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Addressing Unprofessional Behaviors In The Clinical Learning Environment: Lessons From A Multi-Year Virtual, Intergenerational, Interdisciplinary Workshop, Stacey Rose, Anita Kusnoor, Phuong Huynh, Jocelyn Greely, Yesenia Rojas-Khalil, Doris Kung, Anne Gill, Nadia Ismail, Nital Appelbaum Dec 2024

Addressing Unprofessional Behaviors In The Clinical Learning Environment: Lessons From A Multi-Year Virtual, Intergenerational, Interdisciplinary Workshop, Stacey Rose, Anita Kusnoor, Phuong Huynh, Jocelyn Greely, Yesenia Rojas-Khalil, Doris Kung, Anne Gill, Nadia Ismail, Nital Appelbaum

Faculty, Staff and Students Publications

INTRODUCTION: Optimizing the clinical learning environment (CLE) is a medical education priority nationwide.

MATERIALS AND METHODS: We developed a virtual, one-hour workshop engaging students, housestaff and faculty in small-group discussions of five case scenarios adapted from reported unprofessional behaviors in the CLE, plus didactics regarding mistreatment, microaggressions and bystander interventions.

RESULTS: Over two sessions (2021-2022), we engaged 340 students and 73 faculty/housestaff facilitators. Post-session surveys showed significant improvement in participants' ability to recognize and respond to challenges in the CLE.

DISCUSSION: Our innovative workshop, including scenarios derived from institutional reports of unprofessional behaviors, advanced participants' knowledge and commitment to improve …


The Significance Of Aldehyde Dehydrogenase 1 In Cancers, Anh L. Nguyen, Caroline O. B. Facey, Bruce M. Boman Dec 2024

The Significance Of Aldehyde Dehydrogenase 1 In Cancers, Anh L. Nguyen, Caroline O. B. Facey, Bruce M. Boman

Department of Pharmacology and Experimental Therapeutics Faculty Papers

The goal of this paper is to discuss the role of ALDH isozymes in different cancers, review advances in ALDH1-targeting cancer therapies, and explore a mechanism that explains how ALDH expression becomes elevated during cancer development. ALDH is often overexpressed in cancer, and each isoform has a unique expression pattern and a distinct role in different cancers. The abnormal expression of ALDHs in different cancer types (breast, colorectal, lung, gastric, cervical, melanoma, prostate, and renal) is presented and correlated with patient prognosis. ALDH plays a significant role in various cellular functions, such as metabolism, oxidative stress response, detoxification, and cellular …


Single Unit-Derived Connectivity Networks In Tuberous Sclerosis Complex Reveal Propensity For Network Hypersynchrony Driven By Tuber-Tuber Interactions., Aswin Chari, Amanda E Hernan, J Matthew Mahoney, Rachel Thornton, M Zubair Tahir, Martin M Tisdall, Rod C Scott Dec 2024

Single Unit-Derived Connectivity Networks In Tuberous Sclerosis Complex Reveal Propensity For Network Hypersynchrony Driven By Tuber-Tuber Interactions., Aswin Chari, Amanda E Hernan, J Matthew Mahoney, Rachel Thornton, M Zubair Tahir, Martin M Tisdall, Rod C Scott

Faculty Research 2024

Network hypersynchrony is emerging as an important system-level mechanism underlying seizures, as well as cognitive and behavioural impairments, in children with structural brain abnormalities. We investigated patterns of single neuron action potential behaviour in 206 neurons recorded from tubers, transmantle tails of tubers and normal looking cortex in 3 children with tuberous sclerosis. The patterns of neuronal firing on a neuron-by-neuron (autocorrelation) basis did not reveal any differences as a function of anatomy. However, at the level of functional networks (cross-correlation), there is a much larger propensity towards hypersynchrony of tuber-tuber neurons than in neurons from any other anatomical site. …


Oxidized Phospholipid And Transcriptomic Signatures Of Thc-Related Vaping Associated Lung Injury, Tomeka L Suber, Zeyu Xiong, Janet S Lee, Et Al. Dec 2024

Oxidized Phospholipid And Transcriptomic Signatures Of Thc-Related Vaping Associated Lung Injury, Tomeka L Suber, Zeyu Xiong, Janet S Lee, Et Al.

2020-Current year OA Pubs

E-cigarette/vaping-associated lung injury (EVALI) is strongly associated with vitamin E acetate and often occurs with concomitant tetrahydrocannabinol (THC) use. To uncover pathways associated with EVALI, we examined cytokines, transcriptomic signatures, and lipidomic profiles in bronchoalveolar lavage fluid (BALF) from THC-EVALI patients. At a single center, we prospectively enrolled mechanically ventilated patients with EVALI from THC-containing products (N = 4) and patients with non-vaping acute lung injury and airway controls (N = 5). BALF samples were analyzed by Luminex multiplex assay, RNA sequencing, and mass spectrometry. After treating BEAS-2B lung epithelial cells with vaping and non-vaping BALF, LDH release was quantified. …


Patient And Parent Knowledge, Understanding, And Concerns After A New Diagnosis Of Ehlers Danlos Syndrome., Jordan T. Jones, Lora L. Black, William R. Black Dec 2024

Patient And Parent Knowledge, Understanding, And Concerns After A New Diagnosis Of Ehlers Danlos Syndrome., Jordan T. Jones, Lora L. Black, William R. Black

Manuscripts, Articles, Book Chapters and Other Papers

INTRODUCTION: After diagnosis of Ehlers Danlos Syndrome (EDS), it is unclear what information patients and parents need and understand about EDS. The objective of this study is to characterize patient and parent knowledge and concerns about EDS after a diagnosis of EDS is made to determine patient and parent concerns and identify barriers that cause discomfort with the diagnosis.6 METHODS: A convenience sample of patient and parent dyads were recruited after new diagnosis of EDS. Patients and parents completed questionnaires that assessed knowledge, comfort, and barriers of EDS before and after diagnosis, EDS education materials accessed, and additional clinical needs …


Approaches And Outcomes Of Adalimumab Discontinuation In Patients With Well-Controlled Inflammatory Arthritis: A Systematic Search And Review, Erin Balay-Dustrude, Jessica Fennell, Kevin Baszis, Y Ingrid Goh, Daniel B Horton, Tzielan Lee, Chloe Rotman, Anna Sutton, Marinka Twilt, Olha Halyabar, Carra Jia Inactive Disease Workgroup Dec 2024

Approaches And Outcomes Of Adalimumab Discontinuation In Patients With Well-Controlled Inflammatory Arthritis: A Systematic Search And Review, Erin Balay-Dustrude, Jessica Fennell, Kevin Baszis, Y Ingrid Goh, Daniel B Horton, Tzielan Lee, Chloe Rotman, Anna Sutton, Marinka Twilt, Olha Halyabar, Carra Jia Inactive Disease Workgroup

2020-Current year OA Pubs

OBJECTIVE: This systematic search and review aimed to evaluate the available literature on discontinuation of adalimumab and other tumor necrosis factor inhibitors (TNFi) for patients with well-controlled chronic inflammatory arthritides.

METHODS: We conducted a publication search on adalimumab discontinuation from 2000-2023 using PubMed, CINAHL, EMBASE, and Cochrane Library. Included studies evaluated adalimumab discontinuation approaches, tapering schemes, and outcomes including successful discontinuation and recapture after flare, in patients with well-controlled disease. Studies included evaluated rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, and juvenile idiopathic arthritis (JIA).

RESULTS: Forty-nine studies were included. Studies evaluating adalimumab alone were limited, and many reported TNFi outcomes …


Effectiveness Of An Online Food Shopping Intervention To Reduce Salt Purchases Among Individuals With Hypertension - Findings Of The Saltswitch Online Grocery Shopping (Ogs) Randomised Trial, Jason Hy Wu, Damian Maganja, Liping Huang, Kathy Trieu, Fraser Taylor, Eden M Barrett, Clare Arnott, Xiaoqi Feng, Aletta E Schutte, Gian Luca Di Tanna, Cliona Ni Mhurchu, Adrian J Cameron, Mark D Huffman, Bruce Neal Dec 2024

Effectiveness Of An Online Food Shopping Intervention To Reduce Salt Purchases Among Individuals With Hypertension - Findings Of The Saltswitch Online Grocery Shopping (Ogs) Randomised Trial, Jason Hy Wu, Damian Maganja, Liping Huang, Kathy Trieu, Fraser Taylor, Eden M Barrett, Clare Arnott, Xiaoqi Feng, Aletta E Schutte, Gian Luca Di Tanna, Cliona Ni Mhurchu, Adrian J Cameron, Mark D Huffman, Bruce Neal

2020-Current year OA Pubs

BACKGROUND: Online grocery shopping is a growing source of food purchases in many countries. We investigated the effect of nudging consumers towards purchases of lower sodium products using a web browser extension.

METHODS: This trial was conducted among individuals with hypertension who shopped for their groceries online in Australia. From July 2021 to June 2023, participants were randomised to use the SaltSwitch Online Grocery Shopping web browser extension or continue their usual grocery shopping for 12 weeks. The SaltSwitch extension modified a retailer's online shopping interface to suggest similar but lower sodium alternative products to those initially selected. The primary …


Food For Thought: A Qualitative Assessment Of Medical Trainee And Faculty Perceptions Of Nutrition Education, Olivia Kunitsky, Mahdi Taye, Karla Feeley, Hugh Johnson, Abigail Glynn, Avery Stivale, Matthew Hamers, Alexis Notarianni, Sireesha Mamillapalli, Gabi Waite, Sonia Lobo Dec 2024

Food For Thought: A Qualitative Assessment Of Medical Trainee And Faculty Perceptions Of Nutrition Education, Olivia Kunitsky, Mahdi Taye, Karla Feeley, Hugh Johnson, Abigail Glynn, Avery Stivale, Matthew Hamers, Alexis Notarianni, Sireesha Mamillapalli, Gabi Waite, Sonia Lobo

Department of Neurology Faculty Papers

BACKGROUND: The American Society of Clinical Nutrition recommends 37 to 44 h of undergraduate medical nutrition education. The Total Health Curriculum at Geisinger Commonwealth School of Medicine (GCSOM) contains 14 h of objective-based nutritional instruction. This study aimed to examine the perceptions of key stakeholders regarding the role of nutrition in medicine and to identify barriers, opportunities for improvement, and roles/responsibilities for innovative implementation of nutrition education.

METHODS: This exploratory, qualitative study employed a phenomenological approach and inductive coding process. Purposive sampling recruited medical students, undergraduate medical education (UME) faculty, physicians, and other healthcare professionals at GCSOM and affiliated clinical …


Surgical Delay-Associated Mortality Risk Varies By Subtype In Loco-Regional Breast Cancer Patients In Seer-Medicare, Macall Leslie Salewon, Rashmi Pathak, William Dooley, Ronald Squires, Hallgeir Rui, Inna Chervoneva, Takemi Tanaka Dec 2024

Surgical Delay-Associated Mortality Risk Varies By Subtype In Loco-Regional Breast Cancer Patients In Seer-Medicare, Macall Leslie Salewon, Rashmi Pathak, William Dooley, Ronald Squires, Hallgeir Rui, Inna Chervoneva, Takemi Tanaka

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Substantial evidence supports that delay of surgery after breast cancer diagnosis is associated with increased mortality risk, leading to the introduction of a new Commission on Cancer quality measure for receipt of surgery within 60 days of diagnosis for non-neoadjuvant patients. Breast cancer subtype is a critical prognostic factor and determines treatment options; however, it remains unknown whether surgical delay-associated breast cancer-specific mortality (BCSM) risk differs by subtype. This retrospective cohort study aimed to assess whether the impact of delayed surgery on survival varies by subtype (hormone [HR] + /HER2 -, HR -/HER2 -, and HER2 +) in patients with …


Transition To Enteral Triazole Antifungal Therapy For Pediatric Invasive Candidiasis: Secondary Analysis Of A Multicenter Cohort Study Conducted By The Pediatric Fungal Network, Robert F T Bucayu, Craig L K Boge, Inci Yildirim, Martha Avilés-Robles, Surabhi B Vora, David M Berman, Tanvi S Sharma, Lillian Sung, Elio Castagnola, Debra L Palazzi, Lara Danziger-Isakov, Dwight E Yin, Emmanuel Roilides, Gabriela Maron, Alison C Tribble, Pere Soler-Palacin, Eduardo López-Medina, José Romero, Kiran Belani, Antonio C Arrieta, Fabianne Carlesse, Dawn Nolt, Natasha Halasa, Daniel Dulek, Sujatha Rajan, William J Muller, Monica I Ardura, Alice Pong, Blanca E Gonzalez, Christine M Salvatore, Anna R Huppler, Catherine Aftandilian, Mark J Abzug, Arunaloke Chakrabarti, Michael Green, Irja Lutsar, Elizabeth D Knackstedt, Sarah K Johnson, William J Steinbach, Brian T Fisher, Rachel L Wattier Dec 2024

Transition To Enteral Triazole Antifungal Therapy For Pediatric Invasive Candidiasis: Secondary Analysis Of A Multicenter Cohort Study Conducted By The Pediatric Fungal Network, Robert F T Bucayu, Craig L K Boge, Inci Yildirim, Martha Avilés-Robles, Surabhi B Vora, David M Berman, Tanvi S Sharma, Lillian Sung, Elio Castagnola, Debra L Palazzi, Lara Danziger-Isakov, Dwight E Yin, Emmanuel Roilides, Gabriela Maron, Alison C Tribble, Pere Soler-Palacin, Eduardo López-Medina, José Romero, Kiran Belani, Antonio C Arrieta, Fabianne Carlesse, Dawn Nolt, Natasha Halasa, Daniel Dulek, Sujatha Rajan, William J Muller, Monica I Ardura, Alice Pong, Blanca E Gonzalez, Christine M Salvatore, Anna R Huppler, Catherine Aftandilian, Mark J Abzug, Arunaloke Chakrabarti, Michael Green, Irja Lutsar, Elizabeth D Knackstedt, Sarah K Johnson, William J Steinbach, Brian T Fisher, Rachel L Wattier

Faculty, Staff and Students Publications

Of 319 children with invasive candidiasis, 67 (21%) transitioned from intravenous to enteral antifungal therapy. Eight (12%) transitioned back to intravenous antifungal therapy, one due to perceived treatment failure defined by clinical progression or worsening. Global treatment response at study completion was successful in 66 participants who transitioned to enteral therapy.


Dlk-Dependent Axonal Mitochondrial Fission Drives Degeneration After Axotomy, Jorge Gómez-Deza, Matthew Nebiyou, Mor R Alkaslasi, Francisco M Nadal-Nicolás, Preethi Somasundaram, Anastasia L Slavutsky, Wei Li, Michael E Ward, Trent A Watkins, Claire E Le Pichon Dec 2024

Dlk-Dependent Axonal Mitochondrial Fission Drives Degeneration After Axotomy, Jorge Gómez-Deza, Matthew Nebiyou, Mor R Alkaslasi, Francisco M Nadal-Nicolás, Preethi Somasundaram, Anastasia L Slavutsky, Wei Li, Michael E Ward, Trent A Watkins, Claire E Le Pichon

Faculty, Staff and Students Publications

Currently there are no effective treatments for an array of neurodegenerative disorders to a large part because cell-based models fail to recapitulate disease. Here we develop a reproducible human iPSC-based model where laser axotomy causes retrograde axon degeneration leading to neuronal cell death. Time-lapse confocal imaging revealed that damage triggers an apoptotic wave of mitochondrial fission proceeding from the site of injury to the soma. We demonstrate that this apoptotic wave is locally initiated in the axon by dual leucine zipper kinase (DLK). We find that mitochondrial fission and resultant cell death are entirely dependent on phosphorylation of dynamin related …


Nos Inhibition Sensitizes Metaplastic Breast Cancer To Pi3k Inhibition And Taxane Therapy Via C-Jun Repression, Tejaswini Reddy, Akshjot Puri, Liliana Guzman-Rojas, Christoforos Thomas, Wei Qian, Jianying Zhou, Hong Zhao, Bijan Mahboubi, Adrian Oo, Young-Jae Cho, Baek Kim, Jose Thaiparambil, Roberto Rosato, Karina Ortega Martinez, Maria Florencia Chervo, Camila Ayerbe, Noah Giese, David Wink, Stephen Lockett, Stephen Wong, Jeffrey Chang, Savitri Krishnamurthy, Clinton Yam, Stacy Moulder, Helen Piwnica-Worms, Funda Meric-Bernstam, Jenny Chang Dec 2024

Nos Inhibition Sensitizes Metaplastic Breast Cancer To Pi3k Inhibition And Taxane Therapy Via C-Jun Repression, Tejaswini Reddy, Akshjot Puri, Liliana Guzman-Rojas, Christoforos Thomas, Wei Qian, Jianying Zhou, Hong Zhao, Bijan Mahboubi, Adrian Oo, Young-Jae Cho, Baek Kim, Jose Thaiparambil, Roberto Rosato, Karina Ortega Martinez, Maria Florencia Chervo, Camila Ayerbe, Noah Giese, David Wink, Stephen Lockett, Stephen Wong, Jeffrey Chang, Savitri Krishnamurthy, Clinton Yam, Stacy Moulder, Helen Piwnica-Worms, Funda Meric-Bernstam, Jenny Chang

Faculty, Staff and Student Publications

Metaplastic breast cancer (MpBC) is a highly chemoresistant subtype of breast cancer with no standardized therapy options. A clinical study in anthracycline-refractory MpBC patients suggested that nitric oxide synthase (NOS) inhibitor NG-monomethyl-l-arginine (L-NMMA) may augment anti-tumor efficacy of taxane. We report that NOS blockade potentiated response of human MpBC cell lines and tumors to phosphoinositide 3-kinase (PI3K) inhibitor alpelisib and taxane. Mechanistically, NOS blockade leads to a decrease in the S-nitrosylation of c-Jun NH


Double-Blind Randomised Trial Of Saline Solution For Gargling And Nasal Rinsing In Sars-Cov-2 Infection, Sebastian R Espinoza, Lexton Trauffler, Amir Shamshirsaz, Alireza Shamshirsaz, Andres Espinoza, Jimmy Espinoza, Alice O'Brien Dec 2024

Double-Blind Randomised Trial Of Saline Solution For Gargling And Nasal Rinsing In Sars-Cov-2 Infection, Sebastian R Espinoza, Lexton Trauffler, Amir Shamshirsaz, Alireza Shamshirsaz, Andres Espinoza, Jimmy Espinoza, Alice O'Brien

Faculty, Staff and Student Publications

Background: Previous studies have shown that hypertonic saline nasal irrigation and gargling reduced the duration of symptoms in upper respiratory infections caused by coronavirus. This study aims to investigate the effects of two saline regimens on symptoms associated with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2).

Methods: Between 2020 and 2022, individuals aged 18-65 years who tested positive for SARS-CoV-2 infection via polymerase chain reaction (PCR) were randomly assigned to either low- or high-saline regimens for 14 days. The low-saline solutions contained 2.13 g of salt dissolved in eight ounces of warm water, while the high-saline solution contained six grams of …


The Win Ratio Approach In Bayesian Monitoring For Two-Arm Phase Ii Clinical Trial Designs With Multiple Time-To-Event Endpoints, Xinran Huang, Jian Wang, Jing Ning Dec 2024

The Win Ratio Approach In Bayesian Monitoring For Two-Arm Phase Ii Clinical Trial Designs With Multiple Time-To-Event Endpoints, Xinran Huang, Jian Wang, Jing Ning

Faculty, Staff and Student Publications

To assess the preliminary therapeutic impact of a novel treatment, futility monitoring is commonly employed in Phase II clinical trials to facilitate informed decisions regarding the early termination of trials. Given the rapid evolution in cancer treatment development, particularly with new agents like immunotherapeutic agents, the focus has often shifted from objective response to time-to-event endpoints. In trials involving multiple time-to-event endpoints, existing monitoring designs typically select one as the primary endpoint or employ a composite endpoint as the time to the first occurrence of any event. However, relying on a single efficacy endpoint may not adequately evaluate an experimental …


Bayesian Nonparametric Model For Heterogeneous Treatment Effects With Zero-Inflated Data, Chanmin Kim, Yisheng Li, Ting Xu, Zhongxing Liao Dec 2024

Bayesian Nonparametric Model For Heterogeneous Treatment Effects With Zero-Inflated Data, Chanmin Kim, Yisheng Li, Ting Xu, Zhongxing Liao

Faculty, Staff and Student Publications

One goal of precision medicine is to develop effective treatments for patients by tailoring to their individual demographic, clinical, and/or genetic characteristics. To achieve this goal, statistical models must be developed that can identify and evaluate potentially heterogeneous treatment effects in a robust manner. The oft-cited existing methods for assessing treatment effect heterogeneity are based upon parametric models with interactions or conditioning on covariate values, the performance of which is sensitive to the omission of important covariates and/or the choice of their values. We propose a new Bayesian nonparametric (BNP) method for estimating heterogeneous causal effects in studies with zero-inflated …


Potential Of Right Ventricular Function Assessment With Echocardiography In Transcatheter Aortic Valve Replacement, Yoshihisa Morita, Taro Kariya, Michael Dougherty, Andrew Peters, Nicholas Ruggiero Dec 2024

Potential Of Right Ventricular Function Assessment With Echocardiography In Transcatheter Aortic Valve Replacement, Yoshihisa Morita, Taro Kariya, Michael Dougherty, Andrew Peters, Nicholas Ruggiero

Division of Cardiology Faculty Papers

BACKGROUND: Right ventricular (RV) function assessment by echocardiography can be challenging due to its complex morphology. Also, increasing use of sedation rather than general anesthesia for transfemoral approach transcatheter aortic valve replacement (TAVR) reduces the need for intraoperative transesophageal echocardiography (TEE). Recent clinical studies have demonstrated the importance of 3-dimensional (3D) echocardiography and a longitudinal strain for RV function assessment. In this study, we compared RV function echocardiographic assessment methodologies in TAVR and investigated its clinical utility.

METHODS: This was a prospective, observational study of TAVR at a large academic hospital. Inclusion criteria were adult patients undergoing TAVR requiring intraoperative …


Orthogonal And Multiplexable Genetic Perturbations With An Engineered Prime Editor And A Diverse Rna Array, Qichen Yuan, Hongzhi Zeng, Tyler C Daniel, Qingzhuo Liu, Yongjie Yang, Emmanuel C Osikpa, Qiaochu Yang, Advaith Peddi, Liliana M Abramson, Boyang Zhang, Yong Xu, Xue Gao Dec 2024

Orthogonal And Multiplexable Genetic Perturbations With An Engineered Prime Editor And A Diverse Rna Array, Qichen Yuan, Hongzhi Zeng, Tyler C Daniel, Qingzhuo Liu, Yongjie Yang, Emmanuel C Osikpa, Qiaochu Yang, Advaith Peddi, Liliana M Abramson, Boyang Zhang, Yong Xu, Xue Gao

Faculty, Staff and Students Publications

Programmable and modular systems capable of orthogonal genomic and transcriptomic perturbations are crucial for biological research and treating human genetic diseases. Here, we present the minimal versatile genetic perturbation technology (mvGPT), a flexible toolkit designed for simultaneous and orthogonal gene editing, activation, and repression in human cells. The mvGPT combines an engineered compact prime editor (PE), a fusion activator MS2-p65-HSF1 (MPH), and a drive-and-process multiplex array that produces RNAs tailored to different types of genetic perturbation. mvGPT can precisely edit human genome via PE coupled with a prime editing guide RNA and a nicking guide RNA, activate endogenous gene expression …


Carboxyl Ester Lipase Hybrid 1 (Cel-Hyb1) Haplotypes Confer Varying Risk For Chronic Pancreatitis, Gergő Berke, Xunjun K Xiao, Mark E Lowe, Et Al. Dec 2024

Carboxyl Ester Lipase Hybrid 1 (Cel-Hyb1) Haplotypes Confer Varying Risk For Chronic Pancreatitis, Gergő Berke, Xunjun K Xiao, Mark E Lowe, Et Al.

2020-Current year OA Pubs

The CEL-HYB1 hybrid allele of the carboxyl ester lipase (CEL) gene and its pseudogene (CELP) has been associated with chronic pancreatitis (CP). Recent work indicated that amino acid positions 488 and 548 in CEL-HYB1 determined pathogenicity. Haplotype Thr488-Ile548 was associated with CP while haplotypes Thr488-Thr548 and Ile488-Thr548 were benign. However, functional analysis revealed that Thr488 is the primary determinant of CEL-HYB1 misfolding and associated endoplasmic reticulum (ER) stress. To address this contradiction, we analyzed a cohort from Hungary and found significantly increased CEL-HYB1 carrier frequency in CP cases (9/319, 2.8%) versus controls (5/618, 0.8%), yielding an odds ratio of 3.6 …


Parp Inhibition Radiosensitizes Brca1 Wildtype And Mutated Breast Cancer To Proton Therapy, Mariam Ben Kacem, Scott J Bright, Emma Moran, David B Flint, David K J Martinus, Broderick X Turner, Ilsa Qureshi, Rishab Kolachina, Mandira Manandhar, Poliana C Marinello, Simona F Shaitelman, Gabriel O Sawakuchi Dec 2024

Parp Inhibition Radiosensitizes Brca1 Wildtype And Mutated Breast Cancer To Proton Therapy, Mariam Ben Kacem, Scott J Bright, Emma Moran, David B Flint, David K J Martinus, Broderick X Turner, Ilsa Qureshi, Rishab Kolachina, Mandira Manandhar, Poliana C Marinello, Simona F Shaitelman, Gabriel O Sawakuchi

Faculty, Staff and Student Publications

Aggressive breast cancers often fail or acquire resistance to radiotherapy. To develop new strategies to improve the outcome of aggressive breast cancer patients, we studied how PARP inhibition radiosensitizes breast cancer models to proton therapy, which is a radiotherapy modality that generates more DNA damage in the tumor than standard radiotherapy using photons. Two human BRCA1-mutated breast cancer cell lines and their isogenic BRCA1-recovered pairs were treated with a PARP inhibitor and irradiated with photons or protons. Protons (9.9 and 3.85 keV/µm) induced higher cell kill independent of BRCA1 status. PARP inhibition amplified the cell kill effect to both photons …


Cancer Organoids As Reliable Disease Models To Drive Clinical Development Of Novel Therapies, Giovanni Blandino, Ronit Satchi-Fainaro, Ingeborg Tinhofer, Giovanni Tonon, Sarah C Heilshorn, Yong-Jun Kwon, Ana Pestana, Carlotta Frascolla, Luca Pompili, Aurora Puce, Sara Iachettini, Annalisa Tocci, Sofia Karkampouna, Marianna Kruithof-De Julio, Piera Tocci, Nicla Porciello, Klizia Maccaroni, Daniela Rutigliano, Xiling Shen, Gennaro Ciliberto Dec 2024

Cancer Organoids As Reliable Disease Models To Drive Clinical Development Of Novel Therapies, Giovanni Blandino, Ronit Satchi-Fainaro, Ingeborg Tinhofer, Giovanni Tonon, Sarah C Heilshorn, Yong-Jun Kwon, Ana Pestana, Carlotta Frascolla, Luca Pompili, Aurora Puce, Sara Iachettini, Annalisa Tocci, Sofia Karkampouna, Marianna Kruithof-De Julio, Piera Tocci, Nicla Porciello, Klizia Maccaroni, Daniela Rutigliano, Xiling Shen, Gennaro Ciliberto

Faculty, Staff and Student Publications

On September 23-24 (2024) the 6th Workshop IRE on Translational Oncology, titled "Cancer Organoids as Reliable Disease Models to Drive Clinical Development of Novel Therapies," took place at the IRCCS Regina Elena Cancer Institute in Rome. This prominent international conference focused on tumor organoids, bringing together leading experts from around the world.A central challenge in precision oncology is modeling the dynamic tumor ecosystem, which encompasses numerous elements that evolve spatially and temporally. Patient-derived 3D culture models, including organoids, explants, and engineered or bioprinted systems, have recently emerged as sophisticated tools capable of capturing the complexity and diversity of cancer cells …


Lack Of Association Of The Pld4 Snp Rs2841277 With Systemic Sclerosis In A European American Population, Yunqing Ma, Maureen D Mayes, Xinjian Guo, Shervin Assassi, Xiaodong Zhou Dec 2024

Lack Of Association Of The Pld4 Snp Rs2841277 With Systemic Sclerosis In A European American Population, Yunqing Ma, Maureen D Mayes, Xinjian Guo, Shervin Assassi, Xiaodong Zhou

Faculty, Staff and Student Publications

This study aimed to examine whether a reported SSc-associated SNP rs2841277 in the PLD4 gene identified in an Asian population was also associated with SSc in European American (EA). The EA cohort consisting of 1005 SSc patients and 961 healthy controls was examined in this study. TaqMan genotyping assays were performed to examine the SNP. Exact P-values were obtained from 2 × 2 tables of allele counts and disease status. In contrast to the previous reports in a Japanese population, SSc patients of EA did not show an association of PLD4 rs2841277 with SSc in general (P = 0.231, OR …


Refinement Of An Algorithm To Detect And Predict Freezing Of Gait In Parkinson Disease Using Wearable Sensors, Allison M Haussler, Lauren E Tueth, David S May, Gammon M Earhart, Pietro Mazzoni Dec 2024

Refinement Of An Algorithm To Detect And Predict Freezing Of Gait In Parkinson Disease Using Wearable Sensors, Allison M Haussler, Lauren E Tueth, David S May, Gammon M Earhart, Pietro Mazzoni

2020-Current year OA Pubs

Freezing of gait (FOG) is a debilitating symptom of Parkinson disease (PD). It is episodic and variable in nature, making assessment difficult. Wearable sensors used in conjunction with specialized algorithms, such as our group's pFOG algorithm, provide objective data to better understand this phenomenon. While these methods are effective at detecting FOG retrospectively, more work is needed. The purpose of this paper is to explore how the existing pFOG algorithm can be refined to improve the detection and prediction of FOG. To accomplish this goal, previously collected data were utilized to assess the prediction ability of the current algorithm, the …


Aperiodic Spectral Slope Tracks The Effects Of Brain State On Saliency Responses In The Human Auditory Cortex, Madaline Mocchi, Eleonora Bartoli, John Magnotti, Jan Willem De Gee, Brian Metzger, Bailey Pascuzzi, Raissa Mathura, Suhruthaa Pulapaka, Wayne Goodman, Sameer Sheth, Matthew J Mcginley, Kelly Bijanki Dec 2024

Aperiodic Spectral Slope Tracks The Effects Of Brain State On Saliency Responses In The Human Auditory Cortex, Madaline Mocchi, Eleonora Bartoli, John Magnotti, Jan Willem De Gee, Brian Metzger, Bailey Pascuzzi, Raissa Mathura, Suhruthaa Pulapaka, Wayne Goodman, Sameer Sheth, Matthew J Mcginley, Kelly Bijanki

Faculty, Staff and Students Publications

Alteration of responses to salient stimuli occurs in a wide range of brain disorders and may be rooted in pathophysiological brain state dynamics. Specifically, tonic and phasic modes of activity in the reticular activating system (RAS) influence, and are influenced by, salient stimuli, respectively. The RAS influences the spectral characteristics of activity in the neocortex, shifting the balance between low- and high-frequency fluctuations. Aperiodic '1/f slope' has emerged as a promising composite measure of these brain state dynamics. However, the relationship of 1/f slope to state-dependent processes, such as saliency, is less explored, particularly intracranially in humans. Here, we record …


Comparing Functional Outcomes Between 3d Printed Acetabular Cups And Traditional Prosthetic Implants In Hip Arthroplasty: A Systematic Review And Meta Analysis, Ryan St. John, Seth Spicer, Mo Hadaya, Hanna Brancaccio, Seungkyu Park, Sean Mcmillan Dec 2024

Comparing Functional Outcomes Between 3d Printed Acetabular Cups And Traditional Prosthetic Implants In Hip Arthroplasty: A Systematic Review And Meta Analysis, Ryan St. John, Seth Spicer, Mo Hadaya, Hanna Brancaccio, Seungkyu Park, Sean Mcmillan

Rowan-Virtua School of Osteopathic Medicine Departmental Research

OBJECTIVE: The primary research aim was to determine if the use of traditional or 3D printed prosthesis resulted in better functional outcome scores in hip arthroplasty.

METHODS: A systematic review and meta-analysis was conducted utilizing the PRISMA 2020 guidelines. Six databases (PubMed, Embase, Scopus, WebOfScience, and Cochrane Library, Google Scholar) were searched yielding 1117 article titles and abstracts. Rayyan.ai was used to detect duplicates (n = 246) and for manual screening for inclusion and exclusion criteria. Included were controlled studies of any publication time that assessed Harris Hip Score (HHS) at baseline and twelve months. Six papers were sought for …


Yy1 Drives Parp1 Expression Essential For Parylation Of Nono In Mrna Maturation During Neuroblastoma Progression, Chunhui Yang, Jiaying Qu, Yang Cheng, Minxiu Tian, Zhijie Wang, Xiaolin Wang, Xinyue Li, Shunchen Zhou, Bosen Zhao, Yanhua Guo, Liduan Zheng, Qiangsong Tong Dec 2024

Yy1 Drives Parp1 Expression Essential For Parylation Of Nono In Mrna Maturation During Neuroblastoma Progression, Chunhui Yang, Jiaying Qu, Yang Cheng, Minxiu Tian, Zhijie Wang, Xiaolin Wang, Xinyue Li, Shunchen Zhou, Bosen Zhao, Yanhua Guo, Liduan Zheng, Qiangsong Tong

Faculty, Staff and Students Publications

Background: Neuroblastoma (NB), the most prevalent solid tumor in children, arises from sympathetic nervous system and accounts for 15% of pediatric cancer mortality. This malignancy exhibits substantial genetic and clinical heterogeneity, thus complicating treatment strategies. Poly(ADP-ribose) polymerase 1 (PARP1), a key enzyme catalyzing polyADP-ribosylation (PARylation), plays critical roles in various cellular processes, and contributes to tumorigenesis and aggressiveness. However, the functions and regulatory mechanisms of PARP1 in NB progression still remain to be determined.

Methods: The association of PARP1 expression with NB patients' survival was analyzed by mining of R2 database. Western blotting, reverse transcription-polymerase chain reaction, MTT colorimetric, soft …


Optimizing Ewing Sarcoma And Osteosarcoma Biopsy Acquisition: A Children's Oncology Group Bone Tumor Committee Consensus Statement, Matthew S Dietz, Alyaa Al-Ibraheemi, Jessica L Davis, C Matthew Hawkins, Brian T Craig, Roshni Dasgupta, David S Geller, David S Shulman, Sarah Cohen-Gogo, Ajay Gupta, Susan L Whiteway, Emily K Slotkin, Christine M Heske, Safia K Ahmed, Daniel J Indelicato, Catherine M Albert, Nicole Montgomery, Jesse K Sandberg, Holcombe E Grier, Mark Krailo, Michael S Isakoff, Elyssa Rubin, Elizabeth R Lawlor, Steven G Dubois, Leo Mascarenhas, Patrick J Grohar, Odion Binitie, Damon Reed, Katherine Janeway, Ryan D Roberts, Kelly M Bailey Dec 2024

Optimizing Ewing Sarcoma And Osteosarcoma Biopsy Acquisition: A Children's Oncology Group Bone Tumor Committee Consensus Statement, Matthew S Dietz, Alyaa Al-Ibraheemi, Jessica L Davis, C Matthew Hawkins, Brian T Craig, Roshni Dasgupta, David S Geller, David S Shulman, Sarah Cohen-Gogo, Ajay Gupta, Susan L Whiteway, Emily K Slotkin, Christine M Heske, Safia K Ahmed, Daniel J Indelicato, Catherine M Albert, Nicole Montgomery, Jesse K Sandberg, Holcombe E Grier, Mark Krailo, Michael S Isakoff, Elyssa Rubin, Elizabeth R Lawlor, Steven G Dubois, Leo Mascarenhas, Patrick J Grohar, Odion Binitie, Damon Reed, Katherine Janeway, Ryan D Roberts, Kelly M Bailey

Faculty, Staff and Students Publications

Trends in diagnostic biopsy sample collection approaches for primary bone sarcomas have shifted in the past 2 decades. Although open/incisional biopsies used to be the predominant approach to obtain diagnostic material for Ewing sarcoma and osteosarcoma, image-guided core needle biopsies have increased in frequency and are safe for patients. These procedures are less invasive and reduce recovery times but have potential limitations. The quantity and quality of tissue obtained through these procedures vary between institutions. Acquired viable tissue volumes can be low, limiting the conduct of downstream expanded clinical workup, molecular analyses, and research. Patients with advanced Ewing sarcoma and …


Visualizing Parcel-Level Lead Risk Using An Exterior Housing-Based Index., Neal J. Wilson, Ryan Allenbrand, Elizabeth Friedman, Kevin Kennedy, Amy Roberts, Stephen Simon Dec 2024

Visualizing Parcel-Level Lead Risk Using An Exterior Housing-Based Index., Neal J. Wilson, Ryan Allenbrand, Elizabeth Friedman, Kevin Kennedy, Amy Roberts, Stephen Simon

Manuscripts, Articles, Book Chapters and Other Papers

Pediatric lead poisoning remains a persistent public health problem. Children in the US spend the preponderance of their time at home; thus, housing is an important social determinant of health. Improving health outcomes derived from housing-based sources involves differentiating the risks posed by the existing housing stock. In this paper, we developed a parcel-level lead risk index (LRI) based on external housing conditions and the year of home construction. The purpose of this study was to introduce a housing-based lead risk index (LRI), developed using retrospective data, to estimate parcel-by-parcel variation in housing-based lead risk. We described how the LRI …


Stereotactic Cardiac Radiotherapy For Refractory Ventricular Tachycardia In Structural Heart Disease Patients: A Systematic Review, Amulya Gupta, Zeeshan Sattar, Nourhan Chaaban, Sagar Ranka, Cameron Carlson, Farhad Sami, Clifford G Robinson, Phillip S Cuculich, Seth H Sheldon, Madhu Reddy, David Akhavan, Amit Noheria Dec 2024

Stereotactic Cardiac Radiotherapy For Refractory Ventricular Tachycardia In Structural Heart Disease Patients: A Systematic Review, Amulya Gupta, Zeeshan Sattar, Nourhan Chaaban, Sagar Ranka, Cameron Carlson, Farhad Sami, Clifford G Robinson, Phillip S Cuculich, Seth H Sheldon, Madhu Reddy, David Akhavan, Amit Noheria

2020-Current year OA Pubs

AIMS: Among patients with structural heart disease with ventricular tachycardia (VT) refractory to medical therapy and catheter ablation, cardiac stereotactic body radiotherapy (SBRT) is a paradigm-changing treatment option. This study aims to assess the efficacy of cardiac SBRT in refractory VT by comparing the rates of VT episodes, anti-tachycardia pacing (ATP) therapies, and implantable cardioverter-defibrillator (ICD) shocks post-SBRT with pre-SBRT.

METHODS AND RESULTS: We performed a comprehensive literature search and included all clinical studies reporting outcomes on cardiac SBRT for VT. Treatment efficacy was evaluated as random-effects pooled rate-ratios of VT episodes, ATP therapies and ICD shocks post-SBRT (after 6-week …


A Conceptual Framework To Assess The Health, Socioeconomic And Environmental Burden Of Chronic Kidney Disease, Charlotte Johnston-Webber, Isaac Bencomo-Bermudez, George Wharton, Robin Van Kessel, Salvatore Barone, Francisco Brotons Muntó, Steven Chadban, Juan Jose Garcia Sanchez, Janwillem Kocks, Kyra Obolensky, Petra Sandow, Neil Skolnik, Ming-Hui Zhao, Alexei Volaco, David Wheeler, Alistair Mcguire, Elias Mossialos Dec 2024

A Conceptual Framework To Assess The Health, Socioeconomic And Environmental Burden Of Chronic Kidney Disease, Charlotte Johnston-Webber, Isaac Bencomo-Bermudez, George Wharton, Robin Van Kessel, Salvatore Barone, Francisco Brotons Muntó, Steven Chadban, Juan Jose Garcia Sanchez, Janwillem Kocks, Kyra Obolensky, Petra Sandow, Neil Skolnik, Ming-Hui Zhao, Alexei Volaco, David Wheeler, Alistair Mcguire, Elias Mossialos

Department of Medicine Faculty Papers

Chronic kidney disease (CKD) is a global health challenge that affects patients, caregivers, healthcare systems, the environment and national economies. Despite its far-reaching impact, there is no framework to systematically evaluate national CKD prevention and management programmes or evaluate the societal burden of disease. This paper has two objectives: first, to introduce a comprehensive framework to assess national programmes, which recognises gaps and weaknesses and identifies feasible policy interventions to reduce overall CKD burden; second, to present some key challenges and success stories in delivering CKD services delivered in eight different country settings. A literature review informed an initial version …


Update On Strategies To Reduce Early Brain Injury After Subarachnoid Hemorrhage, Bosco Seong Kyu Yang, Aaron M Gusdon, Xuefang Sophie Ren, Han-Gil Jeong, Chang-Hun Lee, Spiros Blackburn, Huimahn Alex Choi Dec 2024

Update On Strategies To Reduce Early Brain Injury After Subarachnoid Hemorrhage, Bosco Seong Kyu Yang, Aaron M Gusdon, Xuefang Sophie Ren, Han-Gil Jeong, Chang-Hun Lee, Spiros Blackburn, Huimahn Alex Choi

Faculty, Staff and Student Publications

Purpose of review: Early brain injury (EBI) after aneurysmal subarachnoid hemorrhage (SAH) is the most influential clinical determinant of outcomes. Despite significant advances in understanding of the pathophysiology of EBI, currently no treatments to target EBI have been developed. This review summarizes recent advances in EBI research over the past five years with a focus on potential therapeutic targets.

Recent findings: Mechanism-specific translational studies are converging on several pathophysiologic pathways: improved antioxidant delivery and the Sirt1/Nrf2 pathway for reactive oxygen species; NLRP3 inflammasome and microglial polarization for inflammation; and the PI3K/Akt pathway for apoptosis. Recently identified mechanistic components, such as …