Digital Commons Network^™

Outcomes Of Patients With Newly Diagnosed Acute Myeloid Leukemia With Flt3-Tyrosine Kinase Domain Mutations: Prognostic Implications Of Npm1 Co-Mutation, Sankalp Arora, Wei-Ying Jen, Musa Yilmaz, Indraneel Deshmukh, Jayastu Senapati, Sanam Loghavi, Ghayas C Issa, Nicholas J Short, Tapan M Kadia, Courtney D Dinardo, Gautam Borthakur, Joseph Jabbour, Naveen Pemmaraju, Michael Andreeff, Koichi Takahashi, Kapil Bhalla, Uday Popat, Elizabeth J Shpall, Betul Oran, Hussein A Abbas, Guillermo Garcia-Manero, Farhad Ravandi, Hagop Kantarjian, Naval Daver

Faculty, Staff and Student Publications

Background: The prognostic impact of Fms-like tyrosine kinase 3 (FLT3)-tyrosine kinase domain (TKD) mutation in patients with acute myeloid leukemia (AML) is not well defined. The authors described outcomes of one of the largest cohorts of patients with FLT3-TKD mutated (FLT3-TKDmut) AML to date.

Methods: This retrospective study included patients with newly diagnosed AML who received frontline treatment at The University of Texas MD Anderson Cancer Center from January 2012 to March 2024 divided into two cohorts: FLT3-TKDmut AML and nucleophosmin-mutated (NPM1mut)/FLT3-TKD wild-type (FLT3-TKDwt) AML. Patients with FLT3 internal tandem duplication mutations were excluded.

Results: In total, 2922 patients were …

Lipidomic And Proteomic Insights From Extracellular Vesicles In The Postmortem Dorsolateral Prefrontal Cortex Reveal Substance Use Disorder-Induced Brain Changes, Chioma M Okeoma, Wasifa Naushad, Bryson C Okeoma, Carlos Gartner, Yulica Santos-Ortega, Calvin Vary, Savio Lima-Bastos, Victor Corasolla Carregari, Martin R Larsen, Alessio Noghero, Consuelo Walss-Bass, Rodrigo Grassi-Oliveira

Faculty, Staff and Student Publications

Substance use disorder (SUD) significantly increases the risk of neurotoxicity, inflammation, oxidative stress, and impaired neuroplasticity. The activation of inflammatory pathways by substances may lead to reactive astrogliosis and chronic neuroinflammation, potentially mediated by the release of extracellular particles (EPs), such as extracellular condensates (ECs) and extracellular vesicles (EVs). These particles, which reflect the physiological, pathophysiological, and metabolic states of their cells of origin, might carry molecular signatures indicative of SUD. In particular, our study investigated neuroinflammatory signatures in SUD patients by isolating EVs from the dorsolateral prefrontal cortex (dlPFC) Brodmann's area 9 (BA9) from postmortem subjects. We isolated BA9-derived …

Randomised, Placebo-Controlled Trial Of Oral Hymecromone In Adults With Pulmonary Hypertension, Kathryn Czepiel, Nadine Nagy, Tamera Panjalingam, Anissa Kalinowski, Adam R Frymoyer, Harry Karmouty-Quintana, Bo Gu, Haley Hedlin, Gernot Kaber, Sylvie Dobrota Lai, Joelle I Rosser, Paul L Bollyky, Vinicio De Jesus Perez, Roham T Zamanian

Faculty, Staff and Student Publications

Background: Pulmonary hypertension (PH) is a progressive cardiopulmonary condition associated with increased morbidity and mortality. The extracellular matrix component hyaluronan (HA) is linked to vascular remodelling and interstitial fibrosis in PH. We hypothesised that inhibition of HA synthesis with hymecromone could serve as a reverse-remodelling therapy in PH.

Methods: We performed a proof-of-concept phase IIa randomised, double-blind, placebo-controlled study in adults with pulmonary arterial hypertension and PH associated with interstitial lung disease (PH-ILD). Patients were randomised to a 5:3 ratio and stratified by PH group to receive oral hymecromone or placebo two times per day over 24 weeks. The primary …

Mathematical Modeling And Association Analysis Decipher The Impact Of The Gut Microbiome On Cancer Immunotherapy, Andreas G Hadjigeorgiou, Constantinos Harkos, Aditya K Mishra, Golnaz Morad, Sarah B Johnson, Nadim J Ajami, Jennifer A Wargo, Lance L Munn, Triantafyllos Stylianopoulos, Rakesh K Jain

Faculty, Staff and Student Publications

The gut microbiome has emerged as a key regulator of response to cancer immunotherapy. However, a better understanding of the underlying mechanisms by which the microbiome influences immunotherapy is needed to identify strategies to optimize outcomes. To this end, we developed a mathematical model to obtain insights into the effect of the microbiome on the immune system and immunotherapy response. This model was based on (i) gut microbiome data derived from preclinical studies, (ii) mathematical modeling of the antitumor immune response, (iii) association analysis of microbiome profiles with model-predicted immune profiles, and (iv) statistical models that correlate model parameters with …

Clinical, Tumor, And Product Features Associated With Outcomes After Axicabtagene Ciloleucel Therapy In Follicular Lymphoma, Soumya Poddar, Jiali Yan, Gayatri Tiwari, Darawan Rinchai, Justin Budka, Wangshu Zhang, Weixin Peng, Shruti Salunkhe, Madison Davis, Qinghua Song, Sara Beygi, Harry Miao, Mike Mattie, Rhine S Shen, Caron A Jacobson, Davide Bedognetti, Simone Filosto, Sattva S Neelapu

Faculty, Staff and Student Publications

Background: Axicabtagene ciloleucel (axi-cel), anti-CD19 chimeric antigen receptor (CAR) T cell therapy, demonstrated remarkable efficacy with manageable toxicity in relapsed/refractory indolent B cell lymphomas in the ZUMA-5 trial.

Methods:Here, we report associations of product attributes, serum biomarkers, clinical features, and tumor characteristics with outcome in 124 patients with follicular lymphoma (FL).

Results: In univariate and multivariate analyses, pretreatment inflammatory markers, including TNF-α and IL-12p40, as well as total metabolic tumor volume (TMTV), associated with disease progression. Conversely, T-naive–like product phenotype associated with improved outcome, particularly in patients with high TMTV. These covariates improved risk stratification when combined with the …

Contemporary Outcomes Of Octa-Nonagenarians With Newly Diagnosed Acute Myeloid Leukemia, Jayastu Senapati, Hagop M Kantarjian, Tapan M Kadia, Jeannot Kekedjian, Gautam Borthakur, Naval Daver, Courtney D Dinardo, Elias Jabbour, Prithviraj Bose, Nicholas J Short, Musa Yilmaz, Nitin Jain, Naveen Pemmaraju, Hussein A Abbas, Ghayas C Issa, Abhishek Maiti, Guillermo Montalban Bravo, Indraneel Deshmukh, Elizabeth Shpall, Partow Kebriaei, Uday Popat, Sanam Loghavi, Beenu Thakral, Guilin Tang, Fadi G Haddad, Yesid Alvarado, Guillermo Garcia Manero, Farhad Ravandi

Faculty, Staff and Student Publications

Background: Octa-nonagenarians with acute myeloid leukemia (AML) represent a high-risk group due to frequently poor performance status, adverse genomics (e.g., TP53 mutations, complex karyotype), a high incidence of secondary AML, and inability to undergo an allogeneic stem cell transplantation. Evaluating their outcomes with modern treatment approaches is important.

Methods: This retrospective study analyzed outcomes of patients ≥80 years old with newly diagnosed AML treated at our center from 2013-2023.

Results: A total of 289 patients (median age, 83 years; range, 80-95 years) were included. Venetoclax containing low-intensity therapy was administered to 107 patients (37.0%). AML subtypes included de novo (123, …

Biological Control Mitigates Spread Of Vector-Borne Plant Pathogens, Kris A.G. Wyckhuys, Yi Zou, David W. Crowder, Evie Adriani, Annabelle B. Albaytar, Marie Joy B. Beltran, Ibtissem Ben Fekih, Carolina Camargo-Gil, Filomena C. Filomena, Lizette Cicero, Yelitza C. Colmenarez, Claudia M. Cuellar-Palacios, Thomas Dubois, Sanford D. Eigenbrode, Frederic Francis, Alberto Fereres, Khalid Haddi, Fathiya M. Khamis, Cécile Le Lann, Anne Le Ralec, Lorena Lopez, Baoqian Lyu, James Montoya-Lerma, Karen Muñoz-Cardenas, Ihsan Nurkomar, Paola A. Palmeros-Suarez, Jermaine D. Perier, Ricardo Ramírez-Romero

All Peer-Reviewed Publications

Diseases caused by vector-borne plant pathogens cause adverse impacts on yield resilience, food security, and farmer livelihoods, which are bound to aggravate under global change. Biological control is routinely discounted as a mitigation strategy for plant diseases, partially due to scarce and inconclusive empirical support. Here, using curated field survey data for 58 persistently or semi-persistently transmitted pathogens, we employ a multi-method approach to assess the role of resident (i.e., naturally occurring) biological control agents in these pathosystems. Our meta-analyses show how in planta pathogen incidence is strongly affected by vector abundance and infectivity. Meanwhile, biological control agent density negatively …

Role Of Immunosuppressive Jnk Pathway In The Tumor Microenvironment Among Tnbc Subtypes In Ibcsg Trial 22–00, Andrea Joaquin Garcia, Takashi Semba, Mattia Rediti, Daniel J Mcgrail, Xuemei Xie, Xiaoping Wang, Dileep R Rampa, David Venet, Laurence Buisseret, Samira Majjaj, Roswitha Kammler, Marco Colleoni, Sherene Loi, Giuseppe Viale, Meredith M Regan, Françoise Rothé, Christos Sotiriou, Naoto T Ueno

Faculty, Staff and Student Publications

Phosphorylation of the JNK (pJNK) protein promotes an immunosuppressive tumor microenvironment (TME), enhancing aggressiveness in inflammatory triple-negative breast cancer (TNBC). This study evaluated the role of JNK signaling using a gene signature. RNA sequencing was performed on 347 TNBC tumors from the phase 3 International Breast Cancer Study Group (IBCSG) 22-00 trial, which evaluated adjuvant low-dose cyclophosphamide and methotrexate (CM). Immune-related tumors were identified by TNBC subtype or tumor-infiltrating lymphocytes (TILs). Associations between JNK and outcomes were analyzed using Cox models. Low pJNK levels were associated with better disease-free survival (DFS) in immune-related tumors. These tumors also had lower Treg …

What Are The Predictors Of Malignancy In Inflammatory Bowel Disease?, Zülal İstemi̇han, Bi̇lger Çavuş, Ali̇ Emre Bardak, Ayşe Merve Kirkoğlu, Cansu Kiziltaş, Rüveyda Si̇lay, İbrahi̇m Volkan Şenkal, Zi̇ya İmanov, Kenan Nuri̇yev, Aynure Rüstemzade, Sezen Genç, Mi̇ne Güllüoğlu, Asli Çi̇fci̇başi Örmeci̇, Kadi̇r Demi̇r, Fati̇h Beşişik, Sabahatti̇n Kaymakoğlu, Fi̇li̇z Akyüz

Turkish Journal of Medical Sciences

Background/aimː This study aims to investigate the prevalence of malignancy in patients with inflammatory bowel disease (IBD) followed up in a tertiary reference center.

Materials and methodsː IBD patients with at least 6 months of follow-up from the gastroenterology clinic between 2000 and 2022 wereevaluated retrospectively in a tertiary center. Patient information was obtained from the patient registration system.

Resultsː There were 697 patients in the study, 320 (45.9%) of these were female. The mean age of the patients at IBD diagnosis was 33.4± 13.1 years. The mean follow-up time was 93.1 ± 64.8 (median 84, IQR (25–75) (36–144)) months. …

Comparison Of Novel Diard-Hbv Dna Qpcr Kit With The Artus Hbv Qs-Rgq Kit For Quantification Of Hbv Dna In Clinical Samples, Ülker Çuhaci, Hande Toptan, Bengül Durmaz, Mehmet Köroğlu, Riza Durmaz

Turkish Journal of Medical Sciences

Background/aim: Hepatitis B virus (HBV) leads to widespread chronic infections that may result in long-term complications such as cirrhosis and hepatocellular carcinoma. The use of sensitive molecular methods for HBV DNA quantitation has provided significant contributions for diagnosis and monitoring of disease. The current study aimed to evaluate the diagnostic performances of a novel DiaRD HBV qPCR kit (novel kit) in comparison with the artus HBV QS-RGQ kit (comparator kit).

Materials and methods: A total of 288 plasma samples—105 HBV DNA-positive and 183 HBV DNA-negative—were tested using both kits. The diagnostic and quantitative results of the novel kit were compared …

Sinapic Acid Alleviates Renal Ischemia-Reperfusion Injury By Regulating Oxidative Stress, Apoptosis, And Inflammation, Mustafa Can Güler, Fazi̇le Nur Eki̇nci̇ Akdemi̇r, Ersen Eraslan, Ayhan Tanyeli̇, Derya Güzel Erdoğan, Behzat Tebri̇zi̇

Turkish Journal of Medical Sciences

Background/aim: Acute kidney injury (AKI) is a major clinical issue, frequently resulting from ischemia-reperfusion (I/R) injury. Sinapic acid (SA), a natural phenolic molecule included in numerous plant-based foods, exhibits antiapoptotic, antioxidant, and antiinflammatory properties. This study aimed to investigate the renoprotective effects of SA in an I/R-induced acute kidney injury (AKI) model.

Materials and methods: Sprague–Dawley male rats (n = 32) were randomly assigned to four groups: sham, I/R, SA 20 mg/kg, and SA 40 mg/kg. SA was administered intraperitoneally before reperfusion. Renal tissues were examined using biochemical, histopathological, and immunohistochemical methods, focusing on oxidative stress, cytokine expression, and apoptosis …

Incidence Of And Risk Factors For Hyperoxemia Among Potentially Critically Ill Patients Treated In The Wards: A Retrospective Study, Mehmet Nuri̇ Yakar, Doğukan Şenberber, Ozan Balkabak, Nurgazy Shermatov, Kaan Köşker, Seli̇n Elden, Emel İbi̇şoğlu, Begüm Ergan, Volkan Hanci, Necati̇ Gökmen

Turkish Journal of Medical Sciences

Background/aim: The literature shows a link between hyperoxemia and poor outcomes, whereas this association remains unclear in hospital wards. This study aims to determine the incidence of hyperoxemia in hospital wards and its risk factors.

Materials and methods: Patients aged ≥ 18 years who underwent an evaluation by an intensivist between 1 January 2020 and 31 December 2020, while receiving treatment in hospital wards, were included in the study following ethics committee approval. Patients with hypoxemia (partial pressure of oxygen [PaO2] < 60 mmHg), a condition related to Coronavirus disease 2019, a hospital stay < 1 day, or missing data were excluded. Patients were divided into two groups: normoxemia (60 mmHg ≤ PaO2 < 120 mmHg) and hyperoxemia.

Results: The incidence of hyperoxemia was 42.2%. Patients with hyperoxemia had longer hospital stays and higher intensive care unit …

Colostrum Extracellular Vesicle Are Neuroprotective In The Mptp Intoxicated Mouse Model Of Parkinson's Disease, Samia Akter

Theses & Dissertations

Parkinson’s Disease (PD) is the second most common neurodegenerative disorder. Dopaminergic neuronal loss in the substantia nigra and the formation of Lewy bodies are the disease pathological hallmarks. We demonstrate that bovine colostrum extracellular vesicles (EVs) induce anti-inflammatory and neuroprotective activities during MPTP (methyl-4-phenyl-1,2,3,6-tetrahydropyridine) intoxication. Treatment these mice with colostrum EVs reduced the extent of activated microglia and neurodegenerative activities. RNA sequencing and transcriptomic analysis revealed a significant decrease in pro- inflammatory responses, as well as reduced recruitment and activation of immunocytes in affected brain tissues. Decreased expression of pro-inflammatory cytokines and chemokines, as well as suppressed canonical inflammasomes, was …

Study Of Peptide Amphiphiles As Antimicrobial Agents, Aramis J. Pereira

Theses & Dissertations

The global antimicrobial resistance (AMR) crisis presents a severe public health threat, with drug-resistant infections now the third leading cause of mortality worldwide. This escalating problem, driven by the rapid proliferation of multidrug-resistant organisms (MDROs) like the "ESKAPE" pathogens, severely limits treatment options and imposes substantial economic burdens. The crisis is further exacerbated by a limited pipeline of new antimicrobial agents, as most recently approved drugs are modifications of existing classes rather than novel compounds. Peptide amphiphiles (PAs) offer a promising alternative due to their membrane-targeting mechanism, which reduces the likelihood of resistance development. These molecules are amphiphilic and positively …

Integration Of Spatial Protein Imaging And Transcriptomics In The Human Kidney Tracks The Regenerative Potential Of Proximal Tubules, Mahla Asghari, Sanjay Jain, Et Al.

2020-Current year OA Pubs

The organizational principles of nephronal segments are based on anatomical and physiological attributes that are linked to the homeostatic functions of the kidney. Recent molecular approaches have uncovered layers of deeper signatures and states in tubular cells that arise at various time points on the disease trajectory. Here, we introduce an analytical pipeline of multiplexed spatial protein imaging integrated with RNA expression to characterize proximal tubular subpopulations and neighborhoods in human kidney tissue. We demonstrate that, in reference tissue, a large proportion of S1 proximal tubular epithelial cells expresses thymus antigen 1 (THY1), a mesenchymal stromal and stem cell marker …

Informatics At The Frontier Of Cancer Research, Kathleen Noller, Malachi Griffith, Daniel Marcus, Et Al.

2020-Current year OA Pubs

Digitized healthcare data, high-throughput profiling technologies, and data repositories have facilitated the emergence of a new era of cancer research. Each data stream requires specialized analysis methods for interpretation. The data-driven era of cancer research requires the development, enhancement, and sustainment of informatics technology software infrastructure, including fundamental methodology development in artificial intelligence and data science. We review current and emerging informatics technology developments for cancer research and discovery, spanning molecular and cellular characterizations, image analysis, informatics, and therapeutics. Summarizing the diverse methods and applications of informatics throughout cancer research identifies themes and emerging areas for the next generation of …

Highly Potent And Subtype-Selective Sperm-Specific Potassium Channel Slo3 Inhibitors Display High Tissue Exposure In The Murine Female Reproductive Tract, Kayla J Temple, Ping Li, Maximilian D Lyon, Shweta Bhagwat, Leila Asadi, Sophia Li, Ronald Mccarthy, Celia M Santi, Et Al.

2020-Current year OA Pubs

To date, the study of drug exposure and distribution throughout the female reproductive tract has often been overlooked and neglected. Herein, we report the first highly potent and subtype-selective sperm-specific potassium channel 3 (SLO3) inhibitors as a new modality of contraceptives. After extensive

Post-Translational Modifications Of Extracellular Matrix Domains As Prognosticators Of Hepatocellular Carcinoma Via Integrative Serum And Spatial Proteomics, Jade K. Macdonald

MUSC Theses and Dissertations

Hepatocellular carcinoma (HCC) remains a major global health challenge, with rising incidence, high mortality, and a five-year survival rate below 20%. Approximately 90% of HCC cases arise in cirrhosis, a stromal disease characterized by excessive deposition and remodeling of collagenous extracellular matrix (ECM). As HCC progresses, alterations in ECM composition and spatial distribution influence disease progression, emphasizing the potential of the ECM as a biomarker for HCC prognosis and treatment response. However, ECM proteomic analysis is challenging due to complex post-translational modifications, crosslinking, and insolubility. This dissertation molecularly and spatially characterizes the stromal landscape in and around HCC tumors in …

Advanced Robotic Multimodal Imaging With Real-Time Motion Compensation For Dynamic Structural Health Monitoring, George Papaioannou, Christos Mitrogiannis, Mark Schweitzer, Maria Pappa, Pegah Khosravi, Apostolos Karantanas, Chris Ruberg, Shawn Owens, Nikolaos Michailidis

Publications and Research

Modern composite materials promise superior performance and load-bearing capabilities, yet evaluating their structural integrity remains challenging. Current testing methods, such as visual, thermographic, ultrasonic, optical, electromagnetic, terahertz, shearography, X-ray, and neutron imaging, are hampered by long scan durations, limited field of view, suboptimal accuracy, and high costs, particularly when applied to large structures.

This paper addresses these issues by introducing a novel robotic multimodal imaging system that overcomes the limitations of traditional methods. This system dynamically captures both static and dynamic properties of materials using advanced motion compensation techniques. By integrating multiple radiographic modalities into a coordinated robotic platform, it …

Highly Oligomeric Drp1 Strategic Positioning At Mitochondria-Sarcoplasmic Reticulum Contacts In Adult Murine Heart Through Actin Anchoring, Celia Fernandez-Sanz, Sergio De La Fuente, Zuzana Nichtova, Marilen Federico, Stephane Duvezin-Caubet, Sebastian Lanvermann, Hui-Ying Tsai, Yanguo Xin, György Csordás, Wang Wang, Arnaud Mourier, Shey-Shing Sheu

Department of Medicine Faculty Papers

Mitochondrial fission and fusion appear to be relatively infrequent in cardiac cells compared to other cell types; however, the proteins involved in these events are highly expressed in adult cardiomyocytes (ACM). Therefore, these proteins likely have additional non-canonical roles. We have previously shown that DRP1 not only participates in mitochondrial fission processes but also regulates mitochondrial bioenergetics in cardiac tissue. However, it is still unknown where the DRP1 that does not participate in mitochondrial fission is located and what its role is at those non-fission spots. Therefore, this manuscript will clarify whether oligomeric DRP1 is located at the SR–mitochondria interface, …

Disentangling The Effect Of Criminal Legal System Involvement On Mental Health In The United States, Pui Ying Chan

Dissertations and Theses

BACKGROUND: Interactions with the criminal legal system (CLS), such as through arrest or incarceration, are relatively common in the United States (US) and are increasingly recognized as social risk factors for poor mental health. Previous studies have reported a positive association between CLS involvement and poor mental health, with some theoretical frameworks, including the ecosocial theory and the stress process paradigm, supporting a plausible causal relationship. However, prior research has significant limitations in providing casual evidence given possible reverse causation in cross-sectional studies and insufficient consideration for the dynamics between CLS exposures, mental health status, and related confounders over time …

Beyond Smoking: A Geospatial Investigation Of Factors Associated With Lung And Bronchus Cancer Risk In Pennsylvania, Tesla D. Dubois, Daniel Wiese, Kevin A. Henry, Shannon M. Lynch

Kimmel Cancer Center Faculty Papers

INTRODUCTION: While smoking is the leading cause of lung and bronchus cancer (LBC), additional exposures have been implicated and may explain the rise in LBC among never-smokers. To better understand the spatial distribution of LBC incidence and associated risk factors, this study aims to identify geographic areas with significantly elevated incidence rates in Pennsylvania and investigate the potential underlying risk factors.

METHODS: Using cancer registry data aggregated to the census tract level, spatial scan statistics were applied to detect areas of higher-than-expected LBC incidence across the state. Associations were then tested between census tract inclusion in a high-incidence area and …

Transcriptional Remodeling Shapes Therapeutic Vulnerability To Necroptosis In Acute Lymphoblastic Leukemia, Anna Saorin, Anna Dehler, Bartimée Galvan, Fabio Steffen, Marine Ray, Dong Lu, Xin Yu, James Kim, Aneta Drakul, Samanta Kisele, Jin Wang, Jean-Pierre Bourquin, Beat C Bornhauser

Faculty, Staff and Students Publications

Insufficient eradication of cancer cells and survival of drug tolerant clones are major relapse driving forces. Underlying molecular mechanisms comprise activated prosurvival and antiapoptotic signaling, leading to insufficient apoptosis and drug resistance. The identification of programmed cell death pathways alternative to apoptosis opens up possibilities to antagonize apoptosis escape routes. We have earlier shown that acute lymphoblastic leukemia (ALL) harbors a distinct propensity to undergo cell death by receptor-interacting protein kinase 1 (RIPK1)-dependent necroptosis, activated by small-molecule second mitochondria-derived activators of caspase (SMAC) mimetics. Despite demonstrated safety and tolerability of SMAC mimetics in clinical trials, their efficacy as single agent …

Multidimensional Analysis Of B7 Homolog 3 Rna Expression In Small Cell Lung Cancer Molecular Subtypes, Carl M Gay, Taofeek K Owonikoko, Lauren A Byers, Noura J Choudhury, Sajid Ahmed, Zachary Cain, Xiaozhong Qian, Matthew Brentnall, Simon Heeke, Ming Poi, Sharon Wu, Charles M Rudin

Faculty, Staff and Student Publications

Purpose: B7 homolog 3 (B7-H3) is a promising target for antibody-drug conjugates, with ifinatamab deruxtecan demonstrating an objective response rate of 54.8% in previously treated extensive-stage small cell lung cancer (SCLC). This analysis aimed to characterize B7-H3 RNA expression with reference to SCLC molecular subtypes (SCLC-A, SCLC-N, SCLC-P, and SCLC-I) and immune-related parameters.

Experimental design: Tumor RNA expression and mutational burden for 1,721 patients with SCLC were derived from a real-world database (Caris Life Sciences). A predominant molecular subtype was assigned based on RNA expression using a gene-ratio classifier. PD-L1 expression was assessed by IHC (antibody 22C3; positive cutoff: tumor …

Large-Scale Crispr Screening In Primary Human 3d Gastric Organoids Enables Comprehensive Dissection Of Gene-Drug Interactions, Yuan-Hung Lo, Hudson T Horn, Mo-Fan Huang, Wei-Chieh Yu, Chia-Mei Young, Qing Liu, Madeline Tomaske, Martina Towers, Antonia Dominguez, Michael C Bassik, Dung-Fang Lee, Lei S Qi, Jonathan S Weissman, Jin Chen, Calvin J Kuo

Faculty, Staff and Student Publications

Understanding how genes influence drug responses is critical for advancing personalized cancer treatments. However, identifying these gene-drug interactions in a physiologically relevant human system remains a challenge, as it requires a model that reflects the complexity and heterogeneity among individuals. Here we show that large-scale CRISPR-based genetic screens, including knockout, interference (CRISPRi), activation (CRISPRa), and single-cell approaches, can be applied in primary human 3D gastric organoids to systematically identify genes that affect sensitivity to cisplatin. Our screens uncover genes that modulate cisplatin response. By combining CRISPR perturbations with single-cell transcriptomics, we resolve how genetic alterations interact with cisplatin at the …

An Investigation Of The Association Of Gdf9-C.260g>A Polymorphism With Lamb Live Weight In The Akkaraman Breed, Şeyma Kökkaya, Fadi̇me Daldaban, Davut Bayram, Mehmet Ulaş Çinar, Korhan Arslan, Bi̇lal Akyüz

Turkish Journal of Veterinary & Animal Sciences

In this study, the relationship between the Growth Differentiation Factor-9 (GDF9) gene polymorphism and birth weight, as well as weights on days 30, 60, 90, was investigated in Akkaraman lambs, one of the indigenous sheep breeds of Türkiye. For this purpose, a total of 314 lambs were genotyped by PCR-RFLP method for the single nucleotide polymorphism (SNP) c.260G>A in the GDF9 gene. While GG and GA genotypes were observed in the studied breed, the AA genotype was not observed. The results showed that Akkaraman lambs were in Hardy–Weinberg (H–W) equilibrium for the GDF9-c.260G>A polymorphism (p < 0.05). In this study, a significant association was observed between GDF9-HhaI polymorphism and 30th day weight and 60th day weight in Akkaraman lambs. When the animals were analyzed according to birth type, it was observed that this factor was associated with birth weight, as well as weights on days 30, 60, and 90. It is suggested that the c.260G>A coded SNP …

Growth Curve And Serum Calcium And Magnesium Concentrations In Duck Breeders (Anas Boschas) From Hatching To The Prelaying Period Reared Under Subtropical Conditions, Vanessa Peripolli, Fabiano Dahlke, Ellen Karen Dos Santos, Maila Palmeira, Stelamaris Dezen, Robert Lenock, Elizabeth Schwegler, Juahil Martins De Oliveira Júnior, Ivan Bianchi, Paula Gabriela Da Silva Pires, Betina Raquel Cunha Dos Santos, Andressa Fernanda Campos, Fabiana Moreira

Turkish Journal of Veterinary & Animal Sciences

Optimizing duck production requires understanding growth variability and monitoring serum calcium and magnesium levelsas health indicators. This study aimed to analyze the growth curve, mortality, and serum calcium (Ca) and magnesium (Mg) levels in White Mallard ducks from hatching to the prelaying period in subtropical conditions. A total of 1100 females and 270 males were raised for 146 days. At hatch, day 6 (D6), D13, D23, D34, D50, D64, D80, D94, D111, and D146, ducks were weighed separately to assess body weight (BW). Blood samples were collected at hatch, D50, D94, and D146 to determine serum calcium and magnesium levels. …

The Morphologic Structure Of Some Wing Muscles In The Common Pheasant (Phasianus Colchicus), Beste Demi̇rci̇, Murat Erdem Gülti̇ken

Turkish Journal of Veterinary & Animal Sciences

Avians use significant amounts of energy during flight that is supplied by muscles. The Common Pheasant, a member of the Phasianidae family, can fly swiftly over short distances and flies to evade predators. Pheasant species are terrestrial and have a global distribution. This investigation aimed to analyze the anatomical structure of skeletal muscles in pheasants. A cohort of 20 adult pheasants consisting of an equal number of females and males (10 each) was used. Dissections were performed on 5 females and 5 male pheasants for macroscopic evaluation. The remaining samples underwent immunohistochemical staining using an antimyoglobin antibody to measure the …

A Morphological Study On Acanthocephalan Species From Wild Birds In Northern Türkiye, Mehmet Öztürk, Şi̇nasi̇ Umur

Turkish Journal of Veterinary & Animal Sciences

The phylum Acanthocephala contains approximately 1300 acanthocephalan species. So far, only nine acanthocephalan species of wild birds have been reported in Türkiye. To study the context of acanthocephalan diversity in wild birds in Türkiye, we examined 193 birds from 69 species belonging to 16 orders. Acanthocephalans were found in seven bird species: Centrorhynchus aluconis in Buteo buteo and Buteo rufinus, Centrorhynchus spinosus in Buteo buteo and Strix aluco, Mediorhynchus papillosus in Iduna icterina, Mediorhynchus tenuis in Luscinia svecica, Plagiorhynchus cylindraceus in Erithacus rubecula and Turdus merula, Polymorphus contortus in Anas platyrhynchos, and Sphaerirostris turdi in Turdus merula. Except for Plagiorhynchus …

Proteomics-Based Aging Clocks In Midlife Or Late-Life And Their Associated Risk Of Dementia, Sanaz Sedaghat, Saeun Park, Rob F Walker, Shuo Wang, Jialing Liu, Timothy M Hughes, Behnam Sabayan, Weihong Tang, Josef Coresh, James S Pankow, Keenan A Walker, Ramon Casanova, Ruth Dubin, Rajat Deo, Jerome I Rotter, Alexis C Wood, Peter Ganz, Pamela L Lutsey, Weihua Guan, Anna Prizment

Children’s Nutrition Research Center Staff Publications

Background: Biological age can be quantified by composite proteomic scores, called proteomics-based aging clocks (PACs). We investigated whether a discrepancy between chronological and biological age in midlife and late-life is associated with cognition and dementia risk.

Methods: We used two longitudinal population-based studies: the Atherosclerosis Risk in Communities (ARIC) Study and the Multi-Ethnic Study of Atherosclerosis (MESA). PACs were created in ARIC at midlife (mean age: 58 years, 57% female, n = 11,758) and late-life (mean age: 77 years, 56% female, n = 4934) using elastic net regression models in two-thirds of dementia-free participants and validated in the remaining one-third …