Digital Commons Network^™

Protein Marker-Dependent Drug Discovery Targeting Breast Cancer Stem Cells, Ashley V. Huang, Yali Kong, Kan Wang, Milton L. Brown, David Mu

Department of Biomedical and Translational Sciences Faculty Publications

Breast cancer is one of the most common cancers globally. Unfortunately, many patients with breast cancer develop resistance to chemotherapy and tumor recurrence, which is primarily driven by breast cancer stem cells (BCSCs). BCSCs behave like stem cells and can self-renew and differentiate into mature tumor cells, enabling the cancer to regrow and metastasize. Key markers like CD44 and aldehyde dehydrogenase-1 (ALDH1), along with pathways like Wingless-related integration site (Wnt), Notch, and Hedgehog, are critical to regulating this stem-like behavior of BCSCs and, thus, are being investigated as targets for various new therapies. This review summarizes marker-dependent strategies for targeting …

Antibiotic Resistance: The Growing Threats And Potential Solutions, Olisaemeka Zikora Akunne, Blessing Nkechi Emmanuel, Umar Faruk Saidu, Ayobami Sunday Akinnawo, Nasiru Ademola Adeyemi, Livia Chinaza Egoh, Malami Aishatu Muhammad, Olusegun Ayo Ade-Adekunle, Deborah Ahuoyiza Peter, Anne Amina Freitas

Department of Biomedical and Translational Sciences Faculty Publications

Antibiotic resistance (AR) has become a critical global health crisis, threatening the efficacy of antibiotics and increasing healthcare costs, morbidity, and mortality. The One Health approach, which emphasizes the interconnectedness of human, animal, and environmental health, is increasingly recognized as an essential framework for addressing the complex drivers of AR. This review explores the mechanisms of resistance, such as genetic mutations, horizontal gene transfer, and biofilm formation, along with contributing factors such as the overuse of antibiotics in healthcare and agriculture. We assess both traditional and emerging strategies to combat AR, including antimicrobial stewardship, the development of new antibiotics, and …

Phenotype Specific Nuclear Lamina Remodeling In Hipsc Derived Cardiomyocytes Bearing Tnnt2 Sarcomeric Variants, Isabella Leite Coscarella, Olalekan H. Usman, Lili Wang, Maicon Landim-Vieira, Lillian Wirstiuk, Amber N. Brown, Diego A. R. Zorio, Brian K. Washburn, Cynthia Vied, Bjorn C. Knollmann, Christopher Solís, Vitold E. Galkin, P. Bryant Chase, J. Travis Hinson, Jerome Irianto, Jose Renato Pinto

Department of Biomedical and Translational Sciences Faculty Publications

[Summary] Cardiomyocytes endure physical stress from the myocardium environment while generating their own mechanical strains. The force generated by sarcomeres is transmitted both longitudinally to adjacent sarcomeres and laterally to the cytoskeleton via intermediate filaments. This mechanical stimulus impacts other organelles, including the nucleus, thus playing a vital role in sensing and signaling nuclear adaptations. However, there is limited understanding of how changes in cardiac contractility affect nuclear mechanics. Here, we sought to investigate the effects of hyper- and hypo-contractility in nuclei of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) bearing TNNT2 pathogenic variants associated with hypertrophic (HCM) or dilated …

Feel Bad To Discard A Fashion Product: How Ai Designers Influence Individuals' Sustainable Consumption, Ha Kyung Lee, Dooyoung Choi

Educational Leadership & Workforce Development Faculty Publications

This study explores how AI technology in fashion design influences consumers' sustainable consumption behaviors, focusing on emotional attachment to products. By comparing AI-generated and human-designed fashion items, the study examines how designer type impacts negative emotions about discarding products, mediated by emotional attachment. Results from two experimental studies reveal that designer type significantly affects negative emotions toward discarding human-designed items, but emotional attachment was not influenced by designer type in the first study. This lack of difference may be due to personal characteristics that moderate the effect. The second study found that individuals who perceive AI as human-like form stronger …

[Review Of The Book Expanding Approaches To Thematic Analysis: Creative Engagements With Qualitative Data By J. R. Wolgemuth, K. W. Guyotte, & S. A. Shelton (Eds.)], Nazmun Nahar Chaitee

Educational Leadership & Workforce Development Faculty Publications

In Expanding Approaches to Thematic Analysis, editors Jennifer R. Wolgemuth, Kelly W. Guyotte, and Stephanie Anne Shelton introduce an expansive, paradigm-shifting book that reimagines thematic analysis beyond conventional coding methods. This edited volume begins with two presumptions: (1) there are multiple methods of theming data, and (2) qualitative researchers are not necessarily required to code to achieve themes. Through the convergence of various qualitative researchers and early-career scholars, this edited collection pushes thematic analysis into new epistemological territories. The 18 chapters of the book reveal new techniques, such as meditative theming, poetic analysis, and making art, underpinned by theoretical …

Understanding Detroit’S Local Food And Urban Agricultural Policy Subsystem Using The Advocacy Coalition Framework, Joann Marie Hennessey Ph.D.

Antioch University Dissertations & Theses

This explanatory qualitative case study applied the Advocacy Coalition Framework (ACF) to study Detroit’s local food policy changes from 2000 to 2022. The research question and sub-questions were framed using three ACF hypotheses that addressed advocacy coalitions, collective action, and policy change. My research showed how actors in the policy subsystem worked to promote policy change during the study period. Using this Advocacy Coalition Framework approach, I explored local food policy change in the context of community resilience and system changes. Since 2000, the local food movement in Detroit attempted system changes by experimenting with ways to provide local residents …

Co-Becoming Our Way From Ecocide To The Pluriverse, Jupong Lin Ph.D.

Antioch University Dissertations & Theses

Coloniality/modernity is dying. Rising temperatures over land and sea, the extreme weather of the past decade, rising sea levels, arctic ice loss, and mass extinction are just a few indicators that the world has moved far beyond climate change to climate catastrophe. My arts-informed research takes the view that climate catastrophe, perhaps more accurately described as “collective trauma,” is part of the prevailing story and worldview of modernity, defined by patterns of domination, conquest, extractivism, and capitalism. East Asian and Indigenous worldviews share an emphasis on relationality with the world of nonhuman beings and animist traditions that do not …

Creating A General Psychology Curriculum That Embeds Humane Education, Kristina Marie Pham

Antioch University Dissertations & Theses

Academic freedom is under attack in the United States, hindering the ability of educators to develop critical thinking skills in students to prepare them for their roles as participating members of a democracy. The inquiry that informed the curriculum development is as follows: How to embed Humane Education and Participatory Action Research into a General Psychology class? The theoretical framework of Humane Education was the basis for utilizing the principles of Participatory Action Research in the General Psychology curriculum co-created with rural community college students. The Backward Design Model was chosen because the curriculum was created using an existing General …

The Lived Experience Of Fly Fishing And Its Significance For Cultivating A Communion Of Subjects, Eric Landon Mcduffie

Antioch University Dissertations & Theses

Inspired by the lived fly fishing experiences encountered with my grandfather and the spiritually ecological writings of Thomas Berry, I explored how the sacred art of fly fishing connects participants with the natural world from a universal perspective given to us by Thomas Berry in The New Story. Berry described three principles that make up the entire universe: Differentiation, Subjectivity and Communion. I wanted to understand how lived fly fishing experiences fit into Berry’s three universal principles and how an individual’s lived fly fishing experience(s) cultivate(s) a “Communion of subjects.”1 Answers to these two questions informed five initial approaches to …

From Fear To Resilience: An Autoethnography Detailing A Teacher's Battle Against Bullying By Public School Principals, Laurie Etta Reif

Antioch University Dissertations & Theses

This paper tells my story within the realm of public education, particularly focusing on the interactions between teachers and the principals overseeing their schools. Grounded in social context, this autoethnography explores the challenges in these relationships while offering insights into best practices for fostering constructive engagement between educators and administrators. The discussion highlights my struggles with the power dynamics that are prevalent in public schools. Through my story, informed by Indigenous Women’s Research Theory and storytelling methodologies, this dissertation recounts experiences of harassment and intimidation I encountered across multiple school settings. The narrative is an analysis of existing resources and …

Collateral Damage: Dual Mechanical Complications From An Apparently Small Myocardial Infarction, Irene Carrión-Sánchez, Luis Manuel García-Linacero, Paola Ramos-Cano, Jesús Ducay-Rico, Ana Pardo-Sanz, Diego Matellán-Alonso, Irene Gámez-Guijarro, Marcelo Sanmartín, José L. Zamorano

Journal of the Hong Kong College of Cardiology

We report a rare case of myocardial infarction complicated by anterolateral papillary muscle rupture and right ventricular infarction in a 49-year-old man. Initial signs suggested pulmonary embolism, but imaging revealed inferolateral infarction with right ventricular involvement. Angiography showed a thrombosed obtuse marginal branch supplying a chronically occluded right coronary artery. Despite intervention, the patient developed refractory cardiogenic shock. Surgery revealed complete papillary muscle rupture; mitral valve replacement and bypass were performed, but the patient died postoperatively. This case highlights the fatal potential of uncommon infarction patterns and the limited success of surgery, emphasizing the need for alternative transcatheter strategies in …

Advancing Medical Applications Of Cancer Nanotechnology: Highlighting Two Decades Of The Nci's Nanotechnology Characterization Laboratory Service To The Research Community, Rachael M Crist, Yechezkel Barenholz, Ahuva Cern, Kate N Clark, Pieter R Cullis, Cheryl Dean, Neil Desai, Mauro Ferrari, Matthieu Germain, Carmen A Giacomantonio, Emma Grabarnik, Piotr Grodzinski, Atara Hod, Barry E Kennedy, Ruvanthi N Kularatne, Glen S Kwon, Emmanuel Loeb, Erin B Noftall, Len Pagliaro, Morteza Rasoulianboroujeni, Alexander Roth, Darren Rowles, Kulbir Singh, Nicole F Steinmetz, Zhanna Yehtina, Yao Zhang, Daniel Zilbersheid, Jeffrey D Clogston, Stephan T Stern, Marina A Dobrovolskaia

Center for Medical Ethics and Health Policy Staff Publications

The Nanotechnology Characterization Laboratory (NCL) is a US federally funded resource providing characterization and expertise to the cancer nanomedicine research community. Founded as a formal partnership among the US National Cancer Institute (NCI), the US Food and Drug Administration (FDA), and the US National Institute of Standards and Technology (NIST), the NCL has spent two decades developing a one-of-a-kind service with broad multidisciplinary expertise to meet the needs of a rapidly evolving drug development field. To mark the 20th anniversary of the lab's founding, the NCL hosted a symposium to highlight the achievements of the cancer nanomedicine field, showcase novel, …

The Human Spinothalamic Tract: Lessons From Cordotomy, Anthony K Allam, Michael Benjamin Larkin, Ishan A Patel, Mohammed Hasen, David Mears, Patrick Dougherty, Ashwin Viswanathan

Faculty, Staff and Student Publications

The spinothalamic tract has long been known as a primary conductor of nociceptive information, with its anatomical and physiological understanding evolving over centuries of research. This comprehensive review traces the history of the spinothalamic tract beginning with Brown-Sequard’s 1860 report of contralateral analgesia following a hemisection of the spinal cord. As clinical and surgical interventions, such as cordotomies have advanced, so did our understanding of the spinothalamic tract’s function and anatomy. The spinothalamic tract’s role as a crossed pathway conducting pain and temperature sensations was solidified by the mid-20th century. However, intricate details of its somatotopic arrangement, anatomical distributions and …

Contributions Of Pathobiological And Translational Science To Understanding And Managing Ischemic Heart Disease: Progress, Impediments, And Future Directions, L Maximilian Buja

The Texas Heart Institute Journal

Key pathobiological components of ischemic heart disease have been identified as follows: (1) In 1970 to 1973, myocardial infarct size was found to be the primary determinant of prognosis after acute myocardial infarction (AMI); (2) in 1973 to 1989, vulnerable coronary artery plaques were found to predispose individuals to coronary plaque disruption and thrombosis, causing major AMI; (3) in 1972, timely coronary reperfusion was demonstrated to limit the size of evolving AMI but with risk of reperfusion injury; and (4) in 1986, myocardial conditioning was found to be a clinically significant modulator capable of delaying AMI progression. Promising cardioprotective strategies …

Commentary: Impact Of Resistance Training Intensity On Body Composition And Nutritional Intake Among College Women With Overweight And Obesity: A Cluster Randomized Controlled Trial, Joshua L Keller, Sarah E Deemer, Gian Luca Di Tanna, Sherri L Pals, Kevin R Fontaine, David B Allison

Children’s Nutrition Research Center Staff Publications

No abstract provided.

Different Responses Involving Tfh Cells Delay Parasite-Specific Antibody Production In Trypanosoma Cruzi Acute Experimental Models, Ana Carolina Leão, Maria Jose Villar, Rakesh Adhikari, Cristina Poveda, Leroy Versteeg, Gregório Almeida, Peter J Hotez, Maria Elena Bottazzi, Kathryn M Jones

Center for Medical Ethics and Health Policy Staff Publications

Introduction: Chagas disease (CD), caused by the parasite Trypanosoma cruzi, affects millions globally. Despite treatment options in the acute phase, most infections progress to a chronic indeterminate form or develop severe cardiac/gastrointestinal complications. Understanding the immune response is crucial for the development of vaccines and more efficient drugs for the disease control.

Methods: This work investigates the immune response to T. cruzi H1 K68 strain infection in female BALB/c and C57BL/6 mice to characterize differences in Tfh and B cell responses that may be involved in the poor parasite-specific antibody production during acute infection. For this, mice were euthanized …

Patient-Centric Federated Learning: Automating Meaningful Consent To Health Data Sharing With Smart Contracts, Kristin M Kostick-Quenet, Marcelo Corrales Compagnucci, Mateo Aboy, Timo Minssen

Center for Medical Ethics and Health Policy Staff Publications

Federated Learning (FL) promises to enhance data-driven health research by enabling collaborative machine learning across distributed datasets without direct data exchange. However, current FL implementations primarily reflect the data-sharing interests of institutional controllers rather than those of individual patients whose data are at stake. Existing consent mechanisms-like broad consent under HIPAA or explicit consent under the GDPR-fail to provide patients with control over how their data is used. This article explores the integration of smart contracts (SCs) into FL as a mechanism for automating, enforcing, and documenting consent in data transactions. SCs, encoded in decentralized ledger technologies, can ensure that …

Goldenbraid20 E Coli: A Comprehensive And Characterized Toolkit For Enterics, Matthew B Cooke, Kobie T Welch, Laura D Ramirez, Alice X Wen, David C Marciano, Christophe Herman

Faculty, Staff and Students Publications

Modular cloning systems streamline laboratory workflows by consolidating genetic 'parts' into reusable and modular collections, enabling researchers to fast-track strain construction. The GoldenBraid 2.0 modular cloning system utilizes the cutting property of type IIS restriction enzymes to create defined genetic 'grammars', which facilitate the reuse of standardized genetic parts and assembly of genetic parts in the right order. Here, we present a GoldenBraid 2.0 toolkit of genetic parts designed to accelerate cloning in the model bacterium

Analysis Of 1,25-Dihydroxyvitamin D Genomic Action In Human Enteroids And Colonoids Reveals Multiple Regulatory Effects Of Vitamin D In Human Intestinal Physiology, Zachary K Criss, Kali Deans-Fielder, James C Fleet, Sylvia Christakos, Noah Shroyer

Faculty, Staff and Students Publications

Introduction: The intestine has molecular and functional diversity across the proximal-distal and the crypt-villus axes, so it is imperative to determine the common and compartment-specific molecular actions of vitamin D. However, very little work on vitamin D mediated gene regulation has been done in normal human intestine. Here, we examined the impact of 1,25-dihydroxyvitamin D (1,25(OH)2D3) on cultures of human intestinal epithelium derived from duodenum (Dd) and distal colon (Co) biopsies of 6 subjects per tissue.

Methods: Human enteroids and colonoids were cultured for 3 days to promote a stem cell phenotype (undifferentiated, Un) or to induce differentiation (Diff) and …

Learning-Associated Astrocyte Ensembles Regulate Memory Recall, Michael R Williamson, Wookbong Kwon, Junsung Woo, Yeunjung Ko, Ehson Maleki, Kwanha Yu, Sanjana Murali, Debosmita Sardar, Benjamin Deneen

Faculty, Staff and Students Publications

The physical manifestations of memory formation and recall are fundamental questions that remain unresolved1. At the cellular level, ensembles of neurons called engrams are activated by learning events and control memory recall1-5. Astrocytes are in close proximity to neurons and engage in a range of activities that support neurotransmission and circuit plasticity6-10. Moreover, astrocytes exhibit experience-dependent plasticity11-13; however whether specific ensembles of astrocytes participate in memory recall remains obscure. Here we show that learning events induce c-Fos expression in a subset of hippocampal astrocytes, which subsequently …

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). …

The Dna Demethylase Tet1 Modifies The Impact Of Maternal Folic Acid Status On Embryonic Brain Development, Lehua Chen, Bernard K Van Der Veer, Qiuying Chen, Spyridon Champeris Tsaniras, Wannes Brangers, Harm H M Kwak, Rita Khoueiry, Yunping Lei, Robert Cabrera, Steven S Gross, Richard H Finnell, Kian Peng Koh

Faculty, Staff and Students Publications

Folic acid (FA) is well known to prevent neural tube defects (NTDs), but we do not know why many human NTD cases still remain refractory to FA supplementation. Here, we investigate how the DNA demethylase TET1 interacts with maternal FA status to regulate mouse embryonic brain development. We determined that cranial NTDs display higher penetrance in non-inbred than in inbred Tet1−/− embryos and are resistant to FA supplementation across strains. Maternal diets that are either too rich or deficient in FA are linked to an increased incidence of cranial deformities in wild type and Tet1+/− offspring and to …

Skewed Adaptive Immune Responses Are Involved In Alpha-1 Antitrypsin Deficiency Emphysema, Joselyn Rojas-Quintero, Scott A Ochsner, Hyun-Sung Lee, Christine Cong, Alan Waich Cohen, Adrianne S Colborg, Konstantin Tsoyi, Maria C Basil, Edward Cantu, Ivan O Rosas, Neil J Mckenna, Raúl San-José Estépar, Igor Barjaktarevic, Andrew A Wilson, Francesca Polverino

Faculty, Staff and Students Publications

No abstract provided.

Early Cerebrospinal Fluid Elevations Of Ptau-217 In Severe Traumatic Brain Injury Subjects, Hamad Yadikar, Firas H Kobeissy, Claudia Robertson, Spyridoula Tsetsou, John B Williamson, Damon G Lamb, Amy K Wagner, Todd Kibaugh, Shih-Han Kao, Zhifeng Kou, Robert D Welch, Jose-Miguel Yamal, Luis Leon-Novelo, Richard Rubenstein, Kevin K W Wang

Faculty, Staff and Students Publications

Introduction: Tauopathies, including Alzheimer's disease (AD), feature abnormal accumulations of hyperphosphorylated Tau protein; however, their biomarker potential in traumatic brain injury (TBI) is not well-defined. This study investigated whether cerebrospinal fluid (CSF) phosphorylated Tau at threonine-217 (pTau-217) could serve as an early biomarker for severe TBI (sTBI).

Methods: CSF samples from 26 sTBI patients, collected between 6 and 240 h post-injury, and 19 healthy controls were analyzed using an optimized direct enzyme-linked immunosorbent assay (ELISA; sensitivity < 4.7 pg/mL) for pTau-217 detection, complemented by Western blot validation. Temporal analysis, ROC curves, and trajectory clustering were used for interpretation.

Results: CSF pTau-217 levels were significantly elevated in sTBI patients at 6, 12, 18, 24, and 48 h post-injury compared to controls (p …

Comparative Analysis Of Aav Serotypes For Transduction Of Olfactory Sensory Neurons, Benjamin D W Belfort, Johnathan D Jia, Alexandra R Garza, Anthony M Insalaco, J P Mcginnis, Brandon T Pekarek, Joshua Ortiz-Guzman, Burak Tepe, Hu Chen, Ascent-Pd Investigators, Zhandong Liu, Benjamin R Arenkiel

Faculty, Staff and Students Publications

Olfactory sensory neurons within the nasal epithelium detect volatile odorants and relay odor information to the central nervous system. Unlike other sensory inputs, olfactory sensory neurons interface with the external environment and project their axons directly into the central nervous system. The use of adeno-associated viruses to target these neurons has garnered interest for applications in gene therapy, probing olfactory sensory neuron biology, and modeling disease. To date, there is no consensus on the optimal AAV serotype for efficient and selective transduction of olfactory sensory neurons

Altering The Intracellular Trafficking Of Necator Americanus Gst-1 Antigen Yields Novel Hookworm Mrna Vaccine Candidates, Athos Silva De Oliveira, Leroy Versteeg, Neima Briggs, Rakesh Adhikari, Maria Jose Villar, Jeanna R Redd, Peter Hotez, Maria Elena Bottazzi, Jeroen Pollet

Faculty, Staff and Students Publications

BACKGROUND: The antigen Na-GST-1, expressed by the hookworm Necator americanus, plays crucial biochemical roles in parasite survival. This study explores the development of mRNA vaccine candidates based on Na-GST-1, building on the success of recombinant Na-GST-1 (rNa-GST-1) protein, currently assessed as a subunit vaccine candidate, which has shown promise in preclinical and clinical studies.

METHODOLOGY/FINDINGS: By leveraging the flexible design of RNA vaccines and protein intracellular trafficking signal sequences, we developed three variants of Na-GST-1 as native (cytosolic), secretory, and plasma membrane-anchored (PM) antigens. After one immunization in mice, mRNA vaccines induced an earlier onset of antigen-specific antibodies compared to …

The Department Of Cardiovascular Anesthesia Of The Texas Heart Institute: An Informal History, John R Cooper, N Martin Giesecke

Faculty, Staff and Students Publications

No abstract provided.

Diagnostic And Prognostic Value Of Cystatin C In Acute Coronary Syndrome: An Up-To-Date Meta-Analysis, Michal Pruc, Damian Swieczkowski, Basar Cander, Milosz J Jaguszewski, Sagar Galwankar, Salvatore Di Somma, Fatimah Lateef, Indrani Sardesai, Ayman El-Menyar, Michal Zembala, Jacek Kubica, Togay Evrin, Burak Katipoglu, Zubaid Rafique, Frank William Peacock, Lukasz Szarpak

Faculty, Staff and Students Publications

Background: The role of Cystatin C (CysC) in the diagnosis and prognosis of cardiovascular disease, particularly acute coronary syndrome (ACS), is increasingly significant. The goal of this meta-analysis was to assess the diagnostic and prognostic value of CysC in patients with ACS, as well as its association with major adverse cardiovascular events (MACE), defined as mortality, myocardial infarction, heart failure, and stroke.

Methods: The present study is a systematic review and meta-analysis. Using PubMed, Web of Science, Cochrane Library, and Embase, a literature review of cohort and case control studies reporting MACE and using the terms ACS and Cystatin C …

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 …

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 …