Medical Specialties Commons^™

Posoleucel, An Allogeneic, Off-The-Shelf Multivirus-Specific T-Cell Therapy, For The Treatment Of Refractory Viral Infections In The Post-Hct Setting, Thomas Pfeiffer, Ifigeneia Tzannou, Mengfen Wu, Carlos Ramos, Ghadir Sasa, Caridad Martinez, Premal Lulla, Robert A Krance, Lauren Scherer, Daniel Ruderfer, Swati Naik, Claire Bocchini, Iain P Fraser, Badrish Patel, Dany Ward, Tao Wang, Helen E Heslop, Ann M Leen, Bilal Omer

Faculty, Staff and Students Publications

PURPOSE: Viral infections are a major cause of morbidity and mortality following allogeneic hematopoietic cell transplantation (allo-HCT). In the absence of safe and effective antiviral treatments, virus-specific T cells have emerged as a promising therapeutic option. Posoleucel is a multivirus-specific T-cell therapy for off-the-shelf use against six viral infections that commonly occur in allo-HCT recipients: adenovirus, BK virus (BKV), cytomegalovirus, Epstein-Barr virus, human herpes virus-6, and JC virus.

PATIENTS AND METHODS: We conducted an open-label, phase II trial to determine the feasibility and safety of posoleucel in allo-HCT recipients infected with one or more of these viruses. Infections were either …

Adar1 Deletion Causes Degeneration Of The Exocrine Pancreas Via Mavs-Dependent Interferon Signaling, Dhwani N Rupani, Fredrik I Thege, Vidhi Chandra, Hajar Rajaei, Robert W Cowan, Sonja M Wörmann, Olivereen Le Roux, Prerna Malaney, Sara L Manning, Jack Hashem, Jennifer Bailey-Lundberg, Andrew D Rhim, Florencia Mcallister

Faculty, Staff and Student Publications

Adenosine deaminase acting on RNA 1 (ADAR1) is an RNA-binding protein that deaminates adenosine (A) to inosine (I). A-to-I editing alters post-transcriptional RNA processing, making ADAR1 a crucial regulator of gene expression. Consequently, Adar1 has been implicated in organogenesis. To determine the role of Adar1 in pancreatic development and homeostasis, we conditionally deleted Adar1 from the murine pancreas (Ptf1aCre/+; Adar1Fl/Fl). The resulting mice had stunted growth, likely due to malabsorption associated with exocrine pancreatic insufficiency. Analyses of pancreata revealed ductal cell expansion, heightened interferon-stimulated gene expression and an increased influx of immune cells. Concurrent deletion of Adar1 and Mavs, a …

African American And Caucasian Perceptions And Attitudes Toward Colorectal Cancer Screening: A Qualitative Study, Peter Warren, Stacie Pankow, Yvette Rother, Peggy Wagner

The Qualitative Report

This study examined the attitudes held by both African Americans and Caucasians regarding colorectal cancer screening and the reasons why they avoid screenings even when clinically indicated by their physicians. Colorectal cancer (CRC) is one of the most common and easily preventable types of cancer in the United States. If diagnosed and treated early prior to metastasis, the five-year colorectal cancer survival rate is approximately 90%. However, many patients avoid screening procedures for colorectal cancer due to a number of reasons. Qualitative data was gathered from focus groups and found four major themes that emerged in both groups: (1) reported …

A Gain-Of-Function Tpc2 Variant R210c Increases Affinity To Pi(3,5)P2 And Causes Lysosome Acidification And Hypopigmentation, Qiaochu Wang, Zengge Wang, Yizhen Wang, Zhan Qi, Dayong Bai, Chentong Wang, Yuanying Chen, Wenjian Xu, Xili Zhu, Jaepyo Jeon, Jian Xiong, Chanjuan Hao, Michael Xi Zhu, Aihua Wei, Wei Li

Faculty, Staff and Student Publications

Albinism is a group of inherited disorders mainly affecting skin, hair and eyes. Here we identify a de novo point mutation, p.R210C, in the TPCN2 gene which encodes Two Pore Channel 2 (TPC2) from a patient with albinism. TPC2 is an endolysosome and melanosome localized non-selective cation channel involved in regulating pigment production. Through inside-out recording of plasma membrane targeted TPC2 and direct recording of enlarged endolysosomal vacuoles, we reveal that the R210C mutant displays constitutive channel activation and markedly increased affinity to PI(3,5)P2. Mice harboring the homologous mutation, R194C, also exhibit hypopigmentation in the fur and skin, as well …

Racial Differences In Perceived Risk And Sunscreen Usage, Rebecca Fliorent, Alicia Podwojniak, Lianne Adolphe, Katharine Milani

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Background Although White individuals have higher incidence of melanoma, clinical outcomes are worse among patients with skin of color. This disparity arises from delayed diagnoses and treatment that are largely due to clinical and sociodemographic factors. Investigating this discrepancy is crucial to decrease melanoma-related mortality rates in minority communities. A survey was used to investigate the presence of racial disparities in perceived sun exposure risks and behaviors. Methods A survey consisting of 16 questions was deployed via social media to assess skin health knowledge. Over 350 responses were recorded, and the extracted data were analyzed using statistical software. Results Of …

Transmission Of Carbapenem-Resistant Klebsiella Pneumoniae In Us Hospitals, Courtney L Luterbach, Liang Chen, Lauren Komarow, Belinda Ostrowsky, Keith S Kaye, Blake Hanson, Cesar A Arias, Samit Desai, Jason C Gallagher, Elizabeth Novick, Stephen Pagkalinawan, Ebbing Lautenbach, Glenn Wortmann, Robert C Kalayjian, Brandon Eilertson, John J Farrell, Todd Mccarty, Carol Hill, Vance G Fowler, Barry N Kreiswirth, Robert A Bonomo, David Van Duin

Faculty, Staff and Student Publications

BACKGROUND: Carbapenem-resistant Klebsiella pneumoniae (CRKp) is the most prevalent carbapenem-resistant Enterobacterales in the United States. We evaluated CRKp clustering in patients in US hospitals.

METHODS: From April 2016 to August 2017, 350 patients with clonal group 258 CRKp were enrolled in the Consortium on Resistance Against Carbapenems in Klebsiella and other Enterobacteriaceae, a prospective, multicenter, cohort study. A maximum likelihood tree was constructed using RAxML. Static clusters shared ≤21 single-nucleotide polymorphisms (SNP) and a most recent common ancestor. Dynamic clusters incorporated SNP distance, culture timing, and rates of SNP accumulation and transmission using the R program TransCluster.

RESULTS: Most patients …

Perspectives Of Health Care Staff On Predictors Of Success In A Food Prescription Program: A Qualitative Study, John Wesley Mcwhorter, Jennifer N Aiyer, Nalini Ranjit, Jack Toups, Esther Liew, Jemima C John, Shreela V Sharma

Faculty, Staff and Student Publications

Partnerships between food prescription programs and food banks can address food insecurity and support health; however, few studies have examined the experience and perceptions of health care partners about these programs. Our objective was to analyze secondary qualitative data from clinicians and clinic staff involved in implementing a food prescription program in Houston, Texas. We collected data from 17 health care clinics from May 2018 through March 2021 to learn how implementation of the food prescription program was perceived, and we received 252 responses. Principal themes were the importance of a value-based care strategy, patient and food pantry barriers to …

Antihuman T Lymphocyte Porcine Immunoglobulin Combined With Cyclosporine As First-Line Immunosuppressive Therapy For Severe Aplastic Anemia In China: A Large Single-Center, 10-Year Retrospective Study, Wenrui Yang, Xu Liu, Xin Zhao, Li Zhang, Guangxin Peng, Lei Ye, Kang Zhou, Yuan Li, Jianping Li, Huihui Fan, Yang Yang, Youzhen Xiong, Liping Jing, Fengkui Zhang

Faculty, Staff and Student Publications

BACKGROUND: Antihuman T lymphocyte porcine immunoglobulin (p-ATG) has been the most common ATG preparation in immunosuppressive therapy (IST) in Chinese patients with severe aplastic anemia (SAA) since 2009.

OBJECTIVES: This study aimed to evaluate the early hematologic response and long-term outcomes of a large cohort of patients with SAA who received p-ATG plus cyclosporine (CsA) as first-line therapy from 2010 to 2019.

DESIGN: This is a single-center retrospective study of medical records.

METHODS: We analyzed the data of 1023 consecutive patients with acquired aplastic anemia (AA) who underwent p-ATG combined with CsA as a first-line IST treatment from 2010 to …

Estimating Dementia Risk In An African American Population Using The Dctclock, Marissa Ciesla, Jeff Pobst, Joyce Gomes-Osman, Melissa Lamar, Lisa L Barnes, Russell Banks, Ali Jannati, David Libon, Rodney Swenson, Sean Tobyne, David Bates, John Showalter, Alvaro Pascual-Leone

Rowan-Virtua School of Osteopathic Medicine Departmental Research

The prevalence of Alzheimer's disease (AD) and related dementias (ADRD) is increasing. African Americans are twice as likely to develop dementia than other ethnic populations. Traditional cognitive screening solutions lack the sensitivity to independently identify individuals at risk for cognitive decline. The DCTclock is a 3-min AI-enabled adaptation of the well-established clock drawing test. The DCTclock can estimate dementia risk for both general cognitive impairment and the presence of AD pathology. Here we performed a retrospective analysis to assess the performance of the DCTclock to estimate future conversion to ADRD in African American participants from the Rush Alzheimer's Disease Research …

Covid-19 Newsletter (Vol. 152), Center For Disaster Medicine, New York Medical College

COVID-19 Newsletter

No abstract provided.

Inhibition Of Ribosome Assembly Factor Pno1 By Crispr/Cas9 Technique Suppresses Lung Adenocarcinoma And Notch Pathway: Clinical Application, Sanjit K. Roy, Shivam Srivastava, Andrew Hancock, Anju Shrivastava, Jason Morvant, Sharmila Shankar, Rakesh K. Srivastava

School of Medicine Faculty Publications

Growth is crucially controlled by the functional ribosomes available in cells. To meet the enhanced energy demand, cancer cells re-wire and increase their ribosome biogenesis. The RNA-binding protein PNO1, a ribosome assembly factor, plays an essential role in ribosome biogenesis. The purpose of this study was to examine whether PNO1 can be used as a biomarker for lung adenocarcinoma and also examine the molecular mechanisms by which PNO1 knockdown by CRISPR/Cas9 inhibited growth and epithelial–mesenchymal transition (EMT). The expression of PNO1 was significantly higher in lung adenocarcinoma compared to normal lung tissues. PNO1 expression in lung adenocarcinoma patients increased with …

Efficacy Of Eltrombopag With Immunosuppressive Therapy For Children With Acquired Aplastic Anemia, Yufei Zhao, Wenrui Yang, Xin Zhao, Xiangrong Hu, Jing Hu, Xu Liu, Jianping Li, Lei Ye, Youzhen Xiong, Yang Yang, Baohang Zhang, Xiaoxia Li, Xiawan Yang, Yimeng Shi, Guangxin Peng, Yuan Li, Huihui Fan, Kang Zhou, Liping Jing, Li Zhang, Fengkui Zhang

Faculty, Staff and Student Publications

BACKGROUND: Eltrombopag (EPAG), an oral thrombopoietin receptor agonist (TPO-RA), has been proven to improve the hematologic response without increasing toxic effects as a first-line therapy combined with standard immunosuppressive treatment (IST) in adults with severe aplastic anemia (SAA). Nevertheless, the clinical evidence on the efficacy of EPAG in children with acquired aplastic anemia is limited and controversial.

METHODS: We performed a single-center, retrospective study to analyze the clinical outcomes of fifteen patients aged ≤18 years with newly diagnosed acquired SAA who received first-line IST and EPAG (EPAG group) compared with those of forty-five patients who received IST alone (IST group) …

Impact Of Enteropathogens On Faltering Growth In A Resource-Limited Setting, Furqan Kabir, Junaid Iqbal, Zehra Jamil, Najeeha Talat Iqbal, Fatima Aziz, Adil Kalam, Sahrish Muneer, Aneeta Hotwani, Sheraz Ahmed, Fayyaz Umrani, Sana Syed, Kamran Sadiq, Syed Asad Ali

Department of Paediatrics and Child Health

Introduction: Environmental enteropathy is an important contributor to childhood malnutrition in the developing world. Chronic exposure to fecal pathogens leads to alteration in intestinal structure and function, resulting in impaired gut immune function, malabsorption, and growth faltering leading to environmental enteropathy.
Methods: A community-based intervention study was carried out on children till 24 months of age in Matiari district, Pakistan. Blood and fecal specimens were collected from the enrolled children aged 3-6 and 9 months. A real-time PCR-based TaqMan array card (TAC) was used to detect enteropathogens.
Results: Giardia, Campylobacter spp., enteroaggregative Escherichia coli (EAEC), Enteropathogenic Escherichia coli (EPEC), …

The Axillary View Typically Does Not Contribute To Decision Making In Care For Proximal Humeral Fractures, Alfadl A Abdulfattah, Hanan A Jawkhab, Altaf A Alhazmi, Nada A Alfaifi, Maryam A Sultan, Rajaa A Alnami, Nada Y Kenani, Shorooq A Hamzi, Shahd M Abu Sharha, Ibrahim M Dighriri

Faculty, Staff and Student Publications

Background: Helicobacter pylori (H. pylori) is a severe infection responsible for upper gastrointestinal symptoms (UGISs). Several causes of H. pylori infection include food ingestion and person-to-person transmission. Many lifestyle variables can affect the occurrence of UGISs such as coffee consumption and smoking.

Objective: To assess the association between smoking and coffee consumption and the occurrence of UGISs in patients with active H. pylori infection in Jazan city in Saudi Arabia.

Methodology: A descriptive cross-sectional research design was used to conduct the study between July 2022 and August 2022 in Jazan, southern Saudi Arabia. Male and female Saudis or …

Many People With Chronic Lymphocytic Leukemia Or Small Lymphocytic Lymphoma Benefit From Ibrutinib Treatment Up To 8 Years: A Plain Language Summary, Paul M Barr, Carolyn Owen, Tadeusz Robak, Alessandra Tedeschi, Osnat Bairey, Jan A Burger, Peter Hillmen, Claire Dearden, Sebastian Grosicki, Helen Mccarthy, Jian Yong Li, Fritz Offner, Carol Moreno, Mandy Jermain, Cathy Zhou, Emily Hsu, Anita Szoke, Thomas J Kipps, Paolo Ghia

Faculty, Staff and Student Publications

What is this summary about?: This is a plain language summary of a publication describing long-term results from the RESONATE-2 study with up to 8 years of follow-up. The original paper was published in Blood Advances in June 2022.

What were the results?: Researchers looked at 269 adults with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who had not received any treatment for their CLL/SLL. Study participants were randomly divided into two groups: 136 participants received treatment with a drug called ibrutinib, and 133 participants received treatment with a drug called chlorambucil. Participants in the study were treated …

Trends And Racial/Ethnic Differences In Predictors Of Cervical Cancer Screening Among Us Women Ages 30-64 Years, Itunu O Sokale, Jane R Montealegre, Abiodun O Oluyomi, Aaron P Thrift

Faculty, Staff and Students Publications

BACKGROUND: Cervical cancer screening (CCS) participation has decreased in the United States over the last several decades, contributing to cervical cancer's sustained incidence and mortality. This study examined recent trends and racial/ethnic differences in predictors of CCS uptake among US women.

METHODS: We analyzed combined data from the 2016 to 2020 Behavioral Risk Factor Surveillance System (BRFSS) and included 235,713 women ages 30 to 64 years without a hysterectomy. We used simple linear regression to assess trends over time and multivariable logistic regression models to evaluate racial/ethnic differences in predictors of up-to-date CCS.

RESULTS: We found little change in CCS …

Histopathologic And Proteogenomic Heterogeneity Reveals Features Of Clear Cell Renal Cell Carcinoma Aggressiveness, Yize Li, Tung-Shing M Lih, Saravana M Dhanasekaran, Rahul Mannan, Lijun Chen, Marcin Cieslik, Yige Wu, Rita Jiu-Hsien Lu, David J Clark, Iga Kołodziejczak, Runyu Hong, Siqi Chen, Yanyan Zhao, Seema Chugh, Wagma Caravan, Nataly Naser Al Deen, Noshad Hosseini, Chelsea J Newton, Karsten Krug, Yuanwei Xu, Kyung-Cho Cho, Yingwei Hu, Yuping Zhang, Chandan Kumar-Sinha, Weiping Ma, Anna Calinawan, Matthew A Wyczalkowski, Michael C Wendl, Yuefan Wang, Shenghao Guo, Cissy Zhang, Anne Le, Aniket Dagar, Alex Hopkins, Hanbyul Cho, Felipe Da Veiga Leprevost, Xiaojun Jing, Guo Ci Teo, Wenke Liu, Melissa A Reimers, Russell Pachynski, Alexander J Lazar, Arul M Chinnaiyan, Brian A Van Tine, Bing Zhang, Karin D Rodland, Gad Getz, D R Mani, Pei Wang, Feng Chen, Galen Hostetter, Mathangi Thiagarajan, W Marston Linehan, David Fenyö, Scott D Jewell, Gilbert S Omenn, Rohit Mehra, Maciej Wiznerowicz, Ana I Robles, Mehdi Mesri, Tara Hiltke, Eunkyung An, Henry Rodriguez, Daniel W Chan, Christopher J Ricketts, Alexey I Nesvizhskii, Hui Zhang, Li Ding, Clinical Proteomic Tumor Analysis Consortium

Faculty, Staff and Students Publications

Clear cell renal cell carcinomas (ccRCCs) represent ∼75% of RCC cases and account for most RCC-associated deaths. Inter- and intratumoral heterogeneity (ITH) results in varying prognosis and treatment outcomes. To obtain the most comprehensive profile of ccRCC, we perform integrative histopathologic, proteogenomic, and metabolomic analyses on 305 ccRCC tumor segments and 166 paired adjacent normal tissues from 213 cases. Combining histologic and molecular profiles reveals ITH in 90% of ccRCCs, with 50% demonstrating immune signature heterogeneity. High tumor grade, along with BAP1 mutation, genome instability, increased hypermethylation, and a specific protein glycosylation signature define a high-risk disease subset, where UCHL1 …

The Impact Of Covid-19 On Pediatric Cardiac Arrest Outcomes: A Systematic Review And Meta-Analysis, Alla Navolokina, Jacek Smereka, Bernd W Böttiger, Michal Pruc, Raúl Juárez-Vela, Mansur Rahnama-Hezavah, Zubaid Rafique, Frank W Peacock, Kamil Safiejko, Lukasz Szarpak

Faculty, Staff and Students Publications

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused a global pandemic, required the donning of personal protective equipment during clinical contact, and continues to be a significant worldwide public health concern. Pediatric cardiac arrest is a rare but critical condition with a high mortality rate, the outcomes of which may be negatively affected by donning personal protective equipment. The aim of this study is to perform a systematic review and meta-analysis of the impact of the COVID-19 pandemic on pediatric cardiac arrest outcomes. We conducted a systematic review with meta-analysis in the following databases: PubMed, EMBASE, Scopus, Web of Science, …

Multicenter International Study Of The Consensus Immunoscore For The Prediction Of Relapse And Survival In Early-Stage Colon Cancer, Bernhard Mlecnik, Alessandro Lugli, Gabriela Bindea, Florence Marliot, Carlo Bifulco, Jiun-Kae Jack Lee, Inti Zlobec, Tilman T Rau, Martin D Berger, Iris D Nagtegaal, Elisa Vink-Börger, Arndt Hartmann, Carol I Geppert, Julie Kolwelter, Susanne Merkel, Robert Grützmann, Marc Van Den Eynde, Anne Jouret-Mourin, Alex Kartheuser, Daniel Léonard, Christophe Remue, Julia Wang, Prashant Bavi, Michael H A Roehrl, Pamela S Ohashi, Linh T Nguyen, Seongjun Han, Heather L Macgregor, Sara Hafezi-Bakhtiari, Bradly G Wouters, Giuseppe V Masucci, Emilia K Andersson, Eva Zavadova, Michal Vocka, Jan Spacek, Lubos Petruzelka, Bohuslav Konopasek, Pavel Dundr, Helena Skalova, Kristyna Nemejcova, Gerardo Botti, Fabiana Tatangelo, Paolo Delrio, Gennaro Ciliberto, Michele Maio, Luigi Laghi, Fabio Grizzi, Tessa Fredriksen, Bénédicte Buttard, Lucie Lafontaine, Pauline Maby, Amine Majdi, Assia Hijazi, Carine El Sissy, Amos Kirilovsky, Anne Berger, Christine Lagorce, Christopher Paustian, Carmen Ballesteros-Merino, Jeroen Dijkstra, Carlijn Van De Water, Shannon Van Lent-Van Vliet, Nikki Knijn, Ana-Maria Mușină, Dragos-Viorel Scripcariu, Boryana Popivanova, Mingli Xu, Tomonobu Fujita, Shoichi Hazama, Nobuaki Suzuki, Hiroaki Nagano, Kiyotaka Okuno, Toshihiko Torigoe, Noriyuki Sato, Tomohisa Furuhata, Ichiro Takemasa, Prabhu Patel, Hemangini H Vora, Birva Shah, Jayendrakumar B Patel, Kruti N Rajvik, Shashank J Pandya, Shilin N Shukla, Yili Wang, Guanjun Zhang, Yutaka Kawakami, Francesco M Marincola, Paolo A Ascierto, Bernard A Fox, Franck Pagès, Jérôme Galon

Faculty, Staff and Student Publications

Background: The prognostic value of Immunoscore was evaluated in Stage II/III colon cancer (CC) patients, but it remains unclear in Stage I/II, and in early-stage subgroups at risk. An international Society for Immunotherapy of Cancer (SITC) study evaluated the pre-defined consensus Immunoscore in tumors from 1885 AJCC/UICC-TNM Stage I/II CC patients from Canada/USA (Cohort 1) and Europe/Asia (Cohort 2). METHODS: Digital-pathology is used to quantify the densities of CD3+ and CD8+ T-lymphocyte in the center of tumor (CT) and the invasive margin (IM). The time to recurrence (TTR) was the primary endpoint. Secondary endpoints were disease-free survival (DFS), overall survival …

Echinococcus Multilocularis Calreticulin Interferes With C1q-Mediated Complement Activation, Siqi Xian, Lujuan Chen, Yan Yan, Jianfang Chen, Guixia Yu, Yuxiao Shao, Bin Zhan, Yanhai Wang, Limei Zhao

Faculty, Staff and Students Publications

As a zoonotic disease caused by Echinococcus multilocularis larvae, alveolar echinococcosis (AE) is one of the most severe forms of parasitic infection. Over a long evolutional process E. multilocularis has developed complex strategies to escape host immune attack and survive within a host. However, the mechanisms underlying immune evasion remain unclear. Here we investigated the binding activity of E. multilocularis calreticulin (EmCRT), a highly conserved Ca2+-binding protein, to human complement C1q and its ability to inhibit classical complement activation. ELISA, Far Western blotting and immunoprecipitation results demonstrated that both recombinant and natural EmCRTs bound to human C1q, …

Family Income And Cardiovascular Disease Risk In American Adults, Abdul Mannan Khan Minhas, Vardhmaan Jain, Monica Li, Robert W. Ariss, Marat Fudim, Erin D. Michos, Salim S. Virani, Laurence Sperling, Anurag Mehta

Office of the Provost

Socioeconomic status is an overlooked risk factor for cardiovascular disease (CVD). Low family income is a measure of socioeconomic status and may portend greater CVD risk. Therefore, we assessed the association of family income with cardiovascular risk factor and disease burden in American adults. This retrospective analysis included data from participants aged ≥ 20 years from the National Health and Nutrition Examination Survey (NHANES) cycles between 2005 and 2018. Family income to poverty ratio (PIR) was calculated by dividing family (or individual) income by poverty guidelines specific to the survey year and used as a measure of socioeconomic status. The …

Excretory/Secretory Proteome Of Females And Males Of The Hookworm Ancylostoma Ceylanicum, Samuel C Uzoechi, Bruce A Rosa, Kumar Sachin Singh, Young-Jun Choi, Bethany K Bracken, Paul J Brindley, R Reid Townsend, Robert Sprung, Bin Zhan, Maria-Elena Bottazzi, John M Hawdon, Yide Wong, Alex Loukas, Sergej Djuranovic, Makedonka Mitreva

Faculty, Staff and Students Publications

The dynamic host-parasite mechanisms underlying hookworm infection establishment and maintenance in mammalian hosts remain poorly understood but are primarily mediated by hookworm’s excretory/secretory products (ESPs), which have a wide spectrum of biological functions. We used ultra-high performance mass spectrometry to comprehensively profile and compare female and male ESPs from the zoonotic human hookworm Ancylostoma ceylanicum, which is a natural parasite of dogs, cats, and humans. We improved the genome annotation, decreasing the number of protein-coding genes by 49% while improving completeness from 92 to 96%. Compared to the previous genome annotation, we detected 11% and 10% more spectra in …

Bcl2l11 Induction Mediates Sensitivity To Src And Mek1/2 Inhibition In Thyroid Cancer, Madison M Rose, Veronica L Espinoza, Katelyn J Hoff, Laura A Pike, Vibha Sharma, Marie-Claude Hofmann, Aik Choon Tan, Nikita Pozdeyev, Rebecca E Schweppe

Faculty, Staff and Student Publications

Patients with advanced thyroid cancer, including advanced papillary thyroid cancer and anaplastic thyroid cancer (ATC), have low survival rates because of the lack of efficient therapies available that can combat their aggressiveness. A total of 90% of thyroid cancers have identifiable driver mutations, which often are components of the MAPK pathway, including BRAF, RAS, and RET-fusions. In addition, Src is a non-receptor tyrosine kinase that is overexpressed and activated in thyroid cancer, which we and others have shown is a clinically relevant target. We have previously demonstrated that combined inhibition of Src with dasatinib and the MAPK …

Qualitative Study Of Pathways To Care Among Adults With Diabetes In Rural Guatemala, Anita Nandkumar Chary, Meghna Nandi, David Flood, Scott Tschida, Katharine Wilcox, Sophie Kurschner, Pablo Garcia, Peter Rohloff

Faculty, Staff and Students Publications

OBJECTIVE: The burden of diabetes mellitus is increasing in low-income and middle-income countries (LMICs). Few studies have explored pathways to care among individuals with diabetes in LMICs. This study evaluates care trajectories among adults with diabetes in rural Guatemala.

DESIGN: A qualitative investigation was conducted as part of a population-based study assessing incidence and risk factors for chronic kidney disease in two rural sites in Guatemala. A random sample of 807 individuals had haemoglobin A1c (HbA1c) screening for diabetes in both sites. Based on results from the first 6 months of the population study, semistructured interviews were performed with 29 …

Optimal Timing Of Antiretroviral Therapy Initiation In Children And Adolescents With Human Immunodeficiency Virus-Associated Pulmonary Tuberculosis, Alexander Kay, Jose Mendez-Reyes, Tara Devezin, Meenakshi Bakaya, Teresa Steffy, Sandile Dlamini, Amos Msekandiana, Tara Ness, Jason Bacha, Pauline Amuge, Mogomotsi Matshaba, Moses Chodota, Phoebe Nyasulu, Lineo Thahane, Lumumbwa Mwita, Adeodata Kekitiinwa, Andrew Dinardo, Bhekumusa Lukhele, H Lester Kirchner, Anna Mandalakas

Faculty, Staff and Students Publications

BACKGROUND: There is insufficient evidence in children and adolescents with human immunodeficiency virus (CAHIV) to guide the timing of antiretroviral treatment (ART) initiation after starting treatment for pulmonary tuberculosis (pTB). To address this knowledge gap, we evaluated the risk of mortality associated with timing of ART initiation in ART-naive CAHIV treated for pTB.

METHODS: Data were extracted from electronic medical records of ART-naive patients, aged 0-19 years, who were treated for HIV-associated pTB at Baylor Centers of Excellence in Botswana, Eswatini, Malawi, Lesotho, Tanzania, or Uganda between 2013 and 2020. Data were analyzed against a primary outcome of all-cause mortality …

Comparison Between The Casia Ss-1000 And Pentacam In Measuring Corneal Curvatures And Corneal Thickness Maps, Robert M Feldman, Gene Kim, Alice Z Chuang, Atsushi Shiraishi, Keiichiro Okamoto, Makoto Tsukamoto

Faculty, Staff and Student Publications

PURPOSE: To compare the intra-device repeatability and inter-device reproducibility between two anterior segment imaging instruments, the CASIA SS-1000 (Tomey Corp., Nagoya, Japan) and Pentacam (OCULUS, Arlington, WA) in measuring anterior segment parameters.

METHODS: Single-center, prospective clinical trial. Participants ≥20 years of age were included. One eye was randomly selected, each imaged by three CASIA SS-1000 devices and three Pentacam devices by three different examiners. Each photographer operated a pair of devices, one CASIA SS-1000 and one Pentacam. The image order for each participant was determined by a random permutation table. Three images were taken from each device. A total of …

Insulin-Like Growth Factor 1 Reduces Coronary Atherosclerosis In Pigs With Familial Hypercholesterolemia, Sergiy Sukhanov, Yusuke Higashi, Tadashi Yoshida, Svitlana Danchuk, Mitzi Alfortish, Traci Goodchild, Amy Scarborough, Thomas Sharp, James S. Jenkins, Daniel Garcia, Jan Ivey, Darla L. Tharp, Jeffrey Schumacher, Zach Rozenbaum, Jay K. Kolls, Douglas Bowles, David Lefer, Patrice Delafontaine

School of Medicine Faculty Publications

Although murine models of coronary atherosclerotic disease have been used extensively to determine mechanisms, limited new therapeutic options have emerged. Pigs with familial hypercholesterolemia (FH pigs) develop complex coronary atheromas that are almost identical to human lesions. We reported previously that insulin-like growth factor 1 (IGF-1) reduced aortic atherosclerosis and promoted features of stable plaque in a murine model. We administered human recombinant IGF-1 or saline (control) in atherosclerotic FH pigs for 6 months. IGF-1 decreased relative coronary atheroma in vivo (intravascular ultrasound) and reduced lesion cross-sectional area (postmortem histology). IGF-1 increased plaque’s fibrous cap thickness, and reduced necrotic core, …

An Intervention Mapping Approach To Developing A Stroke Literacy Video For Recent Stroke Survivors: Development And Usability Study, Mary Carter Denny, Andrea Ancer Leal, Tahani Casameni Montiel, Keona J Wynne, Gabrielle Edquilang, Kim Yen Thi Vu, Farhaan Vahidy, Sean I Savitz, Jennifer Es Beauchamp, Anjail Sharrief

Faculty, Staff and Student Publications

BACKGROUND: Most vascular events after stroke may be prevented by modifying vascular risk factors through medical and behavioral interventions. Stroke literacy-an understanding of stroke symptoms, risk factors, and treatment-likely contributes to vascular risk factor control and in turn stroke recurrence risk. Stroke literacy is the lowest among adults belonging to racial and ethnic minority populations in the United States. Video-based interventions targeting stroke literacy may help acute stroke survivors understand stroke and subsequently reduce the risk of stroke recurrence. However, the failure of prior stroke literacy interventions may be due in part to the fact that the interventions were not …

A Low-Fat/Sucrose Diet Rich In Complex Carbohydrates Reverses High-Fat/Sucrose Diet-Induced Corneal Dysregulation, Prince K Akowuah, Carolina Lema, Rolando E Rumbaut, Alan R Burns

Faculty, Staff and Students Publications

High-fat/sucrose diet feeding in mice causes loss of corneal nerve function and impairs corneal wound healing. While changing to a diet with a low fat/sugar composition and enrichments in complex carbohydrates mitigates the reduction in nerve function, it remains to be determined if it has an effect on corneal wound healing. In this study, 6-week-old C57BL/6 male mice were fed either a normal diet or a high-fat/sucrose diet for 20 weeks. A third group (diet reversal) was placed on a high-fat/sucrose diet for 10 weeks followed by a normal diet for an additional 10 weeks. A central corneal epithelial abrasion …

Notch Blockade Specifically In Bone Marrow-Derived Fsp-1-Positive Cells Ameliorates Renal Fibrosis, Yongdong Wu, Ming Liang, Fengzhang Huang, Owen H Cheng, Xiaoguang Xiao, Tae Hoon Lee, Luan Truong, Jizhong Cheng

Faculty, Staff and Students Publications

Background: The infiltration of inflammatory cells during a kidney injury stimulates myofibroblast activation leading to kidney fibrosis. Fibroblast-specific protein 1 (FSP-1) positive cells have been reported as either myofibroblasts or monocytes during tissue fibrosis. The functions of FSP-1+ cells that are associated with the development of renal fibrosis and the signaling pathways that regulate FSP-1+ cell activation have not been well defined. Methods: In mice with unilateral ureteral obstruction (UUO), we characterized FSP-1+ cells and determined the role of the Notch signaling pathway in the activation of bone marrow-derived FSP-1+ cells during kidney fibrosis. Results: In kidneys from mice with …