Digital Commons Network^™

Awareness On Breast Cancer Screening In Malaysia: A Cross Sectional Study, Mun-Seng Lee, Choiriyatul ‘Azmiyaty Amar Ma’ Ruf, Dayang Puteri Nadhirah Izhar, Sayyida Nafisah Ishak, Wan Syazana Wan Jamaluddin, Syafiqah Nadiah Mohd Ya’Acob, Muhammad Nazrullah Kamaluddin

BioMedicine

Introduction: The increasing rate of breast cancer (BC) incidence in Malaysia hints a lack of awareness among Malaysians. One (1) woman out of nineteen (19) is at risk with BC and almost up to fifty percent (50%) of women diagnosed with BC were reported to be under the age of fifty (50). Our main concern is to study the level of awareness among the women on risk factors, clinical manifestations, diagnosis, preventions and treatments.

Method: A cross-sectional study was conducted exclusively among women in the public with total sample of three hundred and forty six (346), questionnaires were distributed using …

The Relationship Between Body Mass Index (Bmi) And Quality Of Life In Iranian Primary School Students In Tehran, Iran, Mostafa Farajpour. Kh, Mohadeseh Pishgahroodsari, Hamid Salehiniya, Fahimeh Soheilipour

BioMedicine

No abstract provided.

Evidence That Crispr-Cas9 Y537s-Mutant Expressing Breast Cancer Cells Activate Yes-Associated Protein 1 To Driving The Conversion Of Normal Fibroblasts Into Cancer-Associated Fibroblasts, Luca Gelsomino, Amanda Caruso, Emine Tasan, Adele Elisabetta Leonetti, Rocco Malivindi, Giuseppina Daniela Naimo, Francesca Giordano, Salvatore Panza, Guowei Gu, Benedetta Perrone, Cinzia Giordano, Loredana Mauro, Bruno Nardo, Gianfranco Filippelli, Daniela Bonofiglio, Ines Barone, Suzanne A W Fuqua, Stefania Catalano, Sebastiano Andò

Faculty, Staff and Students Publications

BACKGROUND: Endocrine therapy (ET) has improved the clinical outcomes of Estrogen receptor alpha-positive (ERɑ +) breast cancer (BC) patients, even though resistance to ET remains a clinical issue. Mutations in the hormone-binding domain of ERɑ represent an acquired intrinsic mechanism of ET resistance. However, the latter also depends on the multiple functional interactions between BC cells and the tumor microenvironment (TME). Here, we investigated how the most common Y537S-ERɑ mutation may influence the behavior of fibroblasts, the most prominent component of the TME.

METHODS: We conducted coculture experiments with normal human foreskin fibroblasts BJ1-hTERT (NFs), cancer-associated fibroblasts (CAFs), isolated from …

The Role Of Kctd13 In Androgen Receptor Ubiquitination​, Faith Abraham, Ahmed Chahdi, Phd, Carolina Jorgez, Phd, Abhishek Seth

HCA-NSU MD Research Day

The Role of KCTD13 in Androgen Receptor Ubiquitination Faith Abraham1, Ahmed Chahdi, PhD2, Caroline Jorgez, PhD3, and Abhishek Seth, MD2 1Class of 2024, Dr. Kiran C. Patel College of Osteopathic Medicine, 2Urology, Nemours Children’s Hospital, Orlando, FL 3Urology, Baylor College of Medicine, Houston, TX Objective: This study was conducted to determine the effect of the KCTD13 gene on major protein effectors of common genitourinary (GU) defects. Background: Hypospadias, characterized by the ventral positioning of the urethral opening, occurs in approximately 1 out of 125 live births. Cryptorchidism, or undescended testes (UDT), is the most common GU birth defect, affecting around …

Complete Genome Sequence Of Borrelia Miyamotoi Strain Mn18-0001, An Am-East-2 Strain Type Isolate Derived From An Ixodes Scapularis Tick (Minnesota), Alexander R Kneubehl, Lynn M Osikowicz, Christina M Parise, Taylor J Van Gundy, Adam J Replogle, Job E Lopez, Rebecca J Eisen, Andrias Hojgaard

Faculty, Staff and Students Publications

We report the genomic sequence of the hard tick relapsing fever spirochete Borrelia miyamotoi strain MN18-0001. B. miyamotoi causes human illness and is geographically widespread in Ixodes spp. (Acari: Ixodidae) ticks. This is a chromosome- and plasmid-resolved genome assembly of an Am-East-2 strain type isolate from the midwestern United States.

Intouch Week Of November 11, 2024, New York Medical College

InTouch

• More than $16,000 Raised by NYMC SOM Marathon Runners
• Department of Pediatrics Hosts Leonard Newman, M.D. ’70, Assistant Professor Research Symposium
• Jonathan Fisher, Ph.D., Presents at the Neighborhood Science Seminar Series
• NYMC Community Visits New York Historical Society Museum
• NYMC SNMA Brings Hope to Tampa Residents Impacted by Hurricanes
• NYMC Blood Drive Brings Community Together to Save Lives
• Health Literacy Club Hosts Educational Vegetable Stand
• Student Spotlight: SOM Student Takes Second Place in International Neurosurgery Innovation Competition
• Faculty Spotlight: From Pupil to Professor: Alumni Lighting the Way at NYMC

Dna Methylation Classifier To Diagnose Pancreatic Ductal Adenocarcinoma Metastases From Different Anatomical Sites, Teodor G Calina, Eilís Perez, Elena Grafenhorst, Jamal Benhamida, Simon Schallenberg, Adrian Popescu, Ines Koch, Tobias Janik, Baoqing Chen, Jana Ihlow, Stephanie Roessler, Benjamin Goeppert, Bruno Sinn, Marcus Bahra, George A Calin, Eliane T Taube, Uwe Pelzer, Christopher C M Neumann, David Horst, Erik Knutsen, David Capper, Mihnea P Dragomir

Faculty, Staff and Student Publications

Background: We have recently constructed a DNA methylation classifier that can discriminate between pancreatic ductal adenocarcinoma (PAAD) liver metastasis and intrahepatic cholangiocarcinoma (iCCA) with high accuracy (PAAD-iCCA-Classifier). PAAD is one of the leading causes of cancer of unknown primary and diagnosis is based on exclusion of other malignancies. Therefore, our focus was to investigate whether the PAAD-iCCA-Classifier can be used to diagnose PAAD metastases from other sites.

Methods: For this scope, the anomaly detection filter of the initial classifier was expanded by 8 additional mimicker carcinomas, amounting to a total of 10 carcinomas in the negative class. We validated the …

Modeling Antisense Oligonucleotide Therapy In Mecp2 Duplication Syndrome Human Ipsc-Derived Neurons Reveals Gene Expression Programs Responsive To Mecp2 Levels, Sameer S Bajikar, Yehezkel Sztainberg, Alexander J Trostle, Harini P Tirumala, Ying-Wooi Wan, Caroline L Harrop, Jesse D Bengtsson, Claudia M B Carvalho, Davut Pehlivan, Bernhard Suter, Jeffrey L Neul, Zhandong Liu, Paymaan Jafar-Nejad, Frank Rigo, Huda Y Zoghbi

Faculty, Staff and Students Publications

Genomic copy-number variations (CNVs) that can cause neurodevelopmental disorders often encompass many genes, which complicates our understanding of how individual genes within a CNV contribute to pathology. MECP2 duplication syndrome (MDS or MRXSL in OMIM; OMIM#300260) is one such CNV disorder caused by duplications spanning methyl CpG-binding protein 2 (MECP2) and other genes on Xq28. Using an antisense oligonucleotide (ASO) to normalize MECP2 dosage is sufficient to rescue abnormal neurological phenotypes in mouse models overexpressing MECP2 alone, implicating the importance of increased MECP2 dosage within CNVs of Xq28. However, because MDS CNVs span MECP2 and additional genes, we generated human …

The Rna Receptor Rig-I Binding Synthetic Oligodeoxynucleotide Promotes Pneumonia Survival, Yongxing Wang, Vikram V Kulkarni, Jezreel Pantaleóngarcía, Michael K Longmire, Mathilde Lethier, Stephen Cusack, Scott E Evans

Faculty, Staff and Student Publications

Pneumonia is a worldwide threat to public health, demanding novel preventative and therapeutic strategies. The lung epithelium is a critical environmental interface that functions as a physical barrier to pathogen invasion while also actively sensing and responding to pathogens. We have reported that stimulating lung epithelial cells with a combination therapeutic consisting of a diacylated lipopeptide and a synthetic CpG oligodeoxynucleotide (ODN) induces synergistic pneumonia protection against a wide range of pathogens. We report here that mice deficient in TLR9, the previously described receptor for ODN, still displayed partial ODN-induced protection. This prompted us to seek an alternate ODN receptor, …

Daily Diagnostic Quality Computed Tomography-On-Rails (Ctor) Image Guidance For Abdominal Stereotactic Body Radiation Therapy (Sbrt), Rachael M Martin-Paulpeter, P James Jensen, Luis A Perles, Gabriel O Sawakuchi, Prajnan Das, Eugene J Koay, Albert C Koong, Ethan B Ludmir, Joshua S Niedzielski, Sam Beddar

Faculty, Staff and Student Publications

BACKGROUND/OBJECTIVES: Stereotactic body radiation therapy (SBRT) for abdominal targets faces a variety of challenges, including motion caused by the respiration and digestion and a relatively poor level of contrast between the tumor and the surrounding tissues. Breath-hold treatments with computed tomography-on-rails (CTOR) image guidance is one way of addressing these challenges, allowing for both the tumor and normal tissues to be well-visualized. Using isodose lines (IDLs) from CT simulations as a guide, the anatomical information can be used to shift the alignment or trigger a replan, such that normal tissues receive acceptable doses of radiation.

METHODS: This study aims to …

High Incidence And Geographic Distribution Of Cleft Palate In Finland Are Associated With The Irf6 Gene, Fedik Rahimov, Pekka Nieminen, Priyanka Kumari, Emma Juuri, Tiit Nikopensius, Kitt Paraiso, Jakob German, Antti Karvanen, Mart Kals, Abdelrahman G Elnahas, Juha Karjalainen, Mitja Kurki, Aarno Palotie, Estonian Biobank Research Team, Finngen, Arja Heliövaara, Tõnu Esko, Sakari Jukarainen, Priit Palta, Andrea Ganna, Anjali P Patni, Daniel Mar, Karol Bomsztyk, Julie Mathieu, Hannele Ruohola-Baker, Axel Visel, Walid D Fakhouri, Brian C Schutte, Robert A Cornell, David P Rice

Faculty, Staff and Student Publications

In Finland, the frequency of isolated cleft palate (CP) is higher than that of isolated cleft lip with or without cleft palate (CL/P). This trend contrasts to that in other European countries but its genetic underpinnings are unknown. We conducted a genome-wide association study in the Finnish population and identified rs570516915, a single nucleotide polymorphism highly enriched in Finns, as strongly associated with CP (P = 5.25 × 10-34, OR = 8.65, 95% CI 6.11-12.25), but not with CL/P (P = 7.2 × 10-5), with genome-wide significance. The risk allele frequency of rs570516915 parallels the regional variation of CP prevalence …

Intouch Week Of November 4, 2024, New York Medical College

InTouch

• SOM Receives Full Eight-Year LCME Accreditation
• NYMC Honors 2023 Faculty Authors
• Five SOM Students Awarded AMSNY Diversity in Medicine Scholarships
• Discover NYMC with Our 2024-2025 Social Media Ambassadors
• NYMC Goes Orange for Physical Therapy
• Dr. Halperin Offers Thoughts on the Controversy at UNC
• Faculty Spotlight: From Pupil to Professor: Alumni Lighting the Way at NYMC
• Student Spotlight: SOM Student Awarded Prestigious AAMC Scholarship for Leadership in Tackling Health Inequities
• Student Spotlight: Professional Dancer Takes a New Step into Medicine

Fc-Enhanced Anti-Ctla-4, Anti-Pd-1, Doxorubicin, And Ultrasound-Mediated Blood-Brain Barrier Opening: A Novel Combinatorial Immunotherapy Regimen For Gliomas, Kwang-Soo Kim, Karl Habashy, Andrew Gould, Junfei Zhao, Hinda Najem, Christina Amidei, Ruth Saganty, Víctor A Arrieta, Crismita Dmello, Li Chen, Daniel Y Zhang, Brandyn Castro, Leah Billingham, Daniel Levey, Olivia Huber, Marilyn Marques, David A Savitsky, Benjamin M Morin, Miguel Muzzio, Michael Canney, Craig Horbinski, Peng Zhang, Jason Miska, Surya Padney, Bin Zhang, Raul Rabadan, Joanna J Phillips, Nicholas Butowski, Amy B Heimberger, Jian Hu, Roger Stupp, Dhan Chand, Catalina Lee-Chang, Adam M Sonabend

Faculty, Staff and Student Publications

Background: Glioblastoma is a highly aggressive brain cancer that is resistant to conventional immunotherapy strategies. Botensilimab, an Fc-enhanced anti-CTLA-4 antibody (FcE-aCTLA-4), has shown durable activity in "cold" and immunotherapy-refractory cancers.

Methods: We evaluated the efficacy and immune microenvironment phenotype of a mouse analogue of FcE-aCTLA-4 in treatment-refractory preclinical models of glioblastoma, both as a monotherapy and in combination with doxorubicin delivered via low-intensity pulsed ultrasound and microbubbles (LIPU/MB). Additionally, we studied 4 glioblastoma patients treated with doxorubicin, anti-PD-1 with concomitant LIPU/MB to investigate the novel effect of doxorubicin modulating FcγR expressions in tumor-associated macrophages/microglia (TAMs).

Results: FcE-aCTLA-4 demonstrated high-affinity binding …

Degree Of Anxiety Among First And Final Year Pharmacy Students: Results From Mosul College Of Pharmacy, Harith Kh Al-Qazaz, Sadeel A. Shanshal, Hussain A. Mohammed, Belal A. Ibrahem, Muath H. Mahmood, Omer H. Ali, Abdullah Ghanim

BioMed Visions Journal

Background and Objectives: Upgrading from schools to university is a pivotal stage for many students. however, the conversion of situation and appearance of new responsibilities will expose university students to extreme stress such as increased academic workloads and involvement in public speaking. The assessment of prevalence and its correlates of anxiety among students at the University of Mosul, College of Pharmacy was the aim in this study, involving 253 participants. Methods: A cross-sectional survey was conducted for short period of time from 20th to 27th of January 2024 in online base. The data collection form consists of two parts: Socio-demographic …

Protein Consumption And Risk Of Cvd Among Us Adults: The Multi-Ethnic Study Of Atherosclerosis (Mesa), Ji Yun Tark, Ruosha Li, Bing Yu, Alexis C Wood, Nikhil S Padhye, Marcia C De Oliveira Otto

Faculty, Staff and Students Publications

BACKGROUND: Although some randomized trials have reported beneficial effects of protein intake on cardiometabolic risk factors, evidence from prospective studies have not supported a strong link between protein intake and cardiovascular disease (CVD) risk. It is also unclear whether diversity in protein intake plays a role in CVD risk.

OBJECTIVE: We investigated prospective associations of (1) protein intake, overall and by food source and (2) diversity of protein sources with risk of CVD, coronary heart disease (CHD), and stroke.

METHODS: In a multi-ethnic cohort of 5879 U.S. adults (45-84 years), who were free of CVD at baseline, protein intake was …

Using Patient-Reported Experiences To Inform The Use Of Foam Dressings For Hard-To-Heal Wounds: Perspectives From A Wound Care Expert Panel, Kevin Woo, Nick Santamaria, Dimitri Beeckman, Paulo Alves, Breda Cullen, Amit Gefen, José Luis Lázaro-Martínez, Hadar Lev-Tov, Bijan Najafi, Andrew Sharpe, Terry Swanson

Center on Aging Staff Publications

Caring for patients with hard-to-heal (chronic) wounds requires a multifaceted approach that addresses their diverse needs, which can contribute to the complexity of care. Wound care providers must have a comprehensive understanding of the patient's comorbid conditions and psychosocial issues to provide personalised and effective treatment. Key quality indicators for effective wound care involves not only selecting appropriate local wound care products, such as foam dressings, but also addressing individual patient experiences of wound-related pain, odour, itch, excessive wound drainage, and self-care needs. The purpose of this review is to inculcate the wound care practice community, research scientists and healthcare …

Roflumilast Cream, 015%, For Atopic Dermatitis In Adults And Children: Integument-1 And Integument-2 Randomized Clinical Trials, Eric L Simpson, Lawrence F Eichenfield, Javier Alonso-Llamazares, Zoe D Draelos, Laura K Ferris, Seth B Forman, Melinda Gooderham, Mercedes E Gonzalez, Adelaide A Hebert, Leon H Kircik, Mark Lomaga, Angela Moore, Kim A Papp, Vimal H Prajapati, Diane Hanna, Scott Snyder, David Krupa, Patrick Burnett, Erin Almaraz, Robert C Higham, David H Chu, David R Berk

Faculty, Staff and Student Publications

Importance: Safe, effective, and well-tolerated topical treatment options available for long-term use in patients with atopic dermatitis (AD) are limited and associated with low adherence rates.

Objective: To evaluate efficacy and safety of once-daily roflumilast cream, 0.15%, vs vehicle cream in patients with AD.

Design, setting, and participants: Two phase 3, randomized, double-blind, vehicle-controlled trials (Interventional Trial Evaluating Roflumilast Cream for the Treatment of Atopic Dermatitis 1 and 2 [INTEGUMENT-1 and INTEGUMENT-2]), included patients from sites in the US, Canada, and Poland. Participants were 6 years or older with mild to moderate AD based on Validated Global Assessment for Atopic …

Anti-Egfr Aptamer Exhibits Direct Anti-Cancer Effects In Nsclc Cells Harboring Egfr L858r Mutations, Brian J. Thomas, Sania Z. Awan, Trupti Joshi, Mark A. Daniels, David Porciani, Donald H. Burke

Biomedical Sciences

Non-small cell lung cancer (NSCLC) adenocarcinoma (LUAD) is a leading cause of death worldwide. Activating mutations in the tyrosine kinase domain of the oncogene epidermal growth factor receptor (EGFR) are responsible for ~10–50% of all LUAD cases. Although tyrosine kinase inhibitors (TKIs) have been effective in prolonging patient survival and quality of life, acquired resistance and disease progression are inevitable, presenting a clear unmet need for alternative or adjuvant therapeutics. Here we show that an anti-EGFR aptamer (EGFRapt) decreases viability and tumor growth of LUAD cell lines harboring the L858R ± T790M mutation in EGFR. Additionally, we elucidate …

Small And Long Non-Coding Rna Analysis For Humantrophoblast-Derived Extracellular Vesicles And Their Effect On The Transcriptome Profile Of Human Neural Progenitor Cells, Jessica A. Kinkade, Pallav Singh, Mohit Verma, Teka Khan, Toshihoko Ezashi, Nathan J. Bivens, R. Michael Roberts, Trupti Joshi, Cheryl S. Rosenfeld

Biomedical Sciences

In mice, the fetal brain is dependent upon the placenta for factors that guide its early development. This linkage between the two organs has given rise to the term, the placenta–brain axis. A similar interrelationship between the two organs may exist in humans. We hypothesize that extracellular vesicles (EVs) released from placental trophoblast (TB) cells transport small RNA and other informational biomolecules from the placenta to the brain where their contents have pleiotropic effects. Here, EVs were isolated from the medium in which human trophoblasts (TBs) had been differentiated in vitro from induced pluripotent stem cells (iPSC) and from cultured …

Tfeb Controls Syncytiotrophoblast Formation And Hormone Production In Placenta, Marcella Cesana, Gennaro Tufano, Francesco Panariello, Nicolina Zampelli, Chiara Soldati, Margherita Mutarelli, Sandro Montefusco, Giuseppina Grieco, Lucia Vittoria Sepe, Barbara Rossi, Edoardo Nusco, Giada Rossignoli, Giorgia Panebianco, Fabrizio Merciai, Emanuela Salviati, Eduardo Maria Sommella, Pietro Campiglia, Graziano Martello, Davide Cacchiarelli, Diego Luis Medina, Andrea Ballabio

Duncan NRI Faculty and Staff Publications

TFEB, a bHLH-leucine zipper transcription factor belonging to the MiT/TFE family, globally modulates cell metabolism by regulating autophagy and lysosomal functions. Remarkably, loss of TFEB in mice causes embryonic lethality due to severe defects in placentation associated with aberrant vascularization and resulting hypoxia. However, the molecular mechanism underlying this phenotype has remained elusive. By integrating in vivo analyses with multi-omics approaches and functional assays, we have uncovered an unprecedented function for TFEB in promoting the formation of a functional syncytiotrophoblast in the placenta. Our findings demonstrate that constitutive loss of TFEB in knock-out mice is associated with defective formation of …

Diverse Pathways In Gpcr-Mediated Activation Of Ca2+ Mobilization In Hek293 Cells, Francesco De Pascali, Asuka Inoue, Jeffrey L. Benovic

Department of Biochemistry and Molecular Biology Faculty Papers

G protein-coupled receptors transduce extracellular stimuli into intracellular signaling. Ca²⁺ is a well-known second messenger that can be induced by G protein-coupled receptor activation through the primary canonical pathways involving Gα_q- and Gβγ-mediated activation of phospholipase C-β (PLCβ). While some G_s-coupled receptors are shown to trigger Ca²⁺ mobilization, underlying mechanisms remain elusive. Here, we evaluated whether G_s-coupled receptors including the β₂-adrenergic receptor (β₂AR) and the prostaglandin EP₂ and EP₄ receptors (EP₂R and EP₄R) that are endogenously expressed in human embryonic kidney 293 …

Metabolic Stress Induces A Double-Positive Feedback Loop Between Ampk And Sqstm1/P62 Conferring Dual Activation Of Ampk And Nfe2l2/Nrf2 To Synergize Antioxidant Defense, Eun-Ji Choi, Hyun-Taek Oh, Seon-Hyeong Lee, Chen-Song Zhang, Mengqi Li, Soo-Youl Kim, Sunghyouk Park, Tong-Shin Chang, Byung-Hoon Lee, Sheng-Cai Lin, Sang-Min Jeon

Staff and Researcher Publications

Co-occurring mutations in KEAP1 in STK11/LKB1-mutant NSCLC activate NFE2L2/NRF2 to compensate for the loss of STK11-AMPK activity during metabolic adaptation. Characterizing the regulatory crosstalk between the STK11-AMPK and KEAP1-NFE2L2 pathways during metabolic stress is crucial for understanding the implications of co-occurring mutations. Here, we found that metabolic stress increased the expression and phosphorylation of SQSTM1/p62, which is essential for the activation of NFE2L2 and AMPK, synergizing antioxidant defense and tumor growth. The SQSTM1-driven dual activation of NFE2L2 and AMPK was achieved by inducing macroautophagic/autophagic degradation of KEAP1 and facilitating the AXIN-STK11-AMPK complex formation on the lysosomal membrane, respectively. In contrast, …

Effects Of Tranexamic Acid On Human Osteoblasts As Proxy For Fracture Healing, Alexander Abraham, D Nicole Meyers, William D Rieger, Ryan Anthony, Humberto Aparicio, Adam Y Park, James F Kellam, Catherine G Ambrose

Faculty, Staff and Student Publications

Objectives: To investigate the effect of tranexamic acid (TXA) through in vitro culture of primary human osteoblasts (HOB) and in vivo using an operative rat femur fracture model. It was hypothesized that there would not be any effect on fracture healing in both studies.

Methods: Primary HOBs were exposed to varying concentrations of TXA over different time periods. Cells were assessed for viability, metabolism, and mineralization. For the in vivo model, fractures were created in the femora of adult rats, exposed to either TXA or saline, and then assessed for healing at different time points. A modified radiographic union score …

Exposure To Statin Therapy Decreases The Incidence Of Venous Thromboembolism After Trauma, Kelly E Sanders, Gabrielle E Hatton, Atharwa R Mankame, Addison C Allen, Sarah Cunningham, Jan Michael Van Gent, Erin E Fox, Xu Zhang, Charles E Wade, Bryan A Cotton, Jessica C Cardenas

Faculty, Staff and Student Publications

Introduction: Venous thromboembolism (VTE) is a leading cause of morbidity and mortality in trauma patients, despite chemoprophylaxis. Statins have been shown capable of acting upon the endothelium. We hypothesized that statin therapy in the pre- or in-hospital settings leads to a decreased incidence of VTE.

Methods: We conducted a retrospective cohort study of injured patients who received statin therapy pre- or in-hospital. Adult, highest-level trauma activation patients admitted from January 2018 to June 2022 were included. Patients on prehospital anticoagulants, had history of inherited bleeding disorder, and who died within the first 24 hours were excluded. Statin users were matched …

The Effect Of Smoking On Functional Outcomes And Implant Survival Of Anatomical Total Shoulder Arthroplasty, Isabella E Amador, Kevin A Hao, Timothy R Buchanan, Derek S Damrow, Keegan M Hones, Trevor Simcox, Bradley S Schoch, Kevin W Farmer, Thomas W Wright, Tyler J Lamonica, Joseph J King, Jonathan O Wright

Faculty, Staff and Student Publications

Aims: We sought to compare functional outcomes and survival between non-smokers, former smokers, and current smokers who underwent anatomical total shoulder arthroplasty (aTSA) in a large cohort of patients.

Methods: A retrospective review of a prospectively collected shoulder arthroplasty database was performed between August 1991 and September 2020 to identify patients who underwent primary aTSA. Patients were excluded for preoperative diagnoses of fracture, infection, or oncological disease. Three cohorts were created based on smoking status: non-smokers, former smokers, and current smokers. Outcome scores (American Shoulder and Elbow Surgeons (ASES), Constant-Murley score, Shoulder Pain and Disability Index (SPADI), Simple Shoulder Test …

Increased Gremlin1 Expression In Pancreatic Ductal Adenocarcinoma Promotes A Fibrogenic Stromal Microenvironment, Rachel R Tindall, Erika Y Faraoni, Jiajing Li, Yinjie Zhang, Shun-Ming Ting, Beanna Okeugo, Xiurong Zhao, Yuying Liu, Mamoun Younes, Qiang Shen, Jennifer M Bailey-Lundberg, Yanna Cao, Tien C Ko

Faculty, Staff and Student Publications

Objective: Pancreatic ductal adenocarcinoma (PDAC) microenvironment is primarily composed of cancer-associated fibroblasts and immune cells. Gremlin1 (Grem1) is a profibrogenic factor that promotes tumorigenesis in several cancers. However, the role of Grem1 in the PDAC microenvironment is not defined.

Materials and methods: We correlated Grem1 levels with activated stroma and immune cells in human PDAC using The Cancer Genome Atlas RNA-sequencing data and characterized expression of Grem1 transcripts and isoforms in pancreatic cell lines and PDAC tissues. We assessed the role of Grem1 in the microenvironment by in vitro studies.

Results: Grem1 expression is associated with an activated stroma and …

Increased White Blood Cell In Young Adults With Family Histories Of Alcohol And Other Substance Use Disorders, Mustafa N Mithaiwala, Nikki S Phillips, Dylan H Nguyen, Melanie S Beehler, Harrison S Ballard, Andrea S Vincent, William R Lovallo, Peter Kochunov, L Elliot Hong, Jason C O'Connor, Steve Cole, Ashley Acheson

Faculty, Staff and Student Publications

Individuals with a family history of alcohol or other substance use disorders (FH+) are at increased risk for developing alcohol and other substance use disorders (AUD/SUD) compared to individuals with no such family histories (FH-). FH+ young adults have blunted stress reactivity, lower cognitive performance and altered frontal white matter microstructure compared to FH- controls. We hypothesized that family history of AUD/SUD disrupts neuroendocrine regulation of the immune system in FH+ individuals, resulting in altered blood immune cell composition, inflammation and neurocognitive alterations that, ultimately, increases risk for AUD/SUD and associated psychopathology. We examined white blood cell (WBC) parameters derived …

Discovery, Characterization, And Structure Of A Cofactor-Independent Histidine Racemase From The Oral Pathogen Fusobacterium Nucleatum, Tess Lamer, Pu Chen, Marie J Venter, Marco J Van Belkum, Anjalee Wijewardane, Chenggang Wu, M Joanne Lemieux, John C Vederas

Faculty, Staff and Student Publications

Fusobacterium nucleatum is an oral commensal bacterium that can act as an opportunistic pathogen and is implicated in diseases such as periodontitis, adverse pregnancy outcomes, colorectal cancer, and Alzheimer's disease. F. nucleatum synthesizes lanthionine for its peptidoglycan, rather than meso-2,6-diaminopimelic acid (DAP) used by most Gram-negative bacteria. Despite lacking the biosynthetic pathway for DAP, the genome of F. nucleatum ATCC 25586 encodes a predicted DAP epimerase. A recent study hypothesized that this enzyme may act as a lanthionine epimerase, but the authors found a very low turnover rate, suggesting that this enzyme likely has another more favored substrate. Here, we …

Shear Stress Induces A Time-Dependent Inflammatory Response In Human Monocyte-Derived Macrophages, Elysa Jui, Griffin Kingsley, Hong Kim T Phan, Kavya L Singampalli, Ravi K Birla, Jennifer P Connell, Sundeep G Keswani, K Jane Grande-Allen

Faculty, Staff and Students Publications

Macrophages are innate immune cells that are known for their extreme plasticity, enabling diverse phenotypes that lie on a continuum. In a simplified model, they switch between pro-inflammatory (M1) and anti-inflammatory (M2) phenotypes depending on surrounding microenvironmental cues, which have been implicated in disease outcomes. Although considerable research has been focused on macrophage response to biochemical cues and mechanical signals, there is a scarcity of knowledge surrounding their behavior in response to shear stress. In this study, we applied varying magnitudes of shear stress on human monocyte-derived macrophages (MDMs) using a cone-and-plate viscometer and evaluated changes in morphology, gene expression, …

Car-Redirected Natural Killer T Cells Demonstrate Superior Antitumor Activity To Car-T Cells Through Multimodal Cd1d-Dependent Mechanisms, Xin Zhou, Ying Wang, Zhangqi Dou, Gloria Delfanti, Ourania Tsahouridis, Caroline Marnata Pellegry, Manuela Zingarelli, Gatphan Atassi, Mark G Woodcock, Giulia Casorati, Paolo Dellabona, William Y Kim, Linjie Guo, Barbara Savoldo, Ageliki Tsagaratou, J Justin Milner, Leonid S Metelitsa, Gianpietro Dotti

Faculty, Staff and Students Publications

Human natural killer T (NKT) cells have been proposed as a promising cell platform for chimeric antigen receptor (CAR) therapy in solid tumors. Here we generated murine CAR-NKT cells and compared them with CAR-T cells in immune-competent mice. Both CAR-NKT cells and CAR-T cells showed similar antitumor effects in vitro, but CAR-NKT cells showed superior antitumor activity in vivo via CD1d-dependent immune responses in the tumor microenvironment. Specifically, we show that CAR-NKT cells eliminate CD1d-expressing M2-like macrophages. In addition, CAR-NKT cells promote epitope spreading and activation of endogenous T cell responses against tumor-associated neoantigens. Finally, we observed that CAR-NKT cells …