Medical Specialties Commons^™

Long-Term Outcomes And Molecular Correlates Of Sotorasib Efficacy In Patients With Pretreated Kras G12c-Mutated Non–Small-Cell Lung Cancer: 2-Year Analysis Of Codebreak 100, Grace K Dy, Ramaswamy Govindan, Vamsidhar Velcheti, Gerald S Falchook, Antoine Italiano, Jürgen Wolf, Adrian G Sacher, Toshiaki Takahashi, Suresh S Ramalingam, Christophe Dooms, Dong-Wan Kim, Alfredo Addeo, Jayesh Desai, Martin Schuler, Pascale Tomasini, David S Hong, Piro Lito, Qui Tran, Simon Jones, Abraham Anderson, Antreas Hindoyan, Wendy Snyder, Ferdinandos Skoulidis, Bob T Li

Faculty, Staff and Student Publications

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.

In the longest follow-up, to our knowledge, for a KRAS^G12C inhibitor, we assessed the long-term efficacy, safety, and biomarkers of sotorasib in patients with KRAS G12C-mutated advanced non–small-cell lung cancer (NSCLC) from the CodeBreaK 100 clinical …

Comparative Outcomes Of Interventions For Femoropopliteal Chronic Total Occlusion Versus Non-Chronic Total Occlusion Lesions From The Multicenter Xlpad Registry, Shirling Tsai, Yulun Liu, Lawrence Hoang, Michael Vu, Hua Lu, Bala Ramanan, David Fernandez Vazquez, Zachary Rosol, Sameh Sayfo, Mohamad Amer Alaiti, Panagiotis Koutakis, Emmanouil S Brilakis, Mehdi H Shishehbor, Subhash Banerjee

Faculty, Staff and Student Publications

Background Endovascular intervention of femoropopliteal chronic total occlusions (CTOs) is technically more complex. However, there is lack of comparative analysis between CTO and non-CTO femoropopliteal interventions. Methods and Results We report procedural details and outcomes of patients treated for femoropopliteal CTO and non-CTO lesions in the XLPAD (Excellence in Peripheral Artery Disease) registry (NCT01904851) between 2006 and 2019. Primary outcomes were procedural success and 1-year major adverse limb events, a composite of all-cause death, target limb revascularization, or major amputation. Analysis included 2895 patients (CTO: n=1516 patients; non-CTO: n=1379 patients) with 3658 lesions (CTO: n=1998 lesions; non-CTO: n=1660 lesions). Conventional …

Prolylcarboxypeptidase Alleviates Hypertensive Cardiac Remodeling By Regulating Myocardial Tissue Angiotensin Ii, Binh Y Nguyen, Fangchao Zhou, Pablo Binder, Wei Liu, Susanne S Hille, Xiaojing Luo, Min Zi, Hongyuan Zhang, Antony Adamson, Fozia Z Ahmed, Sam Butterworth, Elizabeth J Cartwright, Oliver J Müller, Kaomei Guan, Elizabeth M Fitzgerald, Xin Wang

Faculty, Staff and Student Publications

Background Prolonged activation of angiotensin II is the main mediator that contributes to the development of heart diseases, so converting angiotensin II into angiotensin 1-7 has emerged as a new strategy to attenuate detrimental effects of angiotensin II. Prolylcarboxypeptidase is a lysosomal pro-X carboxypeptidase that is able to cleave angiotensin II at a preferential acidic pH optimum. However, insufficient attention has been given to the cardioprotective functions of prolylcarboxylpeptidase. Methods and Results We established a CRISPR/CRISPR-associated protein 9-mediated global prolylcarboxylpeptidase-knockout and adeno-associated virus serotype 9-mediated cardiac prolylcarboxylpeptidase overexpression mouse models, which were challenged with the angiotensin II infusion (2 mg/kg …

Pentoxifylline For Treatment Of Sepsis And Necrotising Enterocolitis In Neonates, Mohan Pammi, Khalid N Haque

Faculty, Staff and Students Publications

BACKGROUND: Mortality and morbidity due to neonatal sepsis and necrotising enterocolitis (NEC) remain high despite the use of potent antimicrobial agents. Agents that modulate inflammation may improve outcomes. Pentoxifylline (PTX), a phosphodiesterase inhibitor, is one such agent. This is an update of a review first published in 2003 and updated in 2011 and 2015.

OBJECTIVES: To assess the effectiveness and safety of intravenous PTX as an adjunct to antibiotic therapy on mortality and morbidity in neonates with suspected or confirmed sepsis and neonates with NEC.

SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, CINAHL, and trial registries in July 2022. We …

Complete Genome Sequences Of 37 Bacteria From The Human Vaginal Tract, Christopher Whidbey, Alyssa N Konopaski, Robel Teshome, Sejal Dhaliwal, M Quinn Peters, Marlyd E Mejia, Mallory B Ballard, Kathryn A Patras

Faculty, Staff and Students Publications

Microorganisms colonizing the human vaginal mucosa are associated with healthy states, as well as conditions such as bacterial vaginosis and infection-associated preterm birth. Here, we report complete genome sequences of 37 bacterial isolates from the human vaginal tract.

Immune Microenvironment Remodeling After Radiation Of A Progressing Brain Metastasis, William H Hudson, Jeffrey J Olson, Lisa J Sudmeier

Faculty, Staff and Students Publications

Radiation is commonly used in the treatment of many cancers. However, its effects on anti-tumor immune responses are incompletely understood. Here, we present a detailed immunological analysis of two tumors from a patient with multiple non-small cell lung cancer metastases to the brain. One tumor was resected without treatment; the second was irradiated to a total dose of 30 Gy and resected following further progression. Comprehensive single-cell analysis reveals a substantially reduced immune cell fraction in the irradiated tumor, including the depletion of tissue-resident macrophages and infiltration of pro-inflammatory monocytes. Despite the presence of similar somatic mutations in both tumors, …

Relative Age Effect Of Female And Male Handball Players Participating In Olympics Games Tokyo 2020, Paweł Krawczyk, Adam Dyjas, Adam Szeląg, Maciej Cedro

Baltic Journal of Health and Physical Activity

Introduction: The aim of this study was to determine whether the relative age effect (RAE) was present among handball players participating in the Tokyo 2020 Olympics. Materials and Methods. The study involved a group of handball players participating in the Tokyo 2020 Olympics. All data was collected from the website of the IHF. The research material consisted of data on the players’ dates of birth, which were broken down by four quarters (Q1: January 1–March 31, Q2: April 1–June 30, Q3: July 1–September 30, Q4: October 1–December 31) and two semesters (S1: January 1–June 30, S2: July 1–December 31). The …

Evaluating Visual Acuity In The American Academy Of Ophthalmology Iris® Registry, Arthur Brant, Natasha N. Kolomeyer, Jeffrey L. Goldberg, Julia A Haller, Cecilia S. Lee, Aaron Y. Lee, Alice C. Lorch, Joan W. Miller, Leslie Hyman, Suzann Pershing

Wills Eye Hospital Papers

OBJECTIVE: To describe visual acuity data representation in the American Academy of Ophthalmology Intelligent Research in Sight (IRIS) Registry and present a data-cleaning strategy.

DESIGN: Reliability and validity study.

PARTICIPANTS: Patients with visual acuity records from 2018 in the IRIS Registry.

METHODS: Visual acuity measurements and metadata were identified and characterized from 2018 IRIS Registry records. Metadata, including laterality, assessment method (distance, near, and unspecified), correction (corrected, uncorrected, and unspecified), and flags for refraction or pinhole assessment were compared between Rome (frozen April 20, 2020) and Chicago (frozen December 24, 2021) versions. We developed a data-cleaning strategy to infer patients' …

Neighborhood Disadvantage And Pediatric Inpatient Opioid Prescription Patterns, Ashley W. Kranjac, Dinko Kranjac, Zeev N. Kain, Louis Ehwerhemuepha, Candice Donaldson, Brooke N. Jenkins

Sociology Faculty Articles and Research

Background

To explore the role of children's residential environment on opioid prescribing patterns in a predominantly Latinx sample.

Methods

We connected geocoded data from electronic medical records in a diverse sample of pediatric patients to neighborhood environments constructed using latent profile modeling techniques. We then estimated a series of multilevel models to determine whether opioid prescribing patterns vary by residential context.

Results

A stepwise pattern exists between neighborhood disadvantage and pediatric opioid prescription patterns, such that higher levels of disadvantage associate with a greater likelihood of opioid prescription, independent of the patient's individual profile.

Conclusion

In a largely Latinx sample …

Anticancer Potential Of Natural Chalcones: In Vitro And In Vivo Evidence, Radka Michalkova, Ladislav Mirossay, Martin Kello, Gabriela Mojzisova, Janette Baloghova, Anna Podracka, Jan Mojzis

Faculty, Staff and Student Publications

There is no doubt that significant progress has been made in tumor therapy in the past decades. However, the discovery of new molecules with potential antitumor properties still remains one of the most significant challenges in the field of anticancer therapy. Nature, especially plants, is a rich source of phytochemicals with pleiotropic biological activities. Among a plethora of phytochemicals, chalcones, the bioprecursors of flavonoid and isoflavonoids synthesis in higher plants, have attracted attention due to the broad spectrum of biological activities with potential clinical applications. Regarding the antiproliferative and anticancer effects of chalcones, multiple mechanisms of action including cell cycle …

State Of The Art Bowel Management For Pediatric Colorectal Problems: Functional Constipation., Elizaveta Bokova, Wendy Jo Svetanoff, John Rosen, Marc A. Levitt, Rebecca M. Rentea

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Functional constipation (FC) affects up to 32% of the pediatric population, and some of these patients are referred to pediatric surgery units to manage their constipation and/or fecal incontinence. The aim of the current paper is to report the recent updates on the evaluation and management of children with FC as a part of a manuscript series on bowel management in patients with anorectal malformations, Hirschsprung disease, spinal anomalies, and FC.

METHODS: A literature search was performed using Medline/PubMed, Google Scholar, Cochrane, and EMBASE databases and focusing on the manuscripts published within the last 5-10 years.

RESULTS: The first …

Wdr5 Facilitates Recruitment Of N-Myc To Conserved Wdr5 Gene Targets In Neuroblastoma Cell Lines, Leigh A Bumpous, Kylie C Moe, Jing Wang, Logan A Carver, Alexandria G Williams, Alexander S Romer, Jesse D Scobee, Jack N Maxwell, Cheyenne A Jones, Dai H Chung, William P Tansey, Qi Liu, April M Weissmiller

Faculty, Staff and Student Publications

Collectively, the MYC family of oncoprotein transcription factors is overexpressed in more than half of all malignancies. The ability of MYC proteins to access chromatin is fundamental to their role in promoting oncogenic gene expression programs in cancer and this function depends on MYC-cofactor interactions. One such cofactor is the chromatin regulator WDR5, which in models of Burkitt lymphoma facilitates recruitment of the c-MYC protein to chromatin at genes associated with protein synthesis, allowing for tumor progression and maintenance. However, beyond Burkitt lymphoma, it is unknown whether these observations extend to other cancers or MYC family members, and whether WDR5 …

Scutellaria Baicalensis Enhances 5-Fluorouracil-Based Chemotherapy Via Inhibition Of Proliferative Signaling Pathways, Haizhou Liu, Hui Liu, Zhiyi Zhou, Jessica Chung, Guojing Zhang, Jin Chang, Robert A Parise, Edward Chu, John C Schmitz

Abington Jefferson Health Papers

Fluoropyridine-based chemotherapy remains the most widely used treatment for colorectal cancer (CRC). In this study, we investigated the mechanism by which the natural product Scutellaria baicalensis (Huang Qin; HQ) and one of its main components baicalin enhanced 5-fluorouracil (5-FU) antitumor activity against CRC. Cell proliferation assays, cell cycle analysis, reverse-phase protein array (RPPA) analysis, immunoblot analysis, and qRT-PCR were performed to investigate the mechanism(s) of action of HQ and its active components on growth of CRC cells. HQ exhibited in vitro antiproliferative activity against drug resistant human CRC cells, against human and mouse CRC cells with different genetic backgrounds and …

Pediatric Eye Care Treatment Rates And Community Compliance To A Spectacle Provision Program In An Underserved School District In San Diego, Ca, Matthew C.H. Rohn, Flynn O'Sullivan, Stuart I. Brown, Eric Hernandez, Shyamanga Borooah, Iliana Molina

Student Papers, Posters & Projects

SIGNIFICANCE: The need for early identification and treatment of young children's refractive error needs has become a public health concern. The UCSD Eyemobile for Children (EyeMobile) provides vision screenings and comprehensive eye exams on the Eyemobile among a population of underserved, predominantly Hispanic preschool and elementary school children. The program also provides spectacles for children who fail eye exams due to refractive error.

METHODS: We performed a retrospective cross-sectional analysis of all children screened from 2011 to 2017 by the Eyemobile across 10 San Diego elementary schools. We examined demographics, distance and near visual acuity, autorefraction, stereopsis, and color vision. …

Sox7 Deficiency Causes Ventricular Septal Defects Through Its Effects On Endocardial-To-Mesenchymal Transition And The Expression Of Wnt4 And Bmp2, Andrés Hernández-García, Katherine E Pendleton, Sangbae Kim, Yumei Li, Bum J Kim, Hitisha P Zaveri, Valerie K Jordan, Aliska M Berry, M Cecilia Ljungberg, Rui Chen, Rainer B Lanz, Daryl A Scott

Faculty, Staff and Students Publications

SOX7 is a transcription factor-encoding gene located in a region on chromosome 8p23.1 that is recurrently deleted in individuals with ventricular septal defects (VSDs). We have previously shown that Sox7-/- embryos die of heart failure around E11.5. Here, we demonstrate that these embryos have hypocellular endocardial cushions with severely reduced numbers of mesenchymal cells. Ablation of Sox7 in the endocardium also resulted in hypocellular endocardial cushions, and we observed VSDs in rare E15.5 Sox7flox/-;Tie2-Cre and Sox7flox/flox;Tie2-Cre embryos that survived to E15.5. In atrioventricular explant studies, we showed that SOX7 deficiency leads to a severe reduction in endocardial-to-mesenchymal transition (EndMT). RNA-seq …

Acute Effects Of Three Different Stretching Techniques On Hamstring Flexibility In Professional Football Players, Erkan Erol, Ramazan Yıldız, Ayşe Yıldız, Fatih Emre Doğan, Bülent Elbasan

Baltic Journal of Health and Physical Activity

Introduction: Hamstring injuries are common in physically active people and athletes. Lack of hamstring flexibility is the one of the most important characteristics of hamstring injuries in athletes. The aim of this study was to investigate effects of three different stretching techniques on hamstring flexibility in professional football players. Materials and Methods: Fifty-five male football players between the ages of 18–20 years old were involved in the study. The participants were divided into 3 groups: static stretching, neuromobilization and Mulligan traction straight leg raise (TSLR), respectively. Each participant’s dominant lower extremity was assessed with a straight leg raise test (SLR) …

Comparative Analyses Of The Clinicopathologic Features Of Short-Term And Long-Term Survivors Of Patients With Pancreatic Ductal Adenocarcinoma Who Received Neoadjuvant Therapy And Pancreatoduodenectomy, Tom Z Liang, Matthew H G Katz, Laura R Prakash, Deyali Chatterjee, Hua Wang, Michael Kim, Ching-Wei D Tzeng, Naruhiko Ikoma, Robert A Wolff, Dan Zhao, Eugene J Koay, Anirban Maitra, Suprateek Kundu, Huamin Wang

Faculty, Staff and Student Publications

Neoadjuvant therapy (NAT) is increasingly used to treat patients with pancreatic ductal adenocarcinoma (PDAC). Patients with PDAC often show heterogenous responses to NAT with variable clinical outcomes, and the clinicopathologic parameters associated with these variable outcomes remain unclear. In this study, we systematically examined the clinicopathologic characteristics of 60 short-term survivors (overall survival < 15 months) and 149 long-term survivors (overall survival > 60 months) and compared them to 352 intermediate-term survivors (overall survival: 15-60 months) of PDAC who received NAT and pancreatoduodenectomy. We found that the short-term survivor group was associated with male gender (p = 0.03), tumor resectability prior to NAT (p = 0.04), poorly differentiated …

Differences In Actn3, Ace, And Adbr3 Polymorphisms Between Croatian National Team And Non-National Team Elite Soccer Players, Lana Ružić, Ivan Radman, Branka R. Matković

Baltic Journal of Health and Physical Activity

Introduction: This study investigated the differences in ACTN3, ACE and ADRB3 variants in top-level soccer players who entered the Croatian National Team and the ones who did not but played for two best Croatian teams. Material and Methods: The buccal swabs were collected from 56 soccer players playing for the Croatian National Team (N = 31) and/or for one of the two most prestigious Croatian soccer clubs (N = 25). Each participant’s genotype was determined by analyzing the single-nucleotide polymorphism. The ACTN3 gene (rs1815739) on chromosome 11 and the ACE (rs1799752) gene on chromosome 17 were determined. Results: No significant …

Distinct Gene Expression Profiles Between Human Preterm-Derived And Adult-Derived Intestinal Organoids Exposed To Enterococcus Faecalis: A Pilot Study, Andrea C. Masi, Tatiana Y. Fofanova, Christopher A. Lamb, Jennifer Auchtung, Robert A. Britton, Mary K. Estes, Sasirekha Ramani, Simon J. Cockell, Jonathan Coxhead, Nicholas D. Embleton, Janet E. Berrington, Joseph F. Petrosino, Christopher J. Stewart

Food for Health: Publications

We read with interest the study by Kayisoglu et al¹ comparing the gene expression between embryo-derived and adult-derived intestinal organoids. Some innate immune system genes were differentially expressed between the two organoid types, suggesting a potential role of exposure to the environment, including gut microbiota, in shaping the intestinal gene expression. In extremely preterm infants (<32 weeks gestation), microbial–host interaction at the epithelial surface has been associated with various morbidities including late onset sepsis and necrotising enterocolitis.² Thus, preterm intestinal organoids may provide a specific and robust model for this population.

Evidence-Based Guide To Using Artificial Introns For Tissue-Specific Knockout In Mice, Elena Mcbeath, Keigi Fujiwara, Marie-Claude Hofmann

Faculty, Staff and Student Publications

Up until recently, methods for generating floxed mice either conventionally or by CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)-Cas9 (CRISPR-associated protein 9) editing have been technically challenging, expensive and error-prone, or time-consuming. To circumvent these issues, several labs have started successfully using a small artificial intron to conditionally knockout (KO) a gene of interest in mice. However, many other labs are having difficulty getting the technique to work. The key problem appears to be either a failure in achieving correct splicing after the introduction of the artificial intron into the gene or, just as crucial, insufficient functional KO of the …

7-Ketocholesterol Promotes Retinal Pigment Epithelium Senescence And Fibrosis Of Choroidal Neovascularization Via Iqgap1 Phosphorylation-Dependent Signaling, Haibo Wang, Aniket Ramshekar, Thaonhi Cung, Chris Wallace-Carrete, Chandler Zaugg, Jasmine Nguyen, Gregory J. Stoddard, M. Elizabeth Hartnett

School of Medicine Faculty Publications

Accumulation of 7-ketocholesterol (7KC) occurs in age-related macular degeneration (AMD) and was found previously to promote fibrosis, an untreatable cause of vision loss, partly through induction of endothelial-mesenchymal transition. To address the hypothesis that 7KC causes mesenchymal transition of retinal pigment epithelial cells (RPE), we exposed human primary RPE (hRPE) to 7KC or a control. 7KC-treated hRPE did not manifest increased mesenchymal markers, but instead maintained RPE-specific proteins and exhibited signs of senescence with increased serine phosphorylation of histone H3, serine/threonine phosphorylation of mammalian target of rapamycin (p-mTOR), p16 and p21, β-galactosidase labeling, and reduced LaminB1, suggesting senescence. The cells …

Action Distance As A Predictor Of Winning And Losing Matches At Fivb Volleyball Men’S World Championship, Dariusz Mroczek, Damian Pawlik

Baltic Journal of Health and Physical Activity

Introduction: Technology determines the emergence of functional tools to monitor and control motor activity during the game. One of the solutions for monitoring the player in indoor sports are computer video analyses, which determine basic kinematic parameters. The study aims to compare team and player activity with the outcome of a given set and the effect of the game status on player activity during a championship-level match. Materials and Methods: The study analysed 140 volleyball players aged 19 to 40 years (27.05 ± 4.33 years, height: 197.15 ± 9.63 cm, body mass: 88.51 ± 9.23 kg) participating in the FIVB …

The Prevalence Of Electronic Cigarette Use Among College Students Of Taibah University And Symptoms Of Cardiovascular Disease, Talal Alzahrani, Marwan Fahad Alhazmi, Ahmed Naji Alharbi, Feras Talal Alahmadi, Amer Nasser Alhubayshi, Bader Ahmed Alzahrani

Journal of the Saudi Heart Association

Background: Electronic cigarettes (e-cigarettes) have been increasing in popularity among young adults due to the misconception about the safety of e-cigarettes. Our study aims to identify the prevalence rate of e-cigarette use among college students, the reason behind their use, and the relationship between the use of electronic cigarettes and cardiovascular symptoms among college students. Methods: An online questionnaire was sent to students of Taibah University between 2021 and 2022. Data from this survey were analyzed to obtain the prevalence of e-cigarette use among Taibah University students and to compare the demographic and health characteristics differences between e-cigarette users and …

Current Best Practice In Pelvic And Hip Fracture Management In The Older Adult Population, Anthony P. Joseph

Journal of Geriatric Emergency Medicine

Fractures of the pelvis and hip are a relatively frequent occurrence in the older population. Pelvic fractures in older patients usually occur after a fall from standing height. CT scan is the investigation of choice. There are several classifications available which are useful in risk stratification and predicting surgical treatment. Haemorrhage is a major complication and can usually be treated by interventional radiology. An Orthopedic opinion should be sought promptly, and surgical stabilisation (if indicated) should be completed as early as possible to enable early mobilisation and the avoidance of complications such as deep vein thrombosis or pneumonia.

Hip fractures …

Bibliometric Analysis Of Spinopelvic Alignment In Total Hip Arthroplasty, Samantha Harrer, Justin A. Magnuson, Gregory R. Toci, Andrew M. Star, Arjun Saxena

Rothman Institute Papers

INTRODUCTION: Postoperative dislocation of unclear etiology remains a concern after total hip arthroplasty (THA). Interest is growing in the importance of spinopelvic alignment on stability in THA. The purpose of this study was to analyze publication trends, areas of interest, and future research direction of spinopelvic alignment in THA.

METHODS: Articles on the topic of spinopelvic alignment in THA published between 1990 and 2022 were obtained through Web of Science Core Collection of Clarivate Analytics (WSCCA). Results were screened by title, abstract, and full text. The inclusion criterion was English-language peer-reviewed journal publications on the clinical topic of spinopelvic alignment …

Novel Potential Targets For Function-Promoting Therapies: Orphan Nuclear Receptors, Anti-Inflammatory Drugs, Troponin Activators, Mas Receptor Agonists, And Urolithin A, Waly Dioh, Vihang Narkar, Anurag Singh, Fady Malik, Luigi Ferrucci, Cendrine Tourette, Jean Mariani, Rob Van Maanen, Roger A Fielding

Faculty, Staff and Student Publications

In recent years, several new classes of therapies have been investigated with their potential for restoring or improving physical functioning in older adults. These have included Mas receptor agonists, regulators of mitophagy, skeletal muscle troponin activators, anti-inflammatory compounds, and targets of orphan nuclear receptors. The present article summarizes recent developments of the function-promoting effects of these exciting new compounds and shares relevant preclinical and clinical data related to their safety and efficacy. The development of novel compounds in this area is expanding and likely will need the advent of a new treatment paradigm for age-associated mobility loss and disability.

Pharmacogenetic Testing For The Pediatric Gastroenterologist: Actionable Drug-Gene Pairs To Know., Tracy L. Sandritter, Rachel Chevalier, Rebecca Abt, Valentina Shakhnovich

Manuscripts, Articles, Book Chapters and Other Papers

Gastroenterologists represent some of the earlier adopters of precision medicine through pharmacogenetic testing by embracing upfront genotyping for thiopurine S-methyltransferase nucleotide diphosphatase (TPMT) before prescribing 6-mercaptopurine or azathioprine for the treatment of inflammatory bowel disease. Over the last two decades, pharmacogenetic testing has become more readily available for other genes relevant to drug dose individualization. Common medications prescribed by gastroenterologists for conditions other than inflammatory bowel disease now have actionable guidelines, which can improve medication efficacy and safety; however, a clear understanding of how to interpret the results remains a challenge for many clinicians, precluding wide implementation of …

Proteogenomic Landscape Of Gastric Adenocarcinoma Peritoneal Metastases, Shuangtao Zhao, Ruiping Wang, Shumei Song, Dapeng Hao, Guangchun Han, Xingzhi Song, Jianhua Zhang, Melissa Pool Pizzi, Namita Shanbhag, Andrew Futreal, Brian Badgwell, Kazuto Harada, George Calin, Jody Vykoukal, Chuan-Yih Yu, Hiroyuki Katayama, Samir M Hanash, Linghua Wang, Jaffer A Ajani

Faculty, Staff and Student Publications

Advanced gastric adenocarcinoma (GAC) often leads to peritoneal carcinomatosis (PC) and is associated with very poor outcome. Here we report the comprehensive proteogenomic study of ascites derived cells from a prospective GAC cohort (n = 26 patients with peritoneal carcinomatosis, PC). A total of 16,449 proteins were detected from whole cell extracts (TCEs). Unsupervised hierarchical clustering resulted in three distinct groups that reflected extent of enrichment in tumor cells. Integrated analysis revealed enriched biological pathways and notably, some druggable targets (cancer-testis antigens, kinases, and receptors) that could be exploited to develop effective therapies and/or tumor stratifications. Systematic comparison of expression …

Gata6-As1 Regulates Intestinal Epithelial Mitochondrial Functions, And Its Reduced Expression Is Linked To Intestinal Inflammation And Less Favourable Disease Course In Ulcerative Colitis, Katya E Sosnovski, Tzipi Braun, Amnon Amir, Danielle Moshel, Marina Benshoshan, Kelli L Vandussen, Nina Levhar, Haya Abbas-Egbariya, Katia Beider, Rakefet Ben-Yishay, Syed Asad Ali, Sean R Moore, Subra Kugathasan, Ifat Abramovich, Efrat Glick Saar, Batya Weiss, Iris Barshack, Eyal Gottlieb, Tamar Geiger, Shomron Ben-Horin, Igor Ulitsky, Jeffrey S Hyams, Lee A Denson, Yael Haberman

Faculty, Staff and Student Publications

BACKGROUND AND AIMS: Widespread dysregulation of long non-coding RNAs [lncRNAs] including a reduction in GATA6-AS1 was noted in inflammatory bowel disease [IBD]. We previously reported a prominent inhibition of epithelial mitochondrial functions in ulcerative colitis [UC]. However, the connection between reduction of GATA6-AS1 expression and attenuated epithelial mitochondrial functions was not defined.

METHODS: Mucosal transcriptomics was used to conform GATA6-AS1 reduction in several treatment-naïve independent human cohorts [n=673]. RNA pull-down followed by mass spectrometry was used to determine the GATA6-AS1 interactome. Metabolomics and mitochondrial respiration following GATA6-AS1 silencing in Caco-2 cells were used to elaborate on GATA6-AS1 functions.

RESULTS: GATA6-AS1 …

Transmembrane Stem Factor Nanodiscs Enhanced Revascularization In A Hind Limb Ischemia Model In Diabetic, Hyperlipidemic Rabbits, Eri Takematsu, Miles Massidda, Gretchen Howe, Julia Goldman, Patricia Felli, Lei Mei, Gregory Callahan, Andrew Sligar, Richard Smalling, Aaron Baker

Faculty, Staff and Student Publications

Therapies to revascularize ischemic tissue have long been a goal for the treatment of vascular disease and other disorders. Therapies using stem cell factor (SCF), also known as a c-Kit ligand, had great promise for treating ischemia for myocardial infarct and stroke, however clinical development for SCF was stopped due to toxic side effects including mast cell activation in patients. We recently developed a novel therapy using a transmembrane form of SCF (tmSCF) delivered in lipid nanodiscs. In previous studies, we demonstrated tmSCF nanodiscs were able to induce revascularization of ischemia limbs in mice and did not activate mast cells. …