signaling evoked by inflammation and nerve injury is mediated by the opening of ligand-gated and voltage-gated receptors or channels localized to cholesterol-rich lipid raft membrane domains. Dorsal root ganglion (DRG) nociceptors express high levels of toll-like receptor 4 (TLR4), which also localize to lipid rafts. Genetic deletion or pharmacologic blocking of TLR4 diminishes pain associated with chemotherapy-induced peripheral neuropathy (CIPN). In DRGs of mice with paclitaxel-induced CIPN, we analyzed DRG neuronal lipid rafts, expression of TLR4, activation of transient receptor potential cation channel subfamily V member 1 (TRPV1), and TLR4-TRPV1 interaction. Using proximity ligation assay, flow cytometry, and …

A Comprehensive Investigation Of Linear Energy Transfer Optimization Effectiveness In Intensity-Modulated Proton Therapy Via Alternating Direction Method Of Multipliers (Impt Let-Admm), Q Fan, G Liu, Lewei Zhao, Xiaoqiang Li, Xuanfeng Ding, S Dai

Conference Presentation Abstracts

Linear energy transfer (LET)-guided optimization in intensity-modulated proton therapy (IMPT) via alternating direction method of multipliers (ADMM) has the potential to improve its biological effectiveness (IMPTLET- ADMM), in which the LET distribution in target can be escalated, while the LET distribution in the organs at risk can be mitigated. This study aims to quantitatively investigate the effectiveness of LET optimization in IMPT via ADMM with different solvers in its iteration loop. Methods: The clinical dose-volume-histogram (DVH) constraint noted dose sub-problem and clinical LET -volume-histogram (LVH) constraint noted LET sub-problem are combined to generate a composite objective function, which is available …

Impact Of Cross-Ancestry Genetic Architecture On Gwass In Admixed Populations, Rachel Mester, Kangcheng Hou, Yi Ding, Gillian Meeks, Kathryn S Burch, Arjun Bhattacharya, Brenna M Henn, Bogdan Pasaniuc

Faculty, Staff and Student Publications

Genome-wide association studies (GWASs) have identified thousands of variants for disease risk. These studies have predominantly been conducted in individuals of European ancestries, which raises questions about their transferability to individuals of other ancestries. Of particular interest are admixed populations, usually defined as populations with recent ancestry from two or more continental sources. Admixed genomes contain segments of distinct ancestries that vary in composition across individuals in the population, allowing for the same allele to induce risk for disease on different ancestral backgrounds. This mosaicism raises unique challenges for GWASs in admixed populations, such as the need to correctly adjust …

Impact Of Covid-19 On Latinx And Black Communities, Carolina Zuluaga

Dissertations

This critical literature review project explored the impact of COVID-19 on Latinx and Black communities. According to the Centers for Disease Control and Prevention, as of September 28, 2022, around 16% of COVID-19 cases in the United States were among Latinx people, and 14% of cases were among Black people (Centers for Disease Control and Prevention, 2022). Since COVID-19 began, clinicians have become more conscious of the effects of health disparities within racial and ethnic minorities, which has warranted increased advocacy by educating health and mental health providers and creating and providing resources to these communities and clinicians. The review …

An Analytic Model Of The External Beam Dose Rate Effect On Immune Cells In Blood Dosimetry, Lewei Zhao, Peilin Liu, G Liu, Xuanfeng Ding

Conference Presentation Abstracts

Purpose: Radiation therapy is a double-edged sword with regard to its immunomodulatory effect. It is critical to find how it is affected by dose rate. Thus, we developed an analytic model for calculating the number of immune cells receiving radiation. Methods: Suppose the blood is received radiation by constant dose rate. The blood is one-way flow without circulation in the radiation delivery at a constant velocity. Two kinds of lung treatment regimens were considered standard delivery 2Gy per fx total 30fx and hypo-fractionation SBRT 12 Gy per fx total 5 fx. Two different dose rates were simulated for standard treatment: …

Birth Weight Moderates The Association Between Obesity And Mortality Rate, Gregory Pavela, Nengjun Yi, Luis Mestre, Pengcheng Xun, David B Allison

Children’s Nutrition Research Center Staff Publications

Purpose: The strength of the association between obesity and mortality rate (MR) varies by body mass index (BMI) and sociodemographic groups. We test the hypothesis that the association between obesity and MR varies, in part, due to the moderating effect of parental BMI and birth weight.

Methods: Data come from the 1958 National Child Development Study, an ongoing longitudinal dataset initiated in 1958 with baseline measures of birth weight from 18,059 infants born in Great Britain over 1 week. We tested whether the association between BMI and MR was moderated by parental BMI and birth weight using generalized additive proportional …

Climate Change Imperils Pediatric Health: Child Advocacy Through Fossil Fuel Divestment., Sandra H. Jee, Elizabeth Friedman, Ruth A. Etzel, Vi T. Nguyen, Todd L. Sack, Kathi J. Kemper

Manuscripts, Articles, Book Chapters and Other Papers

Climate change poses an existential threat to children's health. Divestment of ownership stakes in fossil fuel companies is one tool available to pediatricians to address climate change. Pediatricians are trusted messengers regarding children's health and therefore bear a unique responsibility to advocate for climate and health policies that affect children. Among the impacts of climate change on pediatric patients are allergic rhinitis and asthma; heat-related illnesses; premature birth; injuries from severe storms and fires; vector-borne diseases; and mental illnesses. Children are disproportionately affected as well by climate-related displacement of populations, drought, water shortages, and famine. The human-generated burning of fossil …

Long Noncoding Rna Expression Independently Predicts Outcome In Pediatric Acute Myeloid Leukemia., Jason E. Farrar, Jenny L. Smith, Megan Othus, Benjamin J. Huang, Yi-Cheng Wang, Rhonda Ries, Tiffany Hylkema, Era L. Pogosova-Agadjanyan, Sneha Challa, Amanda Leonti, Timothy I. Shaw, Timothy J. Triche, Alan S. Gamis, Richard Aplenc, E Anders Kolb, Xiaotu Ma, Derek L. Stirewalt, Todd A. Alonzo, Soheil Meshinchi

Manuscripts, Articles, Book Chapters and Other Papers

Purpose: Optimized strategies for risk classification are essential to tailor therapy for patients with biologically distinctive disease. Risk classification in pediatric acute myeloid leukemia (pAML) relies on detection of translocations and gene mutations. Long noncoding RNA (lncRNA) transcripts have been shown to associate with and mediate malignant phenotypes in acute myeloid leukemia (AML) but have not been comprehensively evaluated in pAML.

Methods: To identify lncRNA transcripts associated with outcomes, we evaluated the annotated lncRNA landscape by transcript sequencing of 1,298 pediatric and 96 adult AML specimens. Upregulated lncRNAs identified in the pAML training set were used to establish a regularized …

Incorporating Sexual And Gender Minority Patient Care Competencies: A Case Based Curriculum For Caring For Gender Diverse Youth, Eileen Cichoskikelly, Suzanne Kingery, Susan Sawning

Faculty and Staff Scholarship

There is a gap in medical education training content specifically focused on the care of Sexual and Gender Minority (SGM) people and people with Differences in Sex Development (DSD). Inadequate training contributes to suboptimal health care access, utilization, and experiences among SGM-DSD people. Improving medical education training can be challenging as many clinician educators received sparse instruction themselves in these areas and there are limited teaching resources that expand beyond didactic instruction. In 2014 the Association of American Medical Colleges (AAMC) Advisory Committee on Sexual Orientation, Gender Identity, and Sex Development published a landmark document identifying 30 specifiers of competence …

A Highly Selective Humanized Ddr1 Mab Reverses Immune Exclusion By Disrupting Collagen Fiber Alignment In Breast Cancer, Junquan Liu, Huai-Chin Chiang, Wei Xiong, Victor Laurent, Samuel C Griffiths, Jasmin Dülfer, Hui Deng, Xiujie Sun, Y Whitney Yin, Wenliang Li, Laurent P Audoly, Zhiqiang An, Thomas Schürpf, Rong Li, Ningyan Zhang

Faculty, Staff and Student Publications

BACKGROUND: Immune exclusion (IE) where tumors deter the infiltration of immune cells into the tumor microenvironment has emerged as a key mechanism underlying immunotherapy resistance. We recently reported a novel role of discoidin domain-containing receptor 1 (DDR1) in promoting IE in breast cancer and validated its critical role in IE using neutralizing rabbit monoclonal antibodies (mAbs) in multiple mouse tumor models.

METHODS: To develop a DDR1-targeting mAb as a potential cancer therapeutic, we humanized mAb9 with a complementarity-determining region grafting strategy. The humanized antibody named PRTH-101 is currently being tested in a Phase 1 clinical trial. We determined the binding …

Maternal Embryonic Leucine Zipper Kinase Is Associated With Metastasis In Triple-Negative Breast Cancer, Xuemei Xie, Gaurav B Chauhan, Ramakrishna Edupuganti, Takahiro Kogawa, Jihyun Park, Moises Tacam, Alex W Tan, Mohd Mughees, Fnu Vidhu, Diane D Liu, Juliana M Taliaferro, Mary Kathryn Pitner, Luke S Browning, Ju-Hyeon Lee, Yu Shen, Jian Wang, Naoto T Ueno, Savitri Krishnamurthy, Gabriel N Hortobagyi, Debu Tripathy, Steven J Van Laere, Geoffrey Bartholomeusz, Kevin N Dalby, Chandra Bartholomeusz

Faculty, Staff and Student Publications

UNLABELLED: Triple-negative breast cancer (TNBC) has high relapse and metastasis rates and a high proportion of cancer stem-like cells (CSC), which possess self-renewal and tumor initiation capacity. MELK (maternal embryonic leucine zipper kinase), a protein kinase of the Snf1/AMPK kinase family, is known to promote CSC maintenance and malignant transformation. However, the role of MELK in TNBC metastasis is unknown; we sought to address this in the current study. We found that

SIGNIFICANCE: These findings indicate that MELK is a driver of aggressiveness and metastasis in TNBC.

Phase Ii Trial Of Nelipepimut-S Peptide Vaccine In Women With Ductal Carcinoma In Situ, Anne E O'Shea, Guy T Clifton, Na Qiao, Brandy M Heckman-Stoddard, Malgorzata Wojtowicz, Eileen Dimond, Isabelle Bedrosian, Diane Weber, Judy E Garber, Alexander Husband, Ricardo Pastorello, J Jack Lee, Mike Hernandez, Diane D Liu, Lana A Vornik, Powel H Brown, Gheath Alatrash, George E Peoples, Elizabeth A Mittendorf

Faculty, Staff and Student Publications

UNLABELLED: NeuVax is a vaccine comprised of the HER2-derived MHC class I peptide E75 (nelipepimut-S, NPS) combined with GM-CSF. We completed a randomized trial of preoperative vaccination with NeuVax versus GM-CSF alone in patients with ductal carcinoma in situ (DCIS). The primary objective was to evaluate for NPS-specific cytotoxic T lymphocyte (CTL) responses. Patients with human leukocyte antigen (HLA)-A2-positive DCIS were enrolled and randomized 2:1 to NeuVax versus GM-CSF alone and received two inoculations prior to surgery. The number of NPS-specific CTL was measured pre-vaccination, at surgery, and 1 and 3 to 6 months post-operation by dextramer assay. Differences in …

Phase I/Ii Sequencing Study Of Azacitidine, Epacadostat, And Pembrolizumab In Advanced Solid Tumors, Jason J Luke, Marwan Fakih, Charles Schneider, E Gabriela Chiorean, Johanna Bendell, Rebecca Kristeleit, Razelle Kurzrock, Sarah P Blagden, Irene Brana, Laura W Goff, Kevin O'Hayer, Ryan Geschwindt, Michael Smith, Feng Zhou, Aung Naing

Faculty, Staff and Student Publications

Background: Indoleamine 2,3-dioxygenase 1 (IDO1), an interferon-inducible enzyme, contributes to tumor immune intolerance. Immune checkpoint inhibition may increase interferon levels; combining IDO1 inhibition with immune checkpoint blockade represents an attractive strategy. Epigenetic agents trigger interferon responses and may serve as an immunotherapy priming method. We evaluated whether epigenetic therapy plus IDO1 inhibition and immune checkpoint blockade confers clinical benefit to patients with advanced solid tumors.

Methods: ECHO-206 was a Phase I/II study where treatment-experienced patients with advanced solid tumors (N = 70) received azacitidine plus an immunotherapy doublet (epacadostat [IDO1 inhibitor] and pembrolizumab). Sequencing of treatment was also assessed. Primary …

Antioxidant Activity And Total Phenolic Compounds Of Commiphora Gileadensis Extracts Obtained By Ultrasonic-Assisted Extraction, With Monitoring Antiaging And Cytotoxicity Activities, Hani Ahmed, Marwan M A Rashed, Marwan Almoiliqy, Mohammed Abdalla, Mohanad Bashari, Mohamed Y Zaky, Zhu Hailin, Taha A A Naji, Ahmed Eibaid, Jinpeng Wang, Li-Ping Jiang

Faculty, Staff and Student Publications

Commiphora gileadensis (C. gileadensis) has been identified and linked with various health benefits and pharmaceutical potential for its phytochemical activities and chemical constituents. This study aimed to evaluate ultrasonic‐assisted extraction (USE) technique for total phenols content from C. gileadensis leaf compared to the hydrodistillation extraction (HDE). Our results showed that the USE operating conditions were identified as: MeOH·H2O solvent‐to‐fresh sample ratio of 80:20 (v/v); ultrasonic power/frequency at 150 W/20 kHz; and a temperature of 40 ± 1°C; subjected to acoustic waves intermittently for a calculated time (5 min) during the total programmed time of 12 min. The USE …

Chronic Hepatitis B, C, And Stroke; Association And Pathophysiology, Hamza Imran, Adnan Yousuf, Mohammad Wasay

Pakistan Journal of Neurological Sciences (PJNS)

Background and Objectives:

Hepatitis infection may raise the incidence of stroke and other cerebrovascular abnormalities, according to several studies. However, its association is controversial. This review looked to compile the most recent research on the relationship between HBV and HCV, atherosclerosis, and stroke.

Methods:This article reviews the literature on the connection between hepatitis B and C viruses with stroke and atherosclerosis. The search included articles from PubMed, PakMediNet, and Google Scholar, as well as a Medline search using specific keywords and MeSH terms. A total of 2655 articles were identified. Out of these 2655 articles we identified 134 articles …

Aryl Hydrocarbon Receptor Maintains Hepatic Mitochondrial Homeostasis In Mice, Mi Jeong Heo, Ji Ho Suh, Sung Ho Lee, Kyle L Poulsen, Yu A An, Bhagavatula Moorthy, Sean M Hartig, David D Moore, Kang Ho Kim

Faculty, Staff and Student Publications

OBJECTIVE: Mitophagy removes damaged mitochondria to maintain cellular homeostasis. Aryl hydrocarbon receptor (AhR) expression in the liver plays a crucial role in supporting normal liver functions, but its impact on mitochondrial function is unclear. Here, we identified a new role of AhR in the regulation of mitophagy to control hepatic energy homeostasis.

METHODS: In this study, we utilized primary hepatocytes from AhR knockout (KO) mice and AhR knockdown AML12 hepatocytes. An endogenous AhR ligand, kynurenine (Kyn), was used to activate AhR in AML12 hepatocytes. Mitochondrial function and mitophagy process were comprehensively assessed by MitoSOX and mt-Keima fluorescence imaging, Seahorse XF-based …

Evolution Of Cisplatin Resistance Through Coordinated Metabolic Reprogramming Of The Cellular Reductive State, Wangie Yu, Yunyun Chen, Nagireddy Putluri, Abdullah Osman, Cristian Coarfa, Vasanta Putluri, Abu H M Kamal, Jennifer Kay Asmussen, Panagiotis Katsonis, Jeffrey N Myers, Stephen Y Lai, Wuhao Lu, Clifford C Stephan, Reid T Powell, Faye M Johnson, Heath D Skinner, Jawad Kazi, Kazi Mokim Ahmed, Linghao Hu, Addison Threet, Matthew D Meyer, James A Bankson, Tony Wang, Jack Davis, Kirby R Parker, Madison A Harris, Mokryun L Baek, Gloria V Echeverria, Xiaoli Qi, Jin Wang, Andy I Frederick, Alex J Walsh, Olivier Lichtarge, Mitchell J Frederick, Vlad C Sandulache

Faculty, Staff and Student Publications

BACKGROUND: Cisplatin (CDDP) is a mainstay treatment for advanced head and neck squamous cell carcinomas (HNSCC) despite a high frequency of innate and acquired resistance. We hypothesised that tumours acquire CDDP resistance through an enhanced reductive state dependent on metabolic rewiring.

METHODS: To validate this model and understand how an adaptive metabolic programme might be imprinted, we performed an integrated analysis of CDDP-resistant HNSCC clones from multiple genomic backgrounds by whole-exome sequencing, RNA-seq, mass spectrometry, steady state and flux metabolomics.

RESULTS: Inactivating KEAP1 mutations or reductions in KEAP1 RNA correlated with Nrf2 activation in CDDP-resistant cells, which functionally contributed to …

Cellular Senescence And Frailty In Transplantation, Elizabeth C Lorenz, Latonya J Hickson, Pascale Khairallah, Bijan Najafi, Cassie C Kennedy

Center on Aging Staff Publications

Purpose of review: To summarizes the literature on cellular senescence and frailty in solid-organ transplantation and highlight the emerging role of senotherapeutics as a treatment for cellular senescence.

Recent findings: Solid-organ transplant patients are aging. Many factors contribute to aging acceleration in this population, including cellular senescence. Senescent cells accumulate in tissues and secrete proinflammatory and profibrotic proteins which result in tissue damage. Cellular senescence contributes to age-related diseases and frailty. Our understanding of the role cellular senescence plays in transplant-specific complications such as allograft immunogenicity and infections is expanding. Promising treatments, including senolytics, senomorphics, cell-based regenerative therapies, and behavioral …

Discordant Calls Across Genotype Discovery Approaches Elucidate Variants With Systematic Errors, Heidi L Rehm, Daniel G Macarthur, Konrad J Karczewski, Benjamin M Neale, Mark J Daly

Faculty, Staff and Students Publications

Large-scale high-throughput sequencing data sets have been transformative for informing clinical variant interpretation and for use as reference panels for statistical and population genetic efforts. Although such resources are often treated as ground truth, we find that in widely used reference data sets such as the Genome Aggregation Database (gnomAD), some variants pass gold-standard filters, yet are systematically different in their genotype calls across genotype discovery approaches. The inclusion of such discordant sites in study designs involving multiple genotype discovery strategies could bias results and lead to false-positive hits in association studies owing to technological artifacts rather than a true …

Transcriptional Differences In Identical Twins With Different Reproductive Capacities: A Case Report, Kyle Schuppe, Armin Ghomeshi, Kajal Khodamoradi, Himanshu Arora, Carolina Jorgez, Ranjith Ramasamy

Faculty, Staff and Students Publications

Disorders of sperm production can be classified quantitatively as oligospermia (low sperm count) or azoospermia (no sperm during ejaculation). Numerous genes have been implicated in spermatogenesis. We describe a case of two identical twins who presented with different reproductive capabilities. One brother was infertile due to azoospermia, and the other, although oligospermic, previously naturally fathered a child. They were found to have differential gene expression based on RNA sequencing analysis. In the man with azoospermia, we found elevated E2F1 and HOXB9 gene expressions when compared with his brother, suggesting that the increased RNA expression of these genes could influence sperm …

Addition Of Metastasis-Directed Therapy To Intermittent Hormone Therapy For Oligometastatic Prostate Cancer: The Extend Phase 2 Randomized Clinical Trial, Tharakeswara Bathala, Suyu Liu, Bryan Fellman, Lorenzo Cohen, Ana Aparicio, Amado J Zurita, Alexandre Reuben, Enrica Marmonti, Stephen G Chun, Jay P Reddy, Amol Ghia, Sean Mcguire, Eleni Efstathiou, Jennifer Wang, Jianbo Wang, Patrick Pilie, Craig Kovitz, Weiliang Du, Samantha J Simiele, Rachit Kumar, Yerko Borghero, Zheng Shi, Brian Chapin, Daniel Gomez, Ignacio Wistuba, Paul G Corn

Faculty, Staff and Students Publications

Importance: Despite evidence demonstrating an overall survival benefit with up-front hormone therapy in addition to established synergy between hormone therapy and radiation, the addition of metastasis-directed therapy (MDT) to hormone therapy for oligometastatic prostate cancer, to date, has not been evaluated in a randomized clinical trial.

Objective: To determine in men with oligometastatic prostate cancer whether the addition of MDT to intermittent hormone therapy improves oncologic outcomes and preserves time with eugonadal testosterone compared with intermittent hormone therapy alone.

Design, setting, participants: The External Beam Radiation to Eliminate Nominal Metastatic Disease (EXTEND) trial is a phase 2, basket randomized clinical …

Association Between Modifiable Social Determinants And Mental Health Among Post-9/11 Veterans: A Systematic Review, Lia Spencer, Sharmily Roy, Amy Sisson, Natalie E Hundt

Faculty, Staff and Students Publications

Introduction: As U.S. Veterans reintegrate from active duty to civilian life, many are at risk for negative modifiable social determinants of health. The prevalence of mental health conditions among Veterans is also high. Awareness of the associations between these two factors is growing. This systematic review provides a comprehensive analysis of the current state of knowledge of the associations between modifiable social determinants and mental health among U.S. Veterans.

Methods: The authors systematically searched four databases and identified 28 articles representing 25 unique studies that met inclusion criteria. Findings from the studies were extracted and synthesized on the basis of …

Functional Response To A Microbial Synbiotic In The Gastrointestinal System Of Children: A Randomized Clinical Trial, Joseph F Petrosino, Bruno P Chumpitazi, Emeran A Mayer, Jared Boetes, Gerard Smits, Shanthi G Parkar, Noah Voreades, Ece Kartal, Gabriel A Al-Ghalith, Marco Pane, Peter A Bron, Gregor Reid, Raja Dhir, Christopher E Mason

Faculty, Staff and Students Publications

BACKGROUND: Oral microbial therapy has been studied as an intervention for a range of gastrointestinal disorders. Though research suggests that microbial exposure may affect the gastrointestinal system, motility, and host immunity in a pediatric population, data have been inconsistent, with most prior studies being in neither a randomized nor placebo-controlled setting. The aim of this randomized, placebo-controlled study was to evaluate the efficacy of a synbiotic on increasing weekly bowel movements (WBMs) in constipated children.

METHODS: Sixty-four children (3-17 years of age) were randomized to receive a synbiotic (n = 33) comprising mixed-chain length oligosaccharides and nine microbial strains, or …

Promoting Ocd Wellness And Resilience (Power) Study: Rationale, Design, And Methods, Alyssa G Hertz, Jessica Garcia, Erika S Trent, Tracey Dibbs, Ogechi Onyeka, Wayne K Goodman, Andrew G Guzick, Andrew D Wiese, Amanda D Palo, Brent J Small, H Blair Simpson, Lauren K Havel, Sohail A Nibras, Kirti Saxena, Eric A Storch

Faculty, Staff and Students Publications

Obsessive-compulsive disorder (OCD) affects 1-2% of children and is associated with functional impairment and diminished quality of life. Several treatments are efficacious: cognitive behavioral therapy (CBT) with exposure and response prevention, serotonin reuptake inhibitor (SRI) monotherapy, and combined treatment (SRI + CBT). Expert clinician-informed practice parameters suggest that youth with mild to moderate OCD should be treated initially with CBT yet SRIs are frequently employed as the first-line intervention or in combination with psychotherapy in applied practice. Empirical data to guide SRI discontinuation in pediatric OCD are very limited. This study, Promoting OCD Wellness and Resiliency (POWER), aims to address …

Physiological Age By Artificial Intelligence-Enhanced Electrocardiograms As A Novel Risk Factor Of Mortality In Kidney Transplant Candidates, Tanya M Petterson, Walter K Kremers, Carrie A Schinstock, Hatem Amer, Andrea L Cheville, Nathan K Lebrasseur, Wolfgang C Winkelmayer, Sankar D Navaneethan, Abraham Baez-Suarez, Zachi I Attia, Francisco Lopez-Jimenez, Paul A Friedman, Cassie C Kennedy, Andrew D Rule

Faculty, Staff and Students Publications

BACKGROUND: Mortality risk assessment before kidney transplantation (KT) is imperfect. An emerging risk factor for death in nontransplant populations is physiological age as determined by the application of artificial intelligence to the electrocardiogram (ECG). The aim of this study was to examine the relationship between ECG age and KT waitlist mortality.

METHODS: We applied a previously developed convolutional neural network to the ECGs of KT candidates evaluated 2014 to 2019 to determine ECG age. We used a Cox proportional hazard model to examine whether ECG age was associated with waitlist mortality.

RESULTS: Of the 2183 patients evaluated, 59.1% were male, …

Distinguishing Renal Cell Carcinoma From Normal Kidney Tissue Using Mass Spectrometry Imaging Combined With Machine Learning, Geoffrey A Sonn, Chia-Sui Kao, Hongjuan Zhao, Ru Wen, Livia S Eberlin, Robert Tibshirani, Richard N Zare, James D Brooks

Faculty, Staff and Students Publications

PURPOSE: Accurately distinguishing renal cell carcinoma (RCC) from normal kidney tissue is critical for identifying positive surgical margins (PSMs) during partial and radical nephrectomy, which remains the primary intervention for localized RCC. Techniques that detect PSM with higher accuracy and faster turnaround time than intraoperative frozen section (IFS) analysis can help decrease reoperation rates, relieve patient anxiety and costs, and potentially improve patient outcomes.

MATERIALS AND METHODS: Here, we extended our combined desorption electrospray ionization mass spectrometry imaging (DESI-MSI) and machine learning methodology to identify metabolite and lipid species from tissue surfaces that can distinguish normal tissues from clear cell …

A Scalable Platform For Fabricating Biodegradable Microparticles With Pulsatile Drug Release, Mei-Li Laracuente, Erin M Euliano, Pujita Munnangi, Brett H Pogostin, Tsvetelina Baryakova, Arnav Garyali, Kevin J Mchugh

Faculty, Staff and Students Publications

Pulsatile drug delivery systems have the potential to improve patient adherence and therapeutic efficacy by providing a sequence of doses in a single injection. Herein, a novel platform, termed Particles Uniformly Liquified and Sealed to Encapsulate Drugs (PULSED) is developed, which enables the high-throughput fabrication of microparticles exhibiting pulsatile release. In PULSED, biodegradable polymeric microstructures with an open cavity are formed using high-resolution 3D printing and soft lithography, filled with drug, and sealed using a contactless heating step in which the polymer flows over the orifice to form a complete shell around a drug-loaded core. Poly(lactic-co-glycolic acid) particles with this …