Digital Commons Network^™

Glioma And The Gut-Brain Axis: Opportunities And Future Perspectives, Antonio Dono, Jack Nickles, Ana G Rodriguez-Armendariz, Braden C Mcfarland, Nadim J Ajami, Leomar Y Ballester, Jennifer A Wargo, Yoshua Esquenazi

Faculty, Staff and Student Publications

The gut-brain axis has presented a valuable new dynamic in the treatment of cancer and central nervous system (CNS) diseases. However, little is known about the potential role of this axis in neuro-oncology. The goal of this review is to highlight potential implications of the gut-brain axis in neuro-oncology, in particular gliomas, and future areas of research. The gut-brain axis is a well-established biochemical signaling axis that has been associated with various CNS diseases. In neuro-oncology, recent studies have described gut microbiome differences in tumor-bearing mice and glioma patients compared to controls. These differences in the composition of the microbiome …

Residual Cancer Burden After Neoadjuvant Chemotherapy And Long-Term Survival Outcomes In Breast Cancer: A Multicentre Pooled Analysis Of 5161 Patients, Christina Yau, Marie Osdoit, Marieke Van Der Noordaa, Sonal Shad, Jane Wei, Diane De Croze, Anne-Sophie Hamy, Marick Laé, Fabien Reyal, Gabe S Sonke, Tessa G Steenbruggen, Maartje Van Seijen, Jelle Wesseling, Miguel Martín, Maria Del Monte-Millán, Sara López-Tarruella, Judy C Boughey, Matthew P Goetz, Tanya Hoskin, Rebekah Gould, Vicente Valero, Stephen B Edge, Jean E Abraham, John M S Bartlett, Carlos Caldas, Janet Dunn, Helena Earl, Larry Hayward, Louise Hiller, Elena Provenzano, Stephen-John Sammut, Jeremy S Thomas, David Cameron, Ashley Graham, Peter Hall, Lorna Mackintosh, Fang Fan, Andrew K Godwin, Kelsey Schwensen, Priyanka Sharma, Angela M Demichele, Kimberly Cole, Lajos Pusztai, Mi-Ok Kim, Laura J Van 'T Veer, Laura J Esserman, W Fraser Symmans

Faculty, Staff and Student Publications

Background: Previous studies have independently validated the prognostic relevance of residual cancer burden (RCB) after neoadjuvant chemotherapy. We used results from several independent cohorts in a pooled patient-level analysis to evaluate the relationship of RCB with long-term prognosis across different phenotypic subtypes of breast cancer, to assess generalisability in a broad range of practice settings.

Methods: In this pooled analysis, 12 institutes and trials in Europe and the USA were identified by personal communications with site investigators. We obtained participant-level RCB results, and data on clinical and pathological stage, tumour subtype and grade, and treatment and follow-up in November, 2019, …

B Cells Are Required To Generate Optimal Anti-Melanoma Immunity In Response To Checkpoint Blockade, Shubhra Singh, Jason Roszik, Neeraj Saini, Vipul Kumar Singh, Karishma Bavisi, Zhiqiang Wang, Long T Vien, Zixi Yang, Suprateek Kundu, Richard E Davis, Laura Bover, Adi Diab, Sattva S Neelapu, Willem W Overwijk, Kunal Rai, Manisha Singh

Faculty, Staff and Student Publications

Immunotherapies such as checkpoint blockade therapies are known to enhance anti-melanoma CD8+ T cell immunity, but only a fraction of patients treated with these therapies achieve durable immune response and disease control. It may be that CD8+ T cells need help from other immune cells to generate effective and long-lasting anti-tumor immunity or that CD8+ T cells alone are insufficient for complete tumor regression and cure. Melanoma contains significant numbers of B cells; however, the role of B cells in anti-melanoma immunity is controversial. In this study, B16 melanoma mouse models were used to determine the role of B cells …

Automated Segmentation Of Colorectal Liver Metastasis And Liver Ablation On Contrast-Enhanced Ct Images, Brian M Anderson, Bastien Rigaud, Yuan-Mao Lin, A Kyle Jones, Hynseon Christine Kang, Bruno C Odisio, Kristy K Brock

Faculty, Staff and Student Publications

Objectives: Colorectal cancer (CRC), the third most common cancer in the USA, is a leading cause of cancer-related death worldwide. Up to 60% of patients develop liver metastasis (CRLM). Treatments like radiation and ablation therapies require disease segmentation for planning and therapy delivery. For ablation, ablation-zone segmentation is required to evaluate disease coverage. We hypothesize that fully convolutional (FC) neural networks, trained using novel methods, will provide rapid and accurate identification and segmentation of CRLM and ablation zones.

Methods: Four FC model styles were investigated: Standard 3D-UNet, Residual 3D-UNet, Dense 3D-UNet, and Hybrid-WNet. Models were trained on 92 patients from …

Contemporary Evidence On Colorectal Liver Metastases Ablation: Toward A Paradigm Shift In Locoregional Treatment, Yuan-Mao Lin, Reto Bale, Kristy K Brock, Bruno C Odisio

Faculty, Staff and Student Publications

Image-guided percutaneous ablation techniques represent an attractive local therapy for the treatment of colorectal liver metastases (CLM) given its low risk of severe complications, which allows for early initiation of adjuvant therapies and spare functional liver parenchyma, allowing repeated treatments at the time of recurrence. However, ablation does not consistently achieve similar oncological outcomes to surgery, with the latter being currently considered the first-line local treatment modality in international guidelines. Recent application of computer-assisted ablation planning, guidance, and intra-procedural response assessment has improved percutaneous ablation outcomes. In addition, the evolving understanding of tumor molecular profiling has brought to light several …

Genetic Studies On Mammalian Dna Methyltransferases, Jiameng Dan, Taiping Chen

Faculty, Staff and Student Publications

Cytosine methylation at the C5-position-generating 5-methylcytosine (5mC)-is a DNA modification found in many eukaryotic organisms, including fungi, plants, invertebrates, and vertebrates, albeit its levels vary greatly in different organisms. In mammals, cytosine methylation occurs predominantly in the context of CpG dinucleotides, with the majority (60-80%) of CpG sites in their genomes being methylated. DNA methylation plays crucial roles in the regulation of chromatin structure and gene expression and is essential for mammalian development. Aberrant changes in DNA methylation and genetic alterations in enzymes and regulators involved in DNA methylation are associated with various human diseases, including cancer and developmental disorders. …

Loss Of Mmr And Tgfbr2 Increases The Susceptibility To Microbiota-Dependent Inflammation-Associated Colon Cancer, Elena Tosti, Ana S Almeida, Tam T T Tran, Mariel Barbachan E Silva, Pilib Ó Broin, Robert Dubin, Ken Chen, Amanda P Beck, Andrew S Mclellan, Eduardo Vilar, Aaron Golden, Paul W O'Toole, Winfried Edelmann

Faculty, Staff and Student Publications

Background and aims: Mutations in DNA mismatch repair (MMR) genes are causative in Lynch syndrome and a significant proportion of sporadic colorectal cancers (CRCs). MMR-deficient (dMMR) CRCs display increased mutation rates, with mutations frequently accumulating at short repetitive DNA sequences throughout the genome (microsatellite instability). The TGFBR2 gene is one of the most frequently mutated genes in dMMR CRCs. Therefore, we generated an animal model to study how the loss of both TGFBR2 signaling impacts dMMR-driven intestinal tumorigenesis in vivo and explore the impact of the gut microbiota.

Methods: We generated VCMsh2/Tgfbr2 mice in which Msh2loxP and Tgfbr2loxP alleles are …

Recent Advances On Dna Base Flipping: A General Mechanism For Writing, Reading, And Erasing Dna Modifications, Ren Ren, John R Horton, Samuel Hong, Xiaodong Cheng

Faculty, Staff and Student Publications

The modification of DNA bases is a classic hallmark of epigenetics. Four forms of modified cytosine-5-methylcytosine, 5-hydroxymethylcytosine, 5-formylcytosine, and 5-carboxylcytosine-have been discovered in eukaryotic DNA. In addition to cytosine carbon-5 modifications, cytosine and adenine methylated in the exocyclic amine-N4-methylcytosine and N6-methyladenine-are other modified DNA bases discovered even earlier. Each modified base can be considered a distinct epigenetic signal with broader biological implications beyond simple chemical changes. Since 1994, several crystal structures of proteins and enzymes involved in writing, reading, and erasing modified bases have become available. Here, we present a structural synopsis of writers, readers, and erasers of the modified …

Use Of The Fully Spectroscopic Pixelated Cadmium Telluride Detector For Benchtop X-Ray Fluorescence Computed Tomography, Sandun Jayarathna, Hem Moktan, Sang Hyun Cho

Faculty, Staff and Student Publications

In this work, we integrated a commercially-available fully-spectroscopic pixelated cadmium telluride (CdTe) detector system as a two-dimensional (2D) array detector into our existing benchtop cone-beam x-ray fluorescence computed tomography (XFCT) system. After integrating this detector, known as High-Energy X-ray Imaging Technology (HEXITEC), we performed quantitative imaging of gold nanoparticle (GNP) distribution in a small animal-sized phantom using our benchtop XFCT system. Owing to the upgraded detector component within our benchtop XFCT system, we were able to conduct this phantom imaging in an unprecedented manner by volumetric XFCT scans followed by XFCT image reconstruction in 3D. The current results showed that …

A Phase I, Open-Label, Dose-Escalation Study Of The Ox40 Agonist Ivuxolimab In Patients With Locally Advanced Or Metastatic Cancers, Adi Diab, Omid Hamid, John A Thompson, Willeke Ros, Ferry A L M Eskens, Toshihiko Doi, Siwen Hu-Lieskovan, Samuel J Klempner, Bishu Ganguly, Catherine Fleener, Xiao Wang, Tenshang Joh, Ken Liao, Shahram Salek-Ardakani, Carrie Turich Taylor, Jeffrey Chou, Anthony B El-Khoueiry

Faculty, Staff and Student Publications

PURPOSE: Stimulation of effector T cells is an appealing immunotherapeutic approach in oncology. OX40 (CD134) is a costimulatory receptor expressed on activated CD4

PATIENTS AND METHODS: Adult patients (

RESULTS: The most common all-causality adverse events were fatigue (46.2%), nausea (28.8%), and decreased appetite (25.0%). Of 31 treatment-related adverse events, 30 (96.8%) were grade ≤2. No dose-limiting toxicities occurred. Ivuxolimab exposure increased in a dose-proportionate manner from 0.3 to 10 mg/kg. Full peripheral blood target engagement occurred at ≥0.3 mg/kg. Three (5.8%) patients achieved a partial response, and disease control was achieved in 56% of patients. Increased CD4

CONCLUSIONS: Ivuxolimab …

Inhibition Of The Cd47-Sirpα Axis For Cancer Therapy: A Systematic Review And Meta-Analysis Of Emerging Clinical Data, Ji Son, Rodney Cheng-En Hsieh, Heather Y Lin, Kate J Krause, Ying Yuan, Amadeo B Biter, James Welsh, Michael A Curran, David S Hong

Faculty, Staff and Student Publications

CD47-SIRPα interaction acts as a "don't eat me" signal and is exploited by cancer to downregulate innate and adaptive immune surveillance. There has been intense interest to develop a mechanism of blockade, and we aimed to analyze the emerging data from early clinical trials. We performed a systematic review and meta-analysis of relevant databases and conference abstracts including clinical trials using CD47 and/or SIRPα inhibitors in cancer treatment. Nonlinear mixed models were applied for comparison of response and toxicity. We retrieved 317 articles, 24 of which were eligible. These included 771 response-evaluable patients with hematologic (47.1%) and solid tumors (52.9%). …

Cell-Directed Aptamer Therapeutic Targeting For Cancers Including Those Within The Central Nervous System, Jun Wei, Renduo Song, Aria Sabbagh, Anantha Marisetty, Neal Shukla, Dexing Fang, Hinda Najem, Martina Ott, James Long, Lijie Zhai, Maciej S Lesniak, Charles David James, Leonidas Platanias, Michael Curran, Amy B Heimberger

Faculty, Staff and Student Publications

Osteopontin (OPN) is produced by tumor cells as well as by myeloid cells and is enriched in the tumor microenvironment (TME) of many cancers. Given the roles of OPN in tumor progression and immune suppression, we hypothesized that targeting OPN with aptamers that have high affinity and specificity could be a promising therapeutic strategy. Bi-specific aptamers targeting ligands for cellular internalization were conjugated to siRNAs to suppress OPN were created, and therapeutic leads were selected based on target engagement and

Cgas-Sting Pathway Targeted Therapies And Their Applications In The Treatment Of High-Grade Glioma, Shashwat Tripathi, Hinda Najem, Akanksha Sanjay Mahajan, Peng Zhang, Justin T Low, Alexander H Stegh, Michael A Curran, David M Ashley, Charles David James, Amy B Heimberger

Faculty, Staff and Student Publications

Median survival of patients with glioblastoma (GBM) treated with standard of care which consists of maximal safe resection of the contrast-enhancing portion of the tumor followed by radiation therapy with concomitant adjuvant temozolomide (TMZ) remains 15 months. The tumor microenvironment (TME) is known to contain immune suppressive myeloid cells with minimal effector T cell infiltration. Stimulator of interferon genes (STING) is an important activator of immune response and results in production of Type 1 interferon and antigen presentation by myeloid cells. This review will discuss important developments in STING agonists, potential biomarkers for STING response, and new combinatorial therapeutic approaches …

Impact Of Psychosocial, Behavioral And Lifestyle Factors On Subjective Cognitive Complaints And Perceived Quality Of Life In A Large Cohort Of Italian Breast Cancer Patients, Thomas West, Corrado Cavallero, Rita Ceccherini, Silva Foladore, Daniele Generali, Francesco Versace, Bruna Scaggiante

Faculty, Staff and Student Publications

The impact of psychosocial and behavioral factors on Cancer Related Cognitive Impairment manifestations is still under debate. Study's purpose is to determine the prevalence rate of cancer related cognitive impairment in a cohort of Italian breast cancer patients and to evaluate the implication of specific behavioral factors. For these purposes, a total of 233 women (106 breast cancer patients and 127 age-matched controls without oncological diagnosis) completed a questionnaire investigating cognitive functionality (FACT-Cog v3.0), sociodemographic characteristics, clinical information, psychosocial and behavioral factors (cognitive reserve, sleep quality, dietary habits, physical activity). The results indicated a higher prevalence rate of subjective cognitive …

Single-Incision Laparoscopic Splenectomy In Children With Massive Splenomegaly: A Prospective, Monocentric Pilot Study, Congjun Wang, Cheng Su, Chao Chen, Xianming Tang, Hong Wang, Wei Li, Yanqiang Li, Qiang Liu, Peng Chen, Yong Li, Yige Luo

Faculty, Staff and Student Publications

BACKGROUND: Single-incision laparoscopic splenectomy (SILS) remains a challenging procedure because of the technical difficulty. In this prospective study, we aimed to evaluate the efficacy and safety of SILS in children with massive splenomegaly.

METHODS: Pediatric patients with massive splenomegaly were recruited for SILS in a university-affiliated hospital. The data on patient demographics, clinical features, operative variables, and perioperative outcomes were collected prospectively and analyzed. According to the different surgical instruments, the patients were randomly assigned into two groups: the SILS with straight surgical instrument (SILS-S) group and the SILS with curved surgical instrument (SILS-C) group. A two-group comparative analysis was …

An Autoencoder-Based Deep Learning Method For Genotype Imputation, Meng Song, Jonathan Greenbaum, Joseph Luttrell, Weihua Zhou, Chong Wu, Zhe Luo, Chuan Qiu, Lan Juan Zhao, Kuan-Jui Su, Qing Tian, Hui Shen, Huixiao Hong, Ping Gong, Xinghua Shi, Hong-Wen Deng, Chaoyang Zhang

Faculty, Staff and Student Publications

Genotype imputation has a wide range of applications in genome-wide association study (GWAS), including increasing the statistical power of association tests, discovering trait-associated loci in meta-analyses, and prioritizing causal variants with fine-mapping. In recent years, deep learning (DL) based methods, such as sparse convolutional denoising autoencoder (SCDA), have been developed for genotype imputation. However, it remains a challenging task to optimize the learning process in DL-based methods to achieve high imputation accuracy. To address this challenge, we have developed a convolutional autoencoder (AE) model for genotype imputation and implemented a customized training loop by modifying the training process with a …

Magi1 Inhibits Interferon Signaling To Promote Influenza A Infection, Yin Wang, Jun-Ichi Abe, Khanh M Chau, Yongxing Wang, Hang Thi Vu, Loka Reddy Velatooru, Fahad Gulraiz, Masaki Imanishi, Venkata S K Samanthapudi, Minh T H Nguyen, Kyung Ae Ko, Ling-Ling Lee, Tamlyn N Thomas, Elizabeth A Olmsted-Davis, Sivareddy Kotla, Keigi Fujiwara, John P Cooke, Di Zhao, Scott E Evans, Nhat-Tu Le

Faculty, Staff and Student Publications

We have shown that membrane-associated guanylate kinase with inverted domain structure-1 (MAGI1), a scaffold protein with six PSD95/DiscLarge/ZO-1 (PDZ) domains, is involved in the regulation of endothelial cell (EC) activation and atherogenesis in mice. In addition to causing acute respiratory disease, influenza A virus (IAV) infection plays an important role in atherogenesis and triggers acute coronary syndromes and fatal myocardial infarction. Therefore, the aim of this study is to investigate the function and regulation of MAGI1 in IAV-induced EC activation. Whereas, EC infection by IAV increases MAGI1 expression, MAGI1 depletion suppresses IAV infection, suggesting that the induction of MAGI1 may …

Engineered Cord Blood Megakaryocytes Evade Killing By Allogeneic T-Cells For Refractory Thrombocytopenia, Bijender Kumar, Vahid Afshar-Kharghan, Mayela Mendt, Robert Sackstein, Mark R Tanner, Uday Popat, Jeremy Ramdial, May Daher, Juan Jimenez, Rafet Basar, Luciana Melo Garcia, Mayra Shanley, Mecit Kaplan, Xinhai Wan, Vandana Nandivada, Francia Reyes Silva, Vernikka Woods, April Gilbert, Ricardo Gonzalez-Delgado, Sunil Acharya, Paul Lin, Hind Rafei, Pinaki Prosad Banerjee, Elizabeth J Shpall

Faculty, Staff and Student Publications

The current global platelet supply is often insufficient to meet all the transfusion needs of patients, in particular for those with alloimmune thrombocytopenia. To address this issue, we have developed a strategy employing a combination of approaches to achieve more efficient production of functional megakaryocytes (MKs) and platelets collected from cord blood (CB)-derived CD34+ hematopoietic cells. This strategy is based on ex-vivo expansion and differentiation of MKs in the presence of bone marrow niche-mimicking mesenchymal stem cells (MSCs), together with two other key components: (1) To enhance MK polyploidization, we used the potent pharmacological Rho-associated coiled-coil kinase (ROCK) inhibitor, KD045, …

Regulation Of T Cell Function By Protein S-Acylation, Savannah J West, Darren Boehning, Askar M Akimzhanov

Faculty, Staff and Student Publications

S-acylation, the reversible lipidation of free cysteine residues with long-chain fatty acids, is a highly dynamic post-translational protein modification that has recently emerged as an important regulator of the T cell function. The reversible nature of S-acylation sets this modification apart from other forms of protein lipidation and allows it to play a unique role in intracellular signal transduction. In recent years, a significant number of T cell proteins, including receptors, enzymes, ion channels, and adaptor proteins, were identified as S-acylated. It has been shown that S-acylation critically contributes to their function by regulating protein localization, stability and protein-protein interactions. …

Morphological Description Of Laevicaulisstuhlmanni (Simroth, 1895) (Pulmonata, Veronicellidae) From Egypt, Reham Fathey Ali, David G Robinson, Fabio Liberto

Faculty, Staff and Student Publications

BACKGROUND: Terrestrial slugs and snails are increasingly becoming serious pests of agricultural, horticultural and ornamental plants in Egypt, resulting in major economic losses.

NEW INFORMATION: This paper provides a detailed morphological and anatomical description of the veronicellid slug Laevicaulisstuhlmanni (Simroth, 1895) that has been recently recorded from Egypt. This population from Egypt is compared with Laevicaulis populations recently reported and described from Libya as L.striatus (Simroth, 1896) and with available data in literature. Some notes and a distribution map of the veronicellids introduced in north-eastern Africa are provided.

The Potential Of Biology-Guided Radiation Therapy In Thoracic Cancer: A Preliminary Treatment Planning Study, Steven N Seyedin, Rostem Bassalow, Osama R Mawlawi, Lehendrick M Turner, Roshal R Patel, Samuel R Mazin, Oluwaseyi M Oderinde, Yevgen Voronenko, Cody A Wages, Peter D Olcott, Joe Y Chang, Peter A Balter, James W Welsh

Faculty, Staff and Student Publications

PURPOSE: We investigated the feasibility of biology-guided radiotherapy (BgRT), a technique that utilizes real-time positron emission imaging to minimize tumor motion uncertainties, to spare nearby organs at risk.

METHODS: Volumetric modulated arc therapy (VMAT), intensity-modulated proton (IMPT) therapy, and BgRT plans were created for a paratracheal node recurrence (case 1; 60 Gy in 10 fractions) and a primary peripheral left upper lobe adenocarcinoma (case 2; 50 Gy in four fractions).

RESULTS: For case 1, BgRT produced lower bronchus V40 values compared to VMAT and IMPT. For case 2, total lung V20 was lower in the BgRT case compared to VMAT …

Leveraging Deep Learning-Based Segmentation And Contours-Driven Deformable Registration For Dose Accumulation In Abdominal Structures, Molly M Mcculloch, Guillaume Cazoulat, Stina Svensson, Sergii Gryshkevych, Bastien Rigaud, Brian M Anderson, Ezgi Kirimli, Brian De, Ryan T Mathew, Mohamed Zaid, Dalia Elganainy, Christine B Peterson, Peter Balter, Eugene J Koay, Kristy K Brock

Faculty, Staff and Student Publications

PURPOSE: Discrepancies between planned and delivered dose to GI structures during radiation therapy (RT) of liver cancer may hamper the prediction of treatment outcomes. The purpose of this study is to develop a streamlined workflow for dose accumulation in a treatment planning system (TPS) during liver image-guided RT and to assess its accuracy when using different deformable image registration (DIR) algorithms.

MATERIALS AND METHODS: Fifty-six patients with primary and metastatic liver cancer treated with external beam radiotherapy guided by daily CT-on-rails (CTOR) were retrospectively analyzed. The liver, stomach and duodenum contours were auto-segmented on all planning CTs and daily CTORs …

A Transgenic Bacterial Artificial Chromosome Approach To Identify Regulatory Regions That Direct Amhr2 And Osterix Expression In Müllerian Duct Mesenchyme, Malcolm M Moses, Rachel D Mullen, Daniel I Idowu, Peter Maye, Soazik P Jamin, Richard R Behringer

Faculty, Staff and Student Publications

A transgenic mouse approach using bacterial artificial chromosomes (BAC) was used to identify regulatory regions that direct Müllerian duct expression for Amhr2 and Osterix (Osx, also known as Sp7). Amhr2 encodes the receptor that mediates anti-Müllerian hormone (AMH) signaling for Müllerian duct regression in male embryos. Amhr2 is expressed in the Müllerian duct mesenchyme of both male and female embryos. A ∼147-kb BAC clone containing the Amhr2 locus was used to generate transgenic mice. The transgene was able to rescue the block in Müllerian duct regression of Amhr2-null males, suggesting that the BAC clone contains regulatory …

Genetic Variants Associated With Circulating Liver Injury Markers In Mexican Americans, A Population At Risk For Non-Alcoholic Fatty Liver Disease, Caroline M Sabotta, Suet-Ying Kwan, Lauren E Petty, Jennifer E Below, Aron Joon, Peng Wei, Susan P Fisher-Hoch, Joseph B Mccormick, Laura Beretta

Faculty, Staff and Student Publications

Objective: Mexican Americans are disproportionally affected by non-alcoholic fatty liver disease (NAFLD), liver fibrosis and hepatocellular carcinoma. Noninvasive means to identify those in this population at high risk for these diseases are urgently needed. Approach: The Cameron County Hispanic Cohort (CCHC) is a population-based cohort with high rates of obesity (51%), type 2 diabetes (28%) and NAFLD (49%). In a subgroup of 564 CCHC subjects, we evaluated 339 genetic variants previously reported to be associated with liver injury markers aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in United Kingdom and Japanese cohorts. Results: Association was confirmed for 86 variants. Among …

Complexities And Complications Of Extreme Obesity, Haval Ali, Udit Naik, Michelle Mcdonald, Mohammad Almosa, Karen Horn, Alexis Staines, Louis Maximilian Buja

Faculty, Staff and Student Publications

Obesity is a common chronic disorder and has detrimental long-term consequences if left untreated. Herein, we report a case of a young lady who suffered from morbid obesity and many of its consequences, and we present a literature review of these complications. While the cause of obesity is multifactorial, the genetic component is particularly important in the pathophysiology of marked obesity. Resistance to Leptin is considered one of the main causes of obesity. There is a unique relationship between polycystic ovary syndrome and obesity, as observed in our case. Obesity is associated with cardiovascular and lung diseases such as heart …

Patients' Preferences For Androgen Deprivation Therapy In The Treatment Of Intermediate-Risk Prostate Cancer, Brian De, Lisa M Lowenstein, Kelsey L Corrigan, Lauren M Andring, Deborah A Kuban, Scott B Cantor, Robert J Volk, Karen E Hoffman

Faculty, Staff and Student Publications

Background. For men with intermediate-risk prostate cancer (IRPC), adding short-term androgen deprivation therapy (ADT) to external beam radiation therapy (EBRT) has shown efficacy, but men are often reluctant to accept it because of its impact on quality of life. Methods. We conducted time tradeoffs (score of 1 = perfect health and 0 = death) and probability tradeoffs with patients aged 51 to 78 y who had received EBRT for IRPC within the past 2 y. Of 40 patients, 20 had received 6 mo of ADT and 20 had declined. Utility assessments explored 4 ADT-related side effects: hot flashes, fatigue, loss …

Predicting Clinical Response To Everolimus In Er+ Breast Cancers Using Machine-Learning, Aritro Nath, Patrick A Cosgrove, Jeffrey T Chang, Andrea H Bild

Faculty, Staff and Student Publications

Endocrine therapy remains the primary treatment choice for ER+ breast cancers. However, most advanced ER+ breast cancers ultimately develop resistance to endocrine. This acquired resistance to endocrine therapy is often driven by the activation of the PI3K/AKT/mTOR signaling pathway. Everolimus, a drug that targets and inhibits the mTOR complex has been shown to improve clinical outcomes in metastatic ER+ breast cancers. However, there are no biomarkers currently available to guide the use of everolimus in the clinic for progressive patients, where multiple therapeutic options are available. Here, we utilized gene expression signatures from 9 ER+ breast cancer cell lines and …

The Impact Of Merkel Cell Polyomavirus Positivity On Prognosis Of Merkel Cell Carcinoma: A Systematic Review And Meta-Analysis, Aimin Yang, Wilson Adrian Wijaya, Lei Yang, Yinhai He, Ying Cen, Junjie Chen

Faculty, Staff and Student Publications

INTRODUCTION: There are numerous findings over the past decade have indicated that Merkel cell carcinoma (MCC) may have two pathways of pathogenesis: one related to ultraviolet irradiation and the other to the Merkel cell polyomavirus (MCPyV). However, the predictive and clinicopathological value of MCPyV positivity in MCC patients is still debatable. This article aims to examine the most recent data regarding this issue.

METHODS: The thorough literature searches were conducted in the Medline Ovid, PubMed, Web of Science, the Cochrane CENTRAL Databases, and Embase Databases until December 31, 2021. The associations between overall survival (OS), Merkel cell carcinoma-specific survival (MSS), …

Left Ventricular Dysfunction In Outpatients With Frequent Ventricular Premature Complexes, Kyoung-Min Park, Sung Il Im, Sung Ho Lee, Hye Bin Gwag, Youngjun Park, Seung-Jung Park, June Soo Kim, Young Keun On

The Texas Heart Institute Journal

Frequent ventricular premature complexes (VPCs) and VPC QRS duration are risk factors for left ventricular (LV) dysfunction. To determine which clinical characteristics and electrocardiographic features are associated with LV dysfunction (ejection fraction,

We identified 412 consecutive outpatients (mean age, 54.7 ± 16.8 yr; 227 women [55.1%]) who were diagnosed with frequent VPCs and had no structural heart disease from January 2010 through December 2017. Available transthoracic echocardiograms and 24-hour Holter monitoring data were evaluated to correlate the occurrence of VPCs and symptoms.

Typical VPC-related symptoms (palpitations or dropped beats) were observed in 251 patients (61.1%). Electrocardiograms revealed VPCs with a …

Iatrogenic Arteriovenous Fistula After Distal Transradial Coronary Angiography, Wah Wah Htun, Myo Maw, Tak Kwan

The Texas Heart Institute Journal

No abstract provided.