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Immune-Related Adverse Event In The Emergency Department: Methodology Of The Immune-Related Emergency Disposition Index (Iredi), Cielito C Reyes-Gibby, Jeffrey M Caterino, Christopher J Coyne, Demetrios N Kyriacou, Aiham Qdaisat, Jennifer Mcquade, Dwight H Owen, Jason J Bischof, Sanjay Shete, Sai-Ching Jim Yeung Jan 2024

Immune-Related Adverse Event In The Emergency Department: Methodology Of The Immune-Related Emergency Disposition Index (Iredi), Cielito C Reyes-Gibby, Jeffrey M Caterino, Christopher J Coyne, Demetrios N Kyriacou, Aiham Qdaisat, Jennifer Mcquade, Dwight H Owen, Jason J Bischof, Sanjay Shete, Sai-Ching Jim Yeung

Faculty, Staff and Student Publications

For many cancer patients, immune checkpoint inhibitors (ICIs) can be life-saving. However, the immune-related adverse events (irAEs) from ICIs can be debilitating and can quickly become severe or even be fatal. Often, irAEs will precipitate visits to the emergency department (ED). Therefore, early recognition and the decision to admit, observe, or discharge these patients from the ED can be key to a cancer patient's morbidity and mortality. ED clinicians typically make their decision for disposition (admit, observe, or discharge) within 2-6 h from their patient's ED presentation. However, irAEs are particularly challenging in the ED because of atypical presentations, the …


A Novel Super-Resolution Microscopy Platform For Cutaneous Alpha-Synuclein Detection In Parkinson's Diseasea Novel Super-Resolution Microscopy Platform For Cutaneous Alpha-Synuclein Detection In Parkinson's Disease, Ofir Sade, Daphna Fischel, Noa Barak-Broner, Shir Halevi, Irit Gottfried, Dana Bar-On, Stefan Sachs, Anat Mirelman, Avner Thaler, Aviv Gour, Meir Kestenbaum, Mali Gana Weisz, Saar Anis, Claudio Soto, Melanie Shanie Roitman, Shimon Shahar, Kathrin Doppler, Markus Sauer, Nir Giladi, Nirit Lev, Roy N Alcalay, Sharon Hassin-Baer, Uri Ashery Jan 2024

A Novel Super-Resolution Microscopy Platform For Cutaneous Alpha-Synuclein Detection In Parkinson's Diseasea Novel Super-Resolution Microscopy Platform For Cutaneous Alpha-Synuclein Detection In Parkinson's Disease, Ofir Sade, Daphna Fischel, Noa Barak-Broner, Shir Halevi, Irit Gottfried, Dana Bar-On, Stefan Sachs, Anat Mirelman, Avner Thaler, Aviv Gour, Meir Kestenbaum, Mali Gana Weisz, Saar Anis, Claudio Soto, Melanie Shanie Roitman, Shimon Shahar, Kathrin Doppler, Markus Sauer, Nir Giladi, Nirit Lev, Roy N Alcalay, Sharon Hassin-Baer, Uri Ashery

Faculty, Staff and Student Publications

Alpha-synuclein (aSyn) aggregates in the central nervous system are the main pathological hallmark of Parkinson’s disease (PD). ASyn aggregates have also been detected in many peripheral tissues, including the skin, thus providing a novel and accessible target tissue for the detection of PD pathology. Still, a well-established validated quantitative biomarker for early diagnosis of PD that also allows for tracking of disease progression remains lacking. The main goal of this research was to characterize aSyn aggregates in skin biopsies as a comparative and quantitative measure for PD pathology. Using direct stochastic optical reconstruction microscopy (dSTORM) and computational tools, …


Sotorasib With Panitumumab In Chemotherapy-Refractory Kras G12c-Mutated Colorectal Cancer: A Phase 1b Trial, Yasutoshi Kuboki, Marwan Fakih, John Strickler, Rona Yaeger, Toshiki Masuishi, Edward J Kim, Christine M Bestvina, Scott Kopetz, Gerald S Falchook, Corey Langer, John Krauss, Sonam Puri, Panli Cardona, Emily Chan, Tracy Varrieur, Lata Mukundan, Abraham Anderson, Qui Tran, David S Hong Jan 2024

Sotorasib With Panitumumab In Chemotherapy-Refractory Kras G12c-Mutated Colorectal Cancer: A Phase 1b Trial, Yasutoshi Kuboki, Marwan Fakih, John Strickler, Rona Yaeger, Toshiki Masuishi, Edward J Kim, Christine M Bestvina, Scott Kopetz, Gerald S Falchook, Corey Langer, John Krauss, Sonam Puri, Panli Cardona, Emily Chan, Tracy Varrieur, Lata Mukundan, Abraham Anderson, Qui Tran, David S Hong

Faculty, Staff and Student Publications

The current third-line (and beyond) treatment options for RAS-mutant metastatic colorectal cancer have yielded limited efficacy. At the time of study start, the combination of sotorasib, a KRAS (Kirsten rat sarcoma viral oncogene homolog)-G12C inhibitor, and panitumumab, an epidermal growth factor receptor (EGFR) inhibitor, was hypothesized to overcome treatment-induced resistance. This phase 1b substudy of the CodeBreaK 101 master protocol evaluated sotorasib plus panitumumab in patients with chemotherapy-refractory KRAS


A Phase 2, Multicenter, Open-Label Study Of Anti-Lag-3 Ieramilimab In Combination With Anti-Pd-1 Spartalizumab In Patients With Advanced Solid Malignancies, Chia-Chi Lin, Elena Garralda, Patrick Schöffski, David S Hong, Lillian L Siu, Miguel Martin, Michela Maur, Rina Hui, Ross A Soo, Joanne Chiu, Tian Zhang, Brigette Ma, Chrisann Kyi, Daniel Sw Tan, Philippe A Cassier, John Sarantopoulos, Andrew Weickhardt, Richard D Carvajal, Jennifer Spratlin, Taito Esaki, Fréderic Rolland, Wallace Akerley, Barbara Deschler-Baier, Lawrence Rispoli, Tanay S Samant, Niladri Roy Chowdhury, Daniel Gusenleitner, Eunice L Kwak, Vasileios Askoxylakis, Filippo De Braud Jan 2024

A Phase 2, Multicenter, Open-Label Study Of Anti-Lag-3 Ieramilimab In Combination With Anti-Pd-1 Spartalizumab In Patients With Advanced Solid Malignancies, Chia-Chi Lin, Elena Garralda, Patrick Schöffski, David S Hong, Lillian L Siu, Miguel Martin, Michela Maur, Rina Hui, Ross A Soo, Joanne Chiu, Tian Zhang, Brigette Ma, Chrisann Kyi, Daniel Sw Tan, Philippe A Cassier, John Sarantopoulos, Andrew Weickhardt, Richard D Carvajal, Jennifer Spratlin, Taito Esaki, Fréderic Rolland, Wallace Akerley, Barbara Deschler-Baier, Lawrence Rispoli, Tanay S Samant, Niladri Roy Chowdhury, Daniel Gusenleitner, Eunice L Kwak, Vasileios Askoxylakis, Filippo De Braud

Faculty, Staff and Student Publications

Ieramilimab, a humanized anti-LAG-3 monoclonal antibody, was well tolerated in combination with the anti-PD-1 antibody spartalizumab in a phase 1 study. This phase 2 study aimed to further investigate the efficacy and safety of combination treatment in patients with selected advanced (locally advanced or metastatic) solid malignancies. Eligible patients with non-small cell lung cancer (NSCLC), melanoma, renal cell carcinoma (RCC), mesothelioma, and triple-negative breast cancer (TNBC) were grouped depending on prior anti-PD-1/L1 therapy (anti-PD-1/L1 naive or anti-PD-1/L1 pretreated). Patients received ieramilimab (400 mg) followed by spartalizumab (300 mg) every 3 weeks. The primary endpoint was objective response rate (ORR), along …


Candidate Circulating Microrna Biomarkers In Dogs With Chronic Pancreatitis, Susan K Armstrong, Robert W Hunter, Wilna Oosthyuzen, Maciej Parys, Adam G Gow, Silke Salavati Schmitz, James W Dear, Richard J Mellanby Jan 2024

Candidate Circulating Microrna Biomarkers In Dogs With Chronic Pancreatitis, Susan K Armstrong, Robert W Hunter, Wilna Oosthyuzen, Maciej Parys, Adam G Gow, Silke Salavati Schmitz, James W Dear, Richard J Mellanby

Faculty, Staff and Student Publications

BACKGROUND: Pancreatitis is an important cause of disease and death in dogs. Available circulating biomarkers are not sufficiently sensitive and specific for a definitive diagnosis.

HYPOTHESIS: Circulating microRNAs would be differentially expressed in dogs with chronic pancreatitis and could have potential as diagnostic biomarkers.

ANIMALS: Healthy controls (n = 19) and dogs with naturally occurring pancreatitis (n = 17).

METHODS: A retrospective case-control study. Dogs with pancreatitis were included if they satisfied diagnostic criteria for pancreatitis as adjudicated by 3 experts. MicroRNA was extracted from stored serum samples and sequenced. Reads were mapped to mature microRNA sequences in the canine, …


From Transcriptomics To Digital Twins Of Organ Function, Jens Hansen, Abhinav R Jain, Philip Nenov, Peter N Robinson, Ravi Iyengar Jan 2024

From Transcriptomics To Digital Twins Of Organ Function, Jens Hansen, Abhinav R Jain, Philip Nenov, Peter N Robinson, Ravi Iyengar

Faculty, Staff and Student Publications

Cell level functions underlie tissue and organ physiology. Gene expression patterns offer extensive views of the pathways and processes within and between cells. Single cell transcriptomics provides detailed information on gene expression within cells, cell types, subtypes and their relative proportions in organs. Functional pathways can be scalably connected to physiological functions at the cell and organ levels. Integrating experimentally obtained gene expression patterns with prior knowledge of pathway interactions enables identification of networks underlying whole cell functions such as growth, contractility, and secretion. These pathways can be computationally modeled using differential equations to simulate cell and organ physiological dynamics …


Phospholipid Metabolic Adaptation Promotes Survival Of Idh2 Mutant Acute Myeloid Leukemia Cells, Tatsuya Morishima, Koichi Takahashi, Desmond Wai Loon Chin, Yuxin Wang, Kenji Tokunaga, Yuichiro Arima, Masao Matsuoka, Toshio Suda, Hitoshi Takizawa Jan 2024

Phospholipid Metabolic Adaptation Promotes Survival Of Idh2 Mutant Acute Myeloid Leukemia Cells, Tatsuya Morishima, Koichi Takahashi, Desmond Wai Loon Chin, Yuxin Wang, Kenji Tokunaga, Yuichiro Arima, Masao Matsuoka, Toshio Suda, Hitoshi Takizawa

Faculty, Staff and Student Publications

Genetic mutations in the isocitrate dehydrogenase (IDH) gene that result in a pathological enzymatic activity to produce oncometabolite have been detected in acute myeloid leukemia (AML) patients. While specific inhibitors that target mutant IDH enzymes and normalize intracellular oncometabolite level have been developed, refractoriness and resistance has been reported. Since acquisition of pathological enzymatic activity is accompanied by the abrogation of the crucial WT IDH enzymatic activity in IDH mutant cells, aberrant metabolism in IDH mutant cells can potentially persist even after the normalization of intracellular oncometabolite level. Comparisons of isogenic AML cell lines with and without IDH2 gene mutations …


New Triazinephosphonate Dopants For Nafion Proton Exchange Membranes (Pem), Fátima C Teixeira, António P S Teixeira, C M Rangel Jan 2024

New Triazinephosphonate Dopants For Nafion Proton Exchange Membranes (Pem), Fátima C Teixeira, António P S Teixeira, C M Rangel

Faculty, Staff and Student Publications

A new paradigm for energy is underway demanding decarbonized energy systems. Some of them rely on emerging electrochemical devices, crucial in hydrogen technologies, including fuel cells, CO2 and water electrolysers, whose applications and performances depend on key components such as their separators/ion-exchange membranes. The most studied and already commercialized Nafion membrane shows great chemical stability, but its water content limits its high proton conduction to a limited range of operating temperatures. Here, we report the synthesis of a new series of triazinephosphonate derivatives and their use as dopants in the preparation of new modified Nafion membranes. The triazinephosphonate derivatives were …


Targeting The Renin-Angiotensin System (Ras) For Neuropsychiatric Disorders, Aline Silva De Miranda, Danielle S Macedo, Natalia P Rocha, Antonio L Teixeira Jan 2024

Targeting The Renin-Angiotensin System (Ras) For Neuropsychiatric Disorders, Aline Silva De Miranda, Danielle S Macedo, Natalia P Rocha, Antonio L Teixeira

Faculty, Staff and Student Publications

BACKGROUND: Neuropsychiatric disorders, such as mood disorders, schizophrenia, and Alzheimer's disease (AD) and related dementias, are associated to significant morbidity and mortality worldwide. The pathophysiological mechanisms of neuropsychiatric disorders remain to be fully elucidated, which has hampered the development of effective therapies. The Renin Angiotensin System (RAS) is classically viewed as a key regulator of cardiovascular and renal homeostasis. The discovery that RAS components are expressed in the brain pointed out a potential role for this system in central nervous system (CNS) pathologies. The understanding of RAS involvement in the pathogenesis of neuropsychiatric disorders may contribute to identifying novel therapeutic …


G-Quadruplex Dna And Rna In Cellular Senescence, Rocio Diaz Escarcega, Paul Marshall, Andrey S Tsvetkov Jan 2024

G-Quadruplex Dna And Rna In Cellular Senescence, Rocio Diaz Escarcega, Paul Marshall, Andrey S Tsvetkov

Faculty, Staff and Student Publications

Normal cells divide, are damaged, and are repaired across their lifetime. As cells age, they enter cellular senescence, characterized by a permanent state of cell-cycle arrest triggered by various stressors. The molecular mechanisms that regulate senescent phenotypes have been actively investigated over the last several decades; however, one area that has been neglected is how G-quadruplex (G4) DNA and RNA (G4-DNA and G4-RNA) mediate senescence. These non-canonical four-stranded DNA and RNA structures regulate most normative DNA and RNA-dependent processes, such as transcription, replication, and translation, as well as pathogenic mechanisms, including genomic instability and abnormal stress granule function. This review …


Induction Of Long-Term Hyperexcitability By Memory-Related Camp Signaling In Isolated Nociceptor Cell Bodies, Alexis Bavencoffe, Michael Y Zhu, Sanjay V Neerukonda, Kayla N Johnson, Carmen W Dessauer, Edgar T Walters Jan 2024

Induction Of Long-Term Hyperexcitability By Memory-Related Camp Signaling In Isolated Nociceptor Cell Bodies, Alexis Bavencoffe, Michael Y Zhu, Sanjay V Neerukonda, Kayla N Johnson, Carmen W Dessauer, Edgar T Walters

Faculty, Staff and Student Publications

Persistent hyperactivity of nociceptors is known to contribute significantly to long-lasting sensitization and ongoing pain in many clinical conditions. It is often assumed that nociceptor hyperactivity is mainly driven by continuing stimulation from inflammatory mediators. We have tested an additional possibility: that persistent increases in excitability promoting hyperactivity can be induced by a prototypical cellular signaling pathway long known to induce late-phase long-term potentiation (LTP) of synapses in brain regions involved in memory formation. This cAMP-PKA-CREB-gene transcription-protein synthesis pathway was tested using whole-cell current clamp methods on small dissociated sensory neurons (primarily nociceptors) from dorsal root ganglia (DRGs) excised from …


Clic1-Mediated Autophagy Confers Resistance To Ddp In Gastric Cancer, Zhen-Liang Nong, Kun Zhao, Ye Wang, Zhu Yu, Cong-Jun Wang, Jun-Qiang Chen Jan 2024

Clic1-Mediated Autophagy Confers Resistance To Ddp In Gastric Cancer, Zhen-Liang Nong, Kun Zhao, Ye Wang, Zhu Yu, Cong-Jun Wang, Jun-Qiang Chen

Faculty, Staff and Student Publications

Gastric cancer has been a constant concern to researchers as one of the most common malignant tumors worldwide. The treatment options for gastric cancer include surgery, chemotherapy and traditional Chinese medicine. Chemotherapy is an effective treatment for patients with advanced gastric cancer. Cisplatin (DDP) has been approved as a critical chemotherapy drug to treat various kinds of solid tumors. Although DDP is an effective chemotherapeutic agent, many patients develop drug resistance during treatment, which has become a severe problem in clinical chemotherapy. This study aims to investigate the mechanism of DDP resistance in gastric cancer. The results show that intracellular …


A Novel Assessment Of Whole-Mount Gleason Grading In Prostate Cancer To Identify Candidates For Radical Prostatectomy: A Machine Learning-Based Multiomics Study, Jing Ning, Clemens P Spielvogel, David Haberl, Karolina Trachtova, Stefan Stoiber, Sazan Rasul, Vojtech Bystry, Gabriel Wasinger, Pascal Baltzer, Elisabeth Gurnhofer, Gerald Timelthaler, Michaela Schlederer, Laszlo Papp, Helga Schachner, Thomas Helbich, Markus Hartenbach, Bernhard Grubmüller, Shahrokh F Shariat, Marcus Hacker, Alexander Haug, Lukas Kenner Jan 2024

A Novel Assessment Of Whole-Mount Gleason Grading In Prostate Cancer To Identify Candidates For Radical Prostatectomy: A Machine Learning-Based Multiomics Study, Jing Ning, Clemens P Spielvogel, David Haberl, Karolina Trachtova, Stefan Stoiber, Sazan Rasul, Vojtech Bystry, Gabriel Wasinger, Pascal Baltzer, Elisabeth Gurnhofer, Gerald Timelthaler, Michaela Schlederer, Laszlo Papp, Helga Schachner, Thomas Helbich, Markus Hartenbach, Bernhard Grubmüller, Shahrokh F Shariat, Marcus Hacker, Alexander Haug, Lukas Kenner

Faculty, Staff and Student Publications

Purpose: This study aims to assess whole-mount Gleason grading (GG) in prostate cancer (PCa) accurately using a multiomics machine learning (ML) model and to compare its performance with biopsy-proven GG (bxGG) assessment.

Materials and Methods: A total of 146 patients with PCa recruited in a pilot study of a prospective clinical trial (NCT02659527) were retrospectively included in the side study, all of whom underwent 68Ga-PSMA-11 integrated positron emission tomography (PET) / magnetic resonance (MR) before radical prostatectomy (RP) between May 2014 and April 2020. To establish a multiomics ML model, we quantified PET radiomics features, pathway-level genomics …


A Pthrp Gradient Drives Mandibular Condylar Chondrogenesis Via Runx2, C Tsutsumi-Arai, Y Arai, A Tran, M Salinas, Y Nakai, S Orikasa, W Ono, N Ono Jan 2024

A Pthrp Gradient Drives Mandibular Condylar Chondrogenesis Via Runx2, C Tsutsumi-Arai, Y Arai, A Tran, M Salinas, Y Nakai, S Orikasa, W Ono, N Ono

Faculty, Staff and Student Publications

The mandibular condylar cartilage (MCC) is an essential component of the temporomandibular joint, which orchestrates the vertical growth of the mandibular ramus through endochondral ossification with distinctive modes of cell differentiation. Parathyroid hormone–related protein (PTHrP) is a master regulator of chondrogenesis; in the long bone epiphyseal growth plate, PTHrP expressed by resting zone chondrocytes promotes chondrocyte proliferation in the adjacent layer. However, how PTHrP regulates chondrogenesis in the MCC remains largely unclear. In this study, we used a Pthrp-mCherry knock-in reporter strain to map the localization of PTHrP+ cells in the MCC and define the function of PTHrP in the …


Independent Regulation Of Piezo1 Activity By Principal And Intercalated Cells Of The Collecting Duct, Kyrylo Pyrshev, Anna Atamanchuk-Stavniichuk, Mariya Kordysh, Oleg Zaika, Viktor N Tomilin, Oleh Pochynyuk Jan 2024

Independent Regulation Of Piezo1 Activity By Principal And Intercalated Cells Of The Collecting Duct, Kyrylo Pyrshev, Anna Atamanchuk-Stavniichuk, Mariya Kordysh, Oleg Zaika, Viktor N Tomilin, Oleh Pochynyuk

Faculty, Staff and Student Publications

The renal collecting duct is continuously exposed to a wide spectrum of fluid flow rates and osmotic gradients. Expression of a mechanoactivated Piezo1 channel is the most prominent in the collecting duct. However, the status and regulation of Piezo1 in functionally distinct principal and intercalated cells (PCs and ICs) of the collecting duct remain to be determined. We used pharmacological Piezo1 activation to quantify Piezo1-mediated [Ca2+]i influx and single-channel activity separately in PCs and ICs of freshly isolated collecting ducts with fluorescence imaging and electrophysiological tools. We also employed a variety of systemic treatments to examine their consequences on Piezo1 …


Rare Genomic Copy Number Variants Implicate New Candidate Genes For Bicuspid Aortic Valve, Steven G Carlisle, Hasan Albasha, Hector I Michelena, Anna Sabate-Rotes, Lisa Bianco, Julie De Backer, Laura Muiño Mosquera, Anji T Yetman, Malenka M Bissell, Maria Grazia Andreassi, Ilenia Foffa, Dawn S Hui, Anthony Caffarelli, Yuli Y Kim, Dongchuan Guo, Rodolfo Citro, Margot De Marco, Justin T Tretter, Kim L Mcbride, Dianna M Milewicz, Simon C Body, Siddharth K Prakash, Ebav Investigators, Bavcon Investigators Jan 2024

Rare Genomic Copy Number Variants Implicate New Candidate Genes For Bicuspid Aortic Valve, Steven G Carlisle, Hasan Albasha, Hector I Michelena, Anna Sabate-Rotes, Lisa Bianco, Julie De Backer, Laura Muiño Mosquera, Anji T Yetman, Malenka M Bissell, Maria Grazia Andreassi, Ilenia Foffa, Dawn S Hui, Anthony Caffarelli, Yuli Y Kim, Dongchuan Guo, Rodolfo Citro, Margot De Marco, Justin T Tretter, Kim L Mcbride, Dianna M Milewicz, Simon C Body, Siddharth K Prakash, Ebav Investigators, Bavcon Investigators

Faculty, Staff and Student Publications

Bicuspid aortic valve (BAV), the most common congenital heart defect, is a major cause of aortic valve disease requiring valve interventions and thoracic aortic aneurysms predisposing to acute aortic dissections. The spectrum of BAV ranges from early onset valve and aortic complications (EBAV) to sporadic late onset disease. Rare genomic copy number variants (CNVs) have previously been implicated in the development of BAV and thoracic aortic aneurysms. We determined the frequency and gene content of rare CNVs in EBAV probands (n = 272) using genome-wide SNP microarray analysis and three complementary CNV detection algorithms (cnvPartition, PennCNV, and QuantiSNP). Unselected control …


Reporting Quality Of Endoscopic Colorectal Cancer Screening Randomized Controlled Trials: Adherence To Recommendations And Interventions, Fouad Jaber, Khalid Ahmed, Osama Hamid, Willie Mohammed Johnson, Saqr Alsakarneh, Abubaker O Abdalla, Yazan Abboud, Mouhand Mohamed, Dushyant Singh Dahiya, Shifa Umar, Mohamed Abdallah, Mohammad Bilal, Aasma Shaukat Jan 2024

Reporting Quality Of Endoscopic Colorectal Cancer Screening Randomized Controlled Trials: Adherence To Recommendations And Interventions, Fouad Jaber, Khalid Ahmed, Osama Hamid, Willie Mohammed Johnson, Saqr Alsakarneh, Abubaker O Abdalla, Yazan Abboud, Mouhand Mohamed, Dushyant Singh Dahiya, Shifa Umar, Mohamed Abdallah, Mohammad Bilal, Aasma Shaukat

Faculty, Staff and Student Publications

BACKGROUND AND AIMS: In 2013, the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) steering group published recommendations to standardize reporting quality in randomized controlled trials (RCTs). We aim to assess adherence to SPIRIT reporting guidelines in RCTs on endoscopic colorectal cancer (CRC) screening and participants' adherence to trial protocols.

METHODS: We searched databases for RCTs evaluating flexible sigmoidoscopy or colonoscopy for CRC screening published in English language through September 2023. Each eligible study was evaluated using the 8 core SPIRIT statement areas, totaling 51 points. Each item received 1 point if it met the criteria and 0 points if …


The Immunobiology Of Myelodysplastic Neoplasms: A Mini-Review, Shruthi Kannan, Rolando A Vedia, Jeffrey J Molldrem Jan 2024

The Immunobiology Of Myelodysplastic Neoplasms: A Mini-Review, Shruthi Kannan, Rolando A Vedia, Jeffrey J Molldrem

Faculty, Staff and Student Publications

This mini review summarizes the immunobiology of myelodysplastic syndromes, specifically focusing on the interactions between immune cells, cytokines, and dysplastic cells within the tumor microenvironment in the bone marrow. We elucidate in detail how immune dysregulation and evasion influence the initiation and progression of myelodysplastic syndromes, as well as resistance to therapy and progression to AML. In addition, we highlight a range of therapeutic strategies, including the most recent breakthroughs and experimental therapies for treating MDS. Finally, we address the existing knowledge gaps in the understanding of the immunobiology of MDS and propose future research directions, promising advancements toward enhancing …


Nasal Bots Carry Relevant Titers Of Cwd Prions In Naturally Infected White-Tailed Deer, Paulina Soto, Francisca Bravo-Risi, Carlos Kramm, Nazaret Gamez, Rebeca Benavente, Denise L Bonilla, J Hunter Reed, Mitch Lockwood, Terry R Spraker, Tracy Nichols, Rodrigo Morales Jan 2024

Nasal Bots Carry Relevant Titers Of Cwd Prions In Naturally Infected White-Tailed Deer, Paulina Soto, Francisca Bravo-Risi, Carlos Kramm, Nazaret Gamez, Rebeca Benavente, Denise L Bonilla, J Hunter Reed, Mitch Lockwood, Terry R Spraker, Tracy Nichols, Rodrigo Morales

Faculty, Staff and Student Publications

Chronic wasting disease (CWD) is a prion disease affecting farmed and free-ranging cervids. CWD is rapidly expanding across North America and its mechanisms of transmission are not completely understood. Considering that cervids are commonly afflicted by nasal bot flies, we tested the potential of these parasites to transmit CWD. Parasites collected from naturally infected white-tailed deer were evaluated for their prion content using the protein misfolding cyclic amplification (PMCA) technology and bioassays. Here, we describe PMCA seeding activity in nasal bot larvae collected from naturally infected, nonclinical deer. These parasites efficiently infect CWD-susceptible mice in ways suggestive of high infectivity …


Laboratory Evaluation Of Essential Oils Extracted From Peppermint And Eucalyptus Plants Against The Rat Flea (Xynopsylla Cheopis) And Evaluate Their Effects On Some Vital Process In Albino Rat, Rasha Ragheb Hassan, Micheal William Mikhail Jan 2024

Laboratory Evaluation Of Essential Oils Extracted From Peppermint And Eucalyptus Plants Against The Rat Flea (Xynopsylla Cheopis) And Evaluate Their Effects On Some Vital Process In Albino Rat, Rasha Ragheb Hassan, Micheal William Mikhail

Journal of Medicine in Scientific Research

The effectiveness of peppermint and eucalyptus oils was examined in the current study to the rat fleas (Xenopsylla cheopis). The constituents of each oil were identified by GC-MS. The LC50 and LC90 for each essential oil were calculated after 1 and 24 hours exposure. The effect of peppermint and eucalyptus oils on some vital process in albino rat treated with 1/10 and 1/20 of LD50 were studied for the ALT, AST, Urea and creatinine levels. TNF-α and IL-6 levels also were studied. Data indicated that peppermint essential oil had more efficacy than that of eucalyptus for 1 and 24 hours …


Evaluation Of Iron, Zinc And Vitamin D Deficiencies In Children With Autism Spectrum Disorder At The Hearing And Speech Institute, In Egypt, Azza Samy, Iman Elrouby, Eman S. Eldin, Eman S. Abd El-Ghaffar Jan 2024

Evaluation Of Iron, Zinc And Vitamin D Deficiencies In Children With Autism Spectrum Disorder At The Hearing And Speech Institute, In Egypt, Azza Samy, Iman Elrouby, Eman S. Eldin, Eman S. Abd El-Ghaffar

Journal of Medicine in Scientific Research

Background Autism spectrum disorder (ASD) is a complex neurodevelopment disorder with a multifactorial etiology. Each iron, zinc and vitamin D are essential for cognitive, behavioral and motor development. Deficiency of any of these micronutrients may affect ASD symptoms.

Objective The aim of this study is to evaluate and compare the level of iron, zinc and vitamin D levels in children with autism spectrum disorder (ASD) with normal children and to associate between the deficiency of these nutrient elements and the severity of ASD symptoms, in order to help in improvement of ASD symptoms by supplying the deficient elements.

Patients and …


Degradable Staples And Delivery Device, Meha Elango, Jessica Cabrera, Makayla Scarpitti, Kareemat Melaiye Jan 2024

Degradable Staples And Delivery Device, Meha Elango, Jessica Cabrera, Makayla Scarpitti, Kareemat Melaiye

Williams Honors College, Honors Research Projects

The scope of this project is to design a method to secure skin grafts to healthy tissue. The ultimate goal for the proposed method is to be dissolvable in some form. Currently, skin grafts procedures utilize staples in most cases to hold a skin graft in place, but there are disadvantages that come with it. Staples are easy to place, but time consuming during the removal procedure. They also cause a lot of pain and discomfort for the patient. The goal of this project is to determine a way a secure skin grafts to healthy skin in order to reduce …


Evaluation Of A Novel 3d-Printed Task Trainer For The Simulation Of Gynecological Procedures At A Medical Academic Center, Jami Monico, Karen S. Carlson Jan 2024

Evaluation Of A Novel 3d-Printed Task Trainer For The Simulation Of Gynecological Procedures At A Medical Academic Center, Jami Monico, Karen S. Carlson

Manuscripts: Obstetrics & Gynecology

Introduction

Learning and mastering the performance of gynecological procedures in a secure and supervised simulation setting is important for learners, especially in the early phases of medical education. This project aims to assess the efficacy of an innovative gynecological task trainer for diverse simulation sessions. Following engagement with the task trainer, learners evaluated their experiences with a comprehensive questionnaire. The results of the survey were scientifically analyzed and interpreted.

Methods

The innovative gynecological task trainer was created with 3D-printed plastic, silicone, and a tabletop base. Learners engaged in simulations in which they performed gynecologic procedures using the task trainer. Subsequently, …


The Body Shamer Within: Incorporating The Teaching Of Weight Bias Internalization Into Weight Bias Education, Jessica Koran-Scholl, Birgit Khandalavala Jan 2024

The Body Shamer Within: Incorporating The Teaching Of Weight Bias Internalization Into Weight Bias Education, Jessica Koran-Scholl, Birgit Khandalavala

Posters and Presentations: Family Medicine

No abstract provided.


Feasibility And Safety Of Early Post-Covid-19 High-Intensity Gait Training: A Pilot Study, Joakim Halvorsen, Christopher Henderson, Wendy Romney, Magnus Hågå, Tonje Barkenæs Eggen, Jan Egil Nordvik, Ingvild Rosseland, Jennifer Moore Jan 2024

Feasibility And Safety Of Early Post-Covid-19 High-Intensity Gait Training: A Pilot Study, Joakim Halvorsen, Christopher Henderson, Wendy Romney, Magnus Hågå, Tonje Barkenæs Eggen, Jan Egil Nordvik, Ingvild Rosseland, Jennifer Moore

Physical Therapy Faculty Publications

Background: The feasibility and safety of rehabilitation interventions for individuals recovering from COVID-19 after the acute stage is not well understood. This pilot study aims to provide a preliminary investigation of the feasibility and safety of providing high-intensity gait training (HIT) with a targeted cardiovascular intensity of 70–85% of the age-predicted maximum heart rate (HRmax) for individuals undergoing rehabilitation post-COVID-19. Methods: Consecutive patients who were medically cleared for HIT were invited to participate in the study. Participants practiced walking in varied contexts (treadmill, overground, and stairs), aiming to spend as much time as possible within their target cardiovascular intensity zone …


Radiation Induced Skin Fibrosis (Risf): Opportunity For Angiotensin Ii-Dependent Intervention, Patricia F. Boothe, Vidya P. Kumar, Yali Kong, Kan Wang, Howard Levinson, David Mu, Milton L. Brown Jan 2024

Radiation Induced Skin Fibrosis (Risf): Opportunity For Angiotensin Ii-Dependent Intervention, Patricia F. Boothe, Vidya P. Kumar, Yali Kong, Kan Wang, Howard Levinson, David Mu, Milton L. Brown

Department of Biomedical and Translational Sciences Faculty Publications

Medical procedures, such as radiation therapy, are a vital element in treating many cancers, significantly contributing to improved survival rates. However, a common long-term complication of such exposure is radiation-induced skin fibrosis (RISF), a complex condition that poses substantial physical and psychological challenges. Notably, about 50% of patients undergoing radiation therapy may achieve long-term remission, resulting in a significant number of survivors managing the aftereffects of their treatment. This article delves into the intricate relationship between RISF, reactive oxygen species (ROS), and angiotensin II (Ang II) signaling. It proposes the underlying mechanisms and examines potential treatments for mitigating skin fibrosis. …


Predicting Radiation-Induced Immune Suppression In Lung Cancer Patients Treated With Stereotactic Body Radiation Therapy, Jonathan Colen, Cam Nguyen, Seth W. Liyanage, Eric Aliotta, Joe Chen, Clayton Alonso, Kara Romano, Sean Peach, Timothy Showalter, Paul Read, James Larner, Krishni Wijesooriya Jan 2024

Predicting Radiation-Induced Immune Suppression In Lung Cancer Patients Treated With Stereotactic Body Radiation Therapy, Jonathan Colen, Cam Nguyen, Seth W. Liyanage, Eric Aliotta, Joe Chen, Clayton Alonso, Kara Romano, Sean Peach, Timothy Showalter, Paul Read, James Larner, Krishni Wijesooriya

Data Science Faculty Publications

BACKGROUND: Stereotactic body radiation therapy (SBRT) is known to modulate the immune system and contribute to the generation of anti-tumor T cells and stimulate T cell infiltration into tumors. Radiation-induced immune suppression (RIIS) is a side effect of radiation therapy that can decrease immunological function by killing naive T cells as well as SBRT-induced newly created effector T cells, suppressing the immune response to tumors and increasing susceptibility to infections.

PURPOSE: RIIS varies substantially among patients and it is currently unclear what drives this variability. Models that can accurately predict RIIS in near real time based on treatment plan characteristics …


High-Grade B-Cell Lymphoma, Not Otherwise Specified: Cns Involvement And Outcomes In A Multi-Institutional Series, Narendranath Epperla, Adam S. Zayac, Daniel J. Landsburg, Allison M. Bock, Grzegorz S. Nowakowski, Emily C. Ayers, Mark Girton, Marie Hu, Amy Beckman, Shaoying Li, L Jeffrey Medeiros, Julie E. Chang, Habibe Kurt, Jose Sandoval-Sus, Mohammad Ali Ansari-Lari, Shalin K. Kothari, Anna Kress, Mina L. Xu, Pallawi Torka, Suchitra Sundaram, Stephen D. Smith, Kikkeri N. Naresh, Yasmin Karimi, David A. Bond, Andrew M. Evens, Seema G. Naik, Manali Kamdar, Bradley M. Haverkos, Reem Karmali, Umar Farooq, Julie M. Vose, Paul Rubinstein, Amina Chaudhry, Adam J. Olszewski Jan 2024

High-Grade B-Cell Lymphoma, Not Otherwise Specified: Cns Involvement And Outcomes In A Multi-Institutional Series, Narendranath Epperla, Adam S. Zayac, Daniel J. Landsburg, Allison M. Bock, Grzegorz S. Nowakowski, Emily C. Ayers, Mark Girton, Marie Hu, Amy Beckman, Shaoying Li, L Jeffrey Medeiros, Julie E. Chang, Habibe Kurt, Jose Sandoval-Sus, Mohammad Ali Ansari-Lari, Shalin K. Kothari, Anna Kress, Mina L. Xu, Pallawi Torka, Suchitra Sundaram, Stephen D. Smith, Kikkeri N. Naresh, Yasmin Karimi, David A. Bond, Andrew M. Evens, Seema G. Naik, Manali Kamdar, Bradley M. Haverkos, Reem Karmali, Umar Farooq, Julie M. Vose, Paul Rubinstein, Amina Chaudhry, Adam J. Olszewski

Journal Articles: Oncology and Hematology

Little is known about the central nervous system (CNS) risk in high-grade B-cell lymphoma, not otherwise specified (HGBL NOS). Hence, we sought to describe the rates of baseline CNS involvement, risk of CNS recurrence after primary therapy, and management strategies in HGBL NOS. In this multicenter retrospective study, we included 160 adults with newly diagnosed HGBL NOS treated between 2016 and 2021 at 20 US institutions. Eleven patients (7%) had baseline CNS involvement at diagnosis (leptomeningeal = 6, parenchymal = 4, and both = 1). Baseline CNS involvement was significantly associated only with MYC rearrangement (OR = 3.5) and testicular …


High-Grade B-Cell Lymphoma Not Otherwise Specified, With Diffuse Large B-Cell Lymphoma Gene Expression Signatures: Genomic Analysis And Potential Therapeutics, Waseem G. Lone, Alyssa Bouska, Tyler A. Herek, Catalina Amador, Joo Song, Alexander M. Xu, Dylan T. Jochum, Issa Ismail Issa, Dennis D. Weisenburger, Xuan Zhang, Sharath Kumar Bhagavathi, Tayla B. Heavican-Foral, Sunandini Sharma, Ab Rauf Shah, Abdul Rouf Mir, Aisha Ahmad Alkhinji, Dalia El-Gamal, Bhavana J. Dave, Keenan Hartert, Jiayu Yu, Mallick Saumyaranjan, Timothy C. Greiner, Julie M. Vose, Timothy W. Mckeithan, Kai Fu, Michael Green, Chengfeng Bi, Akil Merchant, Wing C. Chan, Javeed Iqbal Jan 2024

High-Grade B-Cell Lymphoma Not Otherwise Specified, With Diffuse Large B-Cell Lymphoma Gene Expression Signatures: Genomic Analysis And Potential Therapeutics, Waseem G. Lone, Alyssa Bouska, Tyler A. Herek, Catalina Amador, Joo Song, Alexander M. Xu, Dylan T. Jochum, Issa Ismail Issa, Dennis D. Weisenburger, Xuan Zhang, Sharath Kumar Bhagavathi, Tayla B. Heavican-Foral, Sunandini Sharma, Ab Rauf Shah, Abdul Rouf Mir, Aisha Ahmad Alkhinji, Dalia El-Gamal, Bhavana J. Dave, Keenan Hartert, Jiayu Yu, Mallick Saumyaranjan, Timothy C. Greiner, Julie M. Vose, Timothy W. Mckeithan, Kai Fu, Michael Green, Chengfeng Bi, Akil Merchant, Wing C. Chan, Javeed Iqbal

Journal Articles: Oncology and Hematology

High-grade B-cell lymphoma not otherwise specified (HGBCL, NOS) has overlapping morphological and genetic features with diffuse large B-cell lymphoma (DLBCL) and Burkitt lymphoma (BL), leading to uncertainty in its diagnosis and clinical management. Using functional genomic approaches, we previously characterized HGBCL and NOS, that demonstrate gene expression profiling (GEP), and genetic signatures similar to BL. Herein, we characterize distinct HGBCL, NOS, cohort (n = 55) in adults (n = 45) and in children (n = 10), and compared the GEP, genomic DNA copy number (CN), and mutational spectrum with de novo DLBCL (n = 85) and BL (n = 52). …


Improving Health Outcomes In Children And Adolescents With Asthma, Elizabeth Kate Coffey Moore Jan 2024

Improving Health Outcomes In Children And Adolescents With Asthma, Elizabeth Kate Coffey Moore

Theses and Dissertations (ETD)

Asthma is among the most prevalent chronic illnesses found in the United States, affecting millions of people under the age of 18 each year. The disease burden for affected children, adolescents, their families, and the healthcare system is immense. Finding ways to mitigate its impact is critical to improving the lives of affected children, adolescents, and their families. The three chapters included in this dissertation aimed to document the asthma triggers that children and adolescents are exposed to and strategies for reducing them and to demonstrate using Imogene King’s conceptual framework to guide nursing practice to care for and nursing …