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Articles 2551 - 2580 of 24686
Full-Text Articles in Entire DC Network
Self-Powered Rapid Antigen-Specific T-Cell Response Assay For Mycobacterium Tuberculosis Infections, Bo Ning, Sutapa Chandra, Yongchun Pan, Riti Sharan, Ngan Ha, Sanjay Singh, Alexandra Portillo Varela, Lin Li, Qingli Wu, Alexander Kay, Gugu P Maphalala, Clement Adu-Gyamfi, Santiago Carrero Longlax, Anna M Mandalakas, Smriti Mehra, Christopher J Lyon, Edward A Graviss, Andrew R Dinardo, Tony Hu
Self-Powered Rapid Antigen-Specific T-Cell Response Assay For Mycobacterium Tuberculosis Infections, Bo Ning, Sutapa Chandra, Yongchun Pan, Riti Sharan, Ngan Ha, Sanjay Singh, Alexandra Portillo Varela, Lin Li, Qingli Wu, Alexander Kay, Gugu P Maphalala, Clement Adu-Gyamfi, Santiago Carrero Longlax, Anna M Mandalakas, Smriti Mehra, Christopher J Lyon, Edward A Graviss, Andrew R Dinardo, Tony Hu
Faculty, Staff and Students Publications
Interferon-gamma release assays (IGRAs) that evaluate an individual’s T-cell activation response to Mycobacterium tuberculosis (M.tb)-specific peptides serve an important role in diagnosing tuberculosis (TB). However, there are substantial challenges to the use of IGRAs in resource-limited settings. Further, IGRA diagnostic performance can also be compromised in anergic individuals. Here we describe a microfluidic chip-based antigen-specific T-cell response assay (ASTRA) that automates the detection of M.tb-specific T-cell activation responses to facilitate screening for latent M.tb infection and TB. We observe that ASTRA demonstrates high specificity for M.tb infection in independent patient cohorts. Compared with IGRA, ASTRA shows greater …
Concurrent Use Of Skeletal Muscle Relaxants And Nsaids In Low Back Pain Management: A Critical Review Of Current Evidence And Future Directions, Rupesh A. Saindane, Nilima A. Thombre
Concurrent Use Of Skeletal Muscle Relaxants And Nsaids In Low Back Pain Management: A Critical Review Of Current Evidence And Future Directions, Rupesh A. Saindane, Nilima A. Thombre
The Thai Journal of Pharmaceutical Sciences
Low back pain (LBP) represents a leading cause of non-fatal disability globally. Its high prevalence and disabling nature highlight the urgent need for effective management strategies. The exact cause of LBP still remains unclear, and thus, its treatment remains symptomatic. LBP is commonly treated with non-steroidal anti-inflammatory drugs (NSAIDs) and skeletal muscle relaxants (SMRs). These agents are frequently used in combination to target both inflammation and muscle spasms. However, the clinical guidelines vary widely on the recommendation for the use of such combination therapy. The present review evaluates evidence from randomized clinical trials and systematic reviews on the concurrent use …
Mis-Splicing-Derived Neoantigens And Cognate Tcrs In Splicing Factor Mutant Leukemias, Won Jun Kim, Edie I Crosse, Emma De Neef, Inaki Etxeberria, Erich Y Sabio, Eric Wang, Jan Philipp Bewersdorf, Kuan-Ting Lin, Sydney X Lu, Andrea Belleville, Nina Fox, Cynthia Castro, Pu Zhang, Takeshi Fujino, Jennifer Lewis, Jahan Rahman, Beatrice Zhang, Jacob H Winick, Alexander M Lewis, Robert F Stanley, Susan Dewolf, Brigita Meškauskaitė Urben, Meril Takizawa, Tobias Krause, Henrik Molina, Ronan Chaligne, Priya Koppikar, Jeffrey Molldrem, Mathieu Gigoux, Taha Merghoub, Anthony Daniyan, Smita S Chandran, Benjamin D Greenbaum, Christopher A Klebanoff, Robert K Bradley, Omar Abdel-Wahab
Mis-Splicing-Derived Neoantigens And Cognate Tcrs In Splicing Factor Mutant Leukemias, Won Jun Kim, Edie I Crosse, Emma De Neef, Inaki Etxeberria, Erich Y Sabio, Eric Wang, Jan Philipp Bewersdorf, Kuan-Ting Lin, Sydney X Lu, Andrea Belleville, Nina Fox, Cynthia Castro, Pu Zhang, Takeshi Fujino, Jennifer Lewis, Jahan Rahman, Beatrice Zhang, Jacob H Winick, Alexander M Lewis, Robert F Stanley, Susan Dewolf, Brigita Meškauskaitė Urben, Meril Takizawa, Tobias Krause, Henrik Molina, Ronan Chaligne, Priya Koppikar, Jeffrey Molldrem, Mathieu Gigoux, Taha Merghoub, Anthony Daniyan, Smita S Chandran, Benjamin D Greenbaum, Christopher A Klebanoff, Robert K Bradley, Omar Abdel-Wahab
Faculty, Staff and Student Publications
Mutations in RNA splicing factors are prevalent across cancers and generate recurrently mis-spliced mRNA isoforms. Here we identified a series of bona fide neoantigens translated from highly stereotyped splicing alterations promoted by neomorphic, leukemia-associated somatic splicing machinery mutations. We utilized feature-barcoded peptide-MHC dextramers to isolate neoantigen-reactive T cell receptors (TCRs) from healthy donors, patients with active myeloid malignancy, and following curative allogeneic stem cell transplant. Neoantigen-reactive CD8+ T cells were present in the blood of patients with active cancer and had a distinct phenotype from virus-reactive T cells with evidence of impaired cytotoxic function. T cells engineered with TCRs recognizing …
Encorafenib, Cetuximab, And Mfolfox6 In Braf-Mutated Colorectal Cancer, Elena Elez, Takayuki Yoshino, Lin Shen, Sara Lonardi, Eric Van Cutsem, Cathy Eng, Tae Won Kim, Harpreet Singh Wasan, Jayesh Desai, Fortunato Ciardiello, Rona Yaeger, Timothy S Maughan, Van K Morris, Christina Wu, Tiziana Usari, Robert Laliberte, Samuel S Dychter, Xiaosong Zhang, Josep Tabernero, Scott Kopetz, Breakwater Trial Investigators
Encorafenib, Cetuximab, And Mfolfox6 In Braf-Mutated Colorectal Cancer, Elena Elez, Takayuki Yoshino, Lin Shen, Sara Lonardi, Eric Van Cutsem, Cathy Eng, Tae Won Kim, Harpreet Singh Wasan, Jayesh Desai, Fortunato Ciardiello, Rona Yaeger, Timothy S Maughan, Van K Morris, Christina Wu, Tiziana Usari, Robert Laliberte, Samuel S Dychter, Xiaosong Zhang, Josep Tabernero, Scott Kopetz, Breakwater Trial Investigators
Faculty, Staff and Student Publications
Background: First-line treatment with encorafenib plus cetuximab (EC) with or without chemotherapy (oxaliplatin, leucovorin, and fluorouracil [mFOLFOX6]) for BRAF V600E-mutated metastatic colorectal cancer, an aggressive subtype with a poor prognosis, was compared with standard care (chemotherapy with or without bevacizumab) in an open-label, phase 3 trial, which showed significance regarding one of the two primary end points, objective response according to blinded independent central review (odds ratio for EC+mFOLFOX6 vs. standard care, 2.44; one-sided P< 0.001). This result led to accelerated Food and Drug Administration approval of this investigational combination therapy for BRAF V600E-mutated metastatic colorectal cancer, including as first-line therapy. Data on progression-free survival (the second primary end point) and an updated interim analysis of overall …
Secondary Youth-Level Mechanisms Of Change In Parent Training For Anxious Youth, Jacey L Anderberg, Kelly Barry, Blake M Upshaw, Katie H Mangen, Samuel D Spencer, Andrew G Guzick, Daphne M Ayton, Amanda D Palo, Abigail E Candelari, Eric A Storch
Secondary Youth-Level Mechanisms Of Change In Parent Training For Anxious Youth, Jacey L Anderberg, Kelly Barry, Blake M Upshaw, Katie H Mangen, Samuel D Spencer, Andrew G Guzick, Daphne M Ayton, Amanda D Palo, Abigail E Candelari, Eric A Storch
Faculty, Staff and Students Publications
Background: Parent-focused treatments are a promising approach for addressing youth anxiety outside of traditional therapist-delivered modalities. Supportive Parenting for Anxious Childhood Emotions (SPACE) has preliminarily demonstrated efficacy for reducing family accommodation (FA), a key treatment outcome for youth anxiety.
Objective: Since the mechanisms of SPACE remain relatively understudied, we examined youth-reported distress tolerance (DT), anxiety sensitivity (AS), and negative automatic thoughts as candidate mechanisms of SPACE using data from a previously conducted clinical trial.
Methods: In a sample of N = 68 youth (M age = 10.2; 52% male; 62% White), we examined: (a) associations among candidate mechanisms and …
Impact Of Optimal Medical Therapy In Heart Failure Certification For Hospitalists On Guideline-Directed Medical Therapy Utilization, Farhan Ishaq, Duc T Nguyen, Edward A Graviss, Ebun Ebunlomo, Arvind Bhimaraj, Nadia Fida
Impact Of Optimal Medical Therapy In Heart Failure Certification For Hospitalists On Guideline-Directed Medical Therapy Utilization, Farhan Ishaq, Duc T Nguyen, Edward A Graviss, Ebun Ebunlomo, Arvind Bhimaraj, Nadia Fida
Faculty, Staff and Students Publications
Background: Significant gaps in guideline-directed medical therapy (GDMT) for heart failure (HF) stem from shortages of cardiologists and advanced HF providers, as well as a lack of optimal HF management knowledge among hospitalists. This study compared the impact of optimal medical therapy in HF (OMT-HF) certification on GDMT implementation and patient outcomes between an intervention group (IG) of hospitalists and a standard-of-care comparison group (SOC-CG).
Aim: To evaluate if OMT-HF has a difference in GDMT and patients in outcomes between IG and SOC-CG.
Methods: This study was implemented from November 2022 to May 2023. Hospitalized cardiology patients with HF and …
Factors Affecting Production Of Scopulariopsis Brevicaulis Spores For Use In Self-Healing Concrete, Lu-Kwang Ju, Ahsanul Kabir Sumon
Factors Affecting Production Of Scopulariopsis Brevicaulis Spores For Use In Self-Healing Concrete, Lu-Kwang Ju, Ahsanul Kabir Sumon
University Research
Concrete durability is compromised by its susceptibility to cracking, necessitating innovative solutions like self-healing concrete (SHC). Scopulariopsis brevicaulis is capable of biomineralization and its spores were found to hold high potential for use in SHC. Realizing this potential requires clean and effective production of S. brevicaulis spores, which remains unexplored. Here the factors and processes conducive to high productivity of S. brevicaulis spores were investigated. Suitability of cheap, renewable soy-based substrates: soy molasses (SM), soy hull (SH), and soy flour (SF) were first evaluated, and SH was found suitable. The comparison of SH-based solid-state fermentation (SSF) with submerged fermentation (SmF) …
A Conditional Point Cloud Diffusion Model For Deformable Liver Motion Tracking Via A Single Arbitrarily-Angled X-Ray Projection, Jiacheng Xie, Hua-Chieh Shao, Yunxiang Li, Shunyu Yan, Chenyang Shen, Jing Wang, You Zhang
A Conditional Point Cloud Diffusion Model For Deformable Liver Motion Tracking Via A Single Arbitrarily-Angled X-Ray Projection, Jiacheng Xie, Hua-Chieh Shao, Yunxiang Li, Shunyu Yan, Chenyang Shen, Jing Wang, You Zhang
Faculty, Staff and Student Publications
Objective. Deformable liver motion tracking using a single x-ray projection enables real-time motion monitoring and treatment intervention. We introduce a conditional point cloud diffusion (PCD) model-based framework for accurate and robust liver motion tracking from arbitrarily angled single x-ray projections. Approach. We propose a conditional PCD model for liver motion tracking (PCD-Liver), which estimates volumetric liver motion by solving deformable vector fields (DVFs) of a prior liver surface point cloud, based on a single x-ray image. It is a patient-specific model of two main components: a rigid alignment model to estimate the liver’s overall shifts, and a conditional PCD …
Multimodal Imaging Directs Decision Making In Intraseptal L-Aaoca, Joseph Burns, Lindsay F Eilers, Stephen J Dolgner, Edward J Hickey, Silvana Molossi
Multimodal Imaging Directs Decision Making In Intraseptal L-Aaoca, Joseph Burns, Lindsay F Eilers, Stephen J Dolgner, Edward J Hickey, Silvana Molossi
Faculty, Staff and Students Publications
Background: Congenital coronary artery abnormalities represent an uncommon class of congenital heart disease with an associated risk of sudden cardiac death. There is a paucity of data for the evaluation and management of affected patients with an intraseptal course.
Case summary: A 27-year-old woman was found to have a single coronary trunk arising from the right sinus with a 2.7 cm intraseptal course of the left main coronary artery. She underwent stress cardiac magnetic resonance and catheterization, to assess for inducible ischemia before surgical repair with transconal unroofing. Her recovery was uneventful, and she remains free of symptoms.
Discussion: Management …
Chemotype- And Target-Driven Genome Mining For A New Natural Product Inhibitor Of Bacterial Peptide Deformylase, Jonas H Costa-Martini, Eva E Adams, Chad W Johnston
Chemotype- And Target-Driven Genome Mining For A New Natural Product Inhibitor Of Bacterial Peptide Deformylase, Jonas H Costa-Martini, Eva E Adams, Chad W Johnston
Faculty, Staff and Students Publications
Antibiotics are essential for modern medicine, but their use drives the evolution of antimicrobial resistance (AMR) that limits the long-term efficacy of any one drug. To keep pace with AMR and preserve our ability to treat bacterial infections, it is essential that we identify antibiotics with new structures and targets that are not affected by clinical resistance. Historically, most developmental candidates for antibiotics have come from microbial natural products, as they feature chemical structures and biological activities that have been honed over millions of years of evolution. Unfortunately, as classical bioactivity screens for natural product discovery are blind to the …
Mapping Mave Data For Use In Human Genomics Applications, Jeremy A Arbesfeld, Estelle Y Da, James S Stevenson, Kori Kuzma, Anika Paul, Tierra Farris, Benjamin J Capodanno, Sally B Grindstaff, Kevin Riehle, Nuno Saraiva-Agostinho, Jordan F Safer, Jonathan Casper, Maximilian Haeussler, Aleksandar Milosavljevic, Julia Foreman, Helen V Firth, Sarah E Hunt, Sumaiya Iqbal, Melissa S Cline, Alan F Rubin, Alex H Wagner
Mapping Mave Data For Use In Human Genomics Applications, Jeremy A Arbesfeld, Estelle Y Da, James S Stevenson, Kori Kuzma, Anika Paul, Tierra Farris, Benjamin J Capodanno, Sally B Grindstaff, Kevin Riehle, Nuno Saraiva-Agostinho, Jordan F Safer, Jonathan Casper, Maximilian Haeussler, Aleksandar Milosavljevic, Julia Foreman, Helen V Firth, Sarah E Hunt, Sumaiya Iqbal, Melissa S Cline, Alan F Rubin, Alex H Wagner
Faculty, Staff and Students Publications
Background: Experimental data from functional assays have a critical role in interpreting the impact of genetic variants. Assay data must be unambiguously mapped to a reference genome to make it accessible, but it is often reported relative to assay-specific sequences, complicating downstream use and integration of variant data across resources. To make multiplexed assays of variant effect (MAVE) data more broadly available to the research and clinical communities, the Atlas of Variant Effects Alliance mapped MAVE data from the MaveDB community database to human reference sequences, creating an extensive set of machine-readable homology mappings that are incorporated into widely used …
The Carsr Two-Component System Directly Controls Radd Expression As A Global Regulator That Senses Bacterial Coaggregation In Fusobacterium Nucleatum, Bibek G C, Chenggang Wu
The Carsr Two-Component System Directly Controls Radd Expression As A Global Regulator That Senses Bacterial Coaggregation In Fusobacterium Nucleatum, Bibek G C, Chenggang Wu
Faculty, Staff and Student Publications
Two-component systems (TCS) enable bacteria to sense and respond to environmental signals, facilitating rapid adaptation. Fusobacterium nucleatum, a key oral pathobiont, employs the CarSR TCS to modulate coaggregation with various gram-positive partners by regulating the expression of radD, encoding a surface adhesion protein, as revealed by RNA-Seq analysis. However, the direct regulation of the radD-containing operon (radABCD) by the response regulator CarR, the broader CarR regulon, and the signals sensed by this system remain unclear. In this study, chromatin immunoprecipitation followed by high-throughput DNA sequencing (ChIP-seq) identified approximately 161 CarR-enriched loci across the genome and …
Intratumoral Neutrophil-To-Lymphocyte Ratio Is Mirrored By Circulating Neutrophil-To-Lymphocyte Ratio In Non-Small Cell Lung Cancer, Kyle G Mitchell, Younghee Lee, Nathaniel Deboever, Marcelo V Negrao, Hai T Tran, Edwin Parra, Lauren Byers, Alexandre Reuben, Lorenzo Federico, Chantale Bernatchez, Jing Wang, Mara B Antonoff, Ara A Vaporciyan, Stephen G Swisher, Tina Cascone, Ignacio I Wistuba, John V Heymach, Don L Gibbons, Jianjun Zhang, Daniel J Mcgrail, Boris Sepesi, Cara L Haymaker
Intratumoral Neutrophil-To-Lymphocyte Ratio Is Mirrored By Circulating Neutrophil-To-Lymphocyte Ratio In Non-Small Cell Lung Cancer, Kyle G Mitchell, Younghee Lee, Nathaniel Deboever, Marcelo V Negrao, Hai T Tran, Edwin Parra, Lauren Byers, Alexandre Reuben, Lorenzo Federico, Chantale Bernatchez, Jing Wang, Mara B Antonoff, Ara A Vaporciyan, Stephen G Swisher, Tina Cascone, Ignacio I Wistuba, John V Heymach, Don L Gibbons, Jianjun Zhang, Daniel J Mcgrail, Boris Sepesi, Cara L Haymaker
Faculty, Staff and Student Publications
Tumor-initiated emergency granulopoiesis results in expansion of the circulating neutrophil compartment and neutrophil recruitment into the tumor microenvironment (TME), which may in turn promote tumor progression. Although an elevated circulating neutrophil-to-lymphocyte ratio (cNLR) has repeatedly been demonstrated to be an adverse prognostic factor in patients with non-small cell lung cancer (NSCLC), whether this neutrophil expansion in circulation reflects a similar relative neutrophil abundance in the TME remains unclear. We sought to characterize the relationships between cNLR and the intratumoral neutrophil-to-lymphocyte ratio (tNLR), between tNLR and proteogenomic and immune features of NSCLC tumors, and between tNLR and prognosis.We analyzed tNLR (transcriptomic …
Decreased Proliferation Of Hepg2 Liver Cancer Cells In Vitro And Exhibited Proteomic Changes In Vivo In Subjects With Metabolic Syndrome And Metabolic Dysfunction-Associated Steatotic Liver Disease Who Performed Four-Week Dawn-To-Dusk Dry Fasting, Ayse L Mindikoglu, Kristin Eckel-Mahan, Antone R Opekun, Mustafa M Alzubaidi, Zoe R Crochet, Prasun K Jalal, Sung Yun Jung
Decreased Proliferation Of Hepg2 Liver Cancer Cells In Vitro And Exhibited Proteomic Changes In Vivo In Subjects With Metabolic Syndrome And Metabolic Dysfunction-Associated Steatotic Liver Disease Who Performed Four-Week Dawn-To-Dusk Dry Fasting, Ayse L Mindikoglu, Kristin Eckel-Mahan, Antone R Opekun, Mustafa M Alzubaidi, Zoe R Crochet, Prasun K Jalal, Sung Yun Jung
The Brown Foundation: Institute of Molecular Medicine
Background: Four-week dawn-to-dusk dry fasting (DDDF) was previously shown to have a potent anti-inflammatory effect and induce an anti-tumorigenic proteome in the serum and peripheral blood mononuclear cells in subjects without cancer. The study goal was to determine if serum obtained from these subjects without cancer who underwent 4-week DDDF has an anti-tumorigenic effect.
Methods: HepG2 cells were treated with serum collected from four individuals with metabolic syndrome and metabolic dysfunction-associated steatotic liver disease (MASLD) and four healthy individuals who performed 4-week DDDF. The objective was to assess cell proliferation/viability in HepG2 cells treated with non-fasted and dry-fasted serum and …
Modeling Reemergence Of Vaccine-Eliminated Infectious Diseases Under Declining Vaccination In The Us, Mathew V Kiang, Kate M Bubar, Yvonne Maldonado, Peter J Hotez, Nathan C Lo
Modeling Reemergence Of Vaccine-Eliminated Infectious Diseases Under Declining Vaccination In The Us, Mathew V Kiang, Kate M Bubar, Yvonne Maldonado, Peter J Hotez, Nathan C Lo
Faculty, Staff and Students Publications
Importance: Widespread childhood vaccination has eliminated many infectious diseases in the US. However, vaccination rates are declining, and there are ongoing policy debates to reduce the childhood vaccine schedule, which may risk reemergence of previously eliminated infectious diseases.
Objective: To estimate the number of cases and complications in the US under scenarios of declining childhood vaccination for measles, rubella, poliomyelitis, and diphtheria.
Design, setting, and participants: A simulation model was used to assess the importation and dynamic spread of vaccine-preventable infectious diseases across 50 US states and the District of Columbia. The model was parameterized with data on area-specific estimates …
Cholesterol Metabolism Regulated By Camkk2-Creb Signaling Promotes Castration-Resistant Prostate Cancer, Chenchu Lin, Thomas L Pulliam, Jenny J Han, Jiaqian Xu, Carlos Vera Recio, Sandi R Wilkenfeld, Yan Shi, Manoj Kushwaha, Sarah Bench, Eduardo Ruiz, Sanjanaa Senthilkumar, Jayasurya Dileep, Peter D A Shepherd, Nora M Navone, Albert R Klekers, Elizabeth M Whitley, Michael M Ittmann, Livia S Eberlin, Wenyi Wang, Daniel E Frigo
Cholesterol Metabolism Regulated By Camkk2-Creb Signaling Promotes Castration-Resistant Prostate Cancer, Chenchu Lin, Thomas L Pulliam, Jenny J Han, Jiaqian Xu, Carlos Vera Recio, Sandi R Wilkenfeld, Yan Shi, Manoj Kushwaha, Sarah Bench, Eduardo Ruiz, Sanjanaa Senthilkumar, Jayasurya Dileep, Peter D A Shepherd, Nora M Navone, Albert R Klekers, Elizabeth M Whitley, Michael M Ittmann, Livia S Eberlin, Wenyi Wang, Daniel E Frigo
Faculty, Staff and Student Publications
Castration-resistant prostate cancer (CRPC) remains an incurable disease in need of improved treatments. CAMKK2 is an emerging therapeutic target whose oncogenic effects in prostate cancer have, to date, been largely attributed to its activation of AMP-activated protein kinase (AMPK). Here, we demonstrate that CAMKK2 promotes prostate cancer growth through an alternative downstream pathway involving CAMKI and CREB. Unbiased transcriptomics identify CREB-mediated transcription as a CAMKK2-regulated process, findings that we validate using diverse molecular, genetic, and pharmacological approaches in vitro and in vivo. CAMKK2 promotes CREB phosphorylation/activation through CAMKIα independently of AMPK, CAMKIV, or other CAMKI isoforms. Functionally, the CREB family …
Exploring Predictors Of Treatment Response To Glp-1 Receptor Agonists For Smoking Cessation, Luba Yammine, Constanza De Dios, Robert Suchting, Charles E Green, David A Nielsen, Consuelo Walss-Bass, Joy M Schmitz
Exploring Predictors Of Treatment Response To Glp-1 Receptor Agonists For Smoking Cessation, Luba Yammine, Constanza De Dios, Robert Suchting, Charles E Green, David A Nielsen, Consuelo Walss-Bass, Joy M Schmitz
Faculty, Staff and Student Publications
Introduction: Understanding predictors of smoking cessation medication efficacy facilitates the ability to enhance treatment effectiveness. In our pilot trial, exenatide, a glucagon-like peptide-1 receptor agonist, adjunct to nicotine patch improved smoking abstinence compared to nicotine patch alone. This secondary analysis explores potential baseline characteristics associated with differential treatment response to exenatide.
Aims and methods: The parent trial randomized (1:1) 84 smokers with prediabetes and/or overweight to once-weekly placebo or exenatide, 2 mg, subcutaneously. All participants received nicotine patch (21 mg) and brief smoking cessation counseling, with biologically confirmed 7-day point prevalence abstinence at week 6 (end-of-treatment) deemed the primary outcome. …
Multiscale Modeling Of Drug-Induced Liver Injury From Organ To Lobule, Alon Malka-Markovitz, Stelian Camara Dit Pinto, Mohammed Cherkaoui, Steven M Levine, Sharmila Anandasabapathy, Gagan K Sood, Sadhna Dhingra, Gao Yujia, John M Vierling, Nicolas R Gallo
Multiscale Modeling Of Drug-Induced Liver Injury From Organ To Lobule, Alon Malka-Markovitz, Stelian Camara Dit Pinto, Mohammed Cherkaoui, Steven M Levine, Sharmila Anandasabapathy, Gagan K Sood, Sadhna Dhingra, Gao Yujia, John M Vierling, Nicolas R Gallo
Center for Medical Ethics and Health Policy Staff Publications
Drug-induced liver injury poses significant challenges in drug development and in clinical care. This study builds on prior work developing a Human Liver Virtual Twin by creating a Multiscale Computational Fluid Dynamics framework that integrates patient-specific anatomical data to predict acetaminophen-induced liver injury as a demonstration of its capability. The model bridges vascular, lobular, and cellular scales to simulate dynamic blood flow, drug transport, and injury mechanisms that accurately reflect clinically observed spatial heterogeneity. Results demonstrate accurate blood flow dynamics, predictions of hepatocellular damage, and a scalable framework for studying spatial heterogeneity applicable to other hepatic pathologies. This work establishes …
Detecting Early Changes In Cartilage Collagen And Proteoglycans Distribution Gradients In Mice Harboring The R992c Collagen Ii Mutant Using 2d Correlation Infrared Spectroscopy, Jolanta Fertala, Andrzej Steplewski, Andrzej Fertala
Detecting Early Changes In Cartilage Collagen And Proteoglycans Distribution Gradients In Mice Harboring The R992c Collagen Ii Mutant Using 2d Correlation Infrared Spectroscopy, Jolanta Fertala, Andrzej Steplewski, Andrzej Fertala
Department of Orthopaedic Surgery Faculty Papers
Collagen II is a vital structural component in developing bones and mature cartilage. Muta- tions in this protein cause spondyloepiphyseal dysplasia, a disease characterized primarily by altered skeletal growth and manifesting with a range of phenotypes, from lethal to mild. This study examined transgenic mice harboring the R992C (p.R1124C) substitution in colla- gen II. Previous research demonstrated significant growth abnormalities and disorganized growth plate structure in these mice, and histological signs of osteoarthritic changes in the knee joints of 9-month-old mice with the R992C mutation. Our study focuses on detecting early structural changes in the articular cartilage that occur before …
Hmga2 Associated Cerna-Hotair Pathway In Breast Cancer Patients From Clinicopathological Perspective, Peli̇n Ercoşkun, Deni̇z Ağirbaşli, Mehmet Veli̇dedeoğlu, Mehmet Seven, Aysel Kalayci
Hmga2 Associated Cerna-Hotair Pathway In Breast Cancer Patients From Clinicopathological Perspective, Peli̇n Ercoşkun, Deni̇z Ağirbaşli, Mehmet Veli̇dedeoğlu, Mehmet Seven, Aysel Kalayci
Turkish Journal of Medical Sciences
Background/aim: Several epigenetic alterations are involved in the development of breast cancer. The long noncoding RNA HOTAIR and related RNAs play a role in initiation of breast cancer and are promising targets for diagnostic biomarker and therapeutic studies. In this study, we aimed to investigate HMGA2 associated ceRNA HOTAIR pathway in breast cancer patients.
Materials and methods: Forty breast cancer patients and ten healthy controls were included in this study, and then patients were divided into clinicopathologic groups. After total cell-free RNA isolation, expression levels of target RNAs were analysed by Real-Time PCR. The amount of gene expression was determined …
Janus Kinase Inhibitors In Localized Scleroderma: A Systematic Literature Review, Seher Şener, Yusuf Zi̇ya Şener, Ezgi̇ Deni̇z Batu, Alper Sari, Ali̇ Akdoğan
Janus Kinase Inhibitors In Localized Scleroderma: A Systematic Literature Review, Seher Şener, Yusuf Zi̇ya Şener, Ezgi̇ Deni̇z Batu, Alper Sari, Ali̇ Akdoğan
Turkish Journal of Medical Sciences
Background/aim: Reports on the use of Janus kinase (JAK) inhibitors in the treatment of localized scleroderma are increasing in the literature. In this review, we examined the published studies regarding the use of JAK inhibitors in patients with localized scleroderma.
Materials and methods: We searched MEDLINE and Scopus for articles on patients with localized scleroderma treated with JAK inhibitors. The search included articles from the inception of these databases through August 1st, 2024.
Results: Our literature search showed 11 articles describing 17 patients with localized scleroderma treated with JAK inhibitors. Generalized morphea (47.1%) was the most common type of localized …
Evaluating Leflunomide And Methotrexate Combination Vs. Monotherapy In Rheumatoid And Psoriatic Arthritis, Mete Kara, Gülay Alp, Mete Pekdi̇ker, Sertaç Ketenci̇, Annamaria Porreca, Haluk Ci̇nakli̇
Evaluating Leflunomide And Methotrexate Combination Vs. Monotherapy In Rheumatoid And Psoriatic Arthritis, Mete Kara, Gülay Alp, Mete Pekdi̇ker, Sertaç Ketenci̇, Annamaria Porreca, Haluk Ci̇nakli̇
Turkish Journal of Medical Sciences
Background/aim: Methotrexate (MTX) and leflunomide (LEF) are conventional synthetic disease-modifying antirheumatic drugs (DMARDs) commonly used for treating rheumatoid arthritis (RA) and psoriatic arthritis (PsA), either as monotherapies or in combination. This study aimed to compare the adverse effects (AEs) and efficacy of combined use of MTX plus LEF with monotherapy in RA and PsA patients.
Materials and methods: This study included 528 patients (385 RA and 143 PsA) with at least 6 months of follow-up. Disease activity was assessed using DAS-28 CRP and DAPSA, and treatment-related AEs were classified based on specific MedDRA categories.
Results: The cumulative incidence of AEs …
Pulmonary Artery Wall Thickness And Systemic Sclerosis: Influence Of Inflammation On Vascular Changes, Eli̇f Altunel Kilinç, Haydar Ali̇ Candan, İpek Türk, Çağlar Özmen
Pulmonary Artery Wall Thickness And Systemic Sclerosis: Influence Of Inflammation On Vascular Changes, Eli̇f Altunel Kilinç, Haydar Ali̇ Candan, İpek Türk, Çağlar Özmen
Turkish Journal of Medical Sciences
Background/aim: Systemic sclerosis (SSc) is a complex autoimmune disease characterized by vascular disorders and fibrosis. This study aimed to compare pulmonary artery wall thickness (PAWT) in SSc patients without PAH with idiopathic PAH (IPAH) and healthy controls and to investigate the effect of increased PAWT and inflammation on vascular changes in SSc patients.
Materials and Methods: This cross-sectional study included 60 SSc patients, 30 IPAH patients, and 40 age- and sex-matched healthy controls, all of whom underwent echocardiographic evaluation. Data were analyzed including patient demographics, disease duration, type of skin involvement, lung involvement, and autoantibody status.
Results: PAWT was significantly …
Il-40 Levels In Treatment-Naïve And Methotrexate-Treated Rheumatoid Arthritis Patients, Hamdi̇ Oğuzman, Mete Pekdi̇ker
Il-40 Levels In Treatment-Naïve And Methotrexate-Treated Rheumatoid Arthritis Patients, Hamdi̇ Oğuzman, Mete Pekdi̇ker
Turkish Journal of Medical Sciences
Background/aim: Rheumatoid arthritis (RA) is an autoimmune disease that is characterized by persistent inflammation and progressive damage to the joints. In this study, it was aimed to explore the role of interleukin (IL)-40, a newly discovered cytokine, in the pathogenesis of RA. We also aimed to investigate the relationship between IL-40 and other cytokines such as IL-4, transforming growth factor (TGF)-β1 and tumor necrosis factor (TNF)-α.
Materials and methods: This single-center, cross-sectional study included 87 participants divided into three groups: healthy controls (n = 29), newly diagnosed RA patients (n = 29), and RA patients with remission under methotrexate (MTX) …
Evaluation And Validation Of 3d-Printed Anatomical Urinary System Model And Virtual Reality Rirs Simulators In Rirs Training: A Comparative Study, Mehmet Ezer, Tahsi̇n Batuhan Aydoğan, Lazaros Tzelves, Andreas Skolarikos, Mehmet Uslu, Kemal Sarica, Emre Huri̇
Evaluation And Validation Of 3d-Printed Anatomical Urinary System Model And Virtual Reality Rirs Simulators In Rirs Training: A Comparative Study, Mehmet Ezer, Tahsi̇n Batuhan Aydoğan, Lazaros Tzelves, Andreas Skolarikos, Mehmet Uslu, Kemal Sarica, Emre Huri̇
Turkish Journal of Medical Sciences
Background/aim: This study evaluates the use of a 3D-printed anatomical urinary system model (3D-AUSM) and a Virtual Reality RIRS Simulator (VRRS), for training in RIRS, based on real user feedback.
Materials and methods: The 3D-AUSM was created using cadaver CT and MRI scans, and the data was transferred to a VR environment for simulation. A total of 43 inexperienced urology trainees participated in the theoretical phase of the RIRS training program. Of these, 32 trainees (Group T) who passed a proficiency exam proceeded to the hands-on training phase with the 3D-AUSM and VRRS models. Additionally, 17 experienced surgeons (Group S) …
Administration Of Adipose Tissue-Derived Mesenchymal Stem Cells And Bone Marrow-Derived Mesenchymal Stem Cells In Anosmic Mice, Burak Hazir, Alper Ceylan, Emi̇n Ümi̇t Bağriaçik, Duygu Dayanir, Betül Öğüt, Ni̇han Örüklü, Mücahi̇t Yalçin, Berkay Şi̇mşek, Muammer Meli̇h Şahi̇n
Administration Of Adipose Tissue-Derived Mesenchymal Stem Cells And Bone Marrow-Derived Mesenchymal Stem Cells In Anosmic Mice, Burak Hazir, Alper Ceylan, Emi̇n Ümi̇t Bağriaçik, Duygu Dayanir, Betül Öğüt, Ni̇han Örüklü, Mücahi̇t Yalçin, Berkay Şi̇mşek, Muammer Meli̇h Şahi̇n
Turkish Journal of Medical Sciences
Background/aim: Anosmia, a serious condition that affects the sense of smell, has no universally agreed-upon treatment. Adult stem cells are considered a potential option for treating anosmia. This study aims to evaluate the efficacy of mesenchymal stem cells derived from different tissues in an anosmic mouse model induced by 3-methylindole (3-MI).
Materials and methods: In our study, 36 mice with 3-MI-induced anosmia were divided into subgroups. Anosmia was confirmed by performing a food-finding test (FFT) in each group. Intranasal phosphate-buffered saline was administered to the first group, adipose tissue-derived mesenchymal stem cells (ADSCs) to the second group, and bone marrow-derived …
Forensic Identification Using Airdna: A Preliminary Study On The Collection, Isolation, Amplification And Sequencing Of Human Dna From Air Samples, Sitki Tiplamaz, Zehra Ömeroğlu Ulu, Bestami̇ Çolak, Hizir Asliyüksek, Fi̇kretti̇n Şahi̇n
Forensic Identification Using Airdna: A Preliminary Study On The Collection, Isolation, Amplification And Sequencing Of Human Dna From Air Samples, Sitki Tiplamaz, Zehra Ömeroğlu Ulu, Bestami̇ Çolak, Hizir Asliyüksek, Fi̇kretti̇n Şahi̇n
Turkish Journal of Medical Sciences
Background/aim: Humans continually release skin cells and DNA fragments into the air. This DNA can either remain airborne or drop onto surfaces as indoor dust. This study investigates the collection, isolation, amplification, and sequencing of human DNA from air samples, focusing on both nuclear DNA and mitochondrial DNA.
Materials and methods: This study was conducted in a 15 m3 room and a meeting room, where air samples were systematically collected and filtered using a vacuum device equipped with various sterile filters. The rigorous protocols were implemented to prevent contamination throughout the process. Thirteen air samples were processed in this research, …
Expert Opinion On Clinical Presentation, Diagnosis And Treatment Of Infantile Onset Pompe Disease: A Delphi Study In Türkiye, Eki̇n Özsaydi Aktaşoğlu, Asli İnci̇, Ridvan Murat Öktem, Gürsel Bi̇beroğlu, İlyas Okur, Fati̇h Süheyl Ezgü, Fi̇li̇z Başak Cengi̇z Ergi̇n, Abdurrahman Akgün, Nur Arslan, Hali̇l İbrahi̇m Aydin, Ayşe Ergül Bozaci, Mahmut Çoker, Fatma Tuba Emi̇noğlu, Meli̇ke Ersoy, Emi̇ne Göksoy, Banu Kadioğlu Yilmaz, Mehtap Kağnici, Mustafa Kiliç, Nesli̇han Önenli̇ Mungan, Burcu Öztürk Hişmi̇, Pembe Soylu Üstkoyuncu, Ayşegül Tokatli, Ayşe Çi̇ğdem Aktuğlu Zeybek, Berrak Bi̇lgi̇ner Gürbüz, Sevi̇l Dorum, Di̇lek Güneş, Çi̇ğdem Seher Kasapkara, Sebi̇le Kilavuz, Erdoğan Soyuçen, Peli̇n Teke Kisa, Özlem Ünal Uzun, Fatma Derya Bulut, Songül Gökay, Selen Has Özhan, Deni̇z Kor, Aynur Küçükcongar Yavaş, Fi̇gen Özçay, Yilmaz Yildiz, Harun Yildiz, Leyla Tümer
Expert Opinion On Clinical Presentation, Diagnosis And Treatment Of Infantile Onset Pompe Disease: A Delphi Study In Türkiye, Eki̇n Özsaydi Aktaşoğlu, Asli İnci̇, Ridvan Murat Öktem, Gürsel Bi̇beroğlu, İlyas Okur, Fati̇h Süheyl Ezgü, Fi̇li̇z Başak Cengi̇z Ergi̇n, Abdurrahman Akgün, Nur Arslan, Hali̇l İbrahi̇m Aydin, Ayşe Ergül Bozaci, Mahmut Çoker, Fatma Tuba Emi̇noğlu, Meli̇ke Ersoy, Emi̇ne Göksoy, Banu Kadioğlu Yilmaz, Mehtap Kağnici, Mustafa Kiliç, Nesli̇han Önenli̇ Mungan, Burcu Öztürk Hişmi̇, Pembe Soylu Üstkoyuncu, Ayşegül Tokatli, Ayşe Çi̇ğdem Aktuğlu Zeybek, Berrak Bi̇lgi̇ner Gürbüz, Sevi̇l Dorum, Di̇lek Güneş, Çi̇ğdem Seher Kasapkara, Sebi̇le Kilavuz, Erdoğan Soyuçen, Peli̇n Teke Kisa, Özlem Ünal Uzun, Fatma Derya Bulut, Songül Gökay, Selen Has Özhan, Deni̇z Kor, Aynur Küçükcongar Yavaş, Fi̇gen Özçay, Yilmaz Yildiz, Harun Yildiz, Leyla Tümer
Turkish Journal of Medical Sciences
Background/aim: Pompe disease (acid maltase deficiency, glycogen storage disease type II, OMIM #606800) is an autosomal recessive disorder characterized by lysosomal acid-α-glucosidase deficiency. The infantile-onset type of the disease is mainly characterized by cardiomegaly, hypotonia, and a high mortality rate. This study aimed to create a national consensus about infantile-onset Pompe disease (IOPD) to raise awareness among clinicians and standardize diagnosis and treatment approaches in Türkiye.
Materials and methods: The Gazi University Division of Metabolic Diseases and Nutrition developed this expert opinion consensus and expanded it to include metabolism specialists across Türkiye. A systematic literature review was performed, and the …
Investigation Of The Relationship Between Triglyceride Glucose Index And Metabolic And Hematological Parameters In Obese Individuals, Özge Baş Aksu, Feri̇de Özkara, Rifat Emral, Volkan Genç, Demet Çorapçioğlu, Mustafa Şahi̇n
Investigation Of The Relationship Between Triglyceride Glucose Index And Metabolic And Hematological Parameters In Obese Individuals, Özge Baş Aksu, Feri̇de Özkara, Rifat Emral, Volkan Genç, Demet Çorapçioğlu, Mustafa Şahi̇n
Turkish Journal of Medical Sciences
Background/aim: This research examined the association between the triglyceride-glucose (TyG) index and metabolic, hepatic, and hematologic variables in a population of severely obese subjects, with a focus on the assessment of glycemic control.
Materials and methods: This retrospective study included 315 adult patients with a body mass index (BMI) ≥ 35 kg/m² who were evaluated for bariatric surgery. Participants were grouped according to HbA1c levels: those with HbA1c ≥ 6.5% and those with HbA1c < 6.5%. TyG, atherogenic index of plasma (AIP), fibrosis-4 (FIB-4), aspartate aminotransferase-to-platelet ratio index (APRI), and hematological inflammation markers were assessed and compared between groups. To investigate associations, correlation and regression analyses were conducted.
Results: Individuals with HbA1c ≥ 6.5% had significantly higher TyG, AIP, APRI, and FIB-4 values than those with lower HbA1c. The TyG index showed a strong …
Protocol For Establishing Genetically Engineered Murine Lung Organoids Mimicking Cell Plasticity And Regeneration, Bongjun Kim, Jae-Il Park
Protocol For Establishing Genetically Engineered Murine Lung Organoids Mimicking Cell Plasticity And Regeneration, Bongjun Kim, Jae-Il Park
Faculty, Staff and Student Publications
Lung endothelial cells (LuECs) play crucial roles in lung regeneration and support lung organoids (LOs). However, detailed guidelines for LO culture using LuECs have not been reported yet. Here, we present an efficient protocol for generating and culturing murine LOs that mimic regeneration. We describe steps for the isolation of LuECs and lung epithelial cells, followed by LO culture. We also describe how to establish genetically engineered LOs using viral transduction. For complete details on the use and execution of this protocol, please refer to Kim et al.