Pathological Conditions, Signs and Symptoms Commons^™

Incidence And Risk Factors For Pneumonitis Associated With Checkpoint Inhibitors In Advanced Non-Small Cell Lung Cancer: A Single Center Experience, Mehmet Altan, Felipe Soto, Linda L Zhong, Fechukwu O Akhmedzhanov, Nathaniel R Wilson, Abdulrazzak Zarifa, Aya A Albittar, Vincent Yang, Jeff Lewis, Waree Rinsurongkawong, J Jack Lee, Vadeerat Rinsurongkawong, Jianjun Zhang, Don L Gibbons, Ara A Vaporciyan, Kristofer Jennings, Fareed Khawaja, Saadia A Faiz, Vickie R Shannon, Girish Shroff, Myrna C B Godoy, Naval G Daver, Saumil Gandhi, Tito R Mendoza, Aung Naing, Carrie Daniel-Macdougall, John V Heymach, Ajay Sheshadri

Faculty, Staff and Student Publications

INTRODUCTION: Immune checkpoint inhibitor (ICI) pneumonitis causes substantial morbidity and mortality. Estimates of real-world incidence and reported risk factors vary substantially.

METHODS: We conducted a retrospective review of 419 patients with advanced non-small cell lung cancer (NSCLC) who were treated with anti-PD-(L)1 with or without anti-CTLA-4 therapy. Clinical, imaging, and microbiological data were evaluated by multidisciplinary adjudication teams. The primary outcome of interest was grade ≥2 (CTCAEv5) pneumonitis. Clinicopathologic variables, tobacco use, cancer therapies, and preexisting lung disease were assessed for univariate effects using Cox proportional hazards models. We created multivariate Cox proportional hazards models to assess risk factors for …

Enolase Inhibitors As Early Lead Therapeutics Against Trypanosoma Brucei, Colm P Roster, Danielle Lavigne, Jillian E Milanes, Emily Knight, Heidi D Anderson, Sabrina Pizarro, Elijah M Harding, Meredith T Morris, Victoria C Yan, Cong-Dat Pham, Florian Muller, Samuel Kwain, Kerrick C Rees, Brian Dominy, Daniel C Whitehead, Md Nasir Uddin, Steven W Millward, James C Morris

Faculty, Staff and Student Publications

Glucose metabolism is critical for the African trypanosome, Trypanosoma brucei, serving as the lone source of ATP production for the bloodstream form (BSF) parasite in the glucose-rich environment of the host blood. Recently, phosphonate inhibitors of human enolase (ENO), the enzyme responsible for the interconversion of 2-phosphoglycerate (2-PG) to phosphoenolpyruvate (PEP) in glycolysis or PEP to 2-PG in gluconeogenesis, have been developed for the treatment of glioblastoma multiforme (GBM). Here, we have tested these agents against T. brucei ENO (TbENO) and found the compounds to be potent enzyme inhibitors and trypanocides. For example, (1-hydroxy-2-oxopyrrolidin-3-yl) phosphonic acid (deoxy-SF2312) …

Sptan1/Numb Axis Senses Cell Density To Restrain Cell Growth And Oncogenesis Through Hippo Signaling, Dongxue Su, Yuxi Li, Weiji Zhang, Huan Gao, Yao Cheng, Yongqiang Hou, Junhong Li, Yi Ye, Zhangjian Lai, Zhe Li, Haitao Huang, Jiaxin Li, Jinhuan Li, Mengyu Cheng, Cheng Nian, Na Wu, Zhien Zhou, Yunzhi Xing, Yu Zhao, He Liu, Jiayu Tang, Qinghua Chen, Lixin Hong, Wengang Li, Zhihai Peng, Bin Zhao, Randy L Johnson, Pingguo Liu, Wanjin Hong, Lanfen Chen, Dawang Zhou

Faculty, Staff and Student Publications

The loss of contact inhibition is a key step during carcinogenesis. The Hippo-Yes-associated protein (Hippo/YAP) pathway is an important regulator of cell growth in a cell density-dependent manner. However, how Hippo signaling senses cell density in this context remains elusive. Here, we report that high cell density induced the phosphorylation of spectrin α chain, nonerythrocytic 1 (SPTAN1), a plasma membrane-stabilizing protein, to recruit NUMB endocytic adaptor protein isoforms 1 and 2 (NUMB1/2), which further sequestered microtubule affinity-regulating kinases (MARKs) in the plasma membrane and rendered them inaccessible for phosphorylation and inhibition of the Hippo kinases sterile 20-like kinases MST1 and …

Novel Treatments For Pxe: Targeting The Systemic And Local Drivers Of Ectopic Calcification, Ida Joely Jacobs, Qiaoli Li

Department of Biochemistry and Molecular Biology Faculty Papers

Pseudoxanthoma elasticum (PXE) is a heritable multisystem ectopic calcification disorder. The gene responsible for PXE, ABCC6, encodes ABCC6, a hepatic efflux transporter regulating extracellular inorganic pyrophosphate (PPi), a potent endogenous calcification inhibitor. Recent studies demonstrated that in addition to the deficiency of plasma PPi, the activated DDR/PARP signaling in calcified tissues provides an additional possible mechanism of ectopic calcification in PXE. This study examined the effects of etidronate (ETD), a stable PPi analog, and its combination with minocycline (Mino), a potent inhibitor of DDR/PARP, on ectopic calcification in an Abcc6-/- mouse model of PXE. Abcc6-/- mice, at 4 weeks of …

Müllerian-Type Clear Cell Carcinoma Of Donor Origin In A Male Patient With A Kidney Transplant: Ascertained By Molecular Testing, J Bryan Iorgulescu, Leah K Shaw, Asif Rashid, Priya Rao, Sreedhar Mandayam, Keyur P Patel, Kathleen M Schmeler, Richard K Yang, Pavlos Msaouel

Faculty, Staff and Student Publications

Clear cell carcinomas of Müllerian origin have a strong female predominance and only extremely rarely will arise within the kidney, presumably due to ectopic Müllerian embryogenesis. Herein, we report a unique case of metastatic Müllerian type clear cell carcinoma in a 37-year-old patient who had previously received a transplanted kidney from his father at age 11 (due to severe bilateral vesicoureteral reflux) and remained on chronic immunosuppression. The tumor was highly aggressive and demonstrated somatic mutations in NF2 and SETD2. Imaging of the transplanted kidney did not reveal any clear evidence of malignancy. However, targeted multigene sequencing and short tandem …

Using Noninvasive Calibrated Cuff Plethysmography To Observe The Effects Of Cold-Water Immersion On Arterial Compliance, Rita M. Grigorian

Master's Theses

As the prevalence of cardiovascular diseases continues to exponentially grow in populations across the globe, the necessity of determining underlying factors, effective methods of diagnoses, and universally available preventive measures also grows. Early detection of endothelial dysfunction, a proven precursor of cardiovascular diseases, can be extremely impactful in encouraging preventative measures and early intervention before medical conditions become chronic. In recent years, ice plunging, a form of cryotherapy involving full body immersion in cold water, has gained popularity within circles of fitness and health practitioners, gaining the interest of people of all backgrounds. Certain parallels observed between the human physiological …

A Review Of The Role Of Tendon Stem Cells In Tendon-Bone Regeneration, Junjie Chen, Chuanfeng Jiang, Lu Yin, Yingqi Liu, Yue He, Sen Li, Huarui Shen

Faculty, Staff and Student Publications

Tendon-bone injuries are a prevalent health concern associated with sports and other physically demanding activities. These injuries have a limited innate healing ability, often leading to the formation of scar tissue rather than the regeneration of healthy tendon tissue. This scar tissue results from excessive fibrosis during the early healing process and often leads to reduced tendon function and an increased risk of reinjury. Traditionally, surgical reconstruction has been the primary treatment for tendon-bone injuries. However, restoring the natural structure and mechanical properties of tendons after surgical reconstruction presents a considerable challenge. Recently, the potential of stem cell therapy has …

Low-Grade Serous Ovarian Cancer: Expert Consensus Report On The State Of The Science, Rachel N Grisham, Brian M Slomovitz, Nicole Andrews, Susana Banerjee, Jubilee Brown, Mark S Carey, Herman Chui, Robert L Coleman, Amanda N Fader, Stephanie Gaillard, Charlie Gourley, Anil K Sood, Bradley J Monk, Kathleen N Moore, Isabelle Ray-Coquard, Ie-Ming Shih, Shannon N Westin, Kwong-Kwok Wong, David M Gershenson

Faculty, Staff and Student Publications

Compared with high-grade serous carcinoma, low-grade serous carcinoma of the ovary or peritoneum is a less frequent epithelial ovarian cancer type that is poorly sensitive to chemotherapy and affects younger women, many of whom endure years of ineffective treatments and poor quality of life. The pathogenesis of this disease and its management remain incompletely understood. However, recent advances in the molecular characterization of the disease and identification of novel targeted therapies with activity in low-grade serous carcinoma offer the promise of improved outcomes. To update clinicians regarding recent scientific and clinical trial advancements and discuss unanswered questions related to low-grade …

Two Structurally Defined Aβ Polymorphs Promote Different Pathological Changes In Susceptible Mice, Ruben Gomez-Gutierrez, Ujjayini Ghosh, Wai-Ming Yau, Nazaret Gamez, Katherine Do, Carlos Kramm, Hamid Shirani, Laura Vegas-Gomez, Jonathan Schulz, Ines Moreno-Gonzalez, Antonia Gutierrez, K Peter R Nilsson, Robert Tycko, Claudio Soto, Rodrigo Morales

Faculty, Staff and Student Publications

Misfolded Aβ is involved in the progression of Alzheimer's disease (AD). However, the role of its polymorphic variants or conformational strains in AD pathogenesis is not fully understood. Here, we study the seeding properties of two structurally defined synthetic misfolded Aβ strains (termed 2F and 3F) using in vitro and in vivo assays. We show that 2F and 3F strains differ in their biochemical properties, including resistance to proteolysis, binding to strain-specific dyes, and in vitro seeding. Injection of these strains into a transgenic mouse model produces different pathological features, namely different rates of aggregation, formation of different plaque types, …

Prame And Lef1 In Combined Deep Penetrating Nevus And Combined Blue Nevus: Utility And Pitfall, Kaitlin Vanderbeck, Aimi T Rothrock, Woo Cheal Cho, Priyadharsini Nagarajan, Phyu P Aung, Courtney Hudgens, Roland L Bassett, Doina Ivan, Victor G Prieto, Jonathan L Curry, Carlos A Torres-Cabala

Faculty, Staff and Student Publications

Deep penetrating nevi (DPN), particularly those showing combined features, or combined deep penetrating nevi (CDPN), may show histopathological resemblance to blue nevus (BN) and melanoma. Preferentially Expressed Antigen in MElanoma (PRAME) is a marker that helps distinguish melanoma from benign melanocytic lesions. Lymphoid enhancer-binding factor 1 (LEF1) has been proposed to be used in conjunction with β-catenin for diagnosis of DPN. The immunohistochemical expression of PRAME and LEF1 was evaluated in 10 DPN (including 6 CDPN and 2 DPN-like proliferations with atypical features), 16 BN (including combined and cellular BN), and 2 melanomas with features of DPN or BN. PRAME …

Pitfalls In Machine Learning-Based Assessment Of Tumor-Infiltrating Lymphocytes In Breast Cancer: A Report Of The International Immuno-Oncology Biomarker Working Group On Breast Cancer, Jeppe Thagaard, Glenn Broeckx, David B Page, Chowdhury Arif Jahangir, Sara Verbandt, Zuzana Kos, Rajarsi Gupta, Reena Khiroya, Khalid Abduljabbar, Gabriela Acosta Haab, Balazs Acs, Guray Akturk, Jonas S Almeida, Isabel Alvarado-Cabrero, Mohamed Amgad, Farid Azmoudeh-Ardalan, Sunil Badve, Nurkhairul Bariyah Baharun, Eva Balslev, Enrique R Bellolio, Vydehi Bheemaraju, Kim Rm Blenman, Luciana Botinelly Mendonça Fujimoto, Najat Bouchmaa, Octavio Burgues, Alexandros Chardas, Maggie Chon U Cheang, Francesco Ciompi, Lee Ad Cooper, An Coosemans, Germán Corredor, Anders B Dahl, Flavio Luis Dantas Portela, Frederik Deman, Sandra Demaria, Johan Doré Hansen, Sarah N Dudgeon, Thomas Ebstrup, Mahmoud Elghazawy, Claudio Fernandez-Martín, Stephen B Fox, William M Gallagher, Jennifer M Giltnane, Sacha Gnjatic, Paula I Gonzalez-Ericsson, Anita Grigoriadis, Niels Halama, Matthew G Hanna, Aparna Harbhajanka, Steven N Hart, Johan Hartman, Søren Hauberg, Stephen Hewitt, Akira I Hida, Hugo M Horlings, Zaheed Husain, Evangelos Hytopoulos, Sheeba Irshad, Emiel Am Janssen, Mohamed Kahila, Tatsuki R Kataoka, Kosuke Kawaguchi, Durga Kharidehal, Andrey I Khramtsov, Umay Kiraz, Pawan Kirtani, Liudmila L Kodach, Konstanty Korski, Anikó Kovács, Anne-Vibeke Laenkholm, Corinna Lang-Schwarz, Denis Larsimont, Jochen K Lennerz, Marvin Lerousseau, Xiaoxian Li, Amy Ly, Anant Madabhushi, Sai K Maley, Vidya Manur Narasimhamurthy, Douglas K Marks, Elizabeth S Mcdonald, Ravi Mehrotra, Stefan Michiels, Fayyaz Ul Amir Afsar Minhas, Shachi Mittal, David A Moore, Shamim Mushtaq, Hussain Nighat, Thomas Papathomas, Frederique Penault-Llorca, Rashindrie D Perera, Christopher J Pinard, Juan Carlos Pinto-Cardenas, Giancarlo Pruneri, Lajos Pusztai, Arman Rahman, Nasir Mahmood Rajpoot, Bernardo Leon Rapoport, Tilman T Rau, Jorge S Reis-Filho, Joana M Ribeiro, David Rimm, Anne Roslind, Anne Vincent-Salomon, Manuel Salto-Tellez, Joel Saltz, Shahin Sayed, Ely Scott, Kalliopi P Siziopikou, Christos Sotiriou, Albrecht Stenzinger, Maher A Sughayer, Daniel Sur, Susan Fineberg, Fraser Symmans, Sunao Tanaka, Timothy Taxter, Sabine Tejpar, Jonas Teuwen, E Aubrey Thompson, Trine Tramm, William T Tran, Jeroen Van Der Laak, Paul J Van Diest, Gregory E Verghese, Giuseppe Viale, Michael Vieth, Noorul Wahab, Thomas Walter, Yannick Waumans, Hannah Y Wen, Wentao Yang, Yinyin Yuan, Reena Md Zin, Sylvia Adams, John Bartlett, Sibylle Loibl, Carsten Denkert, Peter Savas, Sherene Loi, Roberto Salgado, Elisabeth Specht Stovgaard

Faculty, Staff and Student Publications

The clinical significance of the tumor-immune interaction in breast cancer is now established, and tumor-infiltrating lymphocytes (TILs) have emerged as predictive and prognostic biomarkers for patients with triple-negative (estrogen receptor, progesterone receptor, and HER2-negative) breast cancer and HER2-positive breast cancer. How computational assessments of TILs might complement manual TIL assessment in trial and daily practices is currently debated. Recent efforts to use machine learning (ML) to automatically evaluate TILs have shown promising results. We review state-of-the-art approaches and identify pitfalls and challenges of automated TIL evaluation by studying the root cause of ML discordances in comparison to manual TIL quantification. …

Brominated Flame Retardants: A Literature Review Of The Toxicity Mechanisms, Clinical Manifestations, And Current Treatments, Yacobus Christian Prasetyo, Eti Nurwening Sholikhah

Occupational and Environmental Medicine Journal of Indonesia

Brominated flame retardants (BFRs) are organohalogen compounds that can inhibit fire formation and delay its spread in manufacturing materials. BFRs are known to be toxic for the environment and humans. BFRs could persist for years prolonging potential exposure and toxicity to living beings. Indonesia had begun to reduce the use, even though some of toxic BFRs are still illegally circulating. This review aims to describe some aspects of BFRs toxicity including the mechanism, its clinical manifestations, and the current possible treatments. Toxicity after BFRs exposure includes endocrine, neurodevelopmental, and genotoxicity. The toxicity is manifested into some clinical conditions such as …

Effects Of Sex And Estrous Cycle On Intravenous Oxycodone Self-Administration And The Reinstatement Of Oxycodone-Seeking Behavior In Rats, Nicole M. Hinds, Ireneusz D. Wojtas, Corinne A. Gallagher, Claire M. Corbett, Daniel F. Manvich

Rowan-Virtua School of Osteopathic Medicine Departmental Research

The increasing misuse of both prescription and illicit opioids has culminated in a national healthcare crisis in the United States. Oxycodone is among the most widely prescribed and misused opioid pain relievers and has been associated with a high risk for transition to compulsive opioid use. Here, we sought to examine potential sex differences and estrous cycle-dependent effects on the reinforcing efficacy of oxycodone, as well as on stress-induced or cue-induced oxycodone-seeking behavior, using intravenous (IV) oxycodone self-administration and reinstatement procedures. In experiment 1, adult male and female Long-Evans rats were trained to self-administer 0.03 mg/kg/inf oxycodone according to a …

Dna Methylation-Based Classifier Differentiates Intrahepatic Pancreato-Biliary Tumours, Mihnea P Dragomir, Teodor G Calina, Eilís Perez, Simon Schallenberg, Meng Chen, Thomas Albrecht, Ines Koch, Peggy Wolkenstein, Benjamin Goeppert, Stephanie Roessler, George A Calin, Christine Sers, David Horst, Florian Roßner, David Capper

Faculty, Staff and Student Publications

BACKGROUND: Differentiating intrahepatic cholangiocarcinomas (iCCA) from hepatic metastases of pancreatic ductal adenocarcinoma (PAAD) is challenging. Both tumours have similar morphological and immunohistochemical pattern and share multiple driver mutations. We hypothesised that DNA methylation-based machine-learning algorithms may help perform this task.

METHODS: We assembled genome-wide DNA methylation data for iCCA (n = 259), PAAD (n = 431), and normal bile duct (n = 70) from publicly available sources. We split this cohort into a reference (n = 399) and a validation set (n = 361). Using the reference cohort, we trained three machine learning models to differentiate between these entities. Furthermore, …

Role Of Chronic Stress-Induced Neuroinflammation In Rodent Locus Coeruleus Physiology And Anxiety-Like Behaviors, Arthur Anthony Alfonso Reyes

Graduate School of Biomedical Sciences Theses and Dissertations

The locus coeruleus (LC), the primary site of brain norepinephrine (NE), is a key anatomical brain region implicated in the stress response. Stress is a neuroendocrine physiologic response to a stressor that promotes organism survival through adaptive change and restoration of homeostasis. The central stress response, which drives behavioral and physiological change, is primarily mediated by activating the hypothalamic-pituitary-adrenal (HPA) axis. While advantageous in the short term, chronic stress exposure can lead to HPA axis and LC dysregulation, which are thought to contribute to the etiology of anxiety disorders. Previous studies demonstrate the effects of acute stress in increasing LC …

Swallowing Disrupts Tongue-Jaw Coordination During Chewing In A Rat Model Of Parkinson's Disease, Meejan Palhang, N. Charles, Francois Gould

Rowan-Virtua Research Day

The primary motor symptoms of Parkinson’s disease, including bradykinesia, rigidity, and tremor, are associated with difficulties regulating transitions between motor behaviors due to basal ganglia dysfunction. Chewing and swallowing, which are disordered in most patients with Parkinson’s disease, are two complex motor behaviors which overlap in time and share some neuromuscular components. The objective of this study is to identify how Parkinson’s disease affects the coordination of chewing and swallowing. We hypothesize that as a result of impaired regulation of shift between motor patterns, chewing cycles that occur with a swallow will be more affected that chewing cycles occurring in …

In Vitro Activity Of Eravacycline And Comparator Agents Against Bacterial Pathogens Isolated From Patients With Cancer, Kenneth Rolston, Bahgat Gerges, Lior Nesher, Samuel A Shelburne, Randall Prince, Issam Raad

Faculty, Staff and Student Publications

BACKGROUND: Bacterial infections are common in patients with cancer, and many bacteria have developed resistance to currently used antibiotics.

OBJECTIVES: We evaluated the

METHODS: Antimicrobial susceptibility testing was performed using CLSI-approved methodology and interpretive criteria for 255 Gram-positive and 310 Gram-negative bacteria. MIC and susceptibility percentage were calculated according to CLSI and FDA breakpoints when available.

RESULTS: Eravacycline had potent activity against most Gram-positive bacteria, including MRSA. Of 80 Gram-positive isolates with available breakpoints, 74 (92.5%) were susceptible to eravacycline. Eravacycline had potent activity against most Enterobacterales, including ESBL-producing organisms. Of 230 Gram-negative isolates with available breakpoints, 201 (87.4%) were …

The In Vitro Activity Of Delafloxacin And Comparator Agents Against Bacterial Pathogens Isolated From Patients With Cancer, Bahgat Gerges, Kenneth Rolston, Samuel A Shelburne, Joel Rosenblatt, Randall Prince, Issam Raad

Faculty, Staff and Student Publications

BACKGROUND: Fluoroquinolones are used for infection prevention in high-risk patients with haematological malignancies. Fluoroquinolones are active against many Gram-negative bacilli (GNB) but are less active against Gram-positive organisms. We evaluated the

METHODS: Antimicrobial susceptibility testing and time-kill studies were performed using CLSI-approved methodology and interpretive criteria for 350 Gram-positive organisms and 210 GNB that had been recently isolated from patients with cancer.

RESULTS: Delafloxacin was more active than ciprofloxacin and levofloxacin against

CONCLUSIONS: Delafloxacin is more active than ciprofloxacin and levofloxacin against

Ferroptosis Hijacking By Mycobacterium Tuberculosis, Boyi Gan

Faculty, Staff and Student Publications

A recent study from Nature Communications reveals that Mycobacterium tuberculosis can hijack epigenetic machinery in host cells and induce host cell ferroptosis, which promotes pathogen pathogenicity and spread. These findings also suggest new therapeutic strategies to treat tuberculosis.

Deep Learning-Based Pathology Image Analysis Predicts Cancer Progression Risk In Patients With Oral Leukoplakia, Xinyi Zhang, Frederico O Gleber-Netto, Shidan Wang, Roberta Rayra Martins-Chaves, Ricardo Santiago Gomez, Nadarajah Vigneswaran, Arunangshu Sarkar, William N William, Vassiliki Papadimitrakopoulou, Michelle Williams, Diana Bell, Doreen Palsgrove, Justin Bishop, John V Heymach, Ann M Gillenwater, Jeffrey N Myers, Renata Ferrarotto, Scott M Lippman, Curtis Rg Pickering, Guanghua Xiao

Faculty, Staff and Student Publications

BACKGROUND: Oral leukoplakia (OL) is associated with an increased risk for oral cancer (OC) development. Prediction of OL cancer progression may contribute to decreased OC morbidity and mortality by favoring early intervention. Current OL progression risk assessment approaches face large interobserver variability and is weakly prognostic. We hypothesized that convolutional neural networks (CNN)-based histology image analyses could accelerate the discovery of better OC progression risk models.

METHODS: Our CNN-based oral mucosa risk stratification model (OMRS) was trained to classify a set of nondysplastic oral mucosa (OM) and a set of OC H&E slides. As a result, the OMRS model could …

Recent Advances In Understanding Of Pathogenesis Of Alcohol-Associated Liver Disease, Xiaoqin Wu, Xiude Fan, Tatsunori Miyata, Adam Kim, Christina K Cajigas-Du Ross, Semanti Ray, Emily Huang, Moyinoluwa Taiwo, Rakesh Arya, Jianguo Wu, Laura E Nagy

Faculty, Staff and Student Publications

Alcohol-associated liver disease (ALD) is one of the major diseases arising from chronic alcohol consumption and is one of the most common causes of liver-related morbidity and mortality. ALD includes asymptomatic liver steatosis, fibrosis, cirrhosis, and alcohol-associated hepatitis and its complications. The progression of ALD involves complex cell-cell and organ-organ interactions. We focus on the impact of alcohol on dysregulation of homeostatic mechanisms and regulation of injury and repair in the liver. In particular, we discuss recent advances in understanding the disruption of balance between programmed cell death and prosurvival pathways, such as autophagy and membrane trafficking, in the pathogenesis …

Characterizing Cellular Injury And Inflammation With Aldob-/-Mouse Model Of Mafld, Andy Rashid

All Master's Theses

Metabolic-associated fatty liver disease (MAFLD) affects 1 in 3 people in the US and is a healthcare burden on the order of billions of dollars. MAFLD is characterized by pathological lipid accumulation in the liver, excess production of triglycerides and cholesterol, and export of LDL particles that raise serum lipid levels. These metabolic perturbations can lead to the development of liver fibrosis, chronic inflammation, and insulin resistance. Diagnosing MAFLD prior to fibrosis is crucial for successful intervention and prevention of advanced liver disease and other metabolic complications. Fructose-1Phospahte (F1P) accumulation from fructose overconsumption can drive hepatic lipogenesis and MAFLD progression. …

Analysis Of Immune Intratumor Heterogeneity Highlights Immunoregulatory And Coinhibitory Lymphocytes As Hallmarks Of Recurrence In Stage I Non-Small Cell Lung Cancer, Alejandro Francisco-Cruz, Pedro Rocha, Alexandre Reuben, Santhoshi N Krishnan, Priyam Das, Runzhe Chen, Kelly Quek, Jun Li, Edwin R Parra, Luisa M Solis, Souptik Barua, Mei Jiang, Rossana Lazcano, Chi-Wan Chow, Carmen Behrens, Curtis Gumb, Latasha Little, Junya Fukuoka, Neda Kalhor, Annikka Weissferdt, Humam Kadara, John V Heymach, Stephen Swisher, Boris Sepesi, Arvind Rao, Cesar Moran, Jianhua Zhang, J Jack Lee, Junya Fujimoto, P Andrew Futreal, Ignacio I Wistuba, Christine B Peterson, Jianjun Zhang

Faculty, Staff and Student Publications

Our understanding of the molecular mechanisms underlying postsurgical recurrence of non-small cell lung cancer (NSCLC) is rudimentary. Molecular and T cell repertoire intratumor heterogeneity (ITH) have been reported to be associated with postsurgical relapse; however, how ITH at the cellular level impacts survival is largely unknown. Here we report the analysis of 2880 multispectral images representing 14.2% to 27% of tumor areas from 33 patients with stage I NSCLC, including 17 cases (relapsed within 3 years after surgery) and 16 controls (without recurrence ≥5 years after surgery) using multiplex immunofluorescence. Spatial analysis was conducted to quantify the minimum distance between …

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

Faculty, Staff and Student Publications

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

Associations Between Cannabis, Psychosis, And Schizophrenia In Adolescents, Lauren Moment

Academic Leadership Journal in Student Research

The effects of cannabis use on the brain, mind, and body have been studied for decades. The developing brain, particularly the adolescent and young adult brain, undergoes critical development that makes it especially susceptible to the effects of cannabis use. Among the adverse effects of cannabis use in adolescence and young adulthood, psychosis and psychotic disorders (e.g., schizophrenia) have been examined. The association of cannabis use with schizophrenia was first elucidated in a Swedish study of army conscripts. Specifically, conscripts reported their cannabis use exposure and were followed longitudinally to assess the emergence of schizophrenia. The authors found that those …

Identifying A Glucocorticoid-Activated Gpcr That Rapidly And Non-Genomically Increases Camp Levels In Mammalian Cells, Francisco Nunez

Pharmaceutical Sciences (PhD) Dissertations

Glucocorticoids (GCs) are steroid hormones that regulate diverse physiological processes. Synthetic versions of GCs are commonly used to treat inflammatory diseases such as asthma by modulating gene expression to suppressing several inflammatory activities. However, it is estimated that 5-10% of asthmatics are unresponsive to GCs, which may be explained by receptor desensitization and/or the presence of a neutrophilic endotype. One understudied phenomenon of GCs is their ability to induce rapid, non-genomic actions. For example, GCs can acutely modulate calcium concentrations levels, induce smooth muscle relaxation and modulate nitric oxide synthase activity, within minutes and sometimes seconds, which is too rapid …

Impact Forces And Patterns Of Axonal Injury Differ Between Two Models Of Tbi, Edward Lai, David M Devilbiss

Rowan-Virtua Research Day

Traumatic brain injury (TBI) affects approximately 3.8 million Americans a year and results in complex neuropathological and neurocognitive sequelae. Animal models of TBI attempt to replicate the impact forces and pathology of injury in humans. However, in these models, the forces generated at the time of impact are poorly understood. Nonetheless, a variety of shear and strain forces generated at the time of impact can produce diffuse axonal injury. Injury to axons and neurons across a variety of brain regions resulting from axonal injury underlies the cognitive and behavioral impairments observed after TBI. Three critical brain regions, the corpus callosum …

A Preliminary Report: The Hippocampus And Surrounding Temporal Cortex Of Patients With Schizophrenia Have Impaired Blood-Brain Barrier, Eric L. Goldwaser, Randel L. Swanson, Edgardo J. Arroyo, Venkat Venkataraman, Mary C. Kosciuk, Robert G. Nagele, L. Elliot Hong, Nimish K. Acharya

Rowan-Virtua Research Day

Schizophrenia (SZ) is one of the most severe forms of mental illness, yet mechanisms remain unclear. A widely established brain finding in SZ is hippocampal atrophy, and a coherent explanation similarly is lacking. Epidemiological evidence suggests increased cerebrovascular and cardiovascular complications in SZ independent of lifestyle and medication, pointing to disease-specific pathology. Endothelial cell contributions to blood-brain barrier (BBB) compromise may influence neurovascular unit and peripheral vascular function, and we hypothesize that downstream functional and structural abnormalities may be explained by impaired BBB.

Paratesticular Solitary Fibrous Tumour Mimicking Cellular Angiofibroma: An Unusual Morphology And Rare Site, Madiha Bilal Qureshi, Muhammad Usman, Qurratulain Chundriger, Nasir Uddin

Department of Pathology and Laboratory Medicine

Solitary fibrous tumour (SFT) is a ubiquitous benign mesenchymal tumour of fibroblastic origin, which occurs most often in middle-aged adults. It usually presents as lung mass originating from pleura, but extrapleural occurrence is also common. Tumour is characterised by hypo- and hyper-cellular areas of spindle-shaped cells, arranged in haphazard manner with dispersed staghorn-shaped vessels. Surgical excision is the curative treatment. SFTs of the primary testicular or paratesticular region are extremely rare, but they exhibit histologic findings similar to SFTs originating at other body sites. Here, we report the case of a paratesticular SFT in a 37-year male, who presented with …

Myelodysplastic/Myeloproliferative Neoplasms-Unclassifiable With Isolated Isochromosome 17q Represents A Distinct Clinico-Biologic Subset: A Multi-Institutional Collaborative Study From The Bone Marrow Pathology Group, Rashmi Kanagal-Shamanna, Attilio Orazi, Robert P Hasserjian, Daniel A Arber, Kaaren Reichard, Eric D Hsi, Adam Bagg, Heesun Joyce Rogers, Julia Geyer, Faezeh Darbaniyan, Kim-Anh Do, Kyle M Devins, Olga Pozdnyakova, Tracy I George, Paola Dal Cin, Patricia T Greipp, Mark J Routbort, Keyur Patel, Guillermo Garcia-Manero, Srdan Verstovsek, L Jeffrey Medeiros, Sa A Wang, Carlos Bueso-Ramos

Faculty, Staff and Student Publications

Classification of myeloid neoplasms with isolated isochromosome i(17q) [17p deletion with inherent monoallelic TP53 loss plus 17q duplication] is controversial. Most cases fall within the WHO unclassifiable myelodysplastic/myeloproliferative neoplasms (MDS/MPN-U) category. The uniformly dismal outcomes warrant better understanding of this entity. We undertook a multi-institutional retrospective study of 92 adult MDS/MPN-U cases from eight institutions. Twenty-nine (32%) patients had isolated i(17q) [MDS/MPN-i(17q)]. Compared to MDS/MPN without i(17q), MDS/MPN-i(17q) patients were significantly younger, had lower platelet and absolute neutrophil counts, and higher frequency of splenomegaly and circulating blasts. MDS/MPN-i(17q) cases showed frequent bilobed neutrophils (75% vs. 23%; P = 0.03), hypolobated …