Digital Commons Network^™

Identifying Colorectal Cancer Caused By Biallelic Mutyh Pathogenic Variants Using Tumor Mutational Signatures, Peter Georgeson, Yin Cao, Et Al

2020-Current year OA Pubs

Carriers of germline biallelic pathogenic variants in the MUTYH gene have a high risk of colorectal cancer. We test 5649 colorectal cancers to evaluate the discriminatory potential of a tumor mutational signature specific to MUTYH for identifying biallelic carriers and classifying variants of uncertain clinical significance (VUS). Using a tumor and matched germline targeted multi-gene panel approach, our classifier identifies all biallelic MUTYH carriers and all known non-carriers in an independent test set of 3019 colorectal cancers (accuracy = 100% (95% confidence interval 99.87-100%)). All monoallelic MUTYH carriers are classified with the non-MUTYH carriers. The classifier provides evidence for a …

Biophysical Physiology Of Phosphoinositide Rapid Dynamics And Regulation In Living Cells, Jill B Jensen, Bjoern H Falkenburger, Eamonn J Dickson, Lizbeth De La Cruz, Gucan Dai, Jongyun Myeong, Seung-Ryoung Jung, Martin Kruse, Oscar Vivas, Byung-Chang Suh, Bertil Hille

2020-Current year OA Pubs

Phosphoinositide membrane lipids are ubiquitous low-abundance signaling molecules. They direct many physiological processes that involve ion channels, membrane identification, fusion of membrane vesicles, and vesicular endocytosis. Pools of these lipids are continually broken down and refilled in living cells, and the rates of some of these reactions are strongly accelerated by physiological stimuli. Recent biophysical experiments described here measure and model the kinetics and regulation of these lipid signals in intact cells. Rapid on-line monitoring of phosphoinositide metabolism is made possible by optical tools and electrophysiology. The experiments reviewed here reveal that as for other cellular second messengers, the dynamic …

Patched 1 Regulates Smoothened By Controlling Sterol Binding To Its Extracellular Cysteine-Rich Domain, Laurel Mydock-Mcgrane, Kathiresan Krishnan, Douglas F Covey, Et Al

2020-Current year OA Pubs

Smoothened (SMO) transduces the Hedgehog (Hh) signal across the plasma membrane in response to accessible cholesterol. Cholesterol binds SMO at two sites: one in the extracellular cysteine-rich domain (CRD) and a second in the transmembrane domain (TMD). How these two sterol-binding sites mediate SMO activation in response to the ligand Sonic Hedgehog (SHH) remains unknown. We find that mutations in the CRD (but not the TMD) reduce the fold increase in SMO activity triggered by SHH. SHH also promotes the photocrosslinking of a sterol analog to the CRD in intact cells. In contrast, sterol binding to the TMD site boosts …

Molecular Imaging Phenotyping For Selecting And Monitoring Radioligand Therapy Of Neuroendocrine Neoplasms, Amir Iravani, Ashwin Singh Parihar, Timothy Akhurst, Rodney J Hicks

2020-Current year OA Pubs

Neuroendocrine neoplasia (NEN) is an umbrella term that includes a widely heterogeneous disease group including well-differentiated neuroendocrine tumours (NETs), and aggressive neuroendocrine carcinomas (NECs). The site of origin of the NENs is linked to the intrinsic tumour biology and is predictive of the disease course. It is understood that NENs demonstrate significant biologic heterogeneity which ultimately translates to widely varying clinical presentations, disease course and prognosis. Thus, significant emphasis is laid on the pre-therapy evaluation of markers that can help predict tumour behavior and dynamically monitors the response during and after treatment. Most well-differentiated NENs express somatostatin receptors (SSTRs) which …

Raising Is A High-Performance Method For Identifying Random Transgene Integration Sites, Yusaku Wada, Ariella L G Coler-Reilly, Et Al

Open Access Publications

Both natural viral infections and therapeutic interventions using viral vectors pose significant risks of malignant transformation. Monitoring for clonal expansion of infected cells is important for detecting cancer. Here we developed a novel method of tracking clonality via the detection of transgene integration sites. RAISING (Rapid Amplification of Integration Sites without Interference by Genomic DNA contamination) is a sensitive, inexpensive alternative to established methods. Its compatibility with Sanger sequencing combined with our CLOVA (Clonality Value) software is critical for those without access to expensive high throughput sequencing. We analyzed samples from 688 individuals infected with the retrovirus HTLV-1, which causes …

Macrophages Disseminate Pathogen Associated Molecular Patterns Through The Direct Extracellular Release Of The Soluble Content Of Their Phagolysosomes, Catherine J Greene, Jenny A Nguyen, Samuel M Cheung, Corey R Arnold, Dale R Balce, Ya Ting Wang, Adrian Soderholm, Neil Mckenna, Devin Aggarwal, Rhiannon I Campden, Benjamin W Ewanchuk, Herbert W Virgin, Robin M Yates

2020-Current year OA Pubs

Recognition of pathogen-or-damage-associated molecular patterns is critical to inflammation. However, most pathogen-or-damage-associated molecular patterns exist within intact microbes/cells and are typically part of non-diffusible, stable macromolecules that are not optimally immunostimulatory or available for immune detection. Partial digestion of microbes/cells following phagocytosis potentially generates new diffusible pathogen-or-damage-associated molecular patterns, however, our current understanding of phagosomal biology would have these molecules sequestered and destroyed within phagolysosomes. Here, we show the controlled release of partially-digested, soluble material from phagolysosomes of macrophages through transient, iterative fusion-fission events between mature phagolysosomes and the plasma membrane, a process we term eructophagy. Eructophagy is most active …

Evolutionarily Stable Gene Clusters Shed Light On The Common Grounds Of Pathogenicity In The Acinetobacter Calcoaceticus-Baumannii Complex, Bardya Djahanschiri, Gisela Di Venanzio, Jesus S. Distel, Jennifer Breisch, Marius Alfred Dieckmann, Alexander Goesmann, Beate Averhoff, Stephan Göttig, Gottfried Wilharm, Mario F. Feldman, Ingo Ebersberger

Open Access Publications

Nosocomial pathogens of the Acinetobacter calcoaceticus-baumannii (ACB) complex are a cautionary example for the world-wide spread of multi- and pan-drug resistant bacteria. Aiding the urgent demand for novel therapeutic targets, comparative genomics studies between pathogens and their apathogenic relatives shed light on the genetic basis of human-pathogen interaction. Yet, existing studies are limited in taxonomic scope, sensing of the phylogenetic signal, and resolution by largely analyzing genes independent of their organization in functional gene clusters. Here, we explored more than 3,000 Acinetobacter genomes in a phylogenomic framework integrating orthology-based phylogenetic profiling and microsynteny conservation analyses. We delineate gene clusters in …

A Powassan Virus Domain Iii Nanoparticle Immunogen Elicits Neutralizing And Protective Antibodies In Mice, Ryan J. Malonis, George I. Georgiev, Denise Haslwanter, Laura A. Vanblargan, Georgia Fallon, Olivia Vergnolle, Sean M. Cahill, Richard Harris, David Cowburn, Kartik Chandran, Michael S Diamond, Jonathan R. Lai

2020-Current year OA Pubs

Powassan virus (POWV) is an emerging tick borne flavivirus (TBFV) that causes severe neuroinvasive disease. Currently, there are no approved treatments or vaccines to combat POWV infection. Here, we generated and characterized a nanoparticle immunogen displaying domain III (EDIII) of the POWV E glycoprotein. Immunization with POWV EDIII presented on nanoparticles resulted in significantly higher serum neutralizing titers against POWV than immunization with monomeric POWV EDIII. Furthermore, passive transfer of EDIII-reactive sera protected against POWV challenge in vivo. We isolated and characterized a panel of EDIII-specific monoclonal antibodies (mAbs) and identified several that potently inhibit POWV infection and engage distinct …

An Antibody Targeting The N-Terminal Domain Of Sars-Cov-2 Disrupts The Spike Trimer, Naveenchandra Suryadevara, Laura A. Vanblargan, Rita E. Chen, James Brett Case, Michael S. Diamond, Et Al

Open Access Publications

The protective human antibody response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) focuses on the spike (S) protein, which decorates the virion surface and mediates cell binding and entry. Most SARS-CoV-2 protective antibodies target the receptor-binding domain or a single dominant epitope ("supersite") on the N-terminal domain (NTD). Using the single B cell technology called linking B cell receptor to antigen specificity through sequencing (LIBRA-Seq), we isolated a large panel of NTD-reactive and SARS-CoV-2-neutralizing antibodies from an individual who had recovered from COVID-19. We found that neutralizing antibodies against the NTD supersite were commonly encoded by the IGHV1-24 gene, …

A Guide For Managing Patients With Stage I Nsclc: Deciding Between Lobectomy, Segmentectomy, Wedge, Sbrt And Ablation-Part 1: A Guide To Decision-Making, Frank C. Detterbeck, Justin D. Blasberg, Gavitt A. Woodard, Roy H. Decker, Ulas Kumbasar, Henry S. Park, Vincent J. Mase Jr, Brett C. Bade, Andrew X. Li, Whitney S. Brandt, David C. Madoff

Open Access Publications

Background: Clinical decision-making for patients with stage I lung cancer is complex. It involves multiple options (lobectomy, segmentectomy, wedge, Stereotactic Body Radiotherapy, thermal ablation), weighing multiple outcomes (e.g., short-, intermediate-, long-term) and multiple aspects of each (e.g., magnitude of a difference, the degree of confidence in the evidence, and the applicability to the patient and setting at hand). A structure is needed to summarize the relevant evidence for an individual patient and to identify which outcomes have the greatest impact on the decision-making.

Methods: Based on a systematic review from 2000-2021, evidence regarding relevant outcomes was assembled, with attention to …

Tgf-Β Signaling In Myeloproliferative Neoplasms Contributes To Myelofibrosis Without Disrupting The Hematopoietic Niche, Juo-Chin Yao, Karolyn A. Oetjen, Tianjiao Wang, Haoliang Xu, Grazia Abou-Ezzi, Joseph R. Krambs, Salil Uttarwar, Eric J. Duncavage, Daniel C. Link

Open Access Publications

Myeloproliferative neoplasms (MPNs) are associated with significant alterations in the bone marrow microenvironment that include decreased expression of key niche factors and myelofibrosis. Here, we explored the contribution of TGF-β to these alterations by abrogating TGF-β signaling in bone marrow mesenchymal stromal cells. Loss of TGF-β signaling in Osx-Cre-targeted MSCs prevented the development of myelofibrosis in both MPLW515L and Jak2V617F models of MPNs. In contrast, despite the absence of myelofibrosis, loss of TGF-β signaling in mesenchymal stromal cells did not rescue the defective hematopoietic niche induced by MPLW515L, as evidenced by decreased bone marrow cellularity, hematopoietic stem/progenitor cell number, and …

Serum Cholesterol Efflux Capacity In Age-Related Macular Degeneration And Polypoidal Choroidal Vasculopathy, Yasuo Yanagi, Richard M C Yu, Waseem Ahamed, Marco Yu, Kelvin Yi Chong Teo, Anna C S Tan, Ching-Yu Cheng, Tien Yin Wong, Rajendra S Apte, Chui Ming Gemmy Cheung

2020-Current year OA Pubs

PURPOSE: To investigate serum cholesterol efflux capacity (the ability of the serum to accept cholesterol) and factors that regulate it using nuclear magnetic resonance-quantified measures of lipoprotein particle composition and size and apolipoproteins metrics in patients with age-related macular degeneration (AMD).

DESIGN: Case-control study.

PARTICIPANTS: Four hundred two serum samples from 80 patients with early AMD (eAMD), and 212 patients with neovascular AMD (nAMD), including 80 with typical nAMD (tAMD) and 132 with polypoidal choroidal vasculopathy (PCV), and 110 age- and gender matched control participants.

METHODS: Serum from participants showed cholesterol efflux capacity measured using in vitro cell assays and …

Association Of The Receptor For Activated C-Kinase 1 With Ribosomes In Plasmodium Falciparum, Jessey Erath, Sergej Djuranovic

2020-Current year OA Pubs

The receptor for activated C-kinase 1 (RACK1), a highly conserved eukaryotic protein, is known to have many varying biological roles and functions. Previous work has established RACK1 as a ribosomal protein, with defined regions important for ribosome binding in eukaryotic cells. In Plasmodium falciparum, RACK1 has been shown to be required for parasite growth, however, conflicting evidence has been presented about RACK1 ribosome binding and its role in mRNA translation. Given the importance of RACK1 as a regulatory component of mRNA translation and ribosome quality control, the case could be made in parasites that RACK1 either binds or does not …

Whole-Exome Sequencing Reveals Damaging Gene Variants Associated With Hypoalphalipoproteinemia, Weilai Dong, Sheng Chih Jin, Et Al.

2020-Current year OA Pubs

Low levels of high density lipoprotein-cholesterol (HDL-C) are associated with an elevated risk of arteriosclerotic coronary heart disease. Heritability of HDL-C levels is high. In this research discovery study, we used whole-exome sequencing to identify damaging gene variants that may play significant roles in determining HDL-C levels. We studied 204 individuals with a mean HDL-C level of 27.8 ± 6.4 mg/dl (range: 4-36 mg/dl). Data were analyzed by statistical gene burden testing and by filtering against candidate gene lists. We found 120 occurrences of probably damaging variants (116 heterozygous; four homozygous) among 45 of 104 recognized HDL candidate genes. Those …

A Guide For Managing Patients With Stage I Nsclc: Deciding Between Lobectomy, Segmentectomy, Wedge, Sbrt And Ablation-Part 2: Systematic Review Of Evidence Regarding Resection Extent In Generally Healthy Patients, Frank C. Detterbeck, Vincent J. Mase, Andrew X. Li, Ulas Kumbasar, Brett C. Bade, Henry S. Park, Roy H. Decker, David C. Madoff, Gavitt A. Woodard, Whitney S Brandt, Justin D. Blasberg

2020-Current year OA Pubs

Background: Clinical decision-making for patients with stage I lung cancer is complex. It involves multiple options (lobectomy, segmentectomy, wedge, stereotactic body radiotherapy, thermal ablation), weighing multiple outcomes (e.g., short-, intermediate-, long-term) and multiple aspects of each (e.g., magnitude of a difference, the degree of confidence in the evidence, and the applicability to the patient and setting at hand). A structure is needed to summarize the relevant evidence for an individual patient and to identify which outcomes have the greatest impact on the decision-making.

Methods: A PubMed systematic review from 2000-2021 of outcomes after lobectomy, segmentectomy and wedge resection in generally …

Covid-19 Outcomes And Vaccination In People With Relapsing Multiple Sclerosis Treated With Ofatumumab, Anne H Cross, Et Al.

2020-Current year OA Pubs

INTRODUCTION: The SARS-CoV-2 pandemic necessitated better understanding of the impact of disease-modifying therapies on COVID-19 outcomes and vaccination. We report characteristics of COVID-19 cases and vaccination status in ofatumumab-treated relapsing multiple sclerosis (RMS) patients.

METHODS: COVID-19 data analyzed were from the ongoing, open-label, long-term extension phase 3b ALITHIOS study from December 2019 (pandemic start) and post-marketing cases from August 2020 (ofatumumab first approval) up to 25 September 2021. COVID-19 cases, severity, seriousness, outcomes, vaccination status, and breakthrough infection were evaluated.

RESULTS: As of 25 September 2021, 245 of 1703 patients (14.4%) enrolled in ALITHIOS receiving ofatumumab (median exposure: 2.45 years) …

Age-Dependent White Matter Disruptions After Military Traumatic Brain Injury: Multivariate Analysis Results From Enigma Brain Injury, Heather C Bouchard, Paul M Thompson, Aristeidis Sotiras, Et Al.

2020-Current year OA Pubs

Mild Traumatic brain injury (mTBI) is a signature wound in military personnel, and repetitive mTBI has been linked to age-related neurogenerative disorders that affect white matter (WM) in the brain. However, findings of injury to specific WM tracts have been variable and inconsistent. This may be due to the heterogeneity of mechanisms, etiology, and comorbid disorders related to mTBI. Non-negative matrix factorization (NMF) is a data-driven approach that detects covarying patterns (components) within high-dimensional data. We applied NMF to diffusion imaging data from military Veterans with and without a self-reported TBI history. NMF identified 12 independent components derived from fractional …

Genetic, Epigenetic, And Environmental Mechanisms Govern Allele-Specific Gene Expression, Celine L St Pierre, Juan F Macias-Velasco, Jessica P Wayhart, Li Yin, Clay F Semenkovich, Heather A Lawson

2020-Current year OA Pubs

Allele-specific expression (ASE) is a phenomenon in which one allele is preferentially expressed over the other. Genetic and epigenetic factors cause ASE by altering the final composition of a gene's product, leading to expression imbalances that can have functional consequences on phenotypes. Environmental signals also impact allele-specific expression, but how they contribute to this cross talk remains understudied. Here, we explored how genotype, parent-of-origin, tissue, sex, and dietary fat simultaneously influence ASE biases. Male and female mice from a F

Translating Data Analytics Into Improved Spine Surgery Outcomes: A Roadmap For Biomedical Informatics Research In 2021, Jacob K. Greenberg, Ayodamola Otun, Zoher Ghogawala, Po-Yin Yen, Camilo A. Molina, David D. Limbrick, Randi E. Foraker, Michael P. Kelly, Wilson Z. Ray

2020-Current year OA Pubs

STUDY DESIGN: Narrative review.

OBJECTIVES: There is growing interest in the use of biomedical informatics and data analytics tools in spine surgery. Yet despite the rapid growth in research on these topics, few analytic tools have been implemented in routine spine practice. The purpose of this review is to provide a health information technology (HIT) roadmap to help translate data assets and analytics tools into measurable advances in spine surgical care.

METHODS: We conducted a narrative review of PubMed and Google Scholar to identify publications discussing data assets, analytical approaches, and implementation strategies relevant to spine surgery practice.

RESULTS: A …

A Guide For Managing Patients With Stage I Nsclc: Deciding Between Lobectomy, Segmentectomy, Wedge, Sbrt And Ablation-Part 4: Systematic Review Of Evidence Involving Sbrt And Ablation, Henry S. Park, Frank C. Detterbeck, David C. Madoff, Brett C. Bade, Ulas Kumbasar, Vincent J. Mase, Andrew X. Li, Justin D. Blasberg, Gavitt A. Woodard, Whitney S. Brandt, Roy H. Decker

2020-Current year OA Pubs

Background: Clinical decision-making for patients with stage I lung cancer is complex. It involves multiple options [lobectomy, segmentectomy, wedge, stereotactic body radiotherapy (SBRT), thermal ablation], weighing multiple outcomes (e.g., short-, intermediate-, long-term) and multiple aspects of each (e.g., magnitude of a difference, the degree of confidence in the evidence, and the applicability to the patient and setting at hand). A structure is needed to summarize the relevant evidence for an individual patient and to identify which outcomes have the greatest impact on the decision-making.

Methods: A PubMed systematic review from 2000-2021 of outcomes after SBRT or thermal ablation

Results: Short-term …

Radiopharmaceutical Quality Control Considerations For Accelerator-Produced Actinium Therapies, Diane S Abou, Patrick Zerkel, James Robben, Mark Mclaughlin, Tim Hazlehurst, David Morse, Thaddeus J Wadas, Darpan N Pandya, Reiko Oyama, Gregory Gaehle, Michael L Nickels, Daniel L J Thorek

2020-Current year OA Pubs

No abstract provided.

Noninvasive Testing And Surrogate Markers In Invasive Fungal Diseases, George R Thompson, Andrej Spec, Et Al.

2020-Current year OA Pubs

Invasive fungal infections continue to increase as at-risk populations expand. The high associated morbidity and mortality with fungal diseases mandate the continued investigation of novel antifungal agents and diagnostic strategies that include surrogate biomarkers. Biologic markers of disease are useful prognostic indicators during clinical care, and their use in place of traditional survival end points may allow for more rapid conduct of clinical trials requiring fewer participants, decreased trial expense, and limited need for long-term follow-up. A number of fungal biomarkers have been developed and extensively evaluated in prospective clinical trials and small series. We examine the evidence for these …

Network Assisted Analysis Of De Novo Variants Using Protein-Protein Interaction Information Identified 46 Candidate Genes For Congenital Heart Disease, Yuhan Xie, Wei Jiang, Weilai Dong, Hongyu Li, Sheng Chih Jin, Martina Brueckner, Hongyu Zhao

2020-Current year OA Pubs

De novo variants (DNVs) with deleterious effects have proved informative in identifying risk genes for early-onset diseases such as congenital heart disease (CHD). A number of statistical methods have been proposed for family-based studies or case/control studies to identify risk genes by screening genes with more DNVs than expected by chance in Whole Exome Sequencing (WES) studies. However, the statistical power is still limited for cohorts with thousands of subjects. Under the hypothesis that connected genes in protein-protein interaction (PPI) networks are more likely to share similar disease association status, we developed a Markov Random Field model that can leverage …

Distinct Developmental And Degenerative Functions Of Sarm1 Require Nad+ Hydrolase Activity, E. J. Brace, Kow Essuman, Xianrong Mao, John Palucki, Yo Sasaki, Jeff Milbrandt, Aaron Diantonio

2020-Current year OA Pubs

SARM1 is the founding member of the TIR-domain family of NAD+ hydrolases and the central executioner of pathological axon degeneration. SARM1-dependent degeneration requires NAD+ hydrolysis. Prior to the discovery that SARM1 is an enzyme, SARM1 was studied as a TIR-domain adaptor protein with non-degenerative signaling roles in innate immunity and invertebrate neurodevelopment, including at the Drosophila neuromuscular junction (NMJ). Here we explore whether the NADase activity of SARM1 also contributes to developmental signaling. We developed transgenic Drosophila lines that express SARM1 variants with normal, deficient, and enhanced NADase activity and tested their function in NMJ development. We find that NMJ …

Association Of Molecular Senescence Markers In Late-Life Depression With Clinical Characteristics And Treatment Outcome, Breno S Diniz, Benoit H Mulsant, Charles F Reynolds, Daniel M Blumberger, Jordan F Karp, Meryl A Butters, Ana Paula Mendes-Silva, Erica L Vieira, George Tseng, Eric J Lenze

2020-Current year OA Pubs

Importance: Many older adults with depression do not experience remission with antidepressant treatment, and markers of cellular senescence in late-life depression (LLD) are associated with greater severity of depression, greater executive dysfunction, and higher medical illness burden. Since these clinical characteristics are associated with remission in LLD, molecular and cellular senescence abnormalities could be a possible biological mechanism underlying poor treatment response in this population.

Objective: To examine whether the senescence-associated secretory phenotype (SASP) index was associated with the likelihood of remission from a depressive episode in older adults.

Design, Setting, and Participants: A nonrandomized, open-label clinical trial was conducted …

A Short-Term Multicenter Analysis Of Radiolucent Lines In A Single Uncemented Rotating Platform Implant For Total Knee Arthroplasty, Jason Desmarais, David Dalury, Thomas L. Bernasek, David A. Fisher, Ryan M. Nunley, Marie-Claire Fickenscher, Robert S Gorab

2020-Current year OA Pubs

BACKGROUND: Uncemented total knee arthroplasty is increasing as a potential solution for aseptic loosening via biologic fixation and to increase operative efficiency. However, postoperative radiolucent lines (RLLs) remain a concern for some clinicians. We report on a multicenter analysis of these RLLs over a 2-year period to identify their incidence, progression, and clinical significance.

MATERIAL AND METHODS: Institutional review board approval was obtained for this retrospective, multicenter case series. A total of 312 patients treated with a single cruciate-retaining, fully porous coated femoral and tibial component design were included in the study. All patients were evaluated clinically and radiographically in …

Peripheral Monocyte-Derived Cells Counter Amyloid Plaque Pathogenesis In A Mouse Model Of Alzheimer's Disease, Ping Yan, Ki-Wook Kim, Qingli Xiao, Xiucui Ma, Leah R. Czerniewski, Haiyan Liu, David R. Rawnsley, Yan Yan, Gwendalyn J. Randolph, Slava Epelman, Jin-Moo Lee, Abhinav Diwan

Open Access Publications

Microglia, the parenchymal tissue macrophages in the brain, surround amyloid plaques in brains of individuals with Alzheimer's disease (AD) but are ineffective at clearing amyloid to mitigate disease progression. Recent studies in mice indicate that microglia are derived exclusively from primitive yolk sac hematopoiesis and self-renew without contribution from ontogenically distinct monocytes/macrophages of definitive adult hematopoietic origin. Using a genetic fate-mapping approach to label cells of definitive hematopoietic origin throughout life span, we discovered that circulating monocytes contribute 6% of plaque-associated macrophages in aged AD mice. Moreover, peripheral monocytes contributed to a higher fraction of macrophages in the choroid plexus, …

Changes In Dynamic Postural Stability After Acl Reconstruction: Results Over 2 Years Of Follow-Up, Robert H Brophy, Kevin A Schafer, Derrick M Knapik, John Motley, Amanda Haas, Matthew J Matava, Rick W Wright, Matthew V Smith

Open Access Publications

Background: The anterior cruciate ligament (ACL) is crucial for knee proprioception and postural stability. While ACL reconstruction (ACLR) and rehabilitation improve postural stability, the timing in improvement of dynamic postural stability after ACLR remains relatively unknown.

Purpose: To evaluate changes in dynamic postural stability after ACLR out to 24 months postoperatively.

Study Design: Case series; Level of evidence, 4.

Methods: Patients undergoing ACLR were prospectively enrolled, and dynamic postural stability was assessed within 2 days before surgery, at 3-month intervals postoperatively to 18 months, then at 24 months. Measurements were made on a multidirectional platform tracking the patient's center of …

Fibroblast Growth Factor-9 Expression In Airway Epithelial Cells Amplifies The Type I Interferon Response And Alters Influenza A Virus Pathogenesis, Bradley E. Hiller, Yongjun Yin, Yi-Chieh Perng, Ítalo De Araujo Castro, Lindsey E. Fox, Marissa C. Locke, Kristen J. Monte, Carolina B. López, David M. Ornitz, Deborah J. Lenschow

2020-Current year OA Pubs

Influenza A virus (IAV) preferentially infects conducting airway and alveolar epithelial cells in the lung. The outcome of these infections is impacted by the host response, including the production of various cytokines, chemokines, and growth factors. Fibroblast growth factor-9 (FGF9) is required for lung development, can display antiviral activity in vitro, and is upregulated in asymptomatic patients during early IAV infection. We therefore hypothesized that FGF9 would protect the lungs from respiratory virus infection and evaluated IAV pathogenesis in mice that overexpress FGF9 in club cells in the conducting airway epithelium (FGF9-OE mice). However, we found that FGF9-OE mice were …

Accuracy Of Chest Computed Tomography In Distinguishing Cystic Pleuropulmonary Blastoma From Benign Congenital Lung Malformations In Children, Abigail J Engwall-Gill, Jacqueline M Saito, Rebecca L Hulett Bowling, Et Al.

2020-Current year OA Pubs

Importance: The ability of computed tomography (CT) to distinguish between benign congenital lung malformations and malignant cystic pleuropulmonary blastomas (PPBs) is unclear.

Objective: To assess whether chest CT can detect malignant tumors among postnatally detected lung lesions in children.

Design, Setting, and Participants: This retrospective multicenter case-control study used a consortium database of 521 pathologically confirmed primary lung lesions from January 1, 2009, through December 31, 2015, to assess diagnostic accuracy. Preoperative CT scans of children with cystic PPB (cases) were selected and age-matched with CT scans from patients with postnatally detected congenital lung malformations (controls). Statistical analysis was performed …