Medical Specialties Commons^™

A Retrospective Analysis Of Ebv-Dna Status With The Prognosis Of Lymphoma, Lihua Qiu, Junqi Si, Junnan Kang, Zehui Chen, Rexidan Nuermaimaiti, Zhengzi Qian, Lanfang Li, Shiyong Zhou, Mingjian James You, Huilai Zhang, Chen Tian

Faculty, Staff and Student Publications

Epstein-Barr virus (EBV) infection is proved to be associated with clinicopathology of lymphoma. However, little is known about the relationship between EBV-DNA status after treatment and prognosis. In this study, real-time polymerase chain reaction (PCR) was used for quantitative detection of EBV-DNA load in peripheral blood of all 26,527 patients with lymphoma, and the clinical characteristics and prognosis of 202 patients were retrospectively analysed, including 100 patients with positive EBV-DNA and 102 randomly selected patients with negative EBV-DNA. We found that the average rate of EBV-DNA positivity in lymphomas was 0.376%, and EBV-DNA-positive patients presented higher risk with elevated lactate …

Lurbinectedin, A Selective Inhibitor Of Oncogenic Transcription, In Patients With Pretreated Germline Brca1/2 Metastatic Breast Cancer: Results From A Phase Ii Basket Study, V Boni, B Pistilli, I Braña, G I Shapiro, J Trigo, V Moreno, D Castellano, C Fernández, C Kahatt, V Alfaro, M Siguero, A Zeaiter, F Longo, K Zaman, A Antón, A Paredes, G Huidobro, V Subbiah

Faculty, Staff and Student Publications

Background: Lurbinectedin, a selective inhibitor of oncogenic transcription, has shown preclinical antitumor activity against homologous recombination repair-deficient models and preliminary clinical activity in BRCA1/2 breast cancer.

Patients and methods: This phase II basket multitumor trial (NCT02454972) evaluated lurbinectedin 3.2 mg/m2 1-h intravenous infusion every 3 weeks in a cohort of 21 patients with pretreated germline BRCA1/2 breast cancer. Patients with any hormone receptor and human epidermal growth factor receptor 2 status were enrolled. The primary efficacy endpoint was overall response rate (ORR) according to RECIST v1.1. Secondary endpoints included duration of response (DoR), progression-free survival (PFS), overall survival …

Gpu Accelerated Estimation Of A Shared Random Effect Joint Model For Dynamic Prediction, Shikun Wang, Zhao Li, Lan Lan, Jieyi Zhao, W Jim Zheng, Liang Li

Faculty, Staff and Student Publications

In longitudinal cohort studies, it is often of interest to predict the risk of a terminal clinical event using longitudinal predictor data among subjects at risk by the time of the prediction. The at-risk population changes over time; so does the association between predictors and the outcome, as well as the accumulating longitudinal predictor history. The dynamic nature of this prediction problem has received increasing interest in the literature, but computation often poses a challenge. The widely used joint model of longitudinal and survival data often comes with intensive computation and excessive model fitting time, due to numerical optimization and …

First-In-Human Study Of An Ox40 (Ivuxolimab) And 4-1bb (Utomilumab) Agonistic Antibody Combination In Patients With Advanced Solid Tumors, Omid Hamid, Alberto A Chiappori, John A Thompson, Toshihiko Doi, Siwen Hu-Lieskovan, Ferry A L M Eskens, Willeke Ros, Adi Diab, Jean-Philippe Spano, Naiyer A Rizvi, Jeffrey S Wasser, Eric Angevin, Patrick A Ott, Alison Forgie, Wenjing Yang, Cen Guo, Jeffrey Chou, Anthony B El-Khoueiry

Faculty, Staff and Student Publications

Background: Ivuxolimab (PF-04518600) and utomilumab (PF-05082566) are humanized agonistic IgG2 monoclonal antibodies against OX40 and 4-1BB, respectively. This first-in-human, multicenter, open-label, phase I, dose-escalation/dose-expansion study explored safety, tolerability, pharmacokinetics, pharmacodynamics, and antitumor activity of ivuxolimab+utomilumab in patients with advanced solid tumors.

Methods: Dose-escalation: patients with advanced bladder, gastric, or cervical cancer, melanoma, head and neck squamous cell carcinoma, or non-small cell lung cancer (NSCLC) who were unresponsive to available therapies, had no standard therapy available or declined standard therapy were enrolled into five dose cohorts: ivuxolimab (0.1-3 mg/kg every 2 weeks (Q2W)) intravenously plus utomilumab (20 or 100 mg every …

Stat3 Inhibits Autocrine Ifn Signaling In Type I Conventional Dendritic Cells, Taylor T Chrisikos, Yifan Zhou, Laura M Kahn, Bhakti Patel, Nina L Denne, Athena Brooks, Li Shen, Jing Wang, Stephanie S Watowich

Faculty, Staff and Student Publications

Type I conventional dendritic cells (cDC1s) are an essential Ag-presenting population required for generating adaptive immunity against intracellular pathogens and tumors. While the transcriptional control of cDC1 development is well understood, the mechanisms by which extracellular stimuli regulate cDC1 function remain unclear. We previously demonstrated that the cytokine-responsive transcriptional regulator STAT3 inhibits polyinosinic:polycytidylic acid [poly(I:C)]-induced cDC1 maturation and cDC1-mediated antitumor immunity in murine breast cancer, indicating an intrinsic, suppressive role for STAT3 in cDC1s. To probe transcriptional mechanisms regulating cDC1 function, we generated novel RNA sequencing datasets representing poly(I:C)-, IL-10-, and STAT3-mediated gene expression responses in murine cDC1s. Bioinformatics analyses …

A Systematic Review And Meta-Analysis Of The Impact Of Radiation-Related Lymphopenia On Outcomes In High-Grade Gliomas, Supriya Mallick, Anjali V R, Prashanth Giridhar, Rituraj Upadhyay, Byung-Kyu Kim, Amrish Sharma, Hagar Elghazawy, Thiraviyam Elumalai, Vinod Solipuram, Cheng En Hsieh, Courtney Hentz, Abhishek A Solanki, Jing Li, Dennis Pai Chan, Emily Ness, Bhanu Prasad Venkatesulu, David R Grosshans

Faculty, Staff and Student Publications

Introduction  Malignant gliomas are the most common primary malignant brain tumors and are typically treated with maximal safe surgical resection followed by chemoradiation. One of the unintended effects of radiation is depletion of circulating lymphocyte pool, which has been correlated with inferior overall survival outcomes.

Methods  A comprehensive and systematic searches of the PubMed, Cochrane Central, and Embase databases were done to assess the studies that have reported radiation-related lymphopenia in high-grade gliomas. Hazard ratios (HRs), odds ratios (OR), and mean differences were represented with Forest plots comparing patients with severe lymphopenia and no severe lymphopenia. Review Manager Version 5.3 …

Comprehensive Multiplexed Immune Profiling Of The Ductal Carcinoma In Situ Immune Microenvironment Regarding Subsequent Ipsilateral Invasive Breast Cancer Risk, Mathilde M Almekinders, Tycho Bismeijer, Tapsi Kumar, Fei Yang, Bram Thijssen, Rianne Van Der Linden, Charlotte Van Rooijen, Shiva Vonk, Baohua Sun, Edwin R Parra Cuentas, Ignacio I Wistuba, Savitri Krishnamurthy, Lindy L Visser, Iris M Seignette, Ingrid Hofland, Joyce Sanders, Annegien Broeks, Jason K Love, Brian Menegaz, Lodewyk Wessels, Alastair M Thompson, Karin E De Visser, Erik Hooijberg, Esther Lips, Andrew Futreal, Jelle Wesseling

Faculty, Staff and Student Publications

Background: Ductal carcinoma in situ (DCIS) is treated to prevent subsequent ipsilateral invasive breast cancer (iIBC). However, many DCIS lesions will never become invasive. To prevent overtreatment, we need to distinguish harmless from potentially hazardous DCIS. We investigated whether the immune microenvironment (IME) in DCIS correlates with transition to iIBC.

Methods: Patients were derived from a Dutch population-based cohort of 10,090 women with pure DCIS with a median follow-up time of 12 years. Density, composition and proximity to the closest DCIS cell of CD20+ B-cells, CD3+CD8+ T-cells, CD3+CD8- T-cells, CD3+FOXP3+ regulatory T-cells, CD68+ cells, and CD8+Ki67+ T-cells was assessed with …

Association Of Renin Angiotensin Aldosterone System Inhibitors And Outcomes Of Hospitalized Patients With Covid-19, Neha Gupta, Lisa Settle, Brent R Brown, Donna L Armaignac, Michael Baram, Nicholas E Perkins, Margit Kaufman, Roman R Melamed, Amy B Christie, Valerie C Danesh, Joshua L Denson, Sreekanth R Cheruku, Karen Boman, Vikas Bansal, Vishakha K Kumar, Allan J Walkey, Juan P Domecq, Rahul Kashyap, Christopher E Aston

Faculty, Staff and Student Publications

OBJECTIVES: To determine the association of prior use of renin-angiotensin-aldosterone system inhibitors (RAASIs) with mortality and outcomes in hospitalized patients with COVID-19.

DESIGN: Retrospective observational study.

SETTING: Multicenter, international COVID-19 registry.

SUBJECTS: Adult hospitalized COVID-19 patients on antihypertensive agents (AHAs) prior to admission, admitted from March 31, 2020, to March 10, 2021.

INTERVENTIONS: None.

MEASUREMENTS AND MAIN RESULTS: Data were compared between three groups: patients on RAASIs only, other AHAs only, and those on both medications. Multivariable logistic and linear regressions were performed after controlling for prehospitalization characteristics to estimate the effect of RAASIs on mortality and other outcomes during …

Association Of Pd-L1 Expression And Other Variables With Benefit From Immune Checkpoint Inhibition In Advanced Gastroesophageal Cancer: Systematic Review And Meta-Analysis Of 17 Phase 3 Randomized Clinical Trials, Harry H Yoon, Zhaohui Jin, Oudom Kour, Lionel Aurelien Kankeu Fonkoua, Kohei Shitara, Michael K Gibson, Larry J Prokop, Markus Moehler, Yoon-Koo Kang, Qian Shi, Jaffer A Ajani

Faculty, Staff and Student Publications

Importance: Approval by the US Food and Drug Administration of immune checkpoint inhibition (ICI) for advanced gastroesophageal cancer (aGEC) irrespective of PD-L1 status has generated controversy. Exploratory analyses from individual trials indicate a lack of meaningful benefit from ICI in patients with absent or low PD-L1 expression; however, analysis of a single variable while ignoring others may not consider the instability inherent in exploratory analyses.

Objective: To systematically examine the predictive value of tissue-based PD-L1 status compared with that of other variables for ICI benefit in aGEC to assess its stability.

Data sources: MEDLINE, Embase, Scopus, Web of Science, Cochrane …

Modeling Multivariate Age-Related Imaging Variables With Dependencies, Hwiyoung Lee, Chixiang Chen, Peter Kochunov, Liyi Elliot Hong, Shuo Chen

Faculty, Staff and Student Publications

Neuroimaging techniques have been increasingly used to understand the neural biology of aging brains. The neuroimaging variables from distinct brain locations and modalities can exhibit age-related patterns that reflect localized neural decline. However, it is a challenge to identify the impacts of risk factors (eg, mental disorders) on multivariate imaging variables while simultaneously accounting for the dependence structure and nonlinear age trajectories using existing tools. We propose a mixed-effects model to address this challenge by building random effects based on the latent brain aging status. We develop computationally efficient algorithms to estimate the parameters of new random effects. The simulations …

Characteristics Of Community-Acquired Carbapenem-Resistant Enterobacterales, Rima Shrestha, Courtney L Luterbach, Weixiao Dai, Lauren Komarow, Michelle Earley, Gregory Weston, Erica Herc, Jesse T Jacob, Robert Salata, Darren Wong, Deverick Anderson, Kirsten B Rydell, Cesar A Arias, Liang Chen, David Van Duin, Mdro Investigators

Faculty, Staff and Student Publications

BACKGROUND: Community-acquired carbapenem-resistant Enterobacterales (CA-CRE) are an important threat.

METHODS: In CRACKLE-2, we defined patients with CA-CRE as admitted from home, without pre-existing conditions, and a positive culture within 48 h of admission. Healthcare-associated CRE (HA-CRE) were those with the lowest likelihood of community acquisition, not admitted from home and cultured >48 h after admission. Specific genetic markers in carbapenemase-producing Klebsiella pneumoniae were evaluated through random forest modelling.

RESULTS: CA-CRE and HA-CRE were detected in 83 (10%) and 208 (26%) of 807 patients. No significant differences were observed in bacterial species or strain type distribution. K. pneumoniae (204/291, 70%) was …

Pin-Pointing The Key Hubs In The Ifn-Γ Pathway Responding To Sars-Cov-2 Infection, Ayelen Toro, Sofia Lage-Vickers, Juan Bizzotto, Felipe Vilicich, Agustina Sabater, Gaston Pascual, Sabrina Ledesma-Bazan, Pablo Sanchis, Maria Sol Ruiz, Ana Paula Arevalo, Jorge L Porfido, Mercedes Abbate, Rocio Seniuk, Estefania Labanca, Nicolas Anselmino, Nora M Navone, Daniel F Alonso, Elba Vazquez, Martina Crispo, Javier Cotignola, Geraldine Gueron

Faculty, Staff and Student Publications

Interferon gamma (IFN-γ) may be potential adjuvant immunotherapy for COVID-19 patients. In this work, we assessed gene expression profiles associated with the IFN-γ pathway in response to SARS-CoV-2 infection. Employing a case-control study from SARS-CoV-2-positive and -negative patients, we identified IFN-γ-associated pathways to be enriched in positive patients. Bioinformatics analyses showed upregulation of MAP2K6, CBL, RUNX3, STAT1, and JAK2 in COVID-19-positive vs. -negative patients. A positive correlation was observed between STAT1/JAK2, which varied alongside the patient's viral load. Expression of MX1, MX2, ISG15, and OAS1 (four well-known IFN-stimulated genes (ISGs)) …

Video-Urodynamics Efficacy Of Sacral Neuromodulation For Neurogenic Bladder Guided By Three-Dimensional Imaging Ct And C-Arm Fluoroscopy: A Single-Center Prospective Study, Shuaishuai Shan, Wen Zhu, Guoxian Zhang, Qinyong Zhang, Yingyu Che, Jianguo Wen, Qingwei Wang

Faculty, Staff and Student Publications

To assess the efficacy of sacral neuromodulation (SNM) for neurogenic bladder (NB), guided by intraoperative three-dimensional imaging of sacral computed tomography (CT) and mobile C-arm fluoroscopy through video-urodynamics examination. We enrolled 52 patients with NB who underwent conservative treatment with poor results between September 2019 and June 2021 and prospectively underwent SNM guided by intraoperative three-dimensional imaging of sacral CT and mobile C-arm fluoroscopy. Video-urodynamics examination, voiding diary, quality of life questionnaire, overactive bladder symptom scale (OABSS) scoring, and bowel dysfunction exam were completed and recorded at baseline, at SNM testing, and at 6-month follow-up phases. Finally, we calculated the …

Prognostic Molecular Biomarkers In Chordomas: A Systematic Review And Identification Of Clinically Usable Biomarker Panels, Franco Rubino, Christopher Alvarez-Breckenridge, Kadir Akdemir, Anthony P Conley, Andrew J Bishop, Wei-Lien Wang, Alexander J Lazar, Laurence D Rhines, Franco Demonte, Shaan M Raza

Faculty, Staff and Student Publications

INTRODUCTION AND OBJECTIVE: Despite the improvements in management and treatment of chordomas over time, the risk of disease recurrence remains high. Consequently, there is a push to develop effective systemic therapeutics for newly diagnosed and recurrent disease. In order to tailor treatment for individual chordoma patients and develop effective surveillance strategies, suitable clinical biomarkers need to be identified. The objective of this study was to systematically review all prognostic biomarkers for chordomas reported to date in order to classify them according to localization, study design and statistical analysis.

METHODS: Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) …

Testing A Behavioral Activation Gaming App For Depression During Pregnancy: Multimethod Pilot Study, Philipp Karschnia, Jacob S Young, Antonio Dono, Levin Häni, Stephanie T Juenger, Tommaso Sciortino, Francesco Bruno, Nico Teske, Ramin A Morshed, Alexander F Haddad, Yalan Zhang, Sophia Stoecklein, Michael A Vogelbaum, Juergen Beck, Nitin Tandon, Shawn Hervey-Jumper, Annette M Molinaro, Roberta Rudà, Lorenzo Bello, Oliver Schnell, Yoshua Esquenazi, Maximilian I Ruge, Stefan J Grau, Martin Van Den Bent, Michael Weller, Mitchel S Berger, Susan M Chang, Joerg-Christian Tonn

Faculty, Staff and Student Publications

In IDH-wildtype glioblastomas which meet the histopathological or molecular diagnosis criteria, it remains unclear whether the presence of TERT promotor mutations provides additional prognostic information. Based on a multicenter cohort of 466 IDH-wildtype glioblastomas (including 396 with and 70 patients without TERT promotor mutations), we found that TERT promotor mutations were neither associated with progression-free survival nor overall survival. This held true in various treatment-based or molecular subgroups. This argues against standardized analysis for TERT promotor mutation status for the purpose of prognostic or therapeutic relevance in newly diagnosed IDH-wildtype glioblastoma that otherwise meets the histopathological and …

Mucus-Degrading Bacteroides Link Carbapenems To Aggravated Graft-Versus-Host Disease, Eiko Hayase, Tomo Hayase, Mohamed A Jamal, Takahiko Miyama, Chia-Chi Chang, Miriam R Ortega, Saira S Ahmed, Jennifer L Karmouch, Christopher A Sanchez, Alexandria N Brown, Rawan K El-Himri, Ivonne I Flores, Lauren K Mcdaniel, Dung Pham, Taylor Halsey, Annette C Frenk, Valerie A Chapa, Brooke E Heckel, Yimei Jin, Wen-Bin Tsai, Rishika Prasad, Lin Tan, Lucas Veillon, Nadim J Ajami, Jennifer A Wargo, Jessica Galloway-Peña, Samuel Shelburne, Roy F Chemaly, Lauren Davey, Robert W P Glowacki, Chen Liu, Gabriela Rondon, Amin M Alousi, Jeffrey J Molldrem, Richard E Champlin, Elizabeth J Shpall, Raphael H Valdivia, Eric C Martens, Philip L Lorenzi, Robert R Jenq

Faculty, Staff and Student Publications

The intestinal microbiota is an important modulator of graft-versus-host disease (GVHD), which often complicates allogeneic hematopoietic stem cell transplantation (allo-HSCT). Broad-spectrum antibiotics such as carbapenems increase the risk for intestinal GVHD, but mechanisms are not well understood. In this study, we found that treatment with meropenem, a commonly used carbapenem, aggravates colonic GVHD in mice via the expansion of Bacteroides thetaiotaomicron (BT). BT has a broad ability to degrade dietary polysaccharides and host mucin glycans. BT in meropenem-treated allogeneic mice demonstrated upregulated expression of enzymes involved in the degradation of mucin glycans. These mice also had thinning of the colonic …

Factors Associated With Depression, Anxiety, And Stress Symptoms Among Men In A Rural Area In Vietnam During Covid-19, Van T H Hoang, Ha T H Nguyen

Faculty, Staff and Student Publications

BACKGROUND: The COVID-19 pandemic has affected health and well-being worldwide, and its psychological effects are receiving substantial attention in the scientific literature. Research to date shows that the pandemic has increased prevalences of depression, anxiety, and stress. This study aimed to estimate the prevalence of mental health symptoms and identify the associated factors among men in a rural area of Vietnam during the COVID-19 pandemic.

METHODS AND FINDINGS: During July 15-31, 2020, we conducted a cross-sectional survey of 1,085 men from 18 years old in 11 rural districts in Thanh Hoa province, Vietnam, and assessed their mental health using the …

Integration Of Mouse Ovary Morphogenesis With Developmental Dynamics Of The Oviduct, Ovarian Ligaments, And Rete Ovarii, Jennifer Mckey, Dilara N Anbarci, Corey Bunce, Alejandra E Ontiveros, Richard R Behringer, Blanche Capel

Faculty, Staff and Student Publications

Morphogenetic events during the development of the fetal ovary are crucial to the establishment of female fertility. However, the effects of structural rearrangements of the ovary and surrounding reproductive tissues on ovary morphogenesis remain largely uncharacterized. Using tissue clearing and lightsheet microscopy, we found that ovary folding correlated with regionalization into cortex and medulla. Relocation of the oviduct to the ventral aspect of the ovary led to ovary encapsulation, and mutual attachment of the ovary and oviduct to the cranial suspensory ligament likely triggered ovary folding. During this process, the rete ovarii (RO) elaborated into a convoluted tubular structure extending …

Molecular Pathways Enhance Drug Response Prediction Using Transfer Learning From Cell Lines To Tumors And Patient-Derived Xenografts, Yi-Ching Tang, Reid T Powell, Assaf Gottlieb

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Computational models have been successful in predicting drug sensitivity in cancer cell line data, creating an opportunity to guide precision medicine. However, translating these models to tumors remains challenging. We propose a new transfer learning workflow that transfers drug sensitivity predicting models from large-scale cancer cell lines to both tumors and patient derived xenografts based on molecular pathways derived from genomic features. We further compute feature importance to identify pathways most important to drug response prediction. We obtained good performance on tumors (AUROC = 0.77) and patient derived xenografts from triple negative breast cancers (RMSE = 0.11). Using feature importance, …

A Facile Synthetic Method For Anhydride From Carboxylic Acid With The Promotion Of Triphenylphosphine Oxide And Oxaloyl Chloride, Mengyu Lu, Huihui Fan, Qing Liu, Xiaoling Sun

Faculty, Staff and Student Publications

A highly efficient synthesis reaction of carboxylic anhydrides catalyzed by triphenylphosphine oxide is described for the quick synthesis of a range of symmetric carboxylic anhydrides and cyclic anhydrides under mild and neutral conditions with a high yield. The system adopts the strong reactive intermediate Ph3PCl2 as the catalyst of carboxylic acid salt; driven by catalytic reaction, the synthesis takes a relatively short time to complete.

Functional Determination Of Calcium-Binding Sites Required For The Activation Of Inositol 1,4,5-Trisphosphate Receptors, Vikas Arige, Lara E Terry, Larry E Wagner, Sundeep Malik, Mariah R Baker, Guizhen Fan, Suresh K Joseph, Irina I Serysheva, David I Yule

Faculty, Staff and Student Publications

Inositol 1,4,5-trisphosphate receptors (IP3Rs) initiate a diverse array of physiological responses by carefully orchestrating intracellular calcium (Ca2+) signals in response to various external cues. Notably, IP3R channel activity is determined by several obligatory factors, including IP3, Ca2+, and ATP. The critical basic amino acid residues in the N-terminal IP3-binding core (IBC) region that facilitate IP3 binding are well characterized. In contrast, the residues conferring regulation by Ca2+ have yet to be ascertained. Using comparative structural analysis of Ca2+-binding sites identified in two main families of intracellular Ca2+-release channels, ryanodine receptors (RyRs) and IP3Rs, we identified putative acidic residues coordinating Ca2+ …

Synthesis, Characterization, Antiglycation Evaluation, Molecular Docking, And Admet Studies Of 4-Thiazolidinone Derivatives, Nam Q H Doan, Ngan T K Nguyen, Vu B Duong, Ha T T Nguyen, Long B Vong, Diem N Duong, Nguyet-Thu T Nguyen, Tuyen L T Nguyen, Tuoi T H Do, Tuyen N Truong

Faculty, Staff and Student Publications

Addressing the growing burden of cancer and the shortcomings of chemotherapy in cancer treatment are the current research goals. Research to overcome the limitations of curcumin and to improve its anticancer activity via its heterocycle-fused monocarbonyl analogues (MACs) has immense potential. In this study, 32 asymmetric MACs fused with 1-aryl-1

Impad1 And Syt11 Work In An Epistatic Pathway That Regulates Emt-Mediated Vesicular Trafficking To Drive Lung Cancer Invasion And Metastasis, Rakhee Bajaj, B Leticia Rodriguez, William K Russell, Amanda N Warner, Lixia Diao, Jing Wang, Maria G Raso, Wei Lu, Khaja Khan, Luisa S Solis, Harsh Batra, Ximing Tang, Jared F Fradette, Samrat T Kundu, Don L Gibbons

Faculty, Staff and Student Publications

Lung cancer is a highly aggressive and metastatic disease responsible for approximately 25% of all cancer-related deaths in the United States. Using high-throughput in vitro and in vivo screens, we have previously established Impad1 as a driver of lung cancer invasion and metastasis. Here we elucidate that Impad1 is a direct target of the epithelial microRNAs (miRNAs) miR-200 and miR∼96 and is de-repressed during epithelial-to-mesenchymal transition (EMT); thus, we establish a mode of regulation of the protein. Impad1 modulates Golgi apparatus morphology and vesicular trafficking through its interaction with a trafficking protein, Syt11. These changes in Golgi apparatus dynamics alter …

Tigit Is The Central Player In T-Cell Suppression Associated With Car T-Cell Relapse In Mantle Cell Lymphoma, Vivian Changying Jiang, Dapeng Hao, Preetesh Jain, Yijing Li, Qingsong Cai, Yixin Yao, Lei Nie, Yang Liu, Jingling Jin, Wei Wang, Heng-Huan Lee, Yuxuan Che, Enyu Dai, Guangchun Han, Ruiping Wang, Kunal Rai, Andrew Futreal, Christopher Flowers, Linghua Wang, Michael Wang

Faculty, Staff and Student Publications

BACKGROUND: Chimeric antigen receptor (CAR) T-cell therapy using brexucabtagene autoleucel (BA) induces remission in many patients with mantle cell lymphoma (MCL), and BA is the only CAR T-cell therapy approved by the FDA for MCL. However, development of relapses to BA is recognized with poor patient outcomes. Multiple CAR T-cell therapies have been approved for other lymphomas and the resistance mechanisms have been investigated. However, the mechanisms underlying BA relapse in MCL have not been investigated and whether any previously reported resistance mechanisms apply to BA-relapsed patients with MCL is unknown.

METHODS: To interrogate BA resistance mechanisms in MCL, we …

Il-6 And Tnf-Α Responses To Acute And Regular Exercise In Adult Individuals With Multiple Sclerosis (Ms): A Systematic Review And Meta-Analysis, Parnian Shobeiri, Homa Seyedmirzaei, Nastaran Karimi, Fatemeh Rashidi, Antônio L Teixeira, Serge Brand, Dena Sadeghi-Bahmani, Nima Rezaei

Faculty, Staff and Student Publications

Background: In both the general population and people with multiple sclerosis (PwMS), physical exercise is associated with improved mental well-being. Moreover, there is evidence of the possible protection of physical activity against disease progression in multiple sclerosis (MS). However, the question arises if acute or regular exercise has any impact on the immune system in PwMS. To answer this question, we performed a systematic review and meta-analysis on both plasma and serum cytokine levels (IL-6 and TNF-α) before and after acute and regular exercise among PwMS and compared to healthy controls.

Method: We performed an online search via PubMed, EMBASE, …

Nasal Nitric Oxide Levels: Improving The Diagnosis Of Primary Ciliary Dyskinesia In Puerto Rico, Wilfredo De Jesús-Rojas, Francisco Alvarado-Huerta, Jesús M Meléndez-Montañez, José Muñiz-Hernández, Arnaldo Santos-López, Ricardo A Mosquera

Faculty, Staff and Student Publications

Primary Ciliary Dyskinesia (PCD) is a rare genetic disease characterized by motile cilia dysfunction with a prevalence of 1 in 16,309 individuals in Hispanic populations. In Puerto Rico, the prevalence of PCD is unknown. Diagnosis of PCD in Puerto Rico is challenging due to the lack of diagnostic technology. Algorithms for PCD diagnosis include clinical history, genetic testing, ciliary biopsy, and nasal Nitric Oxide (nNO) levels. For the first time, this study successfully implemented and measured the nNO levels in subjects with the RSPH4A (c.921+3_921+6del (intronic)) as a diagnostic tool to complement the current algorithm for PCD diagnosis on the …

Effect Of Al2o3 On Nanostructure And Ion Transport Properties Of Pva/Peg/Ssa Polymer Electrolyte Membrane, Hamdy F M Mohamed, Esam E Abdel-Hady, Mostafa M Y Abdel-Moneim, Mohamed A M Bakr, Mohamed A M Soliman, Mahmoud G H Shehata, Mahmoud A T Ismail

Faculty, Staff and Student Publications

Polymer electrolyte membrane (PEM) fuel cells have the potential to reduce our energy consumption, pollutant emissions, and dependence on fossil fuels. To achieve a wide range of commercial PEMs, many efforts have been made to create novel polymer-based materials that can transport protons under anhydrous conditions. In this study, cross-linked poly(vinyl) alcohol (PVA)/poly(ethylene) glycol (PEG) membranes with varying alumina (Al2O3) content were synthesized using the solvent solution method. Wide-angle X-ray diffraction (XRD), water uptake, ion exchange capacity (IEC), and proton conductivity were then used to characterize the membranes. XRD results showed that the concentration of Al2O3 affected the degree of …

Analysis Of The Efficacy Of Autologous Peripheral Blood Stem Cell Transplantation In High-Risk Neuroblastoma, Jin Yan, Li Jie, Yang Jiaxing, Cao Yanna, Li Zhanglin, Li Zhongyuan, Wang Daowei, Zhao Guangzong, Zhong Benfu, Yan Jie, Zhao Qiang

Faculty, Staff and Student Publications

Objective: This study aimed to analyze the efficacy of autologous peripheral blood stem cell transplantation for high-risk neuroblastoma in China.

Methods: The data of 90 high-risk neuroblastoma patients treated with the CCCG-NB 2015 regimen were reviewed. The baseline clinicopathological characteristics and prognosis were analyzed and compared. In addition, the prognoses of tandem autologous stem cell transplantation and single autologous stem cell transplantation groups were compared.

Results: The results of survival analysis showed that autologous peripheral blood stem cell transplantation based on this pretreatment regimen significantly improved the prognosis of children in the high-risk group. The 3-year event-free survival (EFS) and …

Temporal Lobe White Matter Asymmetry And Language Laterality In Epilepsy Patients, Nikolaos Soldatos, Huy Pham, Walid D Fakhouri, Binh Ngo, Panagiotis Lampropoulos, Tiffany Tran, Robin Weltman

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(1) Background: Several studies showed a sustained temperature of 47 °C or 50 °C for one minute resulted in vascular stasis and bone resorption with only limited bone regrowth over a 3–4-week healing period. The purpose of the present study was to evaluate the temperature changes (ΔΤ) that occur during the preparation of dental implant osteotomies using MIS® straight drills versus Densah® burs in a clockwise (cutting) drilling protocol. (2) Methods: Two hundred forty (240) osteotomies of two different systems’ drills were prepared at 6 mm depth at 800, 1000, and 1200 revolutions per minute (RPM), in fresh, unembalmed tibiae, …

To Bind Or Not To Bind: Cistromic Reprogramming In Prostate Cancer, Michelle Shen, Léa-Kristine Demers, Swneke D Bailey, David P Labbé

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The term "cistrome" refers to the genome-wide location of regulatory elements associated with transcription factor binding-sites. The cistrome of key regulatory factors in prostate cancer etiology are substantially reprogrammed and altered during prostatic transformation and disease progression. For instance, the cistrome of the androgen receptor (AR), a ligand-inducible transcription factor central in normal prostate epithelium biology, is directly impacted and substantially reprogrammed during malignant transformation. Accumulating evidence demonstrates that additional transcription factors that are frequently mutated, or aberrantly expressed in prostate cancer, such as the pioneer transcription factors Forkhead Box A1 (FOXA1), the homeobox protein HOXB13, and the GATA binding …