Life Sciences Commons^™

Field Evaluation Of Perennial Ryegrass Selected For Aluminum Tolerance On Fertile Soils, D M. Wheeler, D R. Smith, D C. Edmeades

IGC Proceedings (1977-2023)

The progeny from 23 perennial ryegrass (Lolium perenne L.) plants which were selected for aluminium (Al) tolerance using a low ionic strength nutrient culture technique, were grown in nursery and field trial, to evaluate the agronomic performance in a fertile soil (i.e., in the absence of stress), There were no differences between the progeny from the Al-tolerant selected plan1s in the lines with low Argentine stem weevil (Listronotus bonariensis) damage and commercial cultivars in the nursery trial. There were also no differences in dry matter yield between an Al selection line consisting of seed bulked from 2 …

Use Of Ld (Linz-Donawitz) Slag As A Liming Material In The Basque Country (Spain): Effect On Chemical Composition Of Pastures, M Pinto, M Rodriguez, C Trueba

IGC Proceedings (1977-2023)

LD (Lintz-Donawit:i:) slag is an iron industry by-product generated at a rate of 10 million I/year in Europe. Its chemical composition (45% Cao and 8% Mg2O) seemed to indicate that a good way of re­utilisation of this waste would be Its use as a corrector of pH for acid soils. The slag effect on chemical composition and yield has been studied in grasslands in the Basque Country during a 2-year field trial. Two different pastures have been considered, Derio (pH 4.75), a resown loliwn pere1me-Trifoli11m repens pasture, and Abadiano (pH 5.45), a natural prairie. Previous studies have shown that slag …

Effect Of Inorganic Nitrogen And Cow Slurry On Yield And Nitrogen Losses In A Natural Pasture In The Basque Country (Spain), J M. Esta Villo, C Gonzalez-Murua, M Rodriguez

IGC Proceedings (1977-2023)

Inappropriate use of fertilisers can cause large losses of nitrogen (N) from the system with different ecological consequences. This study tried to make a first approach to N cycling by comparing N inputs and outputs in an imperfectly drained natural grassland soil receiving different rates of N fertiliser as ammonium nitrate or cow slurry, The acetylene inhibition technique· is used for measuring denitrification, Fertiliser response and decrease in white clover (Trifolium repens) content was greater for the inorganic treatment. The highest rates of denitrification occurred when nitrate and soil water were high. Losses in the inorganic treatment were …

Identifying Invasive Species Sightings From Geoai-Validated Social Media Posts, Nathan Fox, Derek Van Berkel

I-GUIDE Forum

The spread of invasive species requires scalable monitoring techniques to help guide management and conservation strategies. Here, we explore the potential of GeoAI for the rapid validation of invasive species sightings through social media data. We utilized the Flickr API to retrieve 23,000 images from posts that contained the names of 72 invasive species across various taxonomic categories within the contiguous USA. Then using BioCLIP, a computer vision model capable of identifying over 450,000 species, we assessed whether these posts genuinely contained the species that the user tagged. Results varied, with some species like the European Starling showing high match …

Phosphorylation-Driven Epichaperome Assembly Is A Regulator Of Cellular Adaptability And Proliferation., Tanaya Roychowdhury, Seth W Mcnutt, Chiranjeevi Pasala, Hieu Nguyen, Daniel T Thornton, Sahil Sharma, Luke Botticelli, Chander S Digwal, Suhasini Joshi, Nan Yang, Palak Panchal, Souparna Chakrabarty, Sadik Bay, Vladimir Markov, Charlene Kwong, Jeanine Lisanti, Sun Young Chung, Stephen D Ginsberg, Pengrong Yan, Elisa De Stanchina, Adriana Corben, Shanu Modi, Mary Alpaugh, Giorgio Colombo, Hediye Erdjument-Bromage, Thomas A Neubert, Robert J Chalkley, Peter R Baker, Alma L Burlingame, Anna Rodina, Gabriela Chiosis, Feixia Chu

College of Science & Mathematics Departmental Research

The intricate network of protein-chaperone interactions is crucial for maintaining cellular function. Recent discoveries have unveiled the existence of specialized chaperone assemblies, known as epichaperomes, which serve as scaffolding platforms that orchestrate the reconfiguration of protein-protein interaction networks, thereby enhancing cellular adaptability and proliferation. This study explores the structural and regulatory aspects of epichaperomes, with a particular focus on the role of post-translational modifications (PTMs) in their formation and function. A key finding is the identification of specific PTMs on HSP90, particularly at residues Ser226 and Ser255 within an intrinsically disordered region, as critical determinants of epichaperome assembly. Our data …

Oregon State Rank Assessment For Warner Basin Tui Chub (Siphateles Bicolor Ssp. 15), Eleanor P. Gaines, Jesse Laney

Institute for Natural Resources Publications

Oregon state conservation status assessment for Warner Basin tui chub (Siphateles bicolor ssp. 15) using NatureServe methodology, 2024.

How To Communicate Your Estate Plan To Family When Dividing Assets Unequally, Anastasia Meyer

Cornhusker Economics

Provides a guide on how to effectively approach estate planning conversations with family members.

Effectively communicating an estate plan with unequal division of assets can be challenging, but approaching it with honesty, clarity, and empathy can help prevent misunderstandings and family disputes. Open, respectful dialogue—paired with thoughtful explanations and transparent documentation—ensures that your family understands your intentions and feels valued, even when tough decisions are involved.

Ultimately, your goal isn’t just to pass down financial assets, but also to preserve family harmony and, where applicable, secure the future of a viable business. By fostering open communication, you can create a …

Effect Of In-Row Spacing On Weed Suppression And Yield Of ‘Covington’ And ‘Monaco’ Sweetpotato, Emmanuel G. Cooper, Stephen L. Meyers, Katherine Jennings, Ashley Adair, Kevin D. Gibson, William G. Johnson

Department of Horticulture & Landscape Architecture Faculty Publications

Organic sweetpotato growers have limited effective weed management options, and most rely on in-season between-row cultivation and hand weeding, which are time consuming, are costly, and deteriorate soil quality. Studies were conducted at the Samuel G. Meigs Horticulture Research Farm, Lafayette, IN, and at the Southwest Purdue Agricultural Center, Vincennes, IN, in 2022 and 2023 to determine the effects of in-row plant spacing and cultivar selection on weed suppression and organic sweetpotato yield. The experiment was a split-split plot design, with in-row spacings of 20, 30, and 40 cm as the main plot factor, weeding frequency (critical weed-free period and …

The Pivotal Role Of Evaporation In Lake Water Isotopic Variability Across Space And Time In A High Arctic Periglacial Landscape, Pete D. Akers, Ben Kopec, Eric S. Klein, Hannah Bailey, Jeffrey M. Welker

Michigan Tech Publications

Rapidly changing climate is disrupting the High Arctic's water systems. As tracers of hydrological processes, stable water isotopes can be used for high quality monitoring of Arctic waters to better reconstruct past changes and assess future environmental threats. However, logistical challenges typically limit the length and scope of isotopic monitoring in High Arctic landscapes. Here, we present a comprehensive isotopic survey of 535 water samples taken in 2018 and 2019 of the lakes and other surface waters of the periglacial Pituffik Peninsula in far northwest Greenland. The δ18O, δ2H, and deuterium-excess values of these samples, representing 196 unique sites, grant …

Bridging Big Data In The Enigma Consortium To Combine Non-Equivalent Cognitive Measures, Eamonn Kennedy, Shashank Vadlamani, Hannah M Lindsey, Pui-Wa Lei, Mary Jo-Pugh, David F Tate, Emily L Dennis, Elisabeth A Wilde, Enigma Clinical Endpoints Working Group Collaborators

Faculty, Staff and Student Publications

Investigators in neuroscience have turned to Big Data to address replication and reliability issues by increasing sample size. These efforts unveil new questions about how to integrate data across distinct sources and instruments. The goal of this study was to link scores across common auditory verbal learning tasks (AVLTs). This international secondary analysis aggregated multisite raw data for AVLTs across 53 studies totaling 10,505 individuals. Using the ComBat-GAM algorithm, we isolated and removed the component of memory scores associated with site effects while preserving instrumental effects. After adjustment, a continuous item response theory model used multiple memory items of varying …

Immuneapp For Hla-I Epitope Prediction And Immunopeptidome Analysis, Haodong Xu, Ruifeng Hu, Xianjun Dong, Lan Kuang, Wenchao Zhang, Zhihong Li

Faculty, Staff and Student Publications

Advances in mass spectrometry accelerates the characterization of HLA ligandome, necessitating the development of efficient methods for immunopeptidomics analysis and (neo)antigen prediction. We develop ImmuneApp, an interpretable deep learning framework trained on extensive HLA ligand datasets, which improves the prediction of HLA-I epitopes, prioritizes neoepitopes, and enhances immunopeptidomics deconvolution. ImmuneApp extracts informative embeddings and identifies key residues for pHLA binding. We also present a more accurate model-based deconvolution approach and systematically analyzed 216 multi-allelic immunopeptidomics samples, identifying 835,551 ligands restricted to over 100 HLA-I alleles. Our investigation reveals the effectiveness of the composite model, denoted as ImmuneApp-MA, which integrates mono- …

A Long-Recognized But Undescribed New Species Of Cyprinella (Cypriniformes: Leuciscidae) From North Carolina And South Carolina, United States, Bryn H. Tracy, Fred C. Rohde, Michael A. Perkins, Laura M. Lee, Kara B. Carlson, Madelyn Mccutcheon, Brena K. Jones, Heather K. Evans

Southeastern Fishes Council Proceedings

Cyprinella leptocheilus sp. nov., Siouan Thinlip Chub, is described as a new species that is endemic to Sand Hills and upper Coastal Plain streams in North Carolina and South Carolina. Recognized as an undescribed species since the early 1970s, this fish was known in the literature and in museum electronic databases as Hybopsis n. sp., H. sp. cf. zanema, Cyprinella n. sp., and C. sp. cf. zanema. Unofficially, it had gone by the common name Thinlip Chub. It was thought to be closely related to the two other barbeled Cyprinella species: Thicklip Chub, …

Neural Correlates Of Socially Rewarding Memories In Posttraumatic Stress Disorder, Kyle P. Blidy

MUSC Theses and Dissertations

Significance. Memory disturbances for emotional content are central to PTSD, yet most research focuses on trauma memories. Recent evidence suggests that enhancing access to positive memories could improve mood, affect regulation, self-esteem, and integration of trauma memories. However, the neurocognitive mechanisms underlying positive memory encoding in PTSD are poorly understood. No study has examined memory for positive social items in PTSD, which is important because PTSD entails social withdrawal and reduced accessibility to positive memory. Additionally, positive memories embedded in a social context have enhanced subjective value and strengthening their accessibility may confer greater benefits to wellbeing compared to non-social …

Antimetastatic Effect Of Nanodiamond-Conjugated Quercetin Against Colon Cancer: An In Vivo Study, Firli Rahmah Primula Dewi, Sephia Tiara Marviella, Sri Puji Astuti Wahyuningsih, A'Liyatur Rosyidah, Vuanghao Lim, Lionel Lian Aun In, Amy Yi Hsan Saik, Bimaji Ariyogo, Mee Lee Looi

Turkish Journal of Biology

Background/aim: Quercetin (Q) is a compound that can inhibit the growth of cancer cells in the colon; however, to do so, a high dose is needed, requiring a drug delivery system to target cancer endothelial cells directly. This study investigates the potency of nanodiamond-conjugated quercetin (NDQ) as an anticancer drug against colon cancer in Rattus norvegicus induced by N-methyl N-Nitrosourea (MNU). Materials and methods: This study is experimental-based and was designed using a six-group treatment method, namely normal control (KN: not treated by MNU, nanodiamond (ND), or Q); negative control (K–: treated by MNU); positive control (K+: treated by MNU …

Disappearance Of Cdc14 From The Daughter Spindle Pole Body Requires Glc7-Bud14, İdi̇l Kirdök, Ayşe Koca Çaydaşi

Turkish Journal of Biology

Background/aim: The conserved phosphatase Cdc14 facilitates mitotic exit in budding yeast by counteracting mitotic Cyclin Dependent Kinase activity. Cdc14 is kept in the nucleolus until anaphase-onset, when its released transiently into the nucleoplasm. In late-anaphase, Cdc14 is fully released into the cytoplasm upon activation of the Mitotic Exit Network (MEN) to trigger mitotic exit. Cdc14 also localizes to yeast Spindle Pole Bodies (SPB) in anaphase and dephosphorylates key targets that resides at SPBs to license SPB duplication and prime the MEN. Protein Phosphatase 1 (Glc7) with its regulatory-subunit Bud14 is another phosphatase that plays a key role in spatiotemporal control …

Correction Of Griscelli Syndrome Type 2 Causing Mutations In The Rab27a Gene With Crispr/Cas9, Özgür Doğuş Erol, Şi̇mal Şenocak, Burcu Özçi̇men, Gülen Güney Esken, Hasan Basri̇ Kiliç, Yusuf Çeti̇n Kocaefe, Niek Peter Van Til, Fatima Aerts Kaya

Turkish Journal of Biology

Background/aimGriscelli Syndrome Type 2 (GS-2) is a rare, inherited immune deficiency caused by a mutation in the RAB27A gene. Current treatment consists of hematopoietic stem cell transplantation. Lack of suitable donors warrants the development of alternative treatment strategies, including gene therapy. The development of mutation-specific CRISPR/Cas9 gene editing technology has opened the way for custom designed gene correction of patient-derived stem cells. Here, we aimed to custom design CRISPR/Cas9 constructs and test their efficiency of homology directed repair (HDR) on the correction of exon 3 and exon 7 mutations in the RAB27A gene of GS-2 patient-derived mesenchymal stem cells (MSCs) …

Delivery Of Bikdd Proapoptotic Gene In Peptide-18 Targeted Poly(2-Oxazoline)-Dope Nanoliposomes For Breast Cancer Models, Zeynep Büşra Bolat, Ayça Ece Nezi̇r, Ongun Mehmet Saka, Itir Ebru Zemheri̇, Sevgi̇ Gülyüz, Umut Uğur Özköse, Özgür Yilmaz, Asuman Bozkir, Di̇lek Telci̇, Fi̇kretti̇n Şahi̇n

Turkish Journal of Biology

Breast cancer is the most common cancer type and the major cause of death in females worldwide. For effective breast cancer treatment, systems with promising delivery of anticancer agents is an important strategy. Peptide 18 (P18), a tumor homing peptide, shows high binding affinity towards breast cancer cells. Nanoliposomes are known to have enhanced accumulation ability in tumors with longer systemic circulation. Poly (2-ethyl-2-oxazoline) (PEtOx) polymers conjugated with DOPE were used to prepare PEtOx-DOPE nanoliposomes. BikDD is a mutant form of Bik gene, a member of the BH3-only proapoptotic genes, mimics the constitutively phosphorylated form of the gene. To the …

Pterostilbene Suppresses Head And Neck Cancer Cell Proliferation Via Induction Of Apoptosis, Tali̇h Özdaş, Si̇bel Özdaş, İpek Canatar, Erdem Kaypak

Turkish Journal of Biology

Background/aim: Head and neck cancer (HNC) is one of the most prevalent causes of death worldwide, and the discovery of anticancer agents for its prevention is very important. Pterostilbene (PS) is a trans-stilbene reported to be beneficial in managing various cancers. The objective of the study was to evaluate the cytotoxic, anti-proliferative, pro-apoptotic and anti-migrative effect of PS on HEp-2, SCC-90, SCC-9, FaDu and Detroit-551 cell lines. Materials and Methods: MTT and live/dead assays were employed to assess cell-viability, while cell migration test was performed to evaluate wound healing capacity. The mRNA, protein and intracellular expression level of CASP-3, BAX …

Optical Imaging And Gene Transfection Potential Of Linear Polyethylenimine Coated Ag2s Near-Infrared Quantum Dots, Altay Savalan

Turkish Journal of Biology

Background/aimApplication of biocompatible heavy metal free and cationic Ag2S NIR QDs, which are highly luminesce in the medical range (700-900 nm), as a non-viral gene delivery system paves the way to overcome the auto-fluorescence and easily track the delivery of the genes in real time as it happens.Materials and methodsHere, the newly developed small and colloidally stable 2-mercaptopropionic acid (MPA)-capped Ag2S aqueous quantum dots electrostatically complexed with linear polyethyleneimine (LPEI) (Ag2S@2MPA/LPEI) was investigated for the first time both as a strong fluorescent probe and as a non-viral gene delivery vector for the highest tracking of the system and delivery of …

Reproduction Has Immediate Effects On Female Mortality, But No Discernible Lasting Physiological Impacts: A Test Of The Disposable Soma Theory, Sharon E Mitchell, Megan Simpson, Lena Coulet, Solenn Gouedard, Catherine Hambly, Juliano Morimoto, David B Allison, John R Speakman

Children’s Nutrition Research Center Staff Publications

The disposable soma theory (DST) posits that organisms age and die because of a direct trade-off in resource allocation between reproduction and somatic maintenance. DST predicts that investments in reproduction accentuate somatic damage which increase senescence and shortens lifespan. Here, we directly tested DST predictions in breeding and nonbreeding female C57BL/6J mice. We measured reproductive outputs, body composition, daily energy expenditure, and oxidative stress at peak lactation and over lifetime. We found that reproduction had an immediate and negative effect on survival due to problems encountered during parturition for some females. However, there was no statistically significant residual effect on …

Npm1-Mutated Myeloid Neoplasms Are A Unique Entity Not Defined By Bone Marrow Blast Percentage, Georgina Gener-Ricos, Alex Bataller, Juan Jose Rodriguez-Sevilla, Kelly S Chien, Andres E Quesada, Danielle Hammond, Courtney Dinardo, Tapan Kadia, Naval Daver, Gautam Borthakur, Ghayas C Issa, Nicholas J Short, Rashmi Kanagal-Shamanna, Hagop M Kantarjian, Guillermo Garcia-Manero, Guillermo Montalban-Bravo

Faculty, Staff and Student Publications

Introduction: NPM1-mutated (NPM1mut) myeloid neoplasms (MNs) with < 20% bone marrow (BM) blasts (NPM1mut MNs< 20) are uncommon, and their classification remains inconsistent.

Methods: The clinicopathologic features of 54 patients with NPM1mut MNs < 20 were evaluated and compared with wild-type NPM1 MNs < 20 and NPM1mut MNs≥20, respectively.

Results: NPM1mut MNs had similar features regardless of blast percentage, except for higher IDH2 (29% vs 7%, p = .023) and FLT3 (70% vs 11%, p < .001) frequency in patients with ≥20% BM blasts. Thirty-three (61%) patients with NPM1mut MNs < 20 received low-intensity chemotherapy (LIC) and 12 (22%) received intensive chemotherapy (IC). Higher complete remission rates (75% vs 27%, p = .006) and median overall survival (mOS) (not reached vs 30.4 months, p = .06) were observed with IC compared to LIC. Young patients (age < 60 years) did not reach mOS either when treated with LIC or IC. Stem cell transplant was associated with increased survival only in patients treated with LIC (HR, 0.24; p = .025). No differences in mOS were observed by BM blast strata (32.2 months, not reached and 46.9 months for < 10%, 10%-19%, and ≥20% blasts, p = .700) regardless of treatment modality (LIC: p = .900; IC: p = .360). Twenty-three patients (43%) with NPM1mut MNs < 20 had marrow blast progression to ≥20%.

Conclusions: Overall, NPM1mut MNs define a unique entity independent of BM blast percentage.

Cdk12 Loss Drives Prostate Cancer Progression, Transcription-Replication Conflicts, And Synthetic Lethality With Paralog Cdk13, Jean Ching-Yi Tien, Jie Luo, Yu Chang, Yuping Zhang, Yunhui Cheng, Jianzhang Yang, Somnath Mahapatra, Palak Shah, Xiao-Ming Wang, Abigail J Todd, Sanjana Eyunni, Caleb Cheng, Ryan J Rebernick, Lanbo Xiao, Yi Bao, James Neiswender, Rachel Brough, Stephen J Pettitt, Xuhong Cao, Stephanie J Miner, Licheng Zhou, Yi-Mi Wu, Estefania Labanca, Yuzhuo Wang, Abhijit Parolia, Marcin Cieslik, Dan R Robinson, Zhen Wang, Felix Y Feng, Jonathan Chou, Christopher J Lord, Ke Ding, Arul M Chinnaiyan

Faculty, Staff and Student Publications

Biallelic loss of cyclin-dependent kinase 12 (CDK12) defines a metastatic castration-resistant prostate cancer (mCRPC) subtype. It remains unclear, however, whether CDK12 loss drives prostate cancer (PCa) development or uncovers pharmacologic vulnerabilities. Here, we show Cdk12 ablation in murine prostate epithelium is sufficient to induce preneoplastic lesions with lymphocytic infiltration. In allograft-based CRISPR screening, Cdk12 loss associates positively with Trp53 inactivation but negatively with Pten inactivation. Moreover, concurrent Cdk12/Trp53 ablation promotes proliferation of prostate-derived organoids, while Cdk12 knockout in Pten-null mice abrogates prostate tumor growth. In syngeneic systems, Cdk12/Trp53-null allografts exhibit luminal morphology and immune checkpoint blockade sensitivity. Mechanistically, Cdk12 inactivation …

Biochemical And Structural Insights Into A 5′ To 3′ Rna Ligase Reveal A Potential Role In Trna Ligation, Yingjie Hu, Victor A Lopez, Hengyi Xu, James P Pfister, Bing Song, Masahiro Sakurai, Joshua T Mendell, Tao Wang, Jun Wu, Alan M Lambowitz, Diana R Tomchick, Krzysztof Pawłowski, Vincent S Tagliabracci

Faculty, Staff and Student Publications

ATP-grasp superfamily enzymes contain a hand-like ATP-binding fold and catalyze a variety of reactions using a similar catalytic mechanism. More than 30 protein families are categorized in this superfamily, and they are involved in a plethora of cellular processes and human diseases. Here, we identify C12orf29 (RLIG1) as an atypical ATP-grasp enzyme that ligates RNA. Human RLIG1 and its homologs autoadenylate on an active site Lys residue as part of a reaction intermediate that specifically ligates RNA halves containing a 5’-phosphate and a 3’-hydroxyl. RLIG1 binds tRNA in cells and can ligate tRNA within the anticodon loop in vitro. Transcriptomic …

Development And Validation Of A Machine Learning Model To Predict Myocardial Blood Flow And Clinical Outcomes From Patients’ Electrocardiogram, Fares Alahdab, Maliazurina Binti Saad, Ahmed Ibrahim Ahmed, Qasem Al Tashi, Muhammad Aminu, Jonathan B Moody, Jia Wu, Mouaz H Al-Mallah

Faculty, Staff and Student Publications

We develop a machine learning (ML) model using electrocardiography (ECG) to predict myocardial blood flow reserve (MFR) and assess its prognostic value for major adverse cardiovascular events (MACEs). Using 3,639 ECG-positron emission tomography (PET) and 17,649 ECG-single-photon emission computed tomography (SPECT) data pairs, the ML model is trained with a swarm intelligence approach and support vector regression (SVR). The model achieves a receiver-operator curve (ROC) area under the curve (AUC) of 0.83, with a sensitivity and specificity of 0.75. An ECG-MFR value below 2 is significantly associated with MACE, with hazard ratios (HRs) of 3.85 and 3.70 in the discovery …

Yap1 Status Defines Two Intrinsic Subtypes Of Lcnec With Distinct Molecular Features And Therapeutic Vulnerabilities, C Allison Stewart, Lixia Diao, Yuanxin Xi, Runsheng Wang, Kavya Ramkumar, Azusa Tanimoto, Benjamin B Morris, Li Shen, Bingnan Zhang, Yan Yang, Samera H Hamad, Robert J Cardnell, Alberto Duarte, Moushumi Sahu, Veronica Y Novegil, Bernard E Weissman, Michael Frumovitz, Neda Kalhor, Luisa Solis Soto, Pedro Da Rocha, Natalie Vokes, Don L Gibbons, Jing Wang, John V Heymach, Bonnie Glisson, Lauren Averett Byers, Carl M Gay

Faculty, Staff and Student Publications

Purpose: Large cell neuroendocrine carcinoma (LCNEC) is a high-grade neuroendocrine malignancy that, like small cell lung cancer (SCLC), is associated with the absence of druggable oncogenic drivers and dismal prognosis. In contrast to SCLC, however, there is little evidence to guide optimal treatment strategies, which are often adapted from SCLC and non-small cell lung cancer approaches.

Experimental design: To better define the biology of LCNEC, we analyzed cell line and patient genomic data and performed IHC and single-cell RNA sequencing of core needle biopsies from patients with LCNEC and preclinical models.

Results: In this study, we demonstrate that the presence …

A Phase Ib/Ii Randomized Clinical Trial Of Oleclumab With Or Without Durvalumab Plus Chemotherapy In Patients With Metastatic Pancreatic Ductal Adenocarcinoma, Andrew L Coveler, Matthew J Reilley, Mark Zalupski, Teresa Macarulla, Christos Fountzilas, Adnan Nagrial, Sophia Frentzas, Michael Overman, Anne Noonan, Wells A Messersmith, Nick Pavlakis, Niharika B Mettu, Ina Bisha, Ying Wang, Paul Smith, Elina Murtomaki, Agata A Bielska, Veronique Bragulat, Zachary A Cooper, Rakesh Kumar, David R Spigel

Faculty, Staff and Student Publications

Purpose: Pancreatic ductal adenocarcinoma upregulates CD73, potentially contributing to immune surveillance evasion. Combining oleclumab (CD73 inhibitor) and durvalumab with chemotherapy may identify an effective treatment option.

Patients and methods: We describe a multicenter phase Ib/II randomized clinical trial in patients with metastatic pancreatic ductal adenocarcinoma, untreated (cohort A) or previously received gemcitabine-based chemotherapy (cohort B; NCT03611556). During escalation, patients received oleclumab 1,500 or 3,000 mg, durvalumab 1,500 mg, and gemcitabine plus nab-paclitaxel (GnP; cohort A; n = 14) or modified FOLFOX (cohort B; n = 11). During expansion, cohort A patients (n = 170) were randomized to GnP (arm …

First-In-Human Clinical Outcomes With Ng-350a, An Anti-Cd40 Expressing Tumor-Selective Vector Designed To Remodel Immunosuppressive Tumor Microenvironments, Aung Naing, Danny Khalil, Oliver Rosen, D Ross Camidge, Tom Lillie, Andrea Stacey, Lee Rosen

Faculty, Staff and Student Publications

Background: Tumor-selective oncolytic viral vectors are promising anticancer therapeutics; however, challenges with dosing and potency in advanced/metastatic cancers have limited efficacy and usage. NG-350A is a next-generation blood-stable adenoviral vector engineered to express an agonist anti-cluster of differentiation (CD)40 antibody without affecting tumor-selectivity and oncolytic potency.

Methods: Intravenous and intratumoral (IT) administration of NG-350A was assessed in a phase Ia/Ib study in patients with metastatic/advanced epithelial tumors (NCT03852511). Dose-escalation was performed separately for intravenous (four dose levels available, each with infusions on Days 1, 3 and 5 of a 57-day treatment period) and IT (single injection on D1 …

Evaluating Debio 1347 In Patients With Fgfr Fusion-Positive Advanced Solid Tumors From The Fuze Multicenter, Open-Label, Phase Ii Basket Trial, Petros Grivas, Elena Garralda, Funda Meric-Bernstam, Ingo K Mellinghoff, Lipika Goyal, E Claire Dees, Nilofer S Azad, Asha Karippot, Razelle Kurzrock, Josep Tabernero, Juha Kononen, Matthew C H Ng, Rutika Mehta, Nataliya V Uboha, Frédéric Bigot, Valentina Boni, Samantha E Bowyer, Valeriy Breder, Andrés Cervantes, Nancy Chan, James M Cleary, Mallika Dhawan, Rikke L Eefsen, James Ewing, Donna M Graham, Tormod K Guren, Jin Won Kim, Krassimir Koynov, Do-Youn Oh, Rebecca Redman, Chia-Jui Yen, David Spetzler, Marie-Claude Roubaudi-Fraschini, Valerie Nicolas-Metral, Rafik Ait-Sarkouh, Claudio Zanna, Abdallah Ennaji, Anna Pokorska-Bocci, Keith T Flaherty

Faculty, Staff and Student Publications

Purpose: This multicenter phase II basket trial investigated the efficacy, safety, and pharmacokinetics of Debio 1347, an investigational, oral, highly selective, ATP-competitive, small molecule inhibitor of FGFR1-3, in patients with solid tumors harboring a functional FGFR1-3 fusion.

Patients and methods: Eligible adults had a previously treated locally advanced (unresectable) or metastatic biliary tract (cohort 1), urothelial (cohort 2), or another histologic cancer type (cohort 3). Debio 1347 was administered at 80 mg once daily, continuously, in 28-day cycles. The primary endpoint was the objective response rate. Secondary endpoints included duration of response, progression-free survival, overall survival, pharmacokinetics, and incidence of …

Accurate Identification Of Locally Aneuploid Cells By Incorporating Cytogenetic Information In Single Cell Data Analysis, Ziyi Li, Ruoxing Li, Irene Ganan-Gomez, Hussein A Abbas, Guillermo Garcia-Manero

Faculty, Staff and Student Publications

Single-cell RNA sequencing is a powerful tool to investigate the cellular makeup of tumor samples. However, due to the sparse data and the complex tumor microenvironment, it can be challenging to identify neoplastic cells that play important roles in tumor growth and disease progression. This is especially relevant for blood cancers, where neoplastic cells may be highly similar to normal cells. To address this challenge, we have developed partCNV and partCNVH, two methods for rapid and accurate detection of aneuploid cells with local copy number deletion or amplification. PartCNV uses an expectation-maximization (EM) algorithm with mixtures of Poisson distributions and …

Proportional Hazards Violations In Phase Iii Cancer Clinical Trials: A Potential Source Of Trial Misinterpretation, Timothy A Lin, Zachary R Mccaw, Alex Koong, Christine Lin, Joseph Abi Jaoude, Ramez Kouzy, Alexander D Sherry, Sonal S Noticewala, Clifton D Fuller, Charles R Thomas, Ryan Sun, J Jack Lee, Ruitao Lin, Ying Yuan, Yu Shyr, Tomer Meirson, Ethan B Ludmir

Faculty, Staff and Student Publications

Purpose: Survival analyses of novel agents with long-term responders often exhibit differential hazard rates over time. Such proportional hazards violations (PHV) may reduce the power of the log-rank test and lead to misinterpretation of trial results. We aimed to characterize the incidence and study attributes associated with PHVs in phase III oncology trials and assess the utility of restricted mean survival time and maximum combination test as additional analyses.

Experimental design: Clinicaltrials.gov and PubMed were searched to identify two-arm, randomized, phase III superiority-design cancer trials with time-to-event primary endpoints and published results through 2020. Patient-level data were reconstructed from published …