Medicine and Health Sciences Commons^™

Echocardiographic Predictors Of Symptomatic Cardiotoxicity Among Patients Undergoing Chemotherapy: A Systematic Review And Meta-Analysis, Muhammad Umer Siddiqui, Youssef Yaacoub, Heidi-Anne Hanson, Joey Junarta, Ahmed K Pasha, Mahek Shah

Division of Internal Medicine Faculty Papers & Presentations

BACKGROUND: Chemotherapeutic agents have been associated with cardiotoxicity; thus, they require close monitoring. Several echocardiographic variables have been investigated as early predictors of symptomatic cardiotoxicity in patients undergoing chemotherapy.

OBJECTIVE: To identify if global longitudinal strain (GLS) is a better predictor of symptomatic cardiotoxicity compared to left ventricular ejection fraction (LVEF) in patients receiving chemotherapy.

METHODS: MEDLINE, Scopus, and Cochrane Central Register of Controlled Trials were searched from inception through December 2020. Adults who developed symptomatic cardiotoxicity (New York Heart Association [NYHA] Class III-IV heart failure, cardiac arrest, or cardiac death) after undergoing chemotherapy with pre- and postchemotherapy echocardiographic measures …

Metabolic Monitoring For Veterans Newly Prescribed Antipsychotic Medications: Enhancing The Process With Nursing Interventions, Charles W. Langnehs Jr

Graduate Theses, Dissertations, and Capstones

People who have severe mental illness are known to experience comorbidities and have shorter lifespans than those in the general population. There are many confounding reasons for those in this population to experience comorbidities that shorten their lives. However, it is commonly recognized that metabolic changes caused by medications taken to treat severe mental illness play a major role in the development of comorbidities and early mortality in those who take them. Drug manufacturers and several major organizations recommend the close monitoring of the metabolic status of those prescribed drugs in the class of medications known as antipsychotics. However, literature …

Retrospective Cohort Evaluating The Comparative Effectiveness Of Ceftaroline And Daptomycin As First-Line Therapies For Inpatient Treatment Of Diabetic Foot Infection In The United States Veterans Health Care System, Alyssa C. Eaves, Chengwen Teng Pharm.D., Ph.D., Kirk E. Evoy, Christopher R. Frei

Faculty Publications

Background Both ceftaroline and daptomycin are possible therapeutic options for diabetic foot infection (DFI) and both are active against methicillin-resistant Staphylococcus aureus (MRSA) infection; however, no previous studies have evaluated their efectiveness head-to-head.

Objective This study compared hospital readmission and mortality proportions among patients receiving ceftaroline fosamil or daptomycin for DFI.

Patients and Methods This was a retrospective cohort, comparative efectiveness study of adults (aged ≥ 18 years) admitted to United States Veterans Health Care System hospitals with a diagnosis code for DFI between 1 October 2010 and 30 September 2014 with an electronic order for ceftaroline or daptomycin as …

Describing Characteristics Of Adults With And Without Congenital Heart Defects Hospitalized With Covid-19, Perla Diaz, Will Coughlin, Wilson Lam, Peter Ermis, David Aguilar, Cecilia M Ganduglia Cazaban, A J Agopian

Faculty, Staff and Student Publications

BACKGROUND: We sought to describe patient characteristics in adults with and without congenital heart defects (CHDs) during hospitalization for COVID-19.

METHODS: We analyzed data collected by Optum®, a nationally representative database of electronic medical records, for 369 adults with CHDs and 41,578 without CHDs hospitalized for COVID-19 between January 1, 2020, and December 10, 2020. We used Poisson regression to describe and compare epidemiologic characteristics, heart-related conditions, and severe outcomes between these two groups.

RESULTS: The distributions of many epidemiologic characteristics were similar between the two groups, but patients with CHDs were significantly more likely to be current or former …

Infiltration Of Peripheral Immune Cells Into The Olfactory Bulb In A Mouse Model Of Acute Nasal Inflammation, Hinami Asano, Sanae Hasegawa-Ishii, Ken Arae, Aki Obara, Geoffroy Laumet, Robert Dantzer, Atsuyoshi Shimada

Faculty, Staff and Student Publications

Chronic nasal inflammation induces robust olfactory bulb (OB) atrophy in mice. Here we examined initial events that occur in the OB after bilateral intranasal administration of lipopolysaccharide, focusing on the olfactory nerve fibers and meninges. We analyzed the time course of OB and meninges inflammation using histological and biochemical approaches. Within 12 h, we observed increased chemokine expression and transient infiltration of peripheral immune cells into the OB, resulting in the development of pro-inflammatory status in the OB. Meningeal immunity was activated. Resident microglia produced anti-inflammatory cytokines within 24 h. These could be the initial events that lead to OB …

The Origin Of Bladder Cancer From Mucosal Field Effects, Jolanta Bondaruk, Roman Jaksik, Ziqiao Wang, David Cogdell, Sangkyou Lee, Yujie Chen, Khanh Ngoc Dinh, Tadeusz Majewski, Li Zhang, Shaolong Cao, Feng Tian, Hui Yao, Paweł Kuś, Huiqin Chen, John N Weinstein, Neema Navai, Colin Dinney, Jianjun Gao, Dan Theodorescu, Christopher Logothetis, Charles C Guo, Wenyi Wang, David Mcconkey, Peng Wei, Marek Kimmel, Bogdan Czerniak

Faculty, Staff and Student Publications

Whole-organ mapping was used to study molecular changes in the evolution of bladder cancer from field effects. We identified more than 100 dysregulated pathways, involving immunity, differentiation, and transformation, as initiators of carcinogenesis. Dysregulation of interleukins signified the involvement of inflammation in the incipient phases of the process. An aberrant methylation/expression of multiple HOX genes signified dysregulation of the differentiation program. We identified three types of mutations based on their geographic distribution. The most common were mutations restricted to individual mucosal samples that targeted uroprogenitor cells. Two types of mutations were associated with clonal expansion and involved large areas of …

Cellular Mechanisms Underlying State-Dependent Neural Inhibition With Magnetic Stimulation, Hui Ye, Vincent Chiun-Fan Chen, Jenna Hendee

Engineering Science Faculty Publications

Novel stimulation protocols for neuromodulation with magnetic fields are explored in clinical and laboratory settings. Recent evidence suggests that the activation state of the nervous system plays a significant role in the outcome of magnetic stimulation, but the underlying cellular and molecular mechanisms of state-dependency have not been completely investigated. We recently reported that high frequency magnetic stimulation could inhibit neural activity when the neuron was in a low active state. In this paper, we investigate state-dependent neural modulation by applying a magnetic field to single neurons, using the novel micro-coil technology. High frequency magnetic stimulation suppressed single neuron activity …

Kras Mutations As Essential Promoters Of Lymphangiogenesis Via Extracellular Vesicles In Pancreatic Cancer, Radu Pirlog, George A Calin

Faculty, Staff and Student Publications

Kirsten rat sarcoma virus (KRAS) gene mutations are present in more than 90% of pancreatic ductal adenocarcinomas (PDACs). KRASG12D is the most frequent alteration, promoting preneoplastic lesions and associating with a more aggressive phenotype. These tumors possess increased intratumoral lymphatic networks and frequent lymph node (LN) metastases. In this issue of the JCI, Luo, Li, et al. explored the relationship between the presence of the KRASG12D mutation and lymphangiogenesis in PDAC. The authors used in vitro and in vivo models and an elegant mechanistic approach to describe an alternative pathway for lymphangiogenesis promotion. KRASG12D induced SUMOylation of heterogenous nuclear ribonucleoprotein …

Pneumonitis After Immune Checkpoint Inhibitor Therapies In Patients With Acute Myeloid Leukemia: A Retrospective Cohort Study, Ajay Sheshadri, Alberto A Goizueta, Vickie R Shannon, David London, Guillermo Garcia-Manero, Hagop M Kantarjian, Farhad Ravandi-Kashani, Tapan M Kadia, Marina Y Konopleva, Courtney D Dinardo, Sherry Pierce, Abdulrazzak Zarifa, Aya A Albittar, Linda L Zhong, Fechukwu O Akhmedzhanov, Muhammad H Arain, Mansour Alfayez, Ahmad Alotaibi, Mehmet Altan, Aung Naing, Tito R Mendoza, Myrna C B Godoy, Girish Shroff, Sang T Kim, Saadia A Faiz, Dimitrios P Kontoyiannis, Fareed Khawaja, Kristofer Jennings, Naval G Daver

Faculty, Staff and Student Publications

Background: Immune checkpoint inhibitors (ICI), combined with hypomethylating agents, can be used to treat acute myeloid leukemia (AML), but this strategy results in a high rate of pneumonitis. The authors sought to determine risk factors for pneumonitis development and whether pneumonitis increased mortality.

Methods: The authors conducted a retrospective review of 258 AML patients who received ICI-containing regimens from 2016 to 2018. A multidisciplinary adjudication committee diagnosed pneumonia and pneumonitis by reviewing symptoms, imaging, microbiology, and response to therapies. To measure risk factors for pneumonitis and mortality, multivariate Cox proportional hazards models were constructed. Pneumonia, pneumonitis, and disease progression were …

Alphafold2 And Cryoem: Revisiting Cryoem Modeling In Near-Atomic Resolution Density Maps, Corey F Hryc, Matthew L Baker

Faculty, Staff and Student Publications

With the advent of new artificial intelligence and machine learning algorithms, predictive modeling can, in some cases, produce structures on par with experimental methods. The combination of predictive modeling and experimental structure determination by electron cryomicroscopy (cryoEM) offers a tantalizing approach for producing robust atomic models of macromolecular assemblies. Here, we apply AlphaFold2 to a set of community standard data sets and compare the results with the corresponding reference maps and models. Moreover, we present three unique case studies from previously determined cryoEM density maps of viruses. Our results show that AlphaFold2 can not only produce reasonably accurate models for …

Impairing Proliferation Of Glioblastoma Multiforme With Cd44+ Selective Conjugated Polymer Nanoparticles, Dorota Lubanska, Sami Alrashed, Gage T Mason, Fatima Nadeem, Angela Awada, Mitchell Dipasquale, Alexandra Sorge, Aleena Malik, Monika Kojic, Mohamed A R Soliman, Ana C Decarvalho, Abdalla Shamisa, Swati Kulkarni, Drew Marquardt, Lisa A Porter, Simon Rondeau-Gagné

Faculty, Staff and Student Publications

Glioblastoma is one of the most aggressive types of cancer with success of therapy being hampered by the existence of treatment resistant populations of stem-like Tumour Initiating Cells (TICs) and poor blood-brain barrier drug penetration. Therapies capable of effectively targeting the TIC population are in high demand. Here, we synthesize spherical diketopyrrolopyrrole-based Conjugated Polymer Nanoparticles (CPNs) with an average diameter of 109 nm. CPNs were designed to include fluorescein-conjugated Hyaluronic Acid (HA), a ligand for the CD44 receptor present on one population of TICs. We demonstrate blood-brain barrier permeability of this system and concentration and cell cycle phase-dependent selective uptake …

Cryo-Em Structure Of The Human Kv3.1 Channel Reveals Gating Control By The Cytoplasmic T1 Domain, Gamma Chi, Qiansheng Liang, Akshay Sridhar, John B Cowgill, Kasim Sader, Mazdak Radjainia, Pu Qian, Pablo Castro-Hartmann, Shayla Venkaya, Nanki Kaur Singh, Gavin Mckinley, Alejandra Fernandez-Cid, Shubhashish M M Mukhopadhyay, Nicola A Burgess-Brown, Lucie Delemotte, Manuel Covarrubias, Katharina L Dürr

Department of Neuroscience Faculty Papers

Kv3 channels have distinctive gating kinetics tailored for rapid repolarization in fast-spiking neurons. Malfunction of this process due to genetic variants in the KCNC1 gene causes severe epileptic disorders, yet the structural determinants for the unusual gating properties remain elusive. Here, we present cryo-electron microscopy structures of the human Kv3.1a channel, revealing a unique arrangement of the cytoplasmic tetramerization domain T1 which facilitates interactions with C-terminal axonal targeting motif and key components of the gating machinery. Additional interactions between S1/S2 linker and turret domain strengthen the interface between voltage sensor and pore domain. Supported by molecular dynamics simulations, electrophysiological and …

The Role Of Natural Products And Their Multitargeted Approach To Treat Solid Cancer, Naoshad Muhammad, Darksha Usmani, Mohammad Tarique, Huma Naz, Mohammad Ashraf, Ramesh Raliya, Shams Tabrez, Torki A Zughaibi, Ahdab Alsaieedi, Israa J Hakeem, Mohd Suhail

2020-Current year OA Pubs

Natural products play a critical role in the discovery and development of numerous drugs for the treatment of various types of cancer. These phytochemicals have demonstrated anti-carcinogenic properties by interfering with the initiation, development, and progression of cancer through altering various mechanisms such as cellular proliferation, differentiation, apoptosis, angiogenesis, and metastasis. Treating multifactorial diseases, such as cancer with agents targeting a single target, might lead to limited success and, in many cases, unsatisfactory outcomes. Various epidemiological studies have shown that the steady consumption of fruits and vegetables is intensely associated with a reduced risk of cancer. Since ancient period, plants, …

Slitrk2 Variants Associated With Neurodevelopmental Disorders Impair Excitatory Synaptic Function And Cognition In Mice, Salima El Chehadeh, Dorothy K Grange, Et Al

2020-Current year OA Pubs

SLITRK2 is a single-pass transmembrane protein expressed at postsynaptic neurons that regulates neurite outgrowth and excitatory synapse maintenance. In the present study, we report on rare variants (one nonsense and six missense variants) in SLITRK2 on the X chromosome identified by exome sequencing in individuals with neurodevelopmental disorders. Functional studies showed that some variants displayed impaired membrane transport and impaired excitatory synapse-promoting effects. Strikingly, these variations abolished the ability of SLITRK2 wild-type to reduce the levels of the receptor tyrosine kinase TrkB in neurons. Moreover, Slitrk2 conditional knockout mice exhibited impaired long-term memory and abnormal gait, recapitulating a subset of …

Factors Affecting Pathways To Care For Children And Adolescents With Complex Vascular Malformations: Parental Perspectives, Bryan A Sisk, Anna Kerr, Katherine A King

2020-Current year OA Pubs

BACKGROUND: Complex vascular malformations (VMs) are rare disorders that can cause pain, coagulopathy, disfigurement, asymmetric growth, and disability. Patients with complex VMs experience misdiagnosis, delayed diagnosis, delayed or inappropriate treatments, and worsened health. Given the potential consequences of delaying expert care, we must identify the factors that impede or facilitate this access to care.

RESULTS: We performed semi-structured interviews with 24 parents (21 mothers; 3 fathers; median age = 42.5 years) of children with complex VMs and overgrowth disorders living in the US, recruited through two patient advocacy groups - CLOVES Syndrome Community, and Klippel-Trenaunay Support Group. We performed thematic …

Cd11bhigh B Cells Increase After Stroke And Regulate Microglia: Cd11bhigh B Cells Increase After Stroke And Regulate Mg, Janelle M Korf, Pedram Honarpisheh, Eric C Mohan, Anik Banerjee, Maria P Blasco-Conesa, Parisa Honarpisheh, Gary U Guzman, Romeesa Khan, Bhanu P Ganesh, Amy L Hazen, Juneyoung Lee, Aditya Kumar, Louise D Mccullough, Anjali Chauhan

Faculty, Staff and Student Publications

Recent studies have highlighted the deleterious contributions of B cells to post-stroke recovery and cognitive decline. Different B cell subsets have been proposed based on expression levels of transcription factors (e.g. T-bet) as well as specific surface proteins. CD11b (α-chain of integrin) is expressed by several immune cell types and is involved in regulation of cell motility, phagocytosis, and other essential functions of host immunity. Although B cells express CD11b, the CD11b^high subset of B cells has not been well characterized, especially in immune dysregulation seen with aging and after stroke. Here, we investigate the role of CD11b^{high …}

Assessment Of A Size-Based Method For Enriching Circulating Tumour Cells In Colorectal Cancer, Sai Shyam Vasantharajan, Edward Barnett, Elin S. Gray, John L. Mccall, Euan J. Rodger, Michael R. Eccles, Fran Munro, Sharon Pattison, Aniruddha Chatterjee

Research outputs 2022 to 2026

Circulating tumour cells (CTC) from solid tumours are a prerequisite for metastasis. Isolating CTCs and understanding their biology is essential for developing new clinical tests and precision oncology. Currently, CellSearch is the only FDA (U.S. Food and Drug Administration)-approved method for CTC enrichment but possesses several drawbacks owing to a reliance on the epithelial cell adhesion molecule (EpCAM) and a resource-intensive nature. Addressing these shortcomings, we optimised an existing size-based method, MetaCell, to enrich CTCs from blood of colorectal cancer (CRC) patients. We evaluated the ability of MetaCell to enrich CTCs by spiking blood with CRC cell lines and assessing …

Lipidomic Profiling In The Strong Heart Study Identified American Indians At Risk Of Chronic Kidney Disease, Wenjie Zeng, Habtamu B. Beyene, Mikko Kuokkanen, Guanhong Miao, Dianna J. Magliano, Jason G. Umans, Nora Franceschini, Joanne E. Curran, John Blangero

School of Medicine Publications

Dyslipidemia associates with and usually precedes the onset of chronic kidney disease (CKD), but a comprehensive assessment of molecular lipid species associated with risk of CKD is lacking. Here, we sought to identify fasting plasma lipids associated with risk of CKD among American Indians in the Strong Heart Family Study, a large-scale community-dwelling of individuals, followed by replication in Mexican Americans from the San Antonio Family Heart Study and Caucasians from the Australian Diabetes, Obesity and Lifestyle Study. We also performed repeated measurement analysis to examine the temporal relationship between the change in the lipidome and change in kidney function …

Emerging Roles And Potential Applications Of Non-Coding Rnas In Cervical Cancer, Deepak Parashar, Anupam Singh, Saurabh Gupta, Aishwarya Sharma, Manish K. Sharma, Kuldeep K. Roy, Subhash Chauhan, Vivek K. Kashyap

School of Medicine Publications

Cervical cancer (CC) is a preventable disease using proven interventions, specifically prophylactic vaccination, pervasive disease screening, and treatment, but it is still the most frequently diagnosed cancer in women worldwide. Patients with advanced or metastatic CC have a very dismal prognosis and current therapeutic options are very limited. Therefore, understanding the mechanism of metastasis and discovering new therapeutic targets are crucial. New sequencing tools have given a full visualization of the human transcriptome’s composition. Non-coding RNAs (NcRNAs) perform various functions in transcriptional, translational, and post-translational processes through their interactions with proteins, RNA, and even DNA. It has been suggested that …

An Updated Assessment Of 43,110 Patients Enrolled In The Childhood Cancer Research Network: A Children’S Oncology Group Report, Austin L Brown, Pagna Sok, Michael E Scheurer, Karen R Rabin, Erin L Marcotte, Douglas S Hawkins, Logan G Spector, Philip J Lupo

Center for Medical Ethics and Health Policy Staff Publications

Background: The Childhood Cancer Research Network (CCRN) was established by the Children's Oncology Group (COG) as a resource for epidemiologic studies of childhood cancer. The objective of this study was to evaluate the representativeness of CCRN and identify factors associated with enrollment.

Method: The number of US childhood patients with cancer diagnosed < 20 years of age enrolled in CCRN (2008-2015) was compared to expected counts, calculated from Surveillance, Epidemiology, and End Results incidence rates and US Census population estimates. Observed-to-expected ratios and corresponding 95% confidence intervals (CI) were estimated across sex, race, diagnosis age, calendar year, and cancer diagnosis groups. Multivariable linear regression models were generated to evaluate the association between open COG phase 3 therapeutic trials and CCRN enrollment rates.

Result: The 43,110 cases enrolled in CCRN represented 36% of the expected childhood cancers diagnosed from 2008 to 2015 (N = 120,118). CCRN enrollment ratios [95% CI] were highest among males (0.38 [95% CI, 0.37-0.38]), non-Hispanics (0.35 [95% CI, 0.35-0.36]), and those diagnosed from 1 to 4 years …

Post-Stroke Reorganization Of Transient Brain Activity Characterizes Deficits And Recovery Of Cognitive Functions, Elvira Pirondini, Nawal Kinany, Cécile Le Sueur, Joseph C Griffis, Gordon L Shulman, Maurizio Corbetta, Dimitri Van De Ville

2020-Current year OA Pubs

Functional magnetic resonance imaging (fMRI) has been widely employed to study stroke pathophysiology. In particular, analyses of fMRI signals at rest were directed at quantifying the impact of stroke on spatial features of brain networks. However, brain networks have intrinsic time features that were, so far, disregarded in these analyses. In consequence, standard fMRI analysis failed to capture temporal imbalance resulting from stroke lesions, hence restricting their ability to reveal the interdependent pathological changes in structural and temporal network features following stroke. Here, we longitudinally analyzed hemodynamic-informed transient activity in a large cohort of stroke patients (n = 103) to …

Brain-Wide Analysis Of The Supraspinal Connectome Reveals Anatomical Correlates To Functional Recovery After Spinal Injury, Zimei Wang, Adam Romanski, Vatsal Mehra, Yunfang Wang, Matthew Brannigan, Benjamin C. Campbell, Gregory A. Petsko, Pantelis Tsoulfas, Murray G. Blackmore

Biomedical Sciences Faculty Research and Publications

The supraspinal connectome is essential for normal behavior and homeostasis and consists of numerous sensory, motor, and autonomic projections from brain to spinal cord. Study of supraspinal control and its restoration after damage has focused mostly on a handful of major populations that carry motor commands, with only limited consideration of dozens more that provide autonomic or crucial motor modulation. Here, we assemble an experimental workflow to rapidly profile the entire supraspinal mesoconnectome in adult mice and disseminate the output in a web-based resource. Optimized viral labeling, 3D imaging, and registration to a mouse digital neuroanatomical atlas assigned tens of …

Neuronal Activity Induces Glucosylceramide That Is Secreted Via Exosomes For Lysosomal Degradation In Glia, Liping Wang, Guang Lin, Zhongyuan Zuo, Yarong Li, Seul Kee Byeon, Akhilesh Pandey, Hugo J Bellen

Duncan NRI Faculty and Staff Publications

Recessive variants in GBA1 cause Gaucher disease, a prevalent form of lysosome storage disease. GBA1 encodes a lysosomal enzyme that hydrolyzes glucosylceramide (GlcCer) into glucose and ceramide. Its loss causes lysosomal dysfunction and increased levels of GlcCer. We generated a null allele of the Drosophila ortholog Gba1b by inserting the Gal4 using CRISPR-Cas9. Here, we show that Gba1b is expressed in glia but not in neurons. Glial-specific knockdown recapitulates the defects found in Gba1b mutants, and these can be rescued by glial expression of human GBA1. We show that GlcCer is synthesized upon neuronal activity, and it is transported …

Publication Dynamics: What Can Be Done To Eliminate Barriers To Publishing Full Manuscripts By The Postgraduate Trainees Of A Low-Middle Income Country?, Hafsa Majid, Lena Jafri, Sibtain Ahmed, Muhammad Abbas Abid, Mohammad Aamir, Aamir Ijaz, Aysha Habib Khan, Imran Siddiqui

Department of Pathology and Laboratory Medicine

Objectives: This study aimed to determine the publication rate of free paper abstracts presented by the postgraduate (PG) trainees and determine the reasons for non-publication. A mixed methods study was conducted. PG trainees presenting free papers at the at the Pakistan Society of Chemical Pathologist conferences from 2012 to 2018 were included. Three databases were searched to identify if the abstracts were published or not. The PG trainee authors of abstracts not published as full manuscript, were surveyed to determine the barriers and challenges in publishing a manuscript.
Results: The average rate of full manuscript publication was 51.8% (n = …

Hybrid-Control Arm Construction Using Historical Trial Data For An Early-Phase, Randomized Controlled Trial In Metastatic Colorectal Cancer, Chen Li, Katrina S Pedersen, Et Al

2020-Current year OA Pubs

Background: Treatment for metastatic colorectal cancer patients beyond the second line remains challenging, highlighting the need for early phase trials of combination therapies for patients who had disease progression during or following two prior lines of therapy. Leveraging hybrid control design in these trials may preserve the benefits of randomization while strengthening evidence by integrating historical trial data. Few examples have been established to assess the applicability of such design in supporting early phase metastatic colorectal cancer trials.

Methods: MORPHEUS-CRC is an umbrella, multicenter, open-label, phase Ib/II, randomized, controlled trial (NCT03555149), with active experimental arms ongoing. Patients enrolled were assigned …

Cd11b Suppresses Tlr Activation Of Nonclassical Monocytes To Reduce Primary Graft Dysfunction After Lung Transplantation, Melissa Querrey, Stephen Chiu, Emilia Lecuona, Qiang Wu, Haiying Sun, Megan Anderson, Megan Kelly, Sowmya Ravi, Alexander V. Misharin, Daniel Kreisel, Ankit Bharat, G. R. Scott Budinger

2020-Current year OA Pubs

Primary graft dysfunction (PGD) is the leading cause of postoperative mortality in lung transplant recipients and the most important risk factor for development of chronic lung allograft dysfunction. The mechanistic basis for the variability in the incidence and severity of PGD between lung transplant recipients is not known. Using a murine orthotopic vascularized lung transplant model, we found that redundant activation of Toll-like receptors 2 and 4 (TLR2 and -4) on nonclassical monocytes activates MyD88, inducing the release of the neutrophil attractant chemokine CXCL2. Deletion of Itgam (encodes CD11b) in nonclassical monocytes enhanced their production of CXCL2 and worsened PGD, …

Single-Cell Transcriptional Regulation And Genetic Evolution Of Neuroendocrine Prostate Cancer, Ziwei Wang, Daofeng Li, Hyung Joo Lee, Et Al.

2020-Current year OA Pubs

Neuroendocrine prostate cancer (NEPC) is a lethal subtype of prostate cancer, with a 10% five-year survival rate. However, little is known about its origin and the mechanisms governing its emergence. Our study characterized ADPC and NEPC in prostate tumors from 7 patients using scRNA-seq. First, we identified two NEPC gene expression signatures representing different phases of

17q21.31 Sub-Haplotypes Underlying H1-Associated Risk For Parkinson's Disease Are Associated With Lrrc37a/2 Expression In Astrocytes, Kathryn R Bowles, Celeste M Karch, Et Al.

2020-Current year OA Pubs

BACKGROUND: Parkinson's disease (PD) is genetically associated with the H1 haplotype of the MAPT 17q.21.31 locus, although the causal gene and variants underlying this association have not been identified.

METHODS: To better understand the genetic contribution of this region to PD and to identify novel mechanisms conferring risk for the disease, we fine-mapped the 17q21.31 locus by constructing discrete haplotype blocks from genetic data. We used digital PCR to assess copy number variation associated with PD-associated blocks, and used human brain postmortem RNA-seq data to identify candidate genes that were then further investigated using in vitro models and human brain …

Back Cover Vol 4 Issue 1

Graduate Medical Education Research Journal

No abstract provided.

Painful Foot Lesions: A Case Report, Trevor Lockard

Graduate Medical Education Research Journal

No abstract provided.