Digestive System Diseases Commons^™

Cd8Α Structural Domains Enhance Gucy2c Car-T Cell Efficacy, Trevor R. Baybutt, Ariana A. Entezari, Adi Caspi, Ross E. Staudt, Robert D. Carlson, Scott A. Waldman, Adam E. Snook

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Despite success in treating some hematological malignancies, CAR-T cells have not yet produced similar outcomes in solid tumors due, in part, to the tumor microenvironment, poor persistence, and a paucity of suitable target antigens. Importantly, the impact of the CAR components on these challenges remains focused on the intracellular signaling and antigen-binding domains. In contrast, the flexible hinge and transmembrane domains have been commoditized and are the least studied components of the CAR. Here, we compared the hinge and transmembrane domains derived from either the CD8ɑ or CD28 molecule in identical GUCY2C-targeted third-generation designs for colorectal cancer. While these structural …

Acute Liver Failure Induced By Menopausal Supplement, Rahul Patel, Ahmed Hassan, Hayle Scanlan, Matthew Everwine, Zhiyong Ren, Charles Snyder, Hisham Elgenaidi

School of Medicine Faculty Publications

Drug-induced liver injury is one of the most common causes of acute liver failure in the Western world. Despite discontinuation of the offending agent, it can still tax a grim prognosis. We describe a case of a menopausal woman taking a herbal supplement to relieve hot flashes and bloating. This is the first case report of liver injury from this supplement. She initially presented with mild jaundice and elevated transaminases. Unfortunately, she rapidly progressed to encephalopathy, experienced multiorgan failure, and then died.

Diagnostic Error In Mental Health: A Review, Andrea Bradford, Ashley N D Meyer, Sundas Khan, Traber D Giardina, Hardeep Singh

Faculty, Staff and Students Publications

Diagnostic errors are associated with patient harm and suboptimal outcomes. Despite national scientific efforts to advance definition, measurement and interventions for diagnostic error, diagnosis in mental health is not well represented in this ongoing work. We aimed to summarise the current state of research on diagnostic errors in mental health and identify opportunities to align future research with the emerging science of diagnostic safety. We review conceptual considerations for defining and measuring diagnostic error, the application of these concepts to mental health settings, and the methods and subject matter focus of recent studies of diagnostic error in mental health. We …

Targeting Ribosome Biogenesis Is A Novel Approach For The Management Of Pancreatic Cancer, Mudassier Ahmad, Haider Ahsan, Carlos Perez, Muhammad Bangash, Andrew Massey, Emmanuel Anning, Manish Tripathi, Dae Kim, Subhash C. Chauhan, Bilal Bin Hafeez

Research Colloquium

Pancreatic ductal adenocarcinoma is the third leading cause of cancer-related deaths in the United States with limited therapeutic options available. Gemcitabine, a deoxycytidine nucleoside analog is currently considered the most effective therapy for PanCa. However, it shows only a marginal survival benefit of six months. Aberrant ribosome biogenesis occurs in most tumor types. We observed that PanCa cells are addicted to ribosome biogenesis, which supports their highly aggressive metastatic phenotypes. Thus, strategically targeting ribosome biogenesis process could be one of the ideal strategies for the prevention and treatment of PanCa. In this study, we elucidated the molecular mechanisms of POLR1A …

Concurrent Challenges: New-Onset Type 2 Diabetes And Invasive Pancreatic Adenocarcinoma: A Case Report, Abhishekh Pokhrel, Alexa Lissete Zarate, Sobia Hassan Memon, Everardo Cobos

Research Colloquium

Background: Pancreatic adenocarcinoma is a highly aggressive cancer with a five-year survival rate of about 10%, and is the third leading cause of cancer-related deaths in the United States. Approximately 53% of patients are diagnosed at stage IV, characterized by distant metastasis to common sites such as the liver and lungs. Liver metastases occur in 60-70% of metastatic cases, while lung metastases are seen in 10-15% of patients. The median survival for stage IV patients is typically around 3 to 6 months, with current treatments primarily focused on palliation. Advances in chemotherapy offer modest survival benefits, but early detection and …

Unexpected Biliary Duct Dilation, A Wise Decision-Making Case., Mario A. Trujillo, Mathew R. Peynado, Muhammad Ali Siddiqui, Laura P. Ackerman

Research Colloquium

Background: Common bile duct dilation is expected in certain healthy populations with specific factors like age or post procedure status. When a size larger than expected is found in an acute setting further investigation is required. In the setting of acute abdominal pain in a patient with past medical history of cholelithiasis, the study protocol for patients with more than expected enlarged common bile duct and no apparently underlying disease in the biliary tree is not well elucidated.

Case: A 68-year-old female with past medical history but not limited to cholelithiasis, hypertension, type 2 diabetes mellitus, end stage renal …

Honey: A Natural Recipe For The Management Of Pancreatic Cancer, Aun A. Bangash, Muhammad A. Bangash, Georgina Villanueva, Haider Ahsan, Shiza Khan, Rida Shareef, Mudassier Ahmad, Dae J. Kim, Sahir S. Alvi, Bilal B. Hafeez

Research Colloquium

Background: Pancreatic cancer (PanCa) is the fourth deadliest cancer worldwide and expected to become the second deadliest cancer by 2030. In the USA, the National Cancer Institute put forth a grim prediction stating that there will be 64,050 new cases in 2023 alone and about 50,000 of these patients will die. The first line treatment for pancreatic cancer is Folfrinox, a three-drug regimen consisting of 5-Fluorouracil, irinotecan, and oxaliplatin. The second line treatment is gemcitabine combined with paclitaxel. Only 19% of patients who are prescribed the former regimen survive past 18 months of treatment while just 6% of patients survive …

Barriers And Opportunities In Pancreatic Cancer Immunotherapy, Yixin Ju, Dongzhi Xu, Miao-Miao Liao, Yutong Sun, Wen-Dai Bao, Fan Yao, Li Ma

Faculty, Staff and Student Publications

Pancreatic ductal adenocarcinoma (PDAC) presents a fatal clinical challenge characterized by a dismal 5-year overall survival rate, primarily due to the lack of early diagnosis and limited therapeutic efficacy. Immunotherapy, a proven success in multiple cancers, has yet to demonstrate significant benefits in PDAC. Recent studies have revealed the immunosuppressive characteristics of the PDAC tumor microenvironment (TME), including immune cells with suppressive properties, desmoplastic stroma, microbiome influences, and PDAC-specific signaling pathways. In this article, we review recent advances in understanding the immunosuppressive TME of PDAC, TME differences among various mouse models of pancreatic cancer, and the mechanisms underlying resistance to …

Bilio-Cecal Stent Migration Presenting As Massive Rectal Bleeding., Lefika Bathobakae, Shady Geris, Mohita Jariwala, Mansi Patel, Jessica Escobar, Ruhin Yuridullah, Kamal Amer, Yana Cavanagh

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Endoscopic biliary stenting is a well-established intervention for the treatment of biliary, hepatic, and pancreatic disorders. The common indications include strictures, neoplasms, stones, infections, and bile leaks. Stents can be occluded, predisposing patients to ascending cholangitis and biliary sepsis. Distal stent migration is another known complication of endoscopic stenting and is usually spontaneous. Bowel perforation, abscesses, bleeding, and pancreatitis are rare complications of distal stent migration and are usually limited to the duodenum. Herein, we describe an extremely rare case of bilio-cecal stent migration presenting as rectal bleeding.

Artificial Intelligence-Based Segmentation Of Residual Pancreatic Cancer In Resection Specimens Following Neoadjuvant Treatment (Isgpp-2): International Improvement And Validation Study, Boris V Janssen, Bart Oteman, Mahsoem Ali, Pieter A Valkema, Volkan Adsay, Olca Basturk, Deyali Chatterjee, Angela Chou, Stijn Crobach, Michael Doukas, Paul Drillenburg, Irene Esposito, Anthony J Gill, Seung-Mo Hong, Casper Jansen, Mike Kliffen, Anubhav Mittal, Jas Samra, Marie-Louise F Van Velthuysen, Aslihan Yavas, Geert Kazemier, Joanne Verheij, Ewout Steyerberg, Marc G Besselink, Huamin Wang, Caroline Verbeke, Arantza Fariña, Onno J De Boer, Pancreatobiliary And Hepatic Artificial Intelligence Research (Phair) Consortium, International Study Group Of Pancreatic Pathologists (Isgpp);

Faculty, Staff and Student Publications

Neoadjuvant therapy (NAT) has become routine in patients with borderline resectable pancreatic cancer. Pathologists examine pancreatic cancer resection specimens to evaluate the effect of NAT. However, an automated scoring system to objectively quantify residual pancreatic cancer (RPC) is currently lacking. Herein, we developed and validated the first automated segmentation model using artificial intelligence techniques to objectively quantify RPC. Digitized histopathological tissue slides were included from resected pancreatic cancer specimens from 14 centers in 7 countries in Europe, North America, Australia, and Asia. Four different scanner types were used: Philips (56%), Hamamatsu (27%), 3DHistech (10%), and Leica (7%). Regions of interest …

An Interdisciplinary Consensus Approach To Pulmonary Hypertension In Developmental Lung Disease, Nidhy P Varghese, Eric D Austin, Csaba Galambos, Mary P Mullen, Delphine Yung, R Paul Guillerman, Sara O Vargas, Catherine M Avitabile, Corey A Chartan, Nahir Cortes-Santiago, Michaela Ibach, Emma O Jackson, Jill Ann Jarrell, Roberta L Keller, Usha S Krishnan, Kalyani R Patel, Jennifer Pogoriler, Elise C Whalen, Kathryn A Wikenheiser-Brokamp, Natalie M Villafranco, Rachel K Hopper, J Usha Raj, Steven H Abman, Pediatric Pulmonary Hypertension Network (Pphnet)

Faculty, Staff and Students Publications

It is increasingly recognised that diverse genetic respiratory disorders present as severe pulmonary hypertension (PH) in the neonate and young infant, but many controversies and uncertainties persist regarding optimal strategies for diagnosis and management to maximise long-term outcomes. To better define the nature of PH in the setting of developmental lung disease (DEVLD), in addition to the common diagnoses of bronchopulmonary dysplasia and congenital diaphragmatic hernia, we established a multidisciplinary group of expert clinicians from stakeholder paediatric specialties to highlight current challenges and recommendations for clinical approaches, as well as counselling and support of families. In this review, we characterise …

Tuberculosis Prevention: Current Strategies And Future Directions, Anca Vasiliu, Leonardo Martinez, Rishi K Gupta, Yohhei Hamada, Tara Ness, Alexander Kay, Maryline Bonnet, Martina Sester, Stefan H E Kaufmann, Christoph Lange, Anna M Mandalakas

Faculty, Staff and Students Publications

BACKGROUND: An estimated one fourth of the world's population is infected with Mycobacterium tuberculosis, and 5-10% of those infected develop tuberculosis in their lifetime. Preventing tuberculosis is one of the most underutilized but essential components of curtailing the tuberculosis epidemic. Moreover, current evidence illustrates that tuberculosis manifestations occur along a dynamic spectrum from infection to disease rather than a binary state as historically conceptualized. Elucidating determinants of transition between these states is crucial to decreasing the tuberculosis burden and reaching the END-TB Strategy goals as defined by the WHO. Vaccination, detection of infection, and provision of preventive treatment are key …

Reply To Yi Et Al, A Jay Freeman, Kenneth Ng, Fuchenchu Wang, Ying Yuan, Mark E Lowe, Aliye Uc

Faculty, Staff and Student Publications

No abstract provided.

Cmtm4 Inhibits Gastric Tumorigenesis And Metastasis, Xiurui Han, Weiwei Fu, Qinghua Sun, Jing Ning, Jing Zhang, Silvio Matsas, Fabrício Freire De Melo, Hejun Zhang, Xinyu Hao, Qiao Meng, Yueqing Gong, Huiling Zheng, Jing Zhang, Shigang Ding

Faculty, Staff and Student Publications

BACKGROUND: CKLF-like MARVEL transmembrane domain-containing 4 (CMTM4) is involved in immune regulation and tumor progression; however, its role in gastric cancer (GC) remains unclear. This study explored the role and mechanism of CMTM4 in GC.

METHODS: Immunohistochemistry was used to analyze CMTM4 expression in human gastric biopsied cells from patients with GC (N=23) or chronic superficial gastritis (N=23). To investigate the function of CMTM4 in GC cells, the gene

RESULTS: CMTM4 expression was more downregulated in the human GC tissues than the gastritis tissues. CMTM4 overexpression significantly inhibited the proliferation, migration, and invasion of the GC cells, whereas CMTM4 knockdown …

Facilitators And Barriers To Initiating And Completing Tuberculosis Preventive Treatment Among Children And Adolescents Living With Hiv In Uganda: A Qualitative Study Of Adolescents, Caretakers And Health Workers, Pauline Mary Amuge, Denis Ndekezi, Moses Mugerwa, Dickson Bbuye, Diana Antonia Rutebarika, Lubega Kizza, Christine Namugwanya, Angella Baita, Peter James Elyanu, Patricia Nahirya Ntege, Dithan Kiragga, Carol Birungi, Adeodata Rukyalekere Kekitiinwa, Agnes Kiragga, Moorine Peninah Sekadde, Nicole-Austin Salazar, Anna Maria Mandalakas, Philippa Musoke

Faculty, Staff and Students Publications

INTRODUCTION: People living with HIV (PLHIV) have a 20-fold risk of tuberculosis (TB) disease compared to HIV-negative people. In 2021, the uptake of TB preventive treatment among the children and adolescents living with HIV at the Baylor-Uganda HIV clinic was 45%, which was below the national target of 90%. Minimal evidence documents the enablers and barriers to TB preventive treatment (TPT) initiation and completion among children and adolescents living with HIV(CALHIV). We explored the facilitators and barriers to TPT initiation and completion among CALHIV among adolescents aged 10-19years and caretakers of children below 18years.

METHODS: We conducted a qualitative study …

Subjective And Objective Sleep Quality Assessment In Adolescent Patients With Inflammatory Bowel Disease, Holly Breeden, Elizabeth Mcdonough, Amanda Glinky, Rebecca Wallace, Robbie Beyl, Colleen Leblanc

School of Medicine Faculty Publications

Objectives: There is a link between inflammatory bowel disease (IBD) and poor sleep quality that is presumed to be multifactorial. The purpose of this study was to identify factors that impact sleep quality in this group including clinical disease activity, depression, anxiety, quality of life, and disordered social media use through questionnaires. Methods: This prospective study analyzed sleep quality in adolescent patients ages 13 to 18 with a diagnosis of IBD using objective data from wrist actigraphy and subjective report from the Pittsburgh Sleep Quality Index (PSQI). Additional screeners including the Short Pediatric Crohn's Disease Activity Index or Pediatric Ulcerative …

Synergistic Effects Of Novel Penicillin-Binding Protein 1a Amino Acid Substitutions Contribute To High-Level Amoxicillin Resistance Of, Alain Cimuanga-Mukanya, Evariste Tshibangu-Kabamba, Patrick De Jesus Ngoma Kisoko, Kartika Afrida Fauzia, Fabien Mbaya Tshibangu, Antoine Tshimpi Wola, Pascal Tshiamala Kashala, Dieudonné Mumba Ngoyi, Steve Ahuka-Mundeke, Gunturu Revathi, Ghislain Disashi-Tumba, Yasutoshi Kido, Takashi Matsumoto, Junko Akada, Yoshio Yamaoka

Faculty, Staff and Students Publications

The growing resistance to amoxicillin (AMX)—one of the main antibiotics used in Helicobacter pylori eradication therapy—is an increasing health concern. Several mutations of penicillin-binding protein 1A (PBP1A) are suspected of causing AMX resistance; however, only a limited set of these mutations have been experimentally explored. This study aimed to investigate four PBP1A mutations (i.e., T558S, N562H, T593A, and G595S) carried by strain KIN76, a high-level AMX-resistant clinical H. pylori isolate with an AMX minimal inhibition concentration (MIC) of 2 µg/mL. We transformed a recipient strain 26695 with the DNA containing one to four mutation allele combinations of the pbp1 gene …

Preventive Effects Of Quercetin On The Leaky Gut By Suppression Of Il-1beta-Induced Transcription Factors Involved In An Inflammatory Pathway In Colonic Epithelial Cells, Wannaporn Chayalak, Sumpun Thammacharoen, Chatsri Deachapunya, Sutthasinee Poonyachoti

The Thai Journal of Veterinary Medicine

Flavonol quercetin (Q), found in vegetables and fruits, demonstrates the most potent anti-inflammatory effect. The preventive effect and cellular mechanisms of Q (Q1, Q10, and Q100 µM) on IL-1β induced leaky gut via the signaling molecules of inflammatory pathway, NF-κB p65-iκB/or p38/ERK1/2/MLCK/phospho(p)-MLC were investigated in Caco-2 cells. The cytotoxic effect of Q was initially determined by MTT assay. Transepithelial electrical resistance (TER) and apical-to-basolateral fluorescein isothiocyanate-labeled dextran (FD-4) flux were used to determine paracellular permeability. The protein expression of signaling molecules was examined by Western blot analysis, and their target MLCK mRNA expression was determined using real-time PCR. All Q …

The Impact Of Bariatric Surgery On Glutathione Synthesis In Individuals With Severe Obesity, Hong Chang Tan, Jean W Hsu, E Shyong Tai, Shaji Chacko, Jean-Paul Kovalik, Farook Jahoor

Faculty, Staff and Students Publications

Glycine is deficient in individuals with obesity but improves following bariatric surgery. Glycine deficiency could impair glutathione (GSH) synthesis and worsen oxidative stress. We examined the impact of obesity-associated glycine deficiency and bariatric surgery on GSH synthesis. Twenty-one participants with severe obesity and twenty-one healthy weight controls were recruited. [1,2-13C2] glycine was infused to measure the erythrocyte (RBC) GSH synthesis rate. Participants with obesity underwent bariatric surgery, and 19 were restudied six months post-surgery. Compared to healthy weight controls, individuals with obesity had significantly lower concentrations of RBC GSH (2.43 ± 0.23 vs. 2.63 ± 0.26 mmol/L, p < 0.01). However, there were no differences in GSH fractional synthesis rate [78.0 (51.4–123.7) vs. 76.9 (49.3–110.1) % pool/day, p = …

Understanding The Role Of Mastl In Colon Homeostasis And Colitis-Associated Cancer Development, Kristina Pravoverov

Theses & Dissertations

Colitis-associated cancer (CAC) is the most devastating complication of longstanding inflammatory bowel disease (IBD). Understanding the mechanisms underlying the switch from damage-repair to dysplasia in IBD is critical for identifying novel therapies to facilitate mucosal healing while mitigating CAC risk. Microtubule-associated serine-threonine kinase-like (MASTL), though crucial in cell growth and repair, is upregulated in sporadic colorectal cancer and CAC. This study sought to delineate the role of MASTL in colitis and CAC development.

First, we examined whether MASTL is associated with colitis and recovery. Review of publicly available data found significant elevation of MASTL and interleukin (IL)-22 in biopsies from …