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Full-Text Articles in Medicine and Health Sciences
Mycoplasma Genitalium In The Us (Mygenius): Surveillance Data From Sexual Health Clinics In 4 Us Regions, Lisa E Manhart, Gina Leipertz, Olusegun O Soge, Stephen J Jordan, Candice Mcneil, Preeti Pathela, Hilary Reno, Karen Wendel, Anika Parker, William M Geisler, Damon Getman, Matthew R Golden, Mygenius Study Team
Mycoplasma Genitalium In The Us (Mygenius): Surveillance Data From Sexual Health Clinics In 4 Us Regions, Lisa E Manhart, Gina Leipertz, Olusegun O Soge, Stephen J Jordan, Candice Mcneil, Preeti Pathela, Hilary Reno, Karen Wendel, Anika Parker, William M Geisler, Damon Getman, Matthew R Golden, Mygenius Study Team
2020-Current year OA Pubs
BACKGROUND: Mycoplasma genitalium (MG) is on the CDC Watch List of Antimicrobial Resistance Threats, yet there is no systematic surveillance to monitor change.
METHODS: We initiated surveillance in sexual health clinics in 6 cities, selecting a quota sample of urogenital specimens tested for gonorrhea and/or chlamydia. We abstracted patient data from medical records and detected MG and macrolide-resistance mutations (MRMs) by nucleic acid amplification testing. We used Poisson regression to estimate adjusted prevalence ratios (aPRs) and 95% CIs, adjusting for sampling criteria (site, birth sex, symptom status).
RESULTS: From October-December 2020 we tested 1743 urogenital specimens: 57.0% from males, 46.1% …
Sustainability Determinants Of An Intervention To Identify Clinical Deterioration And Improve Childhood Cancer Survival In Latin American Hospitals: The Inspire Study Protocol, Virginia Mckay, Bobbi Carothers, Dylan Graetz, Sara Malone, Maria Puerto-Torres, Kim Prewitt, Adolfo Cardenas, Yichen Chen, Meenakshi Devidas, Douglas A Luke, Asya Agulnik
Sustainability Determinants Of An Intervention To Identify Clinical Deterioration And Improve Childhood Cancer Survival In Latin American Hospitals: The Inspire Study Protocol, Virginia Mckay, Bobbi Carothers, Dylan Graetz, Sara Malone, Maria Puerto-Torres, Kim Prewitt, Adolfo Cardenas, Yichen Chen, Meenakshi Devidas, Douglas A Luke, Asya Agulnik
2020-Current year OA Pubs
BACKGROUND: More than 90% of children with cancer live in low-resourced settings, where survival is only 20%. Sustainable evidence-based (EB) interventions yielding ongoing beneficial patient outcomes are critical to improve childhood cancer survival. A better understanding of factors promoting intervention sustainability in these settings is urgently needed. The aim of this study is to provide an empirical understanding of how clinical capacity for sustainability, or the resources needed to sustain an intervention, impacts the sustainment of Pediatric Early Warning System (PEWS), an EB intervention that improves pediatric oncology outcomes in low-resource hospitals by detecting clinical deterioration and preventing the need …
Effects Of Hepatic Mitochondrial Pyruvate Carrier Deficiency On De Novo Lipogenesis And Gluconeogenesis In Mice, Nicole K H Yiew, Stanislaw Deja, Daniel Ferguson, Kevin Cho, Chaowapong Jarasvaraparn, Miriam Jacome-Sosa, Andrew J Lutkewitte, Sandip Mukherjee, Xiaorong Fu, Jason M Singer, Gary J Patti, Shawn C Burgess, Brian N Finck
Effects Of Hepatic Mitochondrial Pyruvate Carrier Deficiency On De Novo Lipogenesis And Gluconeogenesis In Mice, Nicole K H Yiew, Stanislaw Deja, Daniel Ferguson, Kevin Cho, Chaowapong Jarasvaraparn, Miriam Jacome-Sosa, Andrew J Lutkewitte, Sandip Mukherjee, Xiaorong Fu, Jason M Singer, Gary J Patti, Shawn C Burgess, Brian N Finck
2020-Current year OA Pubs
The liver coordinates the systemic response to nutrient deprivation and availability by producing glucose from gluconeogenesis during fasting and synthesizing lipids via
Simulation Study Of A Novel Small Animal Flash Irradiator (Safi) With Integrated Inverse-Geometry Ct Based On Circularly Distributed Kv X-Ray Sources, Yuewen Tan, Shuang Zhou, Jonathan Haefner, Qinghao Chen, Thomas R Mazur, Arash Darafsheh, Tiezhi Zhang
Simulation Study Of A Novel Small Animal Flash Irradiator (Safi) With Integrated Inverse-Geometry Ct Based On Circularly Distributed Kv X-Ray Sources, Yuewen Tan, Shuang Zhou, Jonathan Haefner, Qinghao Chen, Thomas R Mazur, Arash Darafsheh, Tiezhi Zhang
2020-Current year OA Pubs
Ultra-high dose rate (UHDR) radiotherapy (RT) or FLASH-RT can potentially reduce normal tissue toxicity. A small animal irradiator that can deliver FLASH-RT treatments similar to clinical RT treatments is needed for pre-clinical studies of FLASH-RT. We designed and simulated a novel small animal FLASH irradiator (SAFI) based on distributed x-ray source technology. The SAFI system comprises a distributed x-ray source with 51 focal spots equally distributed on a 20 cm diameter ring, which are used for both FLASH-RT and onboard micro-CT imaging. Monte Carlo simulation was performed to estimate the dosimetric characteristics of the SAFI treatment beams. The maximum dose …
Mutation Of Key Signaling Regulators Of Cerebrovascular Development In Vein Of Galen Malformations, Shujuan Zhao, Po-Ying Fu, Yung-Chun Wang, Sheng Chih Jin, Et Al.
Mutation Of Key Signaling Regulators Of Cerebrovascular Development In Vein Of Galen Malformations, Shujuan Zhao, Po-Ying Fu, Yung-Chun Wang, Sheng Chih Jin, Et Al.
2020-Current year OA Pubs
To elucidate the pathogenesis of vein of Galen malformations (VOGMs), the most common and most severe of congenital brain arteriovenous malformations, we performed an integrated analysis of 310 VOGM proband-family exomes and 336,326 human cerebrovasculature single-cell transcriptomes. We found the Ras suppressor p120 RasGAP (RASA1) harbored a genome-wide significant burden of loss-of-function de novo variants (2042.5-fold, p = 4.79 x 10
Behavioral Mechanisms That Mediate Mental And Physical Health Improvements In People With Chronic Pain Who Receive A Digital Health Intervention: Prospective Cohort Pilot Study, Abby L Cheng, Mansi Agarwal, Melissa A Armbrecht, Joanna Abraham, Ryan P Calfee, Charles W Goss
Behavioral Mechanisms That Mediate Mental And Physical Health Improvements In People With Chronic Pain Who Receive A Digital Health Intervention: Prospective Cohort Pilot Study, Abby L Cheng, Mansi Agarwal, Melissa A Armbrecht, Joanna Abraham, Ryan P Calfee, Charles W Goss
2020-Current year OA Pubs
BACKGROUND: Preliminary evidence suggests that digital mental health intervention (Wysa for Chronic Pain) can improve mental and physical health in people with chronic musculoskeletal pain and coexisting symptoms of depression or anxiety. However, the behavioral mechanisms through which this intervention acts are not fully understood.
OBJECTIVE: The purpose of this study was to identify behavioral mechanisms that may mediate changes in mental and physical health associated with use of Wysa for Chronic Pain during orthopedic management of chronic musculoskeletal pain. We hypothesized that improved behavioral activation, pain acceptance, and sleep quality mediate improvements in self-reported mental and physical health.
METHODS: …
Mixed Methods Evaluation Of Handshake Antimicrobial Stewardship On Adult Inpatient Medicine Floors, Elizabeth A Neuner, Andrew Atkinson, Dan Ilges, Tamara Krekel, David J Ritchie, Alice F Bewley, Michael J Durkin, Kevin Hsueh, Sena Sayood
Mixed Methods Evaluation Of Handshake Antimicrobial Stewardship On Adult Inpatient Medicine Floors, Elizabeth A Neuner, Andrew Atkinson, Dan Ilges, Tamara Krekel, David J Ritchie, Alice F Bewley, Michael J Durkin, Kevin Hsueh, Sena Sayood
2020-Current year OA Pubs
OBJECTIVE: To evaluate the effects of handshake antimicrobial stewardship on medicine floors at a large tertiary care hospital.
DESIGN: Retrospective observational study.
SETTING: 1,278-bed academic hospital.
PATIENTS: Adults admitted to non-ICU medicine services.
INTERVENTIONS: A handshake stewardship team consisting of an infectious diseases (ID) physician and pharmacist reviewed charts of patients receiving antimicrobials on medicine floors without a formal ID consult. Recommendations were communicated in-person to providers and acceptance rates were examined with descriptive statistics. Additional data regarding program perception among providers were obtained via surveys. Antibiotic usage trends were extracted from National Healthcare Safety Network Antimicrobial Use option data …
Two Phase 3 Trials Of Gantenerumab In Early Alzheimer's Disease, Randall J Bateman, Et Al.
Two Phase 3 Trials Of Gantenerumab In Early Alzheimer's Disease, Randall J Bateman, Et Al.
2020-Current year OA Pubs
BACKGROUND: Monoclonal antibodies that target amyloid-beta (Aβ) have the potential to slow cognitive and functional decline in persons with early Alzheimer's disease. Gantenerumab is a subcutaneously administered, fully human, anti-Aβ IgG1 monoclonal antibody with highest affinity for aggregated Aβ that has been tested for the treatment of Alzheimer's disease.
METHODS: We conducted two phase 3 trials (GRADUATE I and II) involving participants 50 to 90 years of age with mild cognitive impairment or mild dementia due to Alzheimer's disease and evidence of amyloid plaques on positron-emission tomography (PET) or cerebrospinal fluid (CSF) testing. Participants were randomly assigned to receive gantenerumab …
Perspectives On Research Needs In Healthcare Epidemiology, Infection Prevention, And Antimicrobial Stewardship: What's On The Horizon-Part Ii, Jonas Marschall, Rachael E Snyders, Hugo Sax, Jason G Newland, Thais Guimarães, Jennie H Kwon
Perspectives On Research Needs In Healthcare Epidemiology, Infection Prevention, And Antimicrobial Stewardship: What's On The Horizon-Part Ii, Jonas Marschall, Rachael E Snyders, Hugo Sax, Jason G Newland, Thais Guimarães, Jennie H Kwon
2020-Current year OA Pubs
In this overview, we articulate research needs and opportunities in the field of infection prevention that have been identified from insights gained during operative infection prevention work, our own research in healthcare epidemiology, and from reviewing the literature. The 10 areas of research need are: 1) Transmissions and interruptions, 2) personal protective equipment and other safety issues in occupational health, 3) climate change and other crises, 4) device, diagnostic, and antimicrobial stewardship, 5) implementation and deimplementation, 6) healthcare outside the acute care hospital, 7) low- and middle-income countries, 8) networking with the "neighbors," 9) novel research methodologies, and 10) the …
Contribution Of Macrophages To Neural Survival And Intracochlear Tissue Remodeling Responses Following Cochlear Implantation, Muhammad Taifur Rahman, Brian J Mostaert, Bryce Hunger, Utsow Saha, Alexander D Claussen, Ibrahim Razu, Farjana Nasrin, Nashwaan Ali Khan, Peter Eckard, Sarah Coleman, Jacob Oleson, Jonathon R Kirk, Keiko Hirose, Marlan R Hansen
Contribution Of Macrophages To Neural Survival And Intracochlear Tissue Remodeling Responses Following Cochlear Implantation, Muhammad Taifur Rahman, Brian J Mostaert, Bryce Hunger, Utsow Saha, Alexander D Claussen, Ibrahim Razu, Farjana Nasrin, Nashwaan Ali Khan, Peter Eckard, Sarah Coleman, Jacob Oleson, Jonathon R Kirk, Keiko Hirose, Marlan R Hansen
2020-Current year OA Pubs
BACKGROUND: Cochlear implants (CIs) restore hearing to deafened patients. The foreign body response (FBR) following cochlear implantation (post-CI) comprises an infiltration of macrophages, other immune and non-immune cells, and fibrosis into the scala tympani, a space that is normally devoid of cells. This FBR is associated with negative effects on CI outcomes including increased electrode impedances and loss of residual acoustic hearing. This study investigates the extent to which macrophage depletion by an orally administered CSF-1R specific kinase (c-FMS) inhibitor, PLX-5622, modulates the tissue response to CI and neural health.
MAIN TEXT: 10- to 12-week-old CX3CR1 + /GFP Thy1 + …
A Paracrine Circuit Of Il-1Β/Il-1r1 Between Myeloid And Tumor Cells Drives Genotype-Dependent Glioblastoma Progression, Zhihong Chen, David H. Gutmann, Et Al.
A Paracrine Circuit Of Il-1Β/Il-1r1 Between Myeloid And Tumor Cells Drives Genotype-Dependent Glioblastoma Progression, Zhihong Chen, David H. Gutmann, Et Al.
2020-Current year OA Pubs
Monocytes and monocyte-derived macrophages (MDMs) from blood circulation infiltrate glioblastoma (GBM) and promote growth. Here, we show that PDGFB-driven GBM cells induce the expression of the potent proinflammatory cytokine IL-1β in MDM, which engages IL-1R1 in tumor cells, activates the NF-κB pathway, and subsequently leads to induction of monocyte chemoattractant proteins (MCPs). Thus, a feedforward paracrine circuit of IL-1β/IL-1R1 between tumors and MDM creates an interdependence driving PDGFB-driven GBM progression. Genetic loss or locally antagonizing IL-1β/IL-1R1 leads to reduced MDM infiltration, diminished tumor growth, and reduced exhausted CD8+ T cells and thereby extends the survival of tumor-bearing mice. In contrast …
Ultra-Deep Sequencing Reveals The Mutational Landscape Of Classical Hodgkin Lymphoma, Felicia Gomez, Bryan Fisk, Joshua F Mcmichael, Matthew Mosior, Jennifer A Foltz, Zachary L Skidmore, Eric J Duncavage, Christopher A Miller, Haley Abel, Yi-Shan Li, David A Russler-Germain, Kilannin Krysiak, Marcus P Watkins, Cody A Ramirez, Alina Schmidt, Fernanda Martins Rodrigues, Lee Trani, Ajay Khanna, Julia A Wagner, Robert S Fulton, Catrina C Fronick, Michelle D O'Laughlin, Timothy Schappe, Amanda F Cashen, Neha Mehta-Shah, Brad S Kahl, Jason Walker, Nancy L Bartlett, Malachi Griffith, Todd A Fehniger, Obi L Griffith
Ultra-Deep Sequencing Reveals The Mutational Landscape Of Classical Hodgkin Lymphoma, Felicia Gomez, Bryan Fisk, Joshua F Mcmichael, Matthew Mosior, Jennifer A Foltz, Zachary L Skidmore, Eric J Duncavage, Christopher A Miller, Haley Abel, Yi-Shan Li, David A Russler-Germain, Kilannin Krysiak, Marcus P Watkins, Cody A Ramirez, Alina Schmidt, Fernanda Martins Rodrigues, Lee Trani, Ajay Khanna, Julia A Wagner, Robert S Fulton, Catrina C Fronick, Michelle D O'Laughlin, Timothy Schappe, Amanda F Cashen, Neha Mehta-Shah, Brad S Kahl, Jason Walker, Nancy L Bartlett, Malachi Griffith, Todd A Fehniger, Obi L Griffith
2020-Current year OA Pubs
UNLABELLED: The malignant Hodgkin and Reed Sternberg (HRS) cells of classical Hodgkin lymphoma (cHL) are scarce in affected lymph nodes, creating a challenge to detect driver somatic mutations. As an alternative to cell purification techniques, we hypothesized that ultra-deep exome sequencing would allow genomic study of HRS cells, thereby streamlining analysis and avoiding technical pitfalls. To test this, 31 cHL tumor/normal pairs were exome sequenced to approximately 1,000× median depth of coverage. An orthogonal error-corrected sequencing approach verified >95% of the discovered mutations. We identified mutations in genes novel to cHL including: CDH5 and PCDH7, novel stop gain mutations in …
Mechanical Loading And Hyperosmolarity As A Daily Resetting Cue For Skeletal Circadian Clocks, Michal Dudek, Dharshika R J Pathiranage, Beatriz Bano-Otalora, Anna Paszek, Natalie Rogers, Cátia F Gonçalves, Craig Lawless, Dong Wang, Zhuojing Luo, Liu Yang, Farshid Guilak, Judith A Hoyland, Qing-Jun Meng
Mechanical Loading And Hyperosmolarity As A Daily Resetting Cue For Skeletal Circadian Clocks, Michal Dudek, Dharshika R J Pathiranage, Beatriz Bano-Otalora, Anna Paszek, Natalie Rogers, Cátia F Gonçalves, Craig Lawless, Dong Wang, Zhuojing Luo, Liu Yang, Farshid Guilak, Judith A Hoyland, Qing-Jun Meng
2020-Current year OA Pubs
Daily rhythms in mammalian behaviour and physiology are generated by a multi-oscillator circadian system entrained through environmental cues (e.g. light and feeding). The presence of tissue niche-dependent physiological time cues has been proposed, allowing tissues the ability of circadian phase adjustment based on local signals. However, to date, such stimuli have remained elusive. Here we show that daily patterns of mechanical loading and associated osmotic challenge within physiological ranges reset circadian clock phase and amplitude in cartilage and intervertebral disc tissues in vivo and in tissue explant cultures. Hyperosmolarity (but not hypo-osmolarity) resets clocks in young and ageing skeletal tissues …
Missense Mutations In Crx Homeodomain Cause Dominant Retinopathies Through Two Distinct Mechanisms, Yiqiao Zheng, Chi Sun, Xiaodong Zhang, Philip A Ruzycki, Shiming Chen
Missense Mutations In Crx Homeodomain Cause Dominant Retinopathies Through Two Distinct Mechanisms, Yiqiao Zheng, Chi Sun, Xiaodong Zhang, Philip A Ruzycki, Shiming Chen
2020-Current year OA Pubs
Homeodomain transcription factors (HD TFs) are instrumental to vertebrate development. Mutations in HD TFs have been linked to human diseases, but their pathogenic mechanisms remain elusive. Here, we use
An Automatic Pipeline For Pet/Mri Attenuation Correction Validation In The Brain, Mahdjoub Hamdi, Chunwei Ying, Hongyu An, Richard Laforest
An Automatic Pipeline For Pet/Mri Attenuation Correction Validation In The Brain, Mahdjoub Hamdi, Chunwei Ying, Hongyu An, Richard Laforest
2020-Current year OA Pubs
PURPOSE: Challenges in PET/MRI quantitative accuracy for neurological uses arise from PET attenuation correction accuracy. We proposed and evaluated an automatic pipeline to assess the quantitative accuracy of four MRI-derived PET AC methods using analytically simulated PET brain lesions and ROIs as ground truth for PET activity.
METHODS: Our proposed pipeline, integrating a synthetic lesion insertion tool and the FreeSurfer neuroimaging framework, inserts simulated spherical and brain ROIs into PET projection space, reconstructing them via four PET MRAC techniques. Utilizing an 11-patient brain PET dataset, we compared the quantitative accuracy of four MRACs (DIXON, DIXONbone, UTE AC, and DL-DIXON) against …
"The Project Did Not Come To Us With A Solution": Perspectives Of Research Teams On Implementing A Study About Electronic Health Record-Embedded Individualized Pain Plans For Emergency Department Treatment Of Vaso-Occlusive Episodes In Adults With Sickle Cell Disease, Ana A Baumann, Elizabeth Taaffe, Nai Qashou, Aimee S James, Allison A King, Et Al.
"The Project Did Not Come To Us With A Solution": Perspectives Of Research Teams On Implementing A Study About Electronic Health Record-Embedded Individualized Pain Plans For Emergency Department Treatment Of Vaso-Occlusive Episodes In Adults With Sickle Cell Disease, Ana A Baumann, Elizabeth Taaffe, Nai Qashou, Aimee S James, Allison A King, Et Al.
2020-Current year OA Pubs
BACKGROUND: This study aimed to capture the implementation process of the ALIGN Study, (An individualized Pain Plan with Patient and Provider Access for Emergency Department care of Sickle Cell Disease). ALIGN aimed to embed Individualized Pain Plans in the electronic health record (E-IPP) and provide access to the plan for both adult patients with sickle cell disease (SCD) and emergency department providers when a person with SCD comes to the emergency department in vaso-occlusive crises.
METHODS: Semi-structured interviews were conducted with research teams from the 8 participating sites from the ALIGN study. Seventeen participants (principal investigators and study coordinators) shared …
A Cre-Dependent Massively Parallel Reporter Assay Allows For Cell-Type Specific Assessment Of The Functional Effects Of Non-Coding Elements In Vivo, Tomas Lagunas Jr, Stephen P Plassmeyer, Anthony D Fischer, Ryan Z Friedman, Michael A Rieger, Din Selmanovic, Simona Sarafinovska, Yvette K Sol, Michael J Kasper, Stuart B Fass, Alessandra F Aguilar Lucero, Joon-Yong An, Stephan J Sanders, Barak A Cohen, Joseph D Dougherty
A Cre-Dependent Massively Parallel Reporter Assay Allows For Cell-Type Specific Assessment Of The Functional Effects Of Non-Coding Elements In Vivo, Tomas Lagunas Jr, Stephen P Plassmeyer, Anthony D Fischer, Ryan Z Friedman, Michael A Rieger, Din Selmanovic, Simona Sarafinovska, Yvette K Sol, Michael J Kasper, Stuart B Fass, Alessandra F Aguilar Lucero, Joon-Yong An, Stephan J Sanders, Barak A Cohen, Joseph D Dougherty
2020-Current year OA Pubs
The function of regulatory elements is highly dependent on the cellular context, and thus for understanding the function of elements associated with psychiatric diseases these would ideally be studied in neurons in a living brain. Massively Parallel Reporter Assays (MPRAs) are molecular genetic tools that enable functional screening of hundreds of predefined sequences in a single experiment. These assays have not yet been adapted to query specific cell types in vivo in a complex tissue like the mouse brain. Here, using a test-case 3'UTR MPRA library with genomic elements containing variants from autism patients, we developed a method to achieve …
Ceramides In Peripheral Arterial Plaque Lead To Endothelial Cell Dysfunction, Rodrigo Meade, Yang Chao, Nikolai Harroun, Chenglong Li, Shahab Hafezi, Fong-Fu Hsu, Clay F Semenkovich, Mohamed A Zayed
Ceramides In Peripheral Arterial Plaque Lead To Endothelial Cell Dysfunction, Rodrigo Meade, Yang Chao, Nikolai Harroun, Chenglong Li, Shahab Hafezi, Fong-Fu Hsu, Clay F Semenkovich, Mohamed A Zayed
2020-Current year OA Pubs
BACKGROUND: Peripheral arterial atheroprogression is increasingly prevalent, and is a risk factor for major limb amputations in individuals with risk factors such as diabetes. We previously demonstrated that bioactive lipids are significantly altered in arterial tissue of individuals with diabetes and advanced peripheral arterial disease.
METHODS: Here we evaluated whether sphingolipid ceramide 18:1/16:0 (C16) is a cellular regulator in endothelial cells and peripheral tibial arterial tissue in individuals with diabetes.
RESULTS: We observed that C16 is the single most elevated ceramide in peripheral arterial tissue from below the knee in individuals with diabetes (11% increase,
CONCLUSIONS: Our findings suggest that …
Distinct Disease Mutations In Dnmt3a Result In A Spectrum Of Behavioral, Epigenetic, And Transcriptional Deficits, Diana C Beard, Xiyun Zhang, Dennis Y Wu, Jenna R Martin, Alyssa Erickson, Jane Valeriane Boua, Nicole Hamagami, Raylynn G Swift, Katherine B Mccullough, Xia Ge, Austin Bell-Hensley, Hongjun Zheng, Cory W Palmer, Nicole A Fuhler, Thomas Papouin, Kevin K Noguchi, Audrey Mcalinden, Joel R Garbow, Joseph D Dougherty, Susan E Maloney, Harrison W Gabel, Et Al.
Distinct Disease Mutations In Dnmt3a Result In A Spectrum Of Behavioral, Epigenetic, And Transcriptional Deficits, Diana C Beard, Xiyun Zhang, Dennis Y Wu, Jenna R Martin, Alyssa Erickson, Jane Valeriane Boua, Nicole Hamagami, Raylynn G Swift, Katherine B Mccullough, Xia Ge, Austin Bell-Hensley, Hongjun Zheng, Cory W Palmer, Nicole A Fuhler, Thomas Papouin, Kevin K Noguchi, Audrey Mcalinden, Joel R Garbow, Joseph D Dougherty, Susan E Maloney, Harrison W Gabel, Et Al.
2020-Current year OA Pubs
Phenotypic heterogeneity in monogenic neurodevelopmental disorders can arise from differential severity of variants underlying disease, but how distinct alleles drive variable disease presentation is not well understood. Here, we investigate missense mutations in DNA methyltransferase 3A (DNMT3A), a DNA methyltransferase associated with overgrowth, intellectual disability, and autism, to uncover molecular correlates of phenotypic heterogeneity. We generate a Dnmt3a
Biochemical Recurrence Surrogacy For Clinical Outcomes After Radiotherapy For Adenocarcinoma Of The Prostate, Soumyajit Roy, Jeff M Michalski, Et Al.
Biochemical Recurrence Surrogacy For Clinical Outcomes After Radiotherapy For Adenocarcinoma Of The Prostate, Soumyajit Roy, Jeff M Michalski, Et Al.
2020-Current year OA Pubs
PURPOSE: The surrogacy of biochemical recurrence (BCR) for overall survival (OS) in localized prostate cancer remains controversial. Herein, we evaluate the surrogacy of BCR using different surrogacy analytic methods.
MATERIALS AND METHODS: Individual patient data from 11 trials evaluating radiotherapy dose escalation, androgen deprivation therapy (ADT) use, and ADT prolongation were obtained. Surrogate candidacy was assessed using the Prentice criteria (including landmark analyses) and the two-stage meta-analytic approach (estimating Kendall's tau and the
RESULTS: Overall, 10,741 patients were included. Dose escalation, addition of short-term ADT, and prolongation of ADT duration significantly improved BCR (hazard ratio [HR], 0.71 [95% CI, 0.63 …
Staphylococcus Aureus Α-Toxin Impairs Early Neutrophil Localization Via Electrogenic Disruption Of Store-Operated Calcium Entry, Fan Yang, Mingyi Suo, Homayemem Weli, Mason Wong, Alex Junidi, Celeste Cummings, Ryan Johnson, Kiara Mallory, Annie Y Liu, Zev J Greenberg, Laura G Schuettpelz, Mark J Miller, Cliff J Luke, Gwendalyn J Randolph, Bernd H Zinselmeyer, Juliane Bubeck Wardenburg, Regina A Clemens
Staphylococcus Aureus Α-Toxin Impairs Early Neutrophil Localization Via Electrogenic Disruption Of Store-Operated Calcium Entry, Fan Yang, Mingyi Suo, Homayemem Weli, Mason Wong, Alex Junidi, Celeste Cummings, Ryan Johnson, Kiara Mallory, Annie Y Liu, Zev J Greenberg, Laura G Schuettpelz, Mark J Miller, Cliff J Luke, Gwendalyn J Randolph, Bernd H Zinselmeyer, Juliane Bubeck Wardenburg, Regina A Clemens
2020-Current year OA Pubs
The pore-forming S. aureus α-toxin (Hla) contributes to virulence and disease pathogenesis. While high concentrations of toxin induce cell death, neutrophils exhibit relative resistance to lysis, suggesting that the action of Hla may not be solely conferred by lytic susceptibility. Using intravital microscopy, we observed that Hla disrupts neutrophil localization and clustering early in infection. Hla forms a narrow, ion-selective pore, suggesting that Hla may dysregulate calcium or other ions to impair neutrophil function. We found that sub-lytic Hla did not permit calcium influx but caused rapid membrane depolarization. Depolarization decreases the electrogenic driving force for calcium, and concordantly, Hla …
A Uniform Human Multimodal Dataset For Emotion Perception And Judgment, Sai Sun, Runnan Cao, Ueli Rutishauser, Rongjun Yu, Shuo Wang
A Uniform Human Multimodal Dataset For Emotion Perception And Judgment, Sai Sun, Runnan Cao, Ueli Rutishauser, Rongjun Yu, Shuo Wang
2020-Current year OA Pubs
Face perception is a fundamental aspect of human social interaction, yet most research on this topic has focused on single modalities and specific aspects of face perception. Here, we present a comprehensive multimodal dataset for examining facial emotion perception and judgment. This dataset includes EEG data from 97 unique neurotypical participants across 8 experiments, fMRI data from 19 neurotypical participants, single-neuron data from 16 neurosurgical patients (22 sessions), eye tracking data from 24 neurotypical participants, behavioral and eye tracking data from 18 participants with ASD and 15 matched controls, and behavioral data from 3 rare patients with focal bilateral amygdala …
Dysregulated Cd200-Cd200r Signaling In Early Diabetes Modulates Microglia-Mediated Retinopathy, Charles W Pfeifer, James T Walsh, Andrea Santeford, Joseph B Lin, Wandy L Beatty, Ryo Terao, Yizhou A Liu, Keitaro Hase, Philip A Ruzycki, Rajendra S Apte
Dysregulated Cd200-Cd200r Signaling In Early Diabetes Modulates Microglia-Mediated Retinopathy, Charles W Pfeifer, James T Walsh, Andrea Santeford, Joseph B Lin, Wandy L Beatty, Ryo Terao, Yizhou A Liu, Keitaro Hase, Philip A Ruzycki, Rajendra S Apte
2020-Current year OA Pubs
Diabetic retinopathy (DR) is a neurovascular complication of diabetes. Recent investigations have suggested that early degeneration of the neuroretina may occur prior to the appearance of microvascular changes; however, the mechanisms underlying this neurodegeneration have been elusive. Microglia are the predominant resident immune cell in the retina and adopt dynamic roles in disease. Here, we show that ablation of retinal microglia ameliorates visual dysfunction and neurodegeneration in a type I diabetes mouse model. We also provide evidence of enhanced microglial contact and engulfment of amacrine cells, ultrastructural modifications, and transcriptome changes that drive inflammation and phagocytosis. We show that CD200-CD200R …
Nk Cell Expansion Requires Hur And Mediates Control Of Solid Tumors And Long-Term Virus Infection, Sytse J Piersma, Sushant Bangru, Jeesang Yoon, Tom W Liu, Liping Yang, Chyi-Song Hsieh, Beatrice Plougastel-Douglas, Auinash Kalsotra, Wayne M Yokoyama
Nk Cell Expansion Requires Hur And Mediates Control Of Solid Tumors And Long-Term Virus Infection, Sytse J Piersma, Sushant Bangru, Jeesang Yoon, Tom W Liu, Liping Yang, Chyi-Song Hsieh, Beatrice Plougastel-Douglas, Auinash Kalsotra, Wayne M Yokoyama
2020-Current year OA Pubs
Natural killer (NK) cells are lymphocytes capable of controlling tumors and virus infections through direct lysis and cytokine production. While both T and NK cells expand and accumulate in affected tissues, the role of NK cell expansion in tumor and viral control is not well understood. Here, we show that posttranscriptional regulation by the RNA-binding protein HuR is essential for NK cell expansion without negatively affecting effector functions. HuR-deficient NK cells displayed defects in the metaphase of the cell cycle, including decreased expression and alternative splicing of Ska2, a component of the spindle and kinetochore complex. HuR-dependent NK cell expansion …
Height With Age Affects Body Mass Index (Bmi) Assessment Of Chronic Disease Risk, Peter R Holt, Osama Altayar, David H Alpers
Height With Age Affects Body Mass Index (Bmi) Assessment Of Chronic Disease Risk, Peter R Holt, Osama Altayar, David H Alpers
2020-Current year OA Pubs
Body mass index (BMI) is a function of weight and height, but changing height has not been emphasized. Using the Framingham Heart Study with 5 decades of data on anthropomorphic measurements and disease states, changing height with age was extracted, and BMI was calculated using current and "young" height (calculated as height at age < 40 years). Decreased height began at age 40, with a mean loss from ages 40 to 80 of 4.8 cm for women and 3.6 cm for men. Using cutoff values of 25 and 30 for overweight and obesity, ~12.5% of women and ~10% of men were misclassified. Comparable figures for obesity classification were ~10 and 8%. At age 70, ~20% of women and ~15% of men were misclassified. Using the BMI corrected to "young" height, obese subjects had an increased risk for developing pre-diabetes and diabetes, with a higher risk for women than men. Using corrected BMI, obese subjects had a higher risk for developing hypertension, lower than for diabetes and higher for men than for women. These data do not establish whether the increased disease risk is clinically important but demonstrate that there is an advantage to using BMI corrected for "young" height when compared with BMI using current age-related height.
Perspectives On Research Needs In Healthcare Epidemiology And Antimicrobial Stewardship: What's On The Horizon - Part I, Jonas Marschall, Rachael E Snyders, Hugo Sax, Jason G Newland, Thais Guimarães, Jennie H Kwon
Perspectives On Research Needs In Healthcare Epidemiology And Antimicrobial Stewardship: What's On The Horizon - Part I, Jonas Marschall, Rachael E Snyders, Hugo Sax, Jason G Newland, Thais Guimarães, Jennie H Kwon
2020-Current year OA Pubs
In this overview, we articulate research needs and opportunities in the field of infection prevention that have been identified from insights gained during operative infection prevention work, our own research in healthcare epidemiology, and from reviewing the literature. The 10 areas of research need are: 1) transmissions and interruptions, 2) personal protective equipment and other safety issues in occupational health, 3) climate change and other crises, 4) device, diagnostic, and antimicrobial stewardship, 5) implementation and de-implementation, 6) health care outside the acute care hospital, 7) low- and middle-income countries, 8) networking with the "neighbors", 9) novel research methodologies, and 10) …
Association Between User Interaction And Treatment Response Of A Voice-Based Coach For Treating Depression And Anxiety: Secondary Analysis Of A Pilot Randomized Controlled Trial, Nan Lv, Thomas Kannampallil, Lan Xiao, Corina R Ronneberg, Vikas Kumar, Nancy E Wittels, Olusola A Ajilore, Joshua M Smyth, Jun Ma
Association Between User Interaction And Treatment Response Of A Voice-Based Coach For Treating Depression And Anxiety: Secondary Analysis Of A Pilot Randomized Controlled Trial, Nan Lv, Thomas Kannampallil, Lan Xiao, Corina R Ronneberg, Vikas Kumar, Nancy E Wittels, Olusola A Ajilore, Joshua M Smyth, Jun Ma
2020-Current year OA Pubs
BACKGROUND: The quality of user interaction with therapeutic tools has been positively associated with treatment response; however, no studies have investigated these relationships for voice-based digital tools.
OBJECTIVE: This study evaluated the relationships between objective and subjective user interaction measures as well as treatment response on Lumen, a novel voice-based coach, delivering problem-solving treatment to patients with mild to moderate depression or anxiety or both.
METHODS: In a pilot trial, 42 adults with clinically significant depression (Patient Health Questionnaire-9 [PHQ-9]) or anxiety (7-item Generalized Anxiety Disorder Scale [GAD-7]) symptoms or both received Lumen, a voice-based coach delivering 8 problem-solving treatment …
Hepatic Palmitoyl-Proteomes And Acyl-Protein Thioesterase Protein Proximity Networks Link Lipid Modification And Mitochondria, Sarah L Speck, Dhaval P Bhatt, Qiang Zhang, Sangeeta Adak, Li Yin, Guifang Dong, Chu Feng, Wei Zhang, M Ben Major, Xiaochao Wei, Clay F Semenkovich
Hepatic Palmitoyl-Proteomes And Acyl-Protein Thioesterase Protein Proximity Networks Link Lipid Modification And Mitochondria, Sarah L Speck, Dhaval P Bhatt, Qiang Zhang, Sangeeta Adak, Li Yin, Guifang Dong, Chu Feng, Wei Zhang, M Ben Major, Xiaochao Wei, Clay F Semenkovich
2020-Current year OA Pubs
Acyl-protein thioesterases 1 and 2 (APT1 and APT2) reverse S-acylation, a potential regulator of systemic glucose metabolism in mammals. Palmitoylation proteomics in liver-specific knockout mice shows that APT1 predominates over APT2, primarily depalmitoylating mitochondrial proteins, including proteins linked to glutamine metabolism. miniTurbo-facilitated determination of the protein-protein proximity network of APT1 and APT2 in HepG2 cells reveals APT proximity networks encompassing mitochondrial proteins including the major translocases Tomm20 and Timm44. APT1 also interacts with Slc1a5 (ASCT2), the only glutamine transporter known to localize to mitochondria. High-fat-diet-fed male mice with dual (but not single) hepatic deletion of APT1 and APT2 have insulin …
Quantifying And Correcting Bias Due To Outcome Dependent Self-Reported Weights In Longitudinal Study Of Weight Loss Interventions, Jiayi Tong, Rui Duan, Ruowang Li, Chongliang Luo, Jason H Moore, Jingsan Zhu, Gary D Foster, Kevin G Volpp, William S Yancy Jr, Pamela A Shaw, Yong Chen
Quantifying And Correcting Bias Due To Outcome Dependent Self-Reported Weights In Longitudinal Study Of Weight Loss Interventions, Jiayi Tong, Rui Duan, Ruowang Li, Chongliang Luo, Jason H Moore, Jingsan Zhu, Gary D Foster, Kevin G Volpp, William S Yancy Jr, Pamela A Shaw, Yong Chen
2020-Current year OA Pubs
In response to the escalating global obesity crisis and its associated health and financial burdens, this paper presents a novel methodology for analyzing longitudinal weight loss data and assessing the effectiveness of financial incentives. Drawing from the Keep It Off trial-a three-arm randomized controlled study with 189 participants-we examined the potential impact of financial incentives on weight loss maintenance. Given that some participants choose not to weigh themselves because of small weight change or weight gains, which is a common phenomenon in many weight-loss studies, traditional methods, for example, the Generalized Estimating Equations (GEE) method tends to overestimate the effect …
Comparison Of Joint Mobilization And Movement Pattern Training For Patients With Hip-Related Groin Pain: A Pilot Randomized Clinical Trial, Marcie Harris-Hayes, Patricia Zorn, Karen Steger-May, Megan M Burgess, Rebecca D Demargel, Suzanne Kuebler, John Clohisy, Simon Haroutounian
Comparison Of Joint Mobilization And Movement Pattern Training For Patients With Hip-Related Groin Pain: A Pilot Randomized Clinical Trial, Marcie Harris-Hayes, Patricia Zorn, Karen Steger-May, Megan M Burgess, Rebecca D Demargel, Suzanne Kuebler, John Clohisy, Simon Haroutounian
2020-Current year OA Pubs
OBJECTIVE: The objective of this study was to assess the feasibility of completing a randomized clinical trial (RCT) and examine the preliminary effects of 2 interventions for hip-related groin pain (HRGP).
METHODS: In this pilot RCT, patients with HRGP, who were 18 to 40 years old, were randomized (1:1 ratio) to a joint mobilization (JtMob) group or a movement pattern training (MoveTrain) group. Both treatments included 10 supervised sessions and a home exercise program. The goal of JtMob was to reduce pain and improve mobility through peripherally and centrally mediated pain mechanisms. The key element was physical therapist-provided JtMob. The …