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Articles 2311 - 2340 of 15644
Full-Text Articles in Entire DC Network
Tagraxofusp Maintenance Post-Hematopoietic Stem Cell Transplantation Provides Long-Term Survival And Manageable Safety For A Patient With Blastic Plasmacytoid Dendritic Cell Neoplasm, Qaiser Bashir, Marina Konopleva, Glorette Abueg, Jeremy Ramdial, Chitra Hosing, Samer A Srour, Amin Alousi, Uday R Popat, Yago Nieto, Gheath Alatrash, Richard E Champlin, Elizabeth J Shpall, Muzaffar Qazilbash, Naveen Pemmaraju
Tagraxofusp Maintenance Post-Hematopoietic Stem Cell Transplantation Provides Long-Term Survival And Manageable Safety For A Patient With Blastic Plasmacytoid Dendritic Cell Neoplasm, Qaiser Bashir, Marina Konopleva, Glorette Abueg, Jeremy Ramdial, Chitra Hosing, Samer A Srour, Amin Alousi, Uday R Popat, Yago Nieto, Gheath Alatrash, Richard E Champlin, Elizabeth J Shpall, Muzaffar Qazilbash, Naveen Pemmaraju
Faculty, Staff and Student Publications
Presented here is the case of a 68-year-old woman with blastic plasmacytoid dendritic cell neoplasm (BPDCN) treated with tagraxofusp (TAG) maintenance therapy post-allogeneic hematopoietic stem cell transplantation (allo-HCT). Prior to allo-HCT, the patient was treated with hydroxyurea and mini-CVD (cyclophosphamide, vincristine, and dexamethasone alternating with methotrexate (Methotrexate) and cytarabine) + venetoclax + TAG for 5 cycles, which induced morphologic complete remission with minimal residual disease. After allo-HCT, the patient had persistent cytogenic abnormalities 45,XX,der(7)add(7)(p13)del(7)(q11.2q22)add(7)(q32),add(12)(p13),-15,del(16)(q23),-17,+22,+2mar[1]/46,XX[19], and was then treated with TAG maintenance therapy at 9 mg/kg on a 28-day cycle for 16 cycles. At mid-treatment (cycle 6 of 16 cycles of …
A Form-Fitting Model For The Simulation Of Traumatic Brain Injury In Zebrafish, Abigail Armstrong
A Form-Fitting Model For The Simulation Of Traumatic Brain Injury In Zebrafish, Abigail Armstrong
Williams Honors College, Honors Research Projects
Developing a model to study traumatic brain injury (TBI) is important as it allows for the better understanding of mechanisms underlying the disease to develop effective treatments and other strategies. Creating a realistic simulation of TBI, permits the research of different types of impacts and severities that can be seen in brain function and structure. The simulation is also valuable for monitoring progression of injuries over time and developing personalized treatment plans. Zebrafish, in particular, are prime candidates given their status as model organisms, affordability, and ease of direct observation in the research setting. Overall, efficient and accurate TBI models …
Environmental Pollution And Early-Life Metabolic Programming, Lisa Koshko
Environmental Pollution And Early-Life Metabolic Programming, Lisa Koshko
Wayne State University Dissertations
Substantial evidence demonstrates that parental pollutant exposures can induce harmful health effects in the offspring, including the predisposition to Type II Diabetes. As rates of Type II Diabetes continue to rise in younger populations, a crucial gap lies in understanding the role of parental influence in the etiology of later-life metabolic disease. Therefore, the central goal of this work was to determine how early life exposure to smoking level benzene, an endocrine-disrupting air pollutant, affects the metabolic health of offspring, and to identify potential developmental mechanisms involved in disease susceptibility. This goal was achieved using two models of early life …
Contract To Kill: Gnas Mutation, Pratima Raut, Poompozhil Mathivanan, Surinder K. Batra, Moorthy P. Ponnusamy
Contract To Kill: Gnas Mutation, Pratima Raut, Poompozhil Mathivanan, Surinder K. Batra, Moorthy P. Ponnusamy
Journal Articles: Biochemistry & Molecular Biology
The mutation in Gsα-coding GNAS exons, popular as gsp oncogene, is the most frequent mutation across all heterotrimeric G proteins involved in oncogenesis. GNAS R201, the most frequently mutated, followed by Q227, are found predominantly across various neoplasms and cancers such as IPMN, pituitary, thyroid, appendiceal, colorectal, etc. This review emphasizes the pivotal significance of the gsp oncogene and its ramifications underpinning the sustained addiction to GNAS mutation. Recent studies delineating the mechanistic intricacies that provide solid evidence of the profound impact of oncogenic GNAS on tumor formation, progression, and maintenance are highlighted. We have leveraged the discoveries of Gsα …
Mutations In Retinal Cyclic Nucleotide-Gated Channels Identified In Familial Cases Of Inherited Retinal Dystrophies From Pakistan, Zainab Akhtar, Kiran Afshan, Yumei Li, Sumaira Altaf, Aleesha Asghar, Ume Sughra, Wajid Ali Khan, Haiba Kaul, Rui Chen, Sabika Firasat
Mutations In Retinal Cyclic Nucleotide-Gated Channels Identified In Familial Cases Of Inherited Retinal Dystrophies From Pakistan, Zainab Akhtar, Kiran Afshan, Yumei Li, Sumaira Altaf, Aleesha Asghar, Ume Sughra, Wajid Ali Khan, Haiba Kaul, Rui Chen, Sabika Firasat
Faculty, Staff and Students Publications
Purpose: Cyclic nucleotide-gated (CNG) channels are ligand-gated ion channels that transduce light signals into electrical signals in the retinal photoreceptors. Pathogenic variants in CNG channel genes are reported to cause inherited retinal dystrophies (IRDs). The current study used targeted panel sequencing to describe the mutational spectrum of CNG channel genes in familial cases of IRDs from eight consanguineous Pakistani families.
Methods: The current study included consanguineous Pakistani families with at least two affected members. DNA was extracted from whole blood samples by the phenol-chloroform method. Two affected members from each family were initially analyzed using targeted panel sequencing of 344 …
The Central Role For Troponin C Amino-Terminal ⍺-Helix In Vertebrate Thin Filiment Ca²⁺-Activation, Yun Shi, Lauren A. Blackwell, Ryan K. Schroy, B. Max Cleland, Cristina M. Risi, Michelle S. Parvatiyar, Jose R. Pinto, Vitold E. Galkin, P. Bryant Chase
The Central Role For Troponin C Amino-Terminal ⍺-Helix In Vertebrate Thin Filiment Ca²⁺-Activation, Yun Shi, Lauren A. Blackwell, Ryan K. Schroy, B. Max Cleland, Cristina M. Risi, Michelle S. Parvatiyar, Jose R. Pinto, Vitold E. Galkin, P. Bryant Chase
Department of Biomedical and Translational Sciences Faculty Publications
Troponin C (TnC) is the Ca²⁺-sensing subunit of troponin that is responsible for activating thin filaments in striated muscle, and, in turn, for regulating the systolic and diastolic contractile function of cardiac muscle. The secondary structure of vertebrate TnC is mainly composed of α-helices, with nine helices named sequentially, starting from the amino terminus, from N to A–H. The N-helix is a 12-residue-long α-helix located at the extreme amino terminus of the protein and is the only helical structure that does not participate in forming Ca²⁺-binding EF-hands. Evolutionarily, the N-helix is found only in TnC from mammalian species and most …
Clinical Significance Of "S" Isoform Of Dclk1 In Different Gastric Cancer Subtypes Using Newly Produced Monoclonal Antibody, Mahdieh Razmi, Ali-Ahmad Bayat, Nafiseh Mortazavi, Elham Kalantari, Leili Saeednejad Zanjani, Sima Saki, Roya Ghods, Zahra Madjd
Clinical Significance Of "S" Isoform Of Dclk1 In Different Gastric Cancer Subtypes Using Newly Produced Monoclonal Antibody, Mahdieh Razmi, Ali-Ahmad Bayat, Nafiseh Mortazavi, Elham Kalantari, Leili Saeednejad Zanjani, Sima Saki, Roya Ghods, Zahra Madjd
Department of Pathology, Anatomy, and Cell Biology Faculty Papers
Background
Doublecortin-like kinase 1 (DCLK1) isoforms play distinct roles in the progression of gastrointestinal cancers. For the first time ever, the current study aimed to generate DCLK1-S-specific monoclonal antibodies (mAbs) to evaluate the clinical value of DCLK1-S (short isoform) in gastric cancer (GC).Materials and methods
Mice were immunized with a unique 7-mer synthetic peptide of DCLK1-S conjugated with keyhole limpet hemocyanin (KLH). Immunoreactivity of hybridomas and mAbs was determined by ELISA assays and immunohistochemistry (IHC). DCLK1-S expression in two GC cell lines was assessed by flow cytometry. After characterization, the expression pattern of DCLK1-S was investigated in different histological …Proteomics Profiling Of Research Models For Studying Pancreatic Ductal Adenocarcinoma, Mathilde Resell, Hanne-Line Rabben, Animesh Sharma, Lars Hagen, Linh Hoang, Nan T. Skogaker, Anne Aarvik, Eirik Knudsen Bjåstad, Magnus K. Svensson, Manoj Amrutkar, Caroline S. Verbeke, Surinder K. Batra, Gunnar Qvigstad, Timothy C. Wang, Anil Rustgi, Duan Chen, Chun-Mei Zhao
Proteomics Profiling Of Research Models For Studying Pancreatic Ductal Adenocarcinoma, Mathilde Resell, Hanne-Line Rabben, Animesh Sharma, Lars Hagen, Linh Hoang, Nan T. Skogaker, Anne Aarvik, Eirik Knudsen Bjåstad, Magnus K. Svensson, Manoj Amrutkar, Caroline S. Verbeke, Surinder K. Batra, Gunnar Qvigstad, Timothy C. Wang, Anil Rustgi, Duan Chen, Chun-Mei Zhao
Journal Articles: Biochemistry & Molecular Biology
Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies, with a five-year survival rate of 10-15% due to late-stage diagnosis and limited efficacy of existing treatments. This study utilized proteomics-based systems modelling to generate multimodal datasets from various research models, including PDAC cells, spheroids, organoids, and tissues derived from murine and human samples. Identical mass spectrometry-based proteomics was applied across the different models. The preparation and validation of the research models and the proteomics were described in detail. The assembly datasets we present here contribute to the data collection on PDAC, which will be useful for systems modelling, …
Brightly Visualizing Pancreatic Cancer Margins In Orthotopic Mouse Models With An Anti-Ca19-9 Antibody Conjugated To A Near-Infrared Fluorophore, Kristin E. Cox, Javier Bravo, Sunidhi Jaiswal, Siamak Amirfakhri, Thinzar M. Lwin, Abhijit Aithal, Sumbal Talib, Lily J. Jih, Aylin Din Parast Saleh, Keita Kobayashi, Kavita Mallya, Maneesh Jain, Robert M. Hoffman, Aaron M. Mohs, Surinder K. Batra, Michael Bouvet
Brightly Visualizing Pancreatic Cancer Margins In Orthotopic Mouse Models With An Anti-Ca19-9 Antibody Conjugated To A Near-Infrared Fluorophore, Kristin E. Cox, Javier Bravo, Sunidhi Jaiswal, Siamak Amirfakhri, Thinzar M. Lwin, Abhijit Aithal, Sumbal Talib, Lily J. Jih, Aylin Din Parast Saleh, Keita Kobayashi, Kavita Mallya, Maneesh Jain, Robert M. Hoffman, Aaron M. Mohs, Surinder K. Batra, Michael Bouvet
Journal Articles: Biochemistry & Molecular Biology
Background/Purpose: The only potentially curative procedure for pancreatic cancer is R0 resection, which is difficult to achieve due to poorly defined tumor margins. In the present study, we used an anti-CA19-9 antibody conjugated to a near-infrared fluorophore in orthotopic mouse models to target and visualize pancreatic cancer. Methods: Orthotopic models of the human pancreatic cancer cell lines SW1990 and BxPC3 were established by implanting tumor fragments into the pancreas of athymic nude mice. Anti-CA19-9 and control IgG were conjugated with IRDye800CW. Mice received 50 µg of CA19-9-IRDye800CW or IgG-IRDye800CW via tail-vein injection and were imaged after 72 h. MIA PaCa-2, …
Diastolic Dysfunction With Vascular Deficits In Hiv-1-Infected Female Humanized Mice Treated With Antiretroviral Drugs, Fadhel A. Alomar, Prasanta K. Dash, Mahendran Ramasamy, Zachary L. Venn, Sean R. Bidasee, Chen Zhang, Bryan T. Hackfort, Santhi Gorantla, Keshore R. Bidasee
Diastolic Dysfunction With Vascular Deficits In Hiv-1-Infected Female Humanized Mice Treated With Antiretroviral Drugs, Fadhel A. Alomar, Prasanta K. Dash, Mahendran Ramasamy, Zachary L. Venn, Sean R. Bidasee, Chen Zhang, Bryan T. Hackfort, Santhi Gorantla, Keshore R. Bidasee
Journal Articles: Cellular & Integrative Physiology
Early-onset heart failure is a major treat to healthy aging individuals with HIV-1 infection. Women with HIV-1 infection (WLWH) are especially vulnerable and develop heart failure with preserved ejection fraction (HFpEF), of which left ventricular diastolic dysfunction, vascular deficits, myocardial infarction, and fibrosis are major components. HIV-infected rodent models that exhibit these pathophysiological features remain under-reported, and this has left a void in our understanding of their molecular causes and therapeutic strategies to blunt its development. Here, we show that female NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ humanized mice (Hu-mice) infected with HIV-1ADA and treated for 13 weeks with dolutegravir …
Development Of The Mechanoresponsive Pericellular Matrix Of Chondrons, Donghee Lee, Sydney E. Greer, Andrew T. Dudley
Development Of The Mechanoresponsive Pericellular Matrix Of Chondrons, Donghee Lee, Sydney E. Greer, Andrew T. Dudley
Journal Articles: Genetics, Cell Biology & Anatomy
Physical properties of cartilage are conferred by the composition and ultrastructure of the extracellular matrix. This study focuses on the development of the pericellular matrix (PCM), a domain that directly contacts the chondrocyte and is a key regulator of biomechanical and biochemical signaling. Using three-dimensional cell culture, microfluidic cell compression platforms, and genetic mouse models, we demonstrated that collagen VI is initially assembled at the cell surface and then displaced to form a shell at the PCM-territorial matrix boundary. Cell surface-bound hyaluronan is crucial for the assembly process, and hyaluronan-aggrecan complexes drive displacement. Integrin adhesion is not required early but …
The Characterization Of Il-27 Production And Its Impact On T Cell Antigen-Specificity And Diversity In A Neonatal Bcg Vaccination Model, Ashley M. Divens
The Characterization Of Il-27 Production And Its Impact On T Cell Antigen-Specificity And Diversity In A Neonatal Bcg Vaccination Model, Ashley M. Divens
Graduate Theses, Dissertations, and Problem Reports (ETD)
Tuberculosis (TB) is caused by Mycobacterium tuberculosis (Mtb), and it has plagued humans for most of recorded history. Despite strong efforts to prevent and treat TB, it remains the leading cause of death due to a pathogen and is most prevalent in certain regions of Asia and Africa. Currently, the only approved vaccine to prevent TB is the live-attenuated Bacillus Calmette-Guérin (BCG) vaccine. Most countries have a universal BCG vaccination policy, but the vaccine ultimately fails to be protective. The BCG vaccine is most effective in children and protects against disseminated TB, but protection wanes 10-15 years after vaccination causing …
Comparative Efficacy Of Hallucinogens In Treating Mood Disorders Through A Meta-Analysis Of Symptom Reduction, Dosage, And Duration, John Marco D.F. Muniz
Comparative Efficacy Of Hallucinogens In Treating Mood Disorders Through A Meta-Analysis Of Symptom Reduction, Dosage, And Duration, John Marco D.F. Muniz
Honors Undergraduate Theses
Background: Hallucinogens including psilocybin, lysergic acid diethylamide (LSD), ketamine, N,N-dimethyltryptamine (DMT) (as ayahuasca), have re-emerged as potential rapid-acting treatments for mood disorders. We conducted a meta-analysis of placebo-controlled trials evaluating their efficacy in depression and anxiety disorders. Methods: A systematic review identified 12 trials (Total ≈ 670) meeting inclusion criteria (randomized, placebo-controlled). Data on Cohen’s d and Hedges’ g effect sizes for depression- and anxiety-related outcomes were extracted. We computed pooled effect sizes (weighted by sample size and inverse variance), performed subgroup analyses by drug, diagnosis, follow-up duration, and outcome measure type, and assessed heterogeneity (I2, Q …
Investigating The Role Of Prostasin In Angiogenesis: A Chorioallantoic Membrane Model Approach, Zaima Aline
Investigating The Role Of Prostasin In Angiogenesis: A Chorioallantoic Membrane Model Approach, Zaima Aline
Honors Undergraduate Theses
Prostasin, also known as PRSS8 or CAP1, is a glycosylphosphatidylinositol (GPI)-anchored extracellular serine protease involved in various physiological and pathophysiological processes. Prostasin expression is observed during key phases of trophoblast invasion and placental development, critical steps in embryo implantation in Rhesus monkeys. This suggests a role for prostasin in extracellular matrix remodeling and tissue invasion, both essential for a healthy pregnancy. Moreover, prostasin appears vital for development as studies in mice show that a germline knockout of the gene leads to significant placental defects and eventual embryonic death, highlighting its importance in vascular and structural development within the placenta.
Building …
Examining The Effect Of A High Fat Diet On The Expression Of Adipokines In A Murine Model Of Barrett's Esophagus, Saagar A. Shah
Examining The Effect Of A High Fat Diet On The Expression Of Adipokines In A Murine Model Of Barrett's Esophagus, Saagar A. Shah
Honors Undergraduate Theses
Chronic acid reflux results in injury to the esophagus and the development of Barrett’s Esophagus (BE). BE elevates the lifetime risk for a patient to develop Esophageal Adenocarcinoma (EAC). Clinically, one of the main risk factors for BE and EAC is obesity, which alters the secretion of inflammatory cytokines by adipocytes, also referred to as adipokines. Conflicting reports have been made to the expression of adipokines and their receptors in the progression to esophageal cancer. Utilizing an inflammation-based mouse model for BE, we hypothesize that alterations in the expression of adipokines and their receptors favor an inflammatory environment associated with …
Facilitation Of Chemotherapy Efficacy Through Targeted Drug Delivery In Lung Cancer Cells Via Ultrasound And Implications On Health Interventions, Ibrahim Nasim
Honors Undergraduate Theses
Lung Cancer (small cell and non-small cell) is the leading cause of cancer death in the US, accounting for about 20% of all cancer deaths. Paclitaxel (PTX) is a chemotherapeutic agent commonly used to treat lung cancer. It works by slowing and stopping cancer growth by stiffening microtubules within cells, promoting mitotic halt and cell death. Carboplatin (CP) is another agent given to lung cancer patients containing platinum and works via direct damage of oncolytic DNA. The exact mechanism of how PTX and CP cause cell death is still an under-studied area. This thesis aims to provide insight into how …
High-Throughput Drug Screening For Disease-Modifying Arthritis Therapy, Janapriya Vijayakumar
High-Throughput Drug Screening For Disease-Modifying Arthritis Therapy, Janapriya Vijayakumar
Honors Undergraduate Theses
Current therapy for arthritis predominantly focuses on the symptoms rather than the underlying causes of disease progression. Thus, it is necessary to identify novel drugs which target the underlying molecular basis of such diseases. Using high-throughput cell-based drug screening, we screened 458 different compounds, narrowed down from 811 starting compounds from the NIH Mechanistic Set. We selected drugs from the Mechanistic Set following Lipinski's Rule of 5 to ensure optimal pharmacokinetic properties. The study used modified primary human chondrocytes (IIAM-PRG4Luc), which secrete a lubricin promoter-driven luciferase reporter. We use this luciferase expression as a proxy to measure lubricin, a compound …
Investigation Of Lubricin-Stimulating Fda-Approved Compounds For A Disease-Modifying Osteoarthritic Drug, Swathi S. Menon
Investigation Of Lubricin-Stimulating Fda-Approved Compounds For A Disease-Modifying Osteoarthritic Drug, Swathi S. Menon
Honors Undergraduate Theses
Osteoarthritis (OA) is a degenerative disease that affects many people worldwide. Current methods of treatment are palliative, and no treatment exists to fully reverse or cure OA once it begins to progress. The discovery of a disease-modifying osteoarthritic drug (DMOAD) would increase the quality of life for millions and reduce the need for invasive procedures. Screening FDA-approved drugs ensures more promise due to their known safety profile and potential for faster translation to the clinic. The goal of this project was to conduct dose-response assays with FDA-approved drugs that have been shown to stimulate lubricin production in cells that mimic …
Development Of A Proposed Selective Medium For The Isolation And Differentiation Of P. Sordellii, Dimyana Bottros
Development Of A Proposed Selective Medium For The Isolation And Differentiation Of P. Sordellii, Dimyana Bottros
Honors Undergraduate Theses
Clostridium, a genus of anaerobic, spore-forming bacteria, includes clinically and ecologically significant species like Clostridium difficile and Paeniclostridium sordellii. C. difficile causes antibiotic-associated colitis, while P. sordellii is linked to fatal infections and spontaneous abortions. Recent studies found both species in marine sediments, suggesting their role in environmental and wildlife health disturbances, including the 2013 mass mortality of over 300 manatees in the Indian River Lagoon. However, isolating and differentiating P. sordellii is challenging due to the lack of selective media optimized for its growth. This thesis proposes a novel selective medium tailored to P. sordellii’s physiological …
Heterologous Prime-Pull Mucosal Vaccination With An Adjuvanted Rbd Vaccine Elicits Robust Iga Production And Protects Against Sars-Cov-2, Allyson H Hirsch, Calder R Ellsworth, William A Lewis, Ryan Craig, Amy E Meyer, Jonatan Maldonado, Frania Ramirez Lopez, Syamala Rani Thimmiraju, James B Mclachlan, Xuebin Qin, Nicholas J Maness, Jeroen Pollet, Ulrich Strych, Maria Elena Bottazzi, Peter J Hotez, Lisa A Morici
Heterologous Prime-Pull Mucosal Vaccination With An Adjuvanted Rbd Vaccine Elicits Robust Iga Production And Protects Against Sars-Cov-2, Allyson H Hirsch, Calder R Ellsworth, William A Lewis, Ryan Craig, Amy E Meyer, Jonatan Maldonado, Frania Ramirez Lopez, Syamala Rani Thimmiraju, James B Mclachlan, Xuebin Qin, Nicholas J Maness, Jeroen Pollet, Ulrich Strych, Maria Elena Bottazzi, Peter J Hotez, Lisa A Morici
Faculty, Staff and Students Publications
Despite the efficacy of approved severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines in preventing severe disease and death, breakthrough infections continue to occur in vaccinated individuals, contributing to further viral mutation and spread. These limitations may be attributable to the poor induction of mucosal immunity by parenteral vaccination. Mucosal adjuvants, such as T-vant, can enhance vaccine-induced immune responses through the generation of antigen-specific antibodies and T cells in the respiratory tract. In this study, we evaluated the protective efficacy of adjuvanted SARS-CoV-2 receptor binding domain (RBD) subunit vaccines administered by homologous and heterologous routes. Immunized mice were challenged with …
Evaluation Of Real-World Evidence To Assess Effectiveness Outcomes Of Janus Kinase Inhibitors For Rheumatoid Arthritis: A Systematic Review Of Us Studies, Chandler Gandy, Shadi Bazzazzadehgan, Sebastian Bruera, Yinan Huang
Evaluation Of Real-World Evidence To Assess Effectiveness Outcomes Of Janus Kinase Inhibitors For Rheumatoid Arthritis: A Systematic Review Of Us Studies, Chandler Gandy, Shadi Bazzazzadehgan, Sebastian Bruera, Yinan Huang
Faculty, Staff and Students Publications
Objective: This review summarized the real-world effectiveness outcomes of Janus kinase inhibitors (JAKi) for rheumatoid arthritis (RA) based on observational studies.
Methods: A systematic review followed PRISMA guidelines, with searches conducted in PubMed, Embase, and CINAHL from each database's inception to June 2, 2023. Studies were included if they evaluated real-world effectiveness outcomes of JAKi for US RA patients. Search terms included "RA", "JAKi", and "real-world". All citations were imported into COVIDENCE platform. Two reviewers independently performed title/abstract screening and full-text eligibility. For each article, study characteristics and effectiveness measures focusing on treatment pattern, clinical response, and patient-reported outcomes (PROs) …
Inclusion Of Patient-Centered, Non-Microbiological Endpoints And Biomarkers In Tuberculosis Drug Trials, Andrew R Dinardo, Wilbert Sabiiti, Stephen H Gillespie, Sophia B Georghiou, Norbert Heinrich, Norbert Hittel, Sami Taghlabi, Danna Carrero Longlax, Mikashmi Kohli, Ursula Panzner, Collins Musia, Christoph Lange, Anca Vasiliu, Rob J W Arts, Anna M Mandalakas, Morten Ruhwald, Lieven J Stuyver, Reinout Van Crevel
Inclusion Of Patient-Centered, Non-Microbiological Endpoints And Biomarkers In Tuberculosis Drug Trials, Andrew R Dinardo, Wilbert Sabiiti, Stephen H Gillespie, Sophia B Georghiou, Norbert Heinrich, Norbert Hittel, Sami Taghlabi, Danna Carrero Longlax, Mikashmi Kohli, Ursula Panzner, Collins Musia, Christoph Lange, Anca Vasiliu, Rob J W Arts, Anna M Mandalakas, Morten Ruhwald, Lieven J Stuyver, Reinout Van Crevel
Faculty, Staff and Students Publications
Tuberculosis drug trials are primarily designed to identify antibiotic regimens with the strongest potency to kill Mycobacterium tuberculosis. However, microbiologic cure is not synonymous with improved health and recovery. Beyond antimicrobial efficacy, parameters such as morbidity and mortality related to lung function, cardiovascular health, and cancer should be prioritized. This narrative review emphasizes the critical need to emphasize clinical outcomes as much, if not more, than microbiological endpoints. We examine the underlying pathophysiological mechanisms and determinants of non-microbiological outcomes in tuberculosis, providing a synthesis of current knowledge. While there is growing evidence for some biomarkers to risk stratify TB …
Htr1b Is Necessary For Normal Retinal Function In Mice, Solomon E Gibson, Xiaofeng Tao, Guofu Shen, Justin Ma, Yong H Park, Maria Polo-Prieto, Benjamin J Frankfort
Htr1b Is Necessary For Normal Retinal Function In Mice, Solomon E Gibson, Xiaofeng Tao, Guofu Shen, Justin Ma, Yong H Park, Maria Polo-Prieto, Benjamin J Frankfort
Faculty, Staff and Students Publications
Introduction: Serotonin (5-HT) is a neurotransmitter that is involved in retinal development, physiology, and vision, yet the specific contribution of individual 5-HT receptors to retinal function is poorly characterized. We identified 5-HT receptor 1B (Htr1b) as a potential key regulator of serotonergic signaling in the retina.
Methods: Htr1b localization was examined using RNAseq and in situ labeling. Retinal structure was assessed using histology and SD-OCT. Visual function was evaluated using optomotor behavioral experiments. Retinal function was characterized in vivo using electroretinography (ERG) and ex vivo using multielectrode array (MEA) recordings.
Results: Htr1b transcript and HTR1B protein localized primarily …
A Natural Small Molecule Isoginkgetin Alleviates Hypercholesterolemia And Atherosclerosis By Targeting Acly, Zhidan Zhang, Meijie Chen, Yitong Xu, Zhihua Wang, Zhenghong Liu, Chenyang He, Fanshun Zhang, Xiaojun Feng, Xiayun Ni, Yuanli Chen, Jixia Wang, Xinmiao Liang, Zhifu Xie, Jingya Li, Maciej Banach, Jaroslav Pelisek, Yuqing Huo, Yunhui Hu, Paul C Evans, Li Wang, Xiao-Yu Tian, Jianbo Xiao, Yuhua Shang, Yijun Zheng, Xunde Xian, Jianping Weng, Suowen Xu
A Natural Small Molecule Isoginkgetin Alleviates Hypercholesterolemia And Atherosclerosis By Targeting Acly, Zhidan Zhang, Meijie Chen, Yitong Xu, Zhihua Wang, Zhenghong Liu, Chenyang He, Fanshun Zhang, Xiaojun Feng, Xiayun Ni, Yuanli Chen, Jixia Wang, Xinmiao Liang, Zhifu Xie, Jingya Li, Maciej Banach, Jaroslav Pelisek, Yuqing Huo, Yunhui Hu, Paul C Evans, Li Wang, Xiao-Yu Tian, Jianbo Xiao, Yuhua Shang, Yijun Zheng, Xunde Xian, Jianping Weng, Suowen Xu
Faculty, Staff and Students Publications
Rationale: Atherosclerotic cardiovascular disease (ASCVD) represents the predominant cause of mortality and morbidity globally. Given the established role of hypercholesterolemia as a significant risk factor for ASCVD, the discovery of new lipid-lowering medications is of paramount importance. ATP citrate lyase (ACLY) is a crucial enzyme in cellular metabolism, providing acetyl-CoA as the building block for the biosynthesis of fatty acids and cholesterol. Consequently, it has emerged as a promising drug target for innovative treatments of lipid metabolic disorders.
Methods: Virtual screening of a natural product library was performed to identify small-molecule ACLY inhibitors, leading to the discovery of isoginkgetin (ISOGK). …
Syndromic Forms Of Inherited Retinal Dystrophies: A Comprehensive Molecular Diagnosis Of Consanguineous Pakistani Families Using Capture Panel Sequencing, Aleesha Asghar, Sumbal Wazir, Shehzeen Fatima, Hussan Bilal, Muhammad Shoaib, Saqib Ur Rehman, Sumaira Altaf, Yumei Li, Kiran Afshan, Rui Chen, Sabika Firasat
Syndromic Forms Of Inherited Retinal Dystrophies: A Comprehensive Molecular Diagnosis Of Consanguineous Pakistani Families Using Capture Panel Sequencing, Aleesha Asghar, Sumbal Wazir, Shehzeen Fatima, Hussan Bilal, Muhammad Shoaib, Saqib Ur Rehman, Sumaira Altaf, Yumei Li, Kiran Afshan, Rui Chen, Sabika Firasat
Faculty, Staff and Students Publications
Background: Inherited retinal dystrophies (IRDs) represent a clinically and genetically heterogeneous group of genetic disorders that involve photoreceptors and/or retinal pigment epithelium degeneration. IRDs may occur as an isolated condition or may represent an ocular manifestation of a multisystemic disorder referred as syndromic IRD. To increase the understanding of the molecular determinants of syndromic IRD-related genes in the Pakistani population, we revealed the genetic profile of 13 consanguineous Pakistani families using capture panel sequencing.
Methods: We performed comprehensive molecular testing on 72 IRD segregating Pakistani families using targeted capture panel sequencing of 344 known genes. The pathogenicity of candidate variants …
The Reprogramming Factor Klf4 In Normal And Malignant Blood Cells, H Daniel Lacorazza
The Reprogramming Factor Klf4 In Normal And Malignant Blood Cells, H Daniel Lacorazza
Faculty, Staff and Students Publications
The Krüppel-like factor 4 (KLF4) is an evolutionarily conserved zinc finger transcription factor that regulates cellular processes in stem cells, epithelial cells, and immune blood cells by controlling gene expression through genetic, epigenetic, and chromatin remodeling. The landmark 2006 publication identified KLF4 as one of the factors involved in reprogramming differentiated cells into pluripotent stem cells, sparking increased interest in KLF4 research a decade after its discovery, particularly in the fields of stem cell research, epithelial cell biology, endothelial cell function, and tumorigenesis. Over the years, KLF4 has emerged as a key transcription factor in modulating innate and adaptive immunity, …
Hidden Markov Model For Acoustic Pesticide Exposure Detection And Hive Identification In Stingless Bees, Alex Otesbelgue, Amara Jean Orth, Chandler David Fong, Carol Anne Fassbinder-Orth, Betina Blochtein, Maria João Ramos Pereira
Hidden Markov Model For Acoustic Pesticide Exposure Detection And Hive Identification In Stingless Bees, Alex Otesbelgue, Amara Jean Orth, Chandler David Fong, Carol Anne Fassbinder-Orth, Betina Blochtein, Maria João Ramos Pereira
Faculty, Staff and Students Publications
Pollinator populations are declining globally at an unprecedented rate, driven by factors such as pathogens, habitat loss, climate change, and the widespread application of pesticides. Although colony losses remain difficult to prevent, precision beekeeping has introduced non-invasive strategies for monitoring hive conditions. Acoustic data, combined with machine learning techniques, has proven effective in detecting stressors and specific events in honeybee colonies; however, such methodologies remain underexplored for stingless bees, a group of native pantropical pollinators. Meliponiculture, the practice of keeping stingless bees, is an expanding field that offers significant economic and conservation benefits. Stingless bees are particularly susceptible to pesticide …
Poststroke Impulsivity: A Narrative Review, Melissa B Jones, Dakota E Broadway, Malena Gimenez-Zapiola, Ricardo E Jorge
Poststroke Impulsivity: A Narrative Review, Melissa B Jones, Dakota E Broadway, Malena Gimenez-Zapiola, Ricardo E Jorge
Faculty, Staff and Students Publications
In this narrative review, the authors examine the multidimensional nature and presentations of impulsivity after stroke. Impulsivity manifests as immediate or premature responses, impaired delayed gratification, perseverance despite punishment, and other displays of impaired emotional and behavioral regulation. The literature on the assessments, outcomes, and treatment of patients with these various manifestations after a cerebrovascular injury is reviewed. Findings from case reports indicate that poststroke impulsivity may manifest across neurobehavioral syndromes that are not well defined in the psychiatric nomenclature, such as alien hand syndrome and atypical impulse control disorders. Overall, impulse control disorders appear to be rare poststroke. Therapeutic …
Nanoparticle Contrast Agents For Photon-Counting Computed Tomography: Recent Developments And Future Opportunities, Laxman Devkota, Rohan Bhavane, Cristian T Badea, Eric A Tanifum, Ananth V Annapragada, Ketan B Ghaghada
Nanoparticle Contrast Agents For Photon-Counting Computed Tomography: Recent Developments And Future Opportunities, Laxman Devkota, Rohan Bhavane, Cristian T Badea, Eric A Tanifum, Ananth V Annapragada, Ketan B Ghaghada
Faculty, Staff and Students Publications
The clinical availability of photon-counting computed tomography (PCCT) has ushered in a new era of CT imaging. Spectral imaging coupled with superior contrast resolution, and ultrahigh spatial resolution (200 μm) offered by PCCT has the potential to revolutionize value-driven imaging. The potential of multicolor PCCT has generated excitement, and renewed interest, in novel contrast agent development for comprehensive disease interrogation, prediction and monitoring of treatment outcomes. Nanoparticles provide a versatile and powerful platform for the development of next generation contrast agents for spectral PCCT. In this article, we review recent developments and use of nanoparticle contrast agents for PCCT. We …
Structural Dynamics And Binding Of Caenorhabditis Elegans Lifespan-Extending Lipid Binding Protein-3 To Polyunsaturated Fatty Acids, André R Cuevas, Matthew C Tillman, Meng C Wang, Eric A Ortlund
Structural Dynamics And Binding Of Caenorhabditis Elegans Lifespan-Extending Lipid Binding Protein-3 To Polyunsaturated Fatty Acids, André R Cuevas, Matthew C Tillman, Meng C Wang, Eric A Ortlund
Faculty, Staff and Students Publications
Intracellular lipid binding proteins (iLBPs) play crucial roles in lipid transport and cellular metabolism across the animal kingdom. Recently, a fat‐to‐neuron axis was described in Caenorhabditis elegans, in which lysosomal activity in the fat liberates polyunsaturated fatty acids (PUFAs) that signal to neurons and extend lifespan with durable fecundity. In this study, we investigate the structure and binding mechanisms of a lifespan‐extending lipid chaperone, lipid binding protein‐3 (LBP‐3), which shuttles dihomo‐γ‐linolenic (DGLA) acid from intestinal fat to neurons. We present the first high‐resolution crystal structure of LBP‐3, which reveals a classic iLBP fold with an unexpected and unique homodimeric …