Medicine and Health Sciences Commons^™

Synthesis And In Vitro Evaluation Of Novel Compounds And Discovery Of A Promising Iodine-125 Radioligand For Purinergic P2x7 Receptor (P2x7r), Lin Qiu, Jinzhi Wang, Manju Tewari, Derek T Rensing, Terrance M Egan, Joel S Perlmutter, Zhude Tu

2020-Current year OA Pubs

The purinergic P2X ligand-gated ion channel 7 receptor (P2X7R) plays a critical role in various inflammatory processes and other diseases. Fast determination of compounds P2X7R binding potency and discovery of a promise PET radiotracer for imaging P2X7R require a P2X7R suitable radioligand for radioactive competitive binding assay. Herein, we designed and synthesized thirteen new P2X7R ligands and determined the in vitro binding potency. The fluorescence screening assay identified the iodide compound 1c with high potency and specificity toward P2X7R with an IC

Differential Gait Features Across Parkinson's Disease Clinical Subtypes, Sidney T Baudendistel, Kerri S Rawson, Christina N Lessov-Schlaggar, Baijayanta Maiti, Paul T Kotzbauer, Joel S Perlmutter, Gammon M Earhart, Meghan C Campbell

2020-Current year OA Pubs

BACKGROUND: Clinical subtypes in Parkinson's disease including non-motor manifestations may be more beneficial than subtypes based upon motor manifestations alone. Inclusion of gait metrics may help identity targets for rehabilitation and potentially predict development of non-motor symptoms for individuals with Parkinson's disease. This study aims to characterize gait differences across established multi-domain subtypes.

METHODS: "Motor Only", "Psychiatric & Motor" and "Cognitive & Motor" clinical subtypes were established through motor, cognitive, and psychiatric assessment. Walking was assessed in the "OFF" medication state. Multivariate analysis of variance identified differences in gait domains across clinical subtypes.

FINDINGS: The "Motor Only" subtype exhibited the …

Analysis Of Predefined Safety Events Across Spesolimab Trials In Dermatological And Non-Dermatological Conditions, Kenneth B Gordon, Yayoi Tada, Milan J Anadkat, Siew Eng Choon, Boni Elewski, Jonathan N Barker, Arash Mostaghimi, Kilian Eyerich, Ming Tang, Thomas Haeufel, Christian Thoma, Diamant Thaçi

2020-Current year OA Pubs

INTRODUCTION: Spesolimab, a selective, humanised monoclonal antibody targeting the interleukin-36 receptor, is approved for the treatment of generalised pustular psoriasis (GPP). As a result of the limited patient numbers in GPP trials of spesolimab, analysing safety events across dermatological and non-dermatological diseases helps to further characterise the known safety profile of spesolimab. Here, we analyse predefined safety events from nine randomised, placebo-controlled spesolimab trials across dermatological (including GPP) and gastrointestinal conditions.

METHODS: Predefined safety events were based on the known safety profile of spesolimab across all diseases investigated to date and potential risks of biological therapeutics, and included serious/severe/opportunistic infections, …

Illustrated Capsules From The Advanced Course In Platelet Research, Christian Andrea Di Buduo, Fan He, Stephen Oh, Jorge Di Paola, Et Al.

2020-Current year OA Pubs

This series of illustrated capsules summarizes the presentations made by the speakers at the first International Advanced Course in Platelet Research held in Murcia (Spain) from 27 to 28 September, 2024. This is the first course to receive a Fundamental Research Workshop Grant from the International Society on Thrombosis and Haemostasis (ISTH) and was also supported administratively and scientifically by the Spanish Society of Thrombosis and Haemostasis (SETH). This unique course focused on new methodologies applied in platelet research and how these are increasing our understanding of platelet formation, their multifunctionality in different physiological and pathological contexts, and contributing to …

Tofersen Treatment Leads To Sustained Stabilization Of Disease In Sod1 Als In A "Real-World" Setting, Sean E Smith, Kelly Mccoy-Gross, Amber Malcolm, Jeri Oranski, Jesse W Markway, Timothy M Miller, Robert C Bucelli

2020-Current year OA Pubs

OBJECTIVE: Patients with amyotrophic lateral sclerosis (ALS) caused by superoxide dismutase 1 (SOD1) gene mutations (SOD1 ALS) treated with tofersen have shown slowing of disease progression, and disease stabilization with recovery of function in some patients. We report our clinical experience with treating patients with SOD1 ALS and the effects of tofersen on outcome measures.

METHODS: This was a single-center observational study of patients with SOD1 ALS receiving treatment with tofersen. The effects of tofersen treatment on neurofilament levels, muscle strength, and clinical outcome measures were assessed. Several patients had outpatient neuromuscular rehabilitation in addition to tofersen treatment and we …

Functional Or Structural Impairment Of Flow-Mediated Epicardial Vasodilation May Precede Coronary Microvascular Dysfunction, Ines Valenta, Salwa Mikhail, Ashwin Singh Parihar, Sudhir Jain, Thomas H Schindler

2020-Current year OA Pubs

BACKGROUND: The aim was to investigate whether functional and/or structural impairment of flow-mediated epicardial vasodilation (IEV) may precede coronary microvascular dysfunction (CMD) in a cardiometabolic risk population.

METHODS:

RESULTS: The prevalence of diffuse coronary artery calcification was highest in G1 with 51 %, followed by G3 with 46 % and G2 with 34 %. The extent of CCS was mild-to-moderate and did not differ significantly among groups (p = 0.222). Overall, IEV was present in 60 %, while there was a comparable prevalence of IEV between G2 and G3 (27 % and 33 %, p = 0.27). The hyperemic MBF …

Endogenous And Fluorescent Sterols Reveal The Molecular Basis For Ligand Selectivity Of Human Sterol Transporters, Laura Depta, Hogan P Bryce-Rogers, Nienke J Dekker, Anna Wiehl Bønke, Nicolò Camporese, Mingxing Qian, Yuanjian Xu, Douglas F Covey, Luca Laraia

2020-Current year OA Pubs

Sterol transport proteins (STPs) play a pivotal role in cholesterol homeostasis and therefore are essential for healthy human physiology. Despite recent advances in dissecting functions of STPs in the human cell, there is still a significant knowledge gap regarding their specific biological functions and a lack of suitable selective probes for their study. Here, we profile fluorescent steroid-based probes across ten STPs, uncovering substantial differences in their selectivity, aiding the retrospective and prospective interpretation of biological results generated with those probes. These results guided the establishment of an STP screening panel combining diverse biophysical assays, enabling the evaluation of 42 …

Prospective Observational Study Of Fkrp-Related Limb-Girdle Muscular Dystrophy R9: A Grasp Consortium Study, Lindsay N Alfano, Stephanie Hunn, Conrad C Weihl, Et Al.

2020-Current year OA Pubs

OBJECTIVE: Limb-girdle muscular dystrophy R9 (LGMDR9, formerly known as LGMD2I), caused by variants in the fukutin-related protein (FKRP) gene leads to progressive muscle weakness of the shoulder and pelvic limb-girdles and loss of motor function over time. Clinical management and future trial design are improved by determining which standardized clinical outcome assessments (COA) of function are most appropriate to capture disease presentation and progression, informing endpoint selection and enrollment criteria. The purpose of our study was to evaluate the cross-sectional validity and reliability of clinical outcome assessments in patients with FKRP-related LGMDR9 participating in the Genetic Resolution and Assessments Solving …

Cracking The Pericellular Matrix Code: Exploring How Mmp-2, -3, And -7 Influence Matrix Breakdown And Biomechanical Properties, Benjamin Tizian Baumann, Jule Nieuwstraten, Christian Konrads, Farshid Guilak, Marina Danalache

2020-Current year OA Pubs

INTRODUCTION: The intricate process of articular cartilage remodeling, pivotal for both physiological functions and osteoarthritis (OA) progression, is orchestrated through a balance of matrix synthesis and breakdown, which is mediated by matrix metalloproteinase enzymes (MMPs). At the heart of this remodeling lies the pericellular matrix (PCM), a specialized microenvironment encapsulating each chondrocyte and composed mainly of collagen type VI and perlecan. The aim of this study was to assess the impact of MMP-2, -3, and -7 on the structural integrity and biomechanical attributes of the PCM.

METHODS: Human articular cartilage explants (N = 10 patients) were incubated with activated MMP-2, …

Dataset And Analysis Of Automated And Manual Methods To Differentiate Wide Qrs Complex Tachycardias, Sarah Lococo, Anthony H Kashou, Abhishek J Deshmukh, Samuel J Asirvatham, Christopher V Desimone, Krasimira M Mikhova, Sandeep S Sodhi, Phillip S Cuculich, Rugheed Ghadban, Daniel H Cooper, Thomas M Maddox, Peter A Noseworthy, Adam M May

2020-Current year OA Pubs

The differentiation of wide complex tachycardias (WCTs) into ventricular tachycardia (VT) and supraventricular wide tachycardia (SWCT) via 12-lead ECG (electrocardiogram) interpretation is a crucial yet demanding clinical task. Decades of research have been dedicated to simplifying and improving this differentiation via manual algorithms. Despite such research, the effectiveness of such algorithms still remains limited, primarily due to reliance on user expertise. To combat this limitation, automated algorithms have been created that show promise as alternatives to manual ECG interpretation. However, direct comparison of the methods' diagnostic performances has not been undertaken. A recent publication (LoCoco et al., 2024) compared the …

Two Cardinal Features Of Als, Reduced Stmn2 And Pathogenic Tdp-43, Synergize To Accelerate Motor Decline In Mice, Kelsey L Krus, Ana Morales Benitez, Amy Strickland, Jeffrey Milbrandt, A Joseph Bloom, Aaron Diantonio

2020-Current year OA Pubs

Pathological TDP-43 loss from the nucleus and cytoplasmic aggregation occurs in almost all cases of ALS and half of frontotemporal dementia patients. Stathmin2 (Stmn2) is a key target of TDP-43 regulation and aberrantly spliced Stmn2 mRNA is found in patients with ALS, frontotemporal dementia, and Alzheimer's Disease. STMN2 participates in the axon injury response and its depletion in vivo partially replicates ALS-like symptoms including progressive motor deficits and distal NMJ denervation. The interaction between STMN2 loss and TDP-43 dysfunction has not been studied in mice because TDP-43 regulates human but not murine Stmn2 splicing. Therefore, we generated trans-heterozygous mice that …

Multi-Modal Prediction Of Extracorporeal Support-A Resource Intensive Therapy, Utilizing A Large National Database, Daoyi Zhu, Bing Xue, Neel Shah, Philip Richard Orrin Payne, Chenyang Lu, Ahmed Sameh Said

2020-Current year OA Pubs

OBJECTIVE: Extracorporeal membrane oxygenation (ECMO) is among the most resource-intensive therapies in critical care. The COVID-19 pandemic highlighted the lack of ECMO resource allocation tools. We aimed to develop a continuous ECMO risk prediction model to enhance patient triage and resource allocation.

MATERIAL AND METHODS: We leveraged multimodal data from the National COVID Cohort Collaborative (N3C) to develop a hierarchical deep learning model, labeled "PreEMPT-ECMO" (Prediction, Early Monitoring, and Proactive Triage for ECMO) which integrates static and multi-granularity time series features to generate continuous predictions of ECMO utilization. Model performance was assessed across time points ranging from 0 to 96 …

Evaluating Dimensionality Reduction Of Comorbidities For Predictive Modeling In Individuals With Neurofibromatosis Type 1, Aditi Gupta, Ethan Hillis, Inez Y Oh, Stephanie M Morris, Zach Abrams, Randi E Foraker, David H Gutmann, Philip R O Payne

2020-Current year OA Pubs

OBJECTIVE: Dimensionality reduction techniques aim to enhance the performance of machine learning (ML) models by reducing noise and mitigating overfitting. We sought to compare the effect of different dimensionality reduction methods for comorbidity features extracted from electronic health records (EHRs) on the performance of ML models for predicting the development of various sub-phenotypes in children with Neurofibromatosis type 1 (NF1).

MATERIALS AND METHODS: EHR-derived data from pediatric subjects with a confirmed clinical diagnosis of NF1 were used to create 10 unique comorbidities code-derived feature sets by incorporating dimensionality reduction techniques using raw International Classification of Diseases codes, Clinical Classifications Software …

A Staged Approach To Resecting A Large Rectal Polyp Using Endoscopic Mucosal Resection And Trans-Anal Endoscopic Microsurgery: A Case Report, Bhavna A Guduguntla, Jared Yee, Paul E Wise, Ahmad Najdat Bazarbashi

2020-Current year OA Pubs

Large rectal adenomatous polyps are not uncommon. Proctectomy sparing interventions are favored when feasible. We present a case of a 62-year-old woman, who presented with diarrhea for several years. Colonoscopy revealed a very large 60 mm rectal polyp, biopsied as tubulovillous adenoma. This was successfully resected using a staged approach with endoscopic mucosal resection and trans-anal endoscopic microsurgery. Endoscopic mucosal resection removed 70% of the lesion with central scarred not amenable to resection but amenable to transanal excision. Pathology demonstrated tubulovillous adenoma with negative margins. Flexible sigmoidoscopy at 6-month follow-up revealed well healed scar without recurrence or residual disease. This …

Nuclear Egfr In Breast Cancer Suppresses Nk Cell Recruitment And Cytotoxicity, Angelica Escoto, Ryan Hecksel, Chance Parkinson, Sara Crane, Benjamin Atwell, Shyanne King, Daniela Ortiz Chavez, Alison Jannuzi, Barbara Sands, Benjamin G Bitler, Todd A Fehniger, Andrew L Paek, Megha Padi, Joyce Schroeder

2020-Current year OA Pubs

Natural Killer (NK) cells can target and destroy cancer cells, yet tumor microenvironments typically suppress NK cell recruitment and cytotoxicity. The epidermal growth factor receptor (EGFR) is a potent oncogene that can activate survival, migration, and proliferation pathways, and clinical data suggests it may also play an immunomodulating role in cancers. Recent work has demonstrated a novel role for nuclear EGFR (nEGFR) in regulating transcriptional events unique from the kinase domain. Using a novel peptide therapeutic (cSNX1.3) that inhibits retrograde trafficking of EGFR and an EGFR nuclear localization mutant, we discovered that nEGFR suppresses NK cell recruitment and cytotoxicity. RNA-Seq …

Ags3-Based Optogenetic Gdi Induces Gpcr-Independent Gβγ Signalling And Macrophage Migration, Waruna Thotamune, Sithurandi Ubeysinghe, Chathuri Rajarathna, Dinesh Kankanamge, Koshala Olupothage, Aditya Chandu, Bryan A Copits, Ajith Karunarathne

2020-Current year OA Pubs

G-protein-coupled receptors (GPCRs) are efficient guanine nucleotide exchange factors (GEFs) and exchange GDP to GTP on the Gα subunit of G-protein heterotrimers in response to various extracellular stimuli, including neurotransmitters and light. GPCRs primarily broadcast signals through activated G proteins, GαGTP and free Gβγ and are major disease drivers. Evidence shows that the ambient low threshold signalling required for cells is likely supplemented by signalling regulators such as non-GPCR GEFs and guanine nucleotide dissociation inhibitors (GDIs). Activators of G-protein signalling 3 (AGS3) are recognized as a GDI involved in multiple health and disease-related processes. Nevertheless, understanding of AGS3 is limited, …

Identification And Characterization Of Factor Xi Autoantibodies In 2 Patients With Systemic Lupus Erythematosus: Insights Into Mechanisms Of Acquired Factor Xi Deficiency, Priyanka Srivastava, Amy Zhou, Christine Fuja, Charles S Eby, Gail Baxter, Anton Matafonov, Serena Fedorov, Miriam Brown, Michael Pettit, Benjamin F Tillman, David Gailani, Jeremy W Jacobs

2020-Current year OA Pubs

BACKGROUND: Factor (F)XI is a zymogen that contributes to thrombin generation through activation of FIX. Patients with a complete absence of FXI are prone to developing alloantibody inhibitors after replacement therapy. Acquired FXI autoantibodies are less common, and data regarding their mechanisms of action are lacking.

OBJECTIVES: We describe 2 patients with severe acquired FXI deficiency and identify the FXI domains to which the autoantibodies bind.

METHODS: FXI and prekallikrein (PK) are homologs with similar structures. We prepared recombinant human FXI and PK, as well as chimeric molecules in which individual domains within FXI or PK are replaced with the …

Occult Ventricular Fibrillation Visualized By Echocardiogram During Cardiac Arrest: A Retrospective Observational Study From The Real-Time Evaluation And Assessment For Sonography-Outcomes Network (Reason), Romolo Gaspari, Srikar Adhikari, Timothy Gleeson, Monica Kapoor, Robert Lindsay, Vicki Noble, Jason T Nomura, Anthony Weekes, Dan Theodoro

2020-Current year OA Pubs

OBJECTIVES: Cardiac arrest patients with a shockable rhythm are more likely to survive an out-of-hospital cardiac arrest (OHCA) compared with a nonshockable rhythm. An electrocardiogram (ECG) is the most common way to identify a shockable rhythm, but it can miss patients with clinically significant ventricular fibrillation (vfib). We sought to determine the percentage of nonshockable OHCA patients that demonstrated vfib on echo.

METHODS: Secondary analysis of echo images recorded from a prior study from our group, Real-Time Evaluation and Assessment for Sonography-Outcomes Network (REASON), a multicenter, observational study of OHCA patients presenting to the emergency department with nonshockable rhythms. Using …

Assessment Of Patient Satisfaction Among Patients Treated With Intravenous Vs Subcutaneous Insulin For Diabetic Ketoacidosis, Richard T Griffey, Ryan M Schneider, Margo Girardi, Gina Larossa, Julianne Yeary, Michael Lehmkuhl, Dan Suarez, Rachel Ancona, Taylor Kaser, Paulina Cruz-Bravo

2020-Current year OA Pubs

OBJECTIVES: We previously implemented the subcutaneous (SQ) insulin in diabetic ketoacidosis (DKA) (SQuID) protocol, demonstrating safe, effective treatment of low to moderate (LTM) severity DKA in a non-intensive care unit setting. SQuID replaces intravenous (IV) insulin with SQ injections and reduces glucose checks from hourly to every 2 hours. We are not aware of any data on patient satisfaction with treatment in DKA. Our objective was to compare satisfaction in patients treated with IV insulin to that in patients treated with the SQ protocol.

METHODS: We conducted a cross-sectional study in an urban academic hospital (March 2023 to March 2024) …

Antiseizure Medication Prescribing In People With Dravet Syndrome: An Analysis Of Real-Time Administrative Data, Kevin Y Xu, Binx Yezhe Lin, M Scott Perry, Fábio A Nascimento

2020-Current year OA Pubs

Since 2018, three new antiseizure medications (ASMs) received FDA approval for Dravet syndrome (DS) in the U.S: cannabidiol, stiripentol, and fenfluramine. Yet, the uptake of these ASMs in routine clinical practice is unknown. We use new ICD-10 codes for DS (implemented in 2020) to estimate ASM receipt in patients with DS. We analyzed the TriNetX Network, a real-time electronic health record-based dataset linked to prescription data encompassing all 50 states of the U.S. After identifying patients with health care encounters for DS in 2021 and 2022 (via ICD-10 codes), we examined ASM prescribing in the year following a DS claim: …

Neuroimaging Findings In Nondemented Frail Individuals: A Systematic Review, Hamid Harandi, Soheil Mohammadi, Ali Jahanshahi, Mahsa Dolatshahi, Sogol Alikarami, Rasa Zafari, Cyrus A Raji

2020-Current year OA Pubs

BACKGROUND: Frailty is a chronic condition characterised by the progressive decline of multiple physiological functions. There is a critical need to investigate neuroimaging findings in nondemented frail individuals to better understand the underlying mechanisms and implications of frailty on brain health. This paper is aimed at reviewing neuroimaging studies assessing brain changes in nondemented frail individuals to understand the neuropsychological basis of frailty.

METHODS: A systematic review was conducted on studies focusing on neuroimaging modalities in frailty, including MRI, fMRI, DTI and PET. The review was based on PRISMA instructions and a two-step screening process. The studies evaluating neuroimaging findings …

Cross-Sectional Comparison Of Structural Mri Markers Of Impairment In A Diverse Cohort Of Older Adults, Julie K Wisch, Kalen Petersen, Peter R Millar, Omar Abdelmoity, Ganesh M Babulal, Karin L Meeker, Meredith N Braskie, Kristine Yaffe, Arthur W Toga, Sid O'Bryant, Beau M Ances, Habs‐Hd Study Team

2020-Current year OA Pubs

Neurodegeneration is presumed to be the pathological process measure most proximal to clinical symptom onset in Alzheimer Disease (AD). Structural MRI is routinely collected in research and clinical trial settings. Several quantitative MRI-based measures of atrophy have been proposed, but their low correspondence with each other has been previously documented. The purpose of this study was to identify which commonly used structural MRI measure (hippocampal volume, cortical thickness in AD signature regions, or brain age gap [BAG]) had the best correspondence with the Clinical Dementia Rating (CDR) in an ethno-racially diverse sample. 2870 individuals recruited by the Healthy and Aging …

Perinatal Arterial Ischemic Stroke Diagnosed In Infants Receiving Therapeutic Hypothermia For Hypoxic-Ischemic Encephalopathy, Fernando F Gonzalez, Sarah E Monsell, Marie-Coralie Cornet, Hannah Glass, Jessica Wisnowski, Amit Mathur, Robert Mckinstry, Yi Li, Tai-Wei Wu, Dennis E Mayock, Patrick J Heagerty, Sandra E Juul, Yvonne W Wu

2020-Current year OA Pubs

BACKGROUND: Both perinatal arterial ischemic stroke (PAIS) and hypoxic-ischemic encephalopathy (HIE) can present with neonatal encephalopathy. We hypothesized that among infants undergoing therapeutic hypothermia, presence of PAIS is associated with a higher risk of seizures and a lower risk of persistent encephalopathy after rewarming.

METHODS: We studied 473 infants with moderate or severe HIE enrolled in the HEAL Trial who received a brain MRI. We defined PAIS as focal ischemic infarct(s) within an arterial distribution, and HIE pattern of brain injury as central gray, peripheral watershed, or global injury. We compared the risk of seizures (clinically suspected or electrographic), and …

Mechanisms Of Uropathogenic E. Coli Mucosal Association In The Gastrointestinal Tract, Philippe N Azimzadeh, Nathaniel C Gualbuerto, Jerome S Pinkner, Kevin O Tamadonfar, Wandy Beatty, Thomas J Hannan, Karen W Dodson, Enid C Ibarra, Seonyoung Kim, Henry L Schreiber, James W Janetka, Andrew L Kau, Mark J Miller, Scott J Hultgren, Et Al.

2020-Current year OA Pubs

Urinary tract infections (UTIs) are highly recurrent and frequently caused by Uropathogenic

Evaluating The World Health Organization's Hearts Model For Hypertension And Diabetes Management: A Pilot Implementation Study In Guatemala, Irmgardt Alicia Wellmann, Luis Fernando Ayala, Taryn M Valley, Vilma Irazola, Mark D Huffman, Michele Heisler, Peter Rohloff, Rocío Donis, Eduardo Palacios, Manuel Ramírez-Zea, David Flood

2020-Current year OA Pubs

BACKGROUND: The World Health Organization HEARTS Technical Package is a widely implemented global initiative to improve the primary care management of cardiovascular disease risk factors. The study's objective is to report outcomes from a pilot implementation trial of integrated hypertension and diabetes management based on the HEARTS model in Guatemala.

METHODS: We conducted a single-arm pilot implementation trial over six months from October 2023 to May 2024 in 11 Guatemalan Ministry of Health primary care facilities in two districts. The pilot evaluated a package of five HEARTS-aligned implementation strategies to improve the pharmacological treatment of hypertension and diabetes. The primary …

Stroma-Derived Dickkopf-1 Contributes To The Suppression Of Nk Cell Cytotoxicity In Breast Cancer, Seunghyun Lee, Biancamaria Ricci, Jennifer Tran, Emily Eul, Jiayu Ye, Qihao Ren, David Clever, Julia Wang, Pamela Wong, Michael S Haas, Sheila A Stewart, Cynthia X Ma, Todd A Fehniger, Roberta Faccio

2020-Current year OA Pubs

Mechanisms related to tumor evasion from NK cell-mediated immune surveillance remain enigmatic. Dickkopf-1 (DKK1) is a Wnt/β-catenin inhibitor, whose levels correlate with breast cancer progression. We find DKK1 to be expressed by tumor cells and cancer-associated fibroblasts (CAFs) in patient samples and orthotopic breast tumors, and in bone. By using genetic approaches, we find that bone-derived DKK1 contributes to the systemic DKK1 elevation in tumor-bearing female mice, while CAFs contribute to DKK1 at primary tumor site. Systemic and bone-specific DKK1 targeting reduce tumor growth. Intriguingly, deletion of CAF-derived DKK1 also limits breast cancer progression, without affecting its levels in circulation, …

The Impact Of Quantitative Platform On Candidacy For Bronchoscopic Lung Volume Reduction: A Multi-Center Retrospective Cohort Study, Max Wayne, Suchitra Pilli, Hee Jae Choi, Nathaniel Moulton, Praveen Chenna, Allen Cole Burks, Alexander Chen

2020-Current year OA Pubs

BACKGROUND: Bronchoscopic lung volume reduction (BLVR) can be an effective treatment for highly selected patients with severe emphysema but only half of carefully selected patients derive clinical benefit. Two commercially available platforms exist to help determine candidacy for BLVR via quantitative analysis of computed tomography (CT) scans.

OBJECTIVES: To determine if the two commercially available quantitative platforms identified the same patient population that may benefit from BLVR.

DESIGN: A multicenter, retrospective cohort study.

METHODS: Consecutive patients referred for BLVR between January 1, 2022 and March 31, 2023 at three medical centers in the United States with the same CT scan …

Emotional Ecosystems: Understanding The Relationship Between Family Interactions And Anxiety Among Cancer Caregivers, Keisha White Makinde, Jacquelyn J Benson, Kyle A Pitzer, Maysara Mitchell, Debra Parker Oliver, George Demiris, Karla T Washington

2020-Current year OA Pubs

OBJECTIVES: Recent studies have challenged the assumption that families are invariable sources of support for cancer caregivers, noting that relationships with family members can have both positive and negative effects on caregiver well-being. This study expands upon prior literature to examine the relationship between cancer caregivers' perceptions of the quality of their family interactions and their symptoms of anxiety.

METHODS: We employed secondary analysis of baseline data from a multisite randomized clinical trial of an intervention for cancer caregivers conducted at 3 large academic palliative care clinics. We performed linear regression analyses to analyze the relationship between caregivers' perceptions of …

Species- And Strain-Specific Microbial Modulation Of Interferon, Innate Immunity, And Epithelial Barrier In 2d Air-Liquid Interface Respiratory Epithelial Cultures, Mian Horvath, Ruoyu Yang, Diana Cadena Castaneda, Megan Callender, Elizabeth S Aiken, Anita Y Voigt, Ryan Caldwell, José Fachi, Blanda Di Luccia, Zoe Scholar, Peter Yu, Andrew Salner, Marco Colonna, Karolina Palucka, Julia Oh

2020-Current year OA Pubs

BACKGROUND: The microbiome regulates the respiratory epithelium's immunomodulatory functions. To explore how the microbiome's biodiversity affects microbe-epithelial interactions, we screened 58 phylogenetically diverse microbes for their transcriptomic effect on human primary bronchial air-liquid interface (ALI) cell cultures.

RESULTS: We found distinct species- and strain-level differences in host innate immunity and epithelial barrier response. Strikingly, we found that host interferon, an antiviral response, was one of the most variable host processes. This variability was not driven by microbial phylogenetic diversity, bioburden, nor by the microbe's ability to stimulate other innate immunity pathways.

CONCLUSIONS: Microbial colonization differentially stimulates host gene expression with …

Propensity Score Matching: Should We Use It In Designing Observational Studies?, Fei Wan

2020-Current year OA Pubs

BACKGROUND: Propensity Score Matching (PSM) stands as a widely embraced method in comparative effectiveness research. PSM crafts matched datasets, mimicking some attributes of randomized designs, from observational data. In a valid PSM design where all baseline confounders are measured and matched, the confounders would be balanced, allowing the treatment status to be considered as if it were randomly assigned. Nevertheless, recent research has unveiled a different facet of PSM, termed "the PSM paradox". As PSM approaches exact matching by progressively pruning matched sets in order of decreasing propensity score distance, it can paradoxically lead to greater covariate imbalance, heightened model …