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Structural Variants Are A Major Source Of Gene Expression Differences In Humans And Often Affect Multiple Nearby Genes, Alexandra J Scott, Colby Chiang, Ira M Hall Sep 2021

Structural Variants Are A Major Source Of Gene Expression Differences In Humans And Often Affect Multiple Nearby Genes, Alexandra J Scott, Colby Chiang, Ira M Hall

2020-Current year OA Pubs

Structural variants (SVs) are an important source of human genome diversity, but their functional effects are poorly understood. We mapped 61,668 SVs in 613 individuals from the GTEx project and measured their effects on gene expression. We estimate that common SVs are causal at 2.66% of eQTLs, a 10.5-fold enrichment relative to their abundance in the genome. Duplications and deletions were the most impactful variant types, whereas the contribution of mobile element insertions was small (0.12% of eQTLs, 1.9-fold enriched). Multitissue analysis of eQTLs revealed that gene-altering SVs show more constitutive effects than other variant types, with 62.09% of coding …


Current Neurologic Treatment And Emerging Therapies In Cdkl5 Deficiency Disorder, Heather E Olson, Judith L Weisenberg, Et Al. Sep 2021

Current Neurologic Treatment And Emerging Therapies In Cdkl5 Deficiency Disorder, Heather E Olson, Judith L Weisenberg, Et Al.

2020-Current year OA Pubs

BACKGROUND: CDKL5 deficiency disorder (CDD) is associated with refractory infantile onset epilepsy, global developmental delay, and variable features that include sleep, behavioral disturbances, and movement disorders. Current treatment is primarily symptom-based and informed by experience in caring for this population.

METHODS: We describe medication and non-medication approaches to treatment of epilepsy and additional key neurologic symptoms (sleep disturbances, behavioral issues, movement disorders, and swallowing dysfunction) in a cohort of 177 individuals meeting criteria for CDD, 154 evaluated at 4 CDKL5 Centers of Excellence in the USA and 40 identified through the NIH Natural History Study of Rett and Related Disorders. …


Genetic Counseling As Preventive Intervention: Toward Individual Specification Of Transgenerational Autism Risk, Natasha Marrus, Tychele N Turner, Elizabeth Forsen, Drew Bolster, Alison Marvin, Andrew Whitehouse, Laura Klinger, Christina A Gurnett, J N Constantino Sep 2021

Genetic Counseling As Preventive Intervention: Toward Individual Specification Of Transgenerational Autism Risk, Natasha Marrus, Tychele N Turner, Elizabeth Forsen, Drew Bolster, Alison Marvin, Andrew Whitehouse, Laura Klinger, Christina A Gurnett, J N Constantino

2020-Current year OA Pubs

BACKGROUND: Although autism spectrum disorders (ASD) are among the most heritable of all neuropsychiatric syndromes, most affected children are born to unaffected parents. Recently, we reported an average increase of 3-5% over general population risk of ASD among offspring of adults who have first-degree relatives with ASD in a large epidemiologic family sample. A next essential step is to investigate whether there are measurable characteristics of individual parents placing them at higher or lower recurrence risk, as this information could allow more personalized genetic counseling.

METHODS: We assembled what is to our knowledge the largest collection of data on the …


Outpatient Prescription Practices In Patients With Atrial Fibrillation (From The Ncdr Pinnacle Registry), Jonathan C Hsu, Matthew R Reynolds, Yang Song, Gheorghe Doros, Steven A Lubitz, Anil K Gehi, Mintu P Turakhia, Thomas M Maddox Sep 2021

Outpatient Prescription Practices In Patients With Atrial Fibrillation (From The Ncdr Pinnacle Registry), Jonathan C Hsu, Matthew R Reynolds, Yang Song, Gheorghe Doros, Steven A Lubitz, Anil K Gehi, Mintu P Turakhia, Thomas M Maddox

2020-Current year OA Pubs

This study sought to evaluate inappropriate prescribing practices in an atrial fibrillation (AF) population, as outlined by the 2016 ACC/AHA Clinical Performance and Quality Measures for Adults with Atrial Fibrillation or Atrial Flutter document. The 2016 AF quality measures document specified medications to avoid in certain AF populations, including aspirin and anticoagulant combination therapy in patients without cardiovascular disease, and non-dihydropyridine calcium channel blockers in patients with reduced ejection fraction. Using data from the NCDR PINNACLE registry, a national outpatient cardiology practice registry, we assessed rates of inappropriate prescription of two types of medications among AF outpatients from 5/1/2008-5/1/2016. Overall …


Nanoparticle T Cell Engagers For The Treatment Of Acute Myeloid Leukemia, Kinan Alhallak, Jennifer Sun, Barbara Muz, Amanda Jeske, Jessica Yavner, Hannah Bash, Chaelee Park, Berit Lubben, Ola Adebayo, Samuel Achilefu, John F Dipersio, Abdel Kareem Azab Sep 2021

Nanoparticle T Cell Engagers For The Treatment Of Acute Myeloid Leukemia, Kinan Alhallak, Jennifer Sun, Barbara Muz, Amanda Jeske, Jessica Yavner, Hannah Bash, Chaelee Park, Berit Lubben, Ola Adebayo, Samuel Achilefu, John F Dipersio, Abdel Kareem Azab

2020-Current year OA Pubs

Acute myeloid leukemia (AML) is the most common type of leukemia and has a 5-year survival rate of 25%. The standard-of-care for AML has not changed in the past few decades. Promising immunotherapy options are being developed for the treatment of AML; yet, these regimens require highly laborious and sophisticated techniques. We create nanoTCEs using liposomes conjugated to monoclonal antibodies to enable specific binding. We also recreate the bone marrow niche using our 3D culture system and use immunocompromised mice to enable use of human AML and T cells with nanoTCEs. We show that CD33 is ubiquitously present on AML …


Predilection For Developing A Hematogenous Orthopaedic Implant-Associated Infection In Older Versus Younger Mice, John M Thompson, Alyssa G Ashbaugh, Yu Wang, Robert J Miller, Julie E Pickett, Daniel L J Thorek, Robert S Sterling, Lloyd S Miller Sep 2021

Predilection For Developing A Hematogenous Orthopaedic Implant-Associated Infection In Older Versus Younger Mice, John M Thompson, Alyssa G Ashbaugh, Yu Wang, Robert J Miller, Julie E Pickett, Daniel L J Thorek, Robert S Sterling, Lloyd S Miller

2020-Current year OA Pubs

BACKGROUND: The pathogenesis of hematogenous orthopaedic implant-associated infections (HOIAI) remains largely unknown, with little understanding of the influence of the physis on bacterial seeding. Since the growth velocity in the physis of long bones decreases during aging, we sought to evaluate the role of the physis on influencing the development of Staphylococcus aureus HOIAI in a mouse model comparing younger versus older mice.

METHODS: In a mouse model of HOIAI, a sterile Kirschner wire was inserted retrograde into the distal femur of younger (5-8-week-old) and older (14-21-week-old) mice. After a 3-week convalescent period, a bioluminescent Staphylococcus aureus strain was inoculated …


Improved Gal4 And Tet Off Drivers For C. Elegans Bipartite Expression, Michael Nonet Sep 2021

Improved Gal4 And Tet Off Drivers For C. Elegans Bipartite Expression, Michael Nonet

2020-Current year OA Pubs

The first generation of


Is Comprehensiveness Critical? Comparing Short And Long Format Cognitive Assessments In Preclinical Alzheimer Disease, Jason Hassenstab, Jessica Nicosia, Megan Larose, Andrew J Aschenbrenner, Brian A Gordon, Tammie L S Benzinger, Chengjie Xiong, John C Morris Sep 2021

Is Comprehensiveness Critical? Comparing Short And Long Format Cognitive Assessments In Preclinical Alzheimer Disease, Jason Hassenstab, Jessica Nicosia, Megan Larose, Andrew J Aschenbrenner, Brian A Gordon, Tammie L S Benzinger, Chengjie Xiong, John C Morris

2020-Current year OA Pubs

BACKGROUND: Comprehensive testing of cognitive functioning is standard practice in studies of Alzheimer disease (AD). Short-form tests like the Montreal Cognitive Assessment (MoCA) use a "sampling" of measures, administering key items in a shortened format to efficiently assess cognition while reducing time requirements, participant burden, and administrative costs. We compared the MoCA to a commonly used long-form cognitive battery in predicting AD symptom onset and sensitivity to AD neuroimaging biomarkers.

METHODS: Survival, area under the receiver operating characteristic (ROC) curve (AUC), and multiple regression analyses compared the MoCA and long-form measures in predicting time to symptom onset in cognitively normal …


Expert Consensus On The Identification, Diagnosis, And Treatment Of Neurotrophic Keratopathy, Reza Dana, Marjan Farid, Preeya K Gupta, Pedram Hamrah, Paul Karpecki, Cathleen M Mccabe, Lisa Nijm, Jay S Pepose, Stephen Pflugfelder, Christopher J Rapuano, Arvind Saini, Sarah N Gibbs, Michael S Broder Sep 2021

Expert Consensus On The Identification, Diagnosis, And Treatment Of Neurotrophic Keratopathy, Reza Dana, Marjan Farid, Preeya K Gupta, Pedram Hamrah, Paul Karpecki, Cathleen M Mccabe, Lisa Nijm, Jay S Pepose, Stephen Pflugfelder, Christopher J Rapuano, Arvind Saini, Sarah N Gibbs, Michael S Broder

2020-Current year OA Pubs

BACKGROUND: Neurotrophic keratopathy (NK) is a relatively uncommon, underdiagnosed degenerative corneal disease that is caused by damage to the ophthalmic branch of the trigeminal nerve by conditions such as herpes simplex or zoster keratitis, intracranial space-occupying lesions, diabetes, or neurosurgical procedures. Over time, epithelial breakdown, corneal ulceration, corneal melting (thinning), perforation, and loss of vision may occur. The best opportunity to reverse ocular surface damage is in the earliest stage of NK. However, patients typically experience few symptoms and diagnosis is often delayed. Increased awareness of the causes of NK, consensus on when and how to screen for NK, and …


Resident And Fellow Financial Literacy: A Student Loan And Debt Management Survey, James D. Turner, Jacob A. Matthews, Gregory B. Russell, Fahd A. Ahmad Sep 2021

Resident And Fellow Financial Literacy: A Student Loan And Debt Management Survey, James D. Turner, Jacob A. Matthews, Gregory B. Russell, Fahd A. Ahmad

2020-Current year OA Pubs

No abstract provided.


Quality Of Life Analyses In Patients With Multiple Myeloma: Results From The Selinexor (Kpt-330) Treatment Of Refractory Myeloma (Storm) Phase 2b Study, Gabriel Tremblay, Ravi Vij, Et Al. Sep 2021

Quality Of Life Analyses In Patients With Multiple Myeloma: Results From The Selinexor (Kpt-330) Treatment Of Refractory Myeloma (Storm) Phase 2b Study, Gabriel Tremblay, Ravi Vij, Et Al.

2020-Current year OA Pubs

BACKGROUND: Selinexor is an oral, selective nuclear export inhibitor. STORM was a phase 2b, single-arm, open-label, multicenter trial of selinexor with low dose dexamethasone in patients with penta-exposed relapsed/refractory multiple myeloma (RRMM) that met its primary endpoint, with overall response of 26% (95% confidence interval [CI], 19 to 35%). Health-related quality of life (HRQoL) was a secondary endpoint measured using the Functional Assessment of Cancer Therapy - Multiple Myeloma (FACT-MM). This study examines impact of selinexor treatment on HRQoL of patients treated in STORM and reports two approaches to calculate minimal clinically important differences for the FACT-MM.

METHODS: FACT-MM data …


Surgical And Percutaneous Revascularization Outcomes Based On Syntax I, Ii, And Residual Scores: A Long-Term Follow-Up Study, Eduardo Bello Martins, Whady Hueb, David L Brown, Thiago Luis Scudeler, Eduardo Gomes Lima, Paulo Cury Rezende, Paulo Rogério Soares, Cibele Larrosa Garzillo, Jaime Paula Pessoa Linhares Filho, Daniel Valente Batista, Jose Antonio Franchini Ramires, Roberto Kalil Filho Sep 2021

Surgical And Percutaneous Revascularization Outcomes Based On Syntax I, Ii, And Residual Scores: A Long-Term Follow-Up Study, Eduardo Bello Martins, Whady Hueb, David L Brown, Thiago Luis Scudeler, Eduardo Gomes Lima, Paulo Cury Rezende, Paulo Rogério Soares, Cibele Larrosa Garzillo, Jaime Paula Pessoa Linhares Filho, Daniel Valente Batista, Jose Antonio Franchini Ramires, Roberto Kalil Filho

2020-Current year OA Pubs

BACKGROUND: The objective of this study was to evaluate the association of SYNTAX scores I, II, and residual with cardiovascular outcomes of patients undergoing coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) and compare both procedures in a long-term follow-up.

METHODS: This is a retrospective single-center study from the MASS registry at the Heart Institute of the University of São Paulo, Brazil in which 969 patients with stable coronary artery disease undergoing CABG (559) or PCI (410) were included. We assessed the SYNTAX scores I, II and residual in both interventions. Clinical endpoints were the first occurrence of …


Genome Assemblies Across The Diverse Evolutionary Spectrum Of Leishmania Protozoan Parasites, Wesley C. Warren, Natalia S. Akopyants, Deborah E. Dobson, Christiane Hertz-Fowler, Lon-Fye Lye, Peter J. Myler, Gowthaman Ramasamy, Achchuthan Shanmugasundram, Fatima Silva-Franco, Sascha Steinbiss, Chad Tomlinson, Richard K. Wilson, Stephen M. Beverley Sep 2021

Genome Assemblies Across The Diverse Evolutionary Spectrum Of Leishmania Protozoan Parasites, Wesley C. Warren, Natalia S. Akopyants, Deborah E. Dobson, Christiane Hertz-Fowler, Lon-Fye Lye, Peter J. Myler, Gowthaman Ramasamy, Achchuthan Shanmugasundram, Fatima Silva-Franco, Sascha Steinbiss, Chad Tomlinson, Richard K. Wilson, Stephen M. Beverley

2020-Current year OA Pubs

We report the high-quality draft assemblies and gene annotations for 13 species and/or strains of the protozoan parasite genera


Msisensor-Ct: Microsatellite Instability Detection Using Cfdna Sequencing Data, Xinyin Han, Shuying Zhang, Daniel Cui Zhou, Dongliang Wang, Xiaoyu He, Danyang Yuan, Ruilin Li, Jiayin He, Xiaohong Duan, Michael C Wendl, Li Ding, Beifang Niu Sep 2021

Msisensor-Ct: Microsatellite Instability Detection Using Cfdna Sequencing Data, Xinyin Han, Shuying Zhang, Daniel Cui Zhou, Dongliang Wang, Xiaoyu He, Danyang Yuan, Ruilin Li, Jiayin He, Xiaohong Duan, Michael C Wendl, Li Ding, Beifang Niu

2020-Current year OA Pubs

MOTIVATION: Microsatellite instability (MSI) is a promising biomarker for cancer prognosis and chemosensitivity. Techniques are rapidly evolving for the detection of MSI from tumor-normal paired or tumor-only sequencing data. However, tumor tissues are often insufficient, unavailable, or otherwise difficult to procure. Increasing clinical evidence indicates the enormous potential of plasma circulating cell-free DNA (cfNDA) technology as a noninvasive MSI detection approach.

RESULTS: We developed MSIsensor-ct, a bioinformatics tool based on a machine learning protocol, dedicated to detecting MSI status using cfDNA sequencing data with a potential stable MSIscore threshold of 20%. Evaluation of MSIsensor-ct on independent testing datasets with various …


A Phase 1 Study Evaluating Rovalpituzumab Tesirine In Frontline Treatment Of Patients With Extensive-Stage Sclc, Christine L. Hann, Timothy F. Burns, Afshin Dowlati, Daniel Morgensztern, Patrick J. Ward, Martina M. Koch, Chris Chen, Carrianne Ludwig, Maulik Patel, Halla Nimeiri, Philip Komarnitsky, D. Ross Camidge Sep 2021

A Phase 1 Study Evaluating Rovalpituzumab Tesirine In Frontline Treatment Of Patients With Extensive-Stage Sclc, Christine L. Hann, Timothy F. Burns, Afshin Dowlati, Daniel Morgensztern, Patrick J. Ward, Martina M. Koch, Chris Chen, Carrianne Ludwig, Maulik Patel, Halla Nimeiri, Philip Komarnitsky, D. Ross Camidge

2020-Current year OA Pubs

INTRODUCTION: Rovalpituzumab tesirine (Rova-T) is an antibody-drug conjugate targeting DLL3, a Notch pathway ligand highly expressed on SCLC cells. Rova-T was evaluated alone or in combination with platinum-based chemotherapy (cisplatin or carboplatin combined with etoposide [CE]) in frontline treatment of extensive-stage SCLC.

METHODS: One cycle of CE pre-enrollment was permitted (later mandated). The following four cohorts were enrolled: Rova-T monotherapy (0.3 mg/kg, every 6 [q6] wk × 2; cohort 1; n = 4); Rova-T induction (0.3 mg/kg, q6 wk × 2) followed by CE every 21 days (q21) × 4 (cohort 2; n = 5); Rova-T (0.1 or 0.2 mg/kg, …


A Phase 1-2 Study Of Rovalpituzumab Tesirine In Combination With Nivolumab Plus Or Minus Ipilimumab In Patients With Previously Treated Extensive-Stage Sclc, Jyoti Malhotra, Daniel Morgensztern, Et Al. Sep 2021

A Phase 1-2 Study Of Rovalpituzumab Tesirine In Combination With Nivolumab Plus Or Minus Ipilimumab In Patients With Previously Treated Extensive-Stage Sclc, Jyoti Malhotra, Daniel Morgensztern, Et Al.

2020-Current year OA Pubs

INTRODUCTION: This open-label, phase 1-2 study evaluated the safety and efficacy of rovalpituzumab tesirine (Rova-T), an antibody-drug conjugate targeting DLL3, plus immune checkpoint inhibitors nivolumab plus or minus ipilimumab in previously treated extensive-stage SCLC (ES SCLC).

METHODS: Patients with histologically or cytologically confirmed, previously treated (two or more lines of therapy) ES SCLC were enrolled into two cohorts. Cohort 1 received 0.3 mg/kg Rova-T (once every 6 wk for two cycles) plus 360 mg nivolumab (two 3-wk cycles beginning on week 4). Cohort 2 received the same dosage of Rova-T as cohort 1 plus 1 mg/kg nivolumab (four 3-wk cycles) …


American Society Of Transplantation And Cellular Therapy, Center Of International Blood And Marrow Transplant Research, And European Society For Blood And Marrow Transplantation Clinical Practice Recommendations For Transplantation And Cellular Therapies In Mantle Cell Lymphoma, Pashna N Munshi, Brad Kahl, Amanda F Cashen, Et Al. Sep 2021

American Society Of Transplantation And Cellular Therapy, Center Of International Blood And Marrow Transplant Research, And European Society For Blood And Marrow Transplantation Clinical Practice Recommendations For Transplantation And Cellular Therapies In Mantle Cell Lymphoma, Pashna N Munshi, Brad Kahl, Amanda F Cashen, Et Al.

2020-Current year OA Pubs

Autologous (auto-) and allogeneic (allo-) hematopoietic cell transplantation (HCT) are accepted treatment modalities in contemporary treatment algorithms for mantle cell lymphoma (MCL). Chimeric antigen receptor (CAR) T cell therapy recently received approval for MCL; however, its exact place and sequence in relation to HCT remain unclear. The American Society of Transplantation and Cellular Therapy, Center of International Blood and Marrow Transplant Research, and the European Society for Blood and Marrow Transplantation jointly convened an expert panel to formulate consensus recommendations for role, timing, and sequencing of auto-HCT, allo-HCT, and CAR T cell therapy for patients with newly diagnosed and relapsed/refractory …


Differential Effects Of The Novel Neurosteroid Hypnotic (3Β,5Β,17Β)-3-Hydroxyandrostane-17-Carbonitrile On Electroencephalogram Activity In Male And Female Rats, Srdjan M Joksimovic, Dayalan Sampath, Kathiresan Krishnan, Douglas F Covey, Vesna Jevtovic-Todorovic, Yogendra H Raol, Slobodan M Todorovic Sep 2021

Differential Effects Of The Novel Neurosteroid Hypnotic (3Β,5Β,17Β)-3-Hydroxyandrostane-17-Carbonitrile On Electroencephalogram Activity In Male And Female Rats, Srdjan M Joksimovic, Dayalan Sampath, Kathiresan Krishnan, Douglas F Covey, Vesna Jevtovic-Todorovic, Yogendra H Raol, Slobodan M Todorovic

2020-Current year OA Pubs

BACKGROUND: We recently showed that a neurosteroid analogue, (3β,5β,17β)-3-hydroxyandrostane-17-carbonitrile (3β-OH), induced hypnosis in rats. The aim of the present study was to evaluate the hypnotic and anaesthetic potential of 3β-OH further using electroencephalography.

METHODS: We used behavioural assessment and cortical electroencephalogram (EEG) spectral power analysis to examine hypnotic and anaesthetic effects of 3β-OH (30 and 60 mg kg

RESULTS: We found dose-dependent sex differences in 3β-OH-induced hypnosis and EEG changes. Both male and female rats responded similarly to i.p. 3β-OH 30 mg kg

CONCLUSIONS: Based on its behavioural effects and EEG signature, 3β-OH is a potent hypnotic in rats, with …


Implementation Of A Non-Emergent Medical Transportation Programme At An Integrated Health System, Patrick G Lyons, Brett A Ramsey, Michael Welker, Megan Guinn, Janice K Ernest, Ali Kosydor, Thomas M Maddox Sep 2021

Implementation Of A Non-Emergent Medical Transportation Programme At An Integrated Health System, Patrick G Lyons, Brett A Ramsey, Michael Welker, Megan Guinn, Janice K Ernest, Ali Kosydor, Thomas M Maddox

2020-Current year OA Pubs

OBJECTIVES: To implement a unified non-emergency medical transportation (NEMT) service across a large integrated healthcare delivery network.

METHODS: We assessed needs among key organisational stakeholders, then reviewed proposals. We selected a single NEMT vendor best aligned with organisational priorities and implemented this solution system-wide.

RESULTS: Our vendor's hybrid approach combined rideshares with contracted vehicles able to serve patients with equipment and other needs. After 6195 rides in the first year, we observed shorter wait times and lower costs compared with our prior state.

DISCUSSION: Essential lessons included (1) understanding user and patient needs, (2) obtaining complete, accurate and comprehensive baseline …


Alzheimer's Disease Alters Oligodendrocytic Glycolytic And Ketolytic Gene Expression, Erin R Saito, Justin B Miller, Oscar Harari, Carlos Cruchaga, Kathie A Mihindukulasuriya, John S K Kauwe, Benjamin T Bikman Sep 2021

Alzheimer's Disease Alters Oligodendrocytic Glycolytic And Ketolytic Gene Expression, Erin R Saito, Justin B Miller, Oscar Harari, Carlos Cruchaga, Kathie A Mihindukulasuriya, John S K Kauwe, Benjamin T Bikman

2020-Current year OA Pubs

INTRODUCTION: Sporadic Alzheimer's disease (AD) is strongly correlated with impaired brain glucose metabolism, which may affect AD onset and progression. Ketolysis has been suggested as an alternative pathway to fuel the brain.

METHODS: RNA-seq profiles of post mortem AD brains were used to determine whether dysfunctional AD brain metabolism can be determined by impairments in glycolytic and ketolytic gene expression. Data were obtained from the Knight Alzheimer's Disease Research Center (62 cases; 13 controls), Mount Sinai Brain Bank (110 cases; 44 controls), and the Mayo Clinic Brain Bank (80 cases; 76 controls), and were normalized to cell type: astrocytes, microglia, …


The Incidence Of Adding-On Or Distal Junctional Kyphosis In Adolescent Idiopathic Scoliosis Treated By Anterior Spinal Fusion To L3 Was Significantly Higher Than By Posterior Spinal Fusion To L3, Seung-Jae Hyun, Lawrence G Lenke, Yongjung Kim, Keith H Bridwell, Meghan Cerpa, Kathy M Blanke Sep 2021

The Incidence Of Adding-On Or Distal Junctional Kyphosis In Adolescent Idiopathic Scoliosis Treated By Anterior Spinal Fusion To L3 Was Significantly Higher Than By Posterior Spinal Fusion To L3, Seung-Jae Hyun, Lawrence G Lenke, Yongjung Kim, Keith H Bridwell, Meghan Cerpa, Kathy M Blanke

2020-Current year OA Pubs

OBJECTIVE: To compare and identify risk factors for distal adding-on (AO) or distal junctional kyphosis (DJK) in adolescent idiopathic scoliosis (AIS) treated by anterior- (ASF) and posterior spinal fusion (PSF) to L3.

METHODS: AIS patients undergoing ASF versus PSF to L3 from 2000-2010 were analyzed. Distal AO and DJK were deemed poor radiographic results. New stable (SV) and neutral vertebra (NV) scores were defined for this study. The total stability (TS) score was the sum of the SV and NV scores.

RESULTS: Twenty of 42 (ASF group: 47.6%) and 8 of 72 patients (PSF group: 11.1%) showed poor radiographic outcome. …


Consensus Recommendations On The Treatment Of Opioid Use Disorder In The Emergency Department, Kathryn Hawk, Jason Hoppe, Eric Ketcham, Alexis Lapietra, Aimee Moulin, Lewis Nelson, Evan Schwarz, Sam Shahid, Donald Stader, Michael P Wilson, Gail D'Onofrio Sep 2021

Consensus Recommendations On The Treatment Of Opioid Use Disorder In The Emergency Department, Kathryn Hawk, Jason Hoppe, Eric Ketcham, Alexis Lapietra, Aimee Moulin, Lewis Nelson, Evan Schwarz, Sam Shahid, Donald Stader, Michael P Wilson, Gail D'Onofrio

2020-Current year OA Pubs

The treatment of opioid use disorder with buprenorphine and methadone reduces morbidity and mortality in patients with opioid use disorder. The initiation of buprenorphine in the emergency department (ED) has been associated with increased rates of outpatient treatment linkage and decreased drug use when compared to patients randomized to receive standard ED referral. As such, the ED has been increasingly recognized as a venue for the identification and initiation of treatment for opioid use disorder, but no formal American College of Emergency Physicians (ACEP) recommendations on the topic have previously been published. The ACEP convened a group of emergency physicians …


Ascaris Suum Informs Extrasynaptic Volume Transmission In Nematodes, Louise E Atkinson, Yang Liu, Fiona Mckay, Elke Vandewyer, Charles Viau, Allister Irvine, Bruce A Rosa, Zihui Li, Qingxiao Liang, Nikki J Marks, Aaron G Maule, Makedonka Mitreva, Isabel Beets, Lingjun Li, Angela Mousley Sep 2021

Ascaris Suum Informs Extrasynaptic Volume Transmission In Nematodes, Louise E Atkinson, Yang Liu, Fiona Mckay, Elke Vandewyer, Charles Viau, Allister Irvine, Bruce A Rosa, Zihui Li, Qingxiao Liang, Nikki J Marks, Aaron G Maule, Makedonka Mitreva, Isabel Beets, Lingjun Li, Angela Mousley

2020-Current year OA Pubs

Neural circuit synaptic connectivities (the connectome) provide the anatomical foundation for our understanding of nematode nervous system function. However, other nonsynaptic routes of communication are known in invertebrates including extrasynaptic volume transmission (EVT), which enables short- and/or long-range communication in the absence of synaptic connections. Although EVT has been highlighted as a facet of


Cognitive Correlates Of Instrumental Activities Of Daily Living Performance In Parkinson Disease Without Dementia, Erin R Foster, Tasha Doty Sep 2021

Cognitive Correlates Of Instrumental Activities Of Daily Living Performance In Parkinson Disease Without Dementia, Erin R Foster, Tasha Doty

2020-Current year OA Pubs

OBJECTIVE: To investigate cognitive correlates of instrumental activities of daily living (IADL) performance among people with Parkinson disease (PD) without dementia.

DESIGN: Cross-sectional.

SETTING: Academic medical center.

PARTICIPANTS: Volunteer sample (N=161) comprising participants with PD without dementia (n=102) and healthy comparison (HC) participants (n=59).

INTERVENTIONS: Not applicable.

MAIN OUTCOME MEASURES: Performance-based assessment of cognitively-demanding IADL (meal preparation, bill paying, shopping, medication management, small home repair), neuropsychological tests (attentional control/flexibility, planning, working memory, memory, crystallized intelligence), and measures of motor function and other characteristics (eg, depressive symptoms).

RESULTS: There were no group differences in neuropsychological test performance (

CONCLUSIONS: The PD …


Bioactive In Situ Crosslinkable Polymer-Peptide Hydrogel For Cell Delivery To The Intervertebral Disc In A Rat Model, Marcos N Barcellona, Julie E Speer, Liufang Jing, Deepanjali S Patil, Munish C Gupta, Jacob M Buchowski, Lori A Setton Sep 2021

Bioactive In Situ Crosslinkable Polymer-Peptide Hydrogel For Cell Delivery To The Intervertebral Disc In A Rat Model, Marcos N Barcellona, Julie E Speer, Liufang Jing, Deepanjali S Patil, Munish C Gupta, Jacob M Buchowski, Lori A Setton

2020-Current year OA Pubs

Degeneration of the intervertebral disc (IVD) is associated with significant biochemical and morphological changes that include a loss of disc height, decreased water content and decreased cellularity. Cell delivery has been widely explored as a strategy to supplement the nucleus pulposus (NP) region of the degenerated IVD in both pre-clinical and clinical trials, using progenitor or primary cell sources. We previously demonstrated an ability for a polymer-peptide hydrogel, serving as a culture substrate, to promote adult NP cells to undergo a shift from a degenerative fibroblast-like state to a juvenile-like NP phenotype. In the current study, we evaluate the ability …


Initial Antimicrobial Management Of Sepsis, Michael S Niederman, Rebecca M Baron, Lila Bouadma, Thierry Calandra, Nick Daneman, Jan Dewaele, Marin H Kollef, Jeffrey Lipman, Girish B Nair Aug 2021

Initial Antimicrobial Management Of Sepsis, Michael S Niederman, Rebecca M Baron, Lila Bouadma, Thierry Calandra, Nick Daneman, Jan Dewaele, Marin H Kollef, Jeffrey Lipman, Girish B Nair

2020-Current year OA Pubs

Sepsis is a common consequence of infection, associated with a mortality rate > 25%. Although community-acquired sepsis is more common, hospital-acquired infection is more lethal. The most common site of infection is the lung, followed by abdominal infection, catheter-associated blood steam infection and urinary tract infection. Gram-negative sepsis is more common than gram-positive infection, but sepsis can also be due to fungal and viral pathogens. To reduce mortality, it is necessary to give immediate, empiric, broad-spectrum therapy to those with severe sepsis and/or shock, but this approach can drive antimicrobial overuse and resistance and should be accompanied by a commitment to …


Improved Integration Of Single-Cell Transcriptome And Surface Protein Expression By Linq-View, Lei Li, Christopher Nelson, Daved H Fremont, Et Al. Aug 2021

Improved Integration Of Single-Cell Transcriptome And Surface Protein Expression By Linq-View, Lei Li, Christopher Nelson, Daved H Fremont, Et Al.

2020-Current year OA Pubs

Multimodal advances in single-cell sequencing have enabled the simultaneous quantification of cell surface protein expression alongside unbiased transcriptional profiling. Here, we present LinQ-View, a toolkit designed for multimodal single-cell data visualization and analysis. LinQ-View integrates transcriptional and cell surface protein expression profiling data to reveal more accurate cell heterogeneity and proposes a quantitative metric for cluster purity assessment. Through comparison with existing multimodal methods on multiple public CITE-seq datasets, we demonstrate that LinQ-View efficiently generates accurate cell clusters, especially in CITE-seq data with routine numbers of surface protein features, by preventing variations in a single surface protein feature from affecting …


The Impact Of A Community Based Rehabilitation Program In Afghanistan: A Longitudinal Analysis Using Propensity Score Matching And Difference In Difference Analysis, Jean-Francois Trani, Juanita Vasquez-Escallon, Parul Bakhshi Aug 2021

The Impact Of A Community Based Rehabilitation Program In Afghanistan: A Longitudinal Analysis Using Propensity Score Matching And Difference In Difference Analysis, Jean-Francois Trani, Juanita Vasquez-Escallon, Parul Bakhshi

2020-Current year OA Pubs

BACKGROUND: The 2006 United Nations Convention on the Rights of Persons with Disabilities states that the achievement of equal rights, empowerment and social inclusion of people with disabilities requires comprehensive rehabilitation services encompassing all components of the World Health Organization Community based rehabilitation (CBR) matrix: health, education, livelihood, social and empowerment. CBR programs specifically aim to deliver such comprehensive interventions. In the present study, we investigate the impact of a CBR program in Afghanistan on all these components.

METHODS: We enrolled 1861 newly recruited CBR participants with disabilities in the study, from 169 villages between July 2012 and December 2013 …


Favorable Outcomes With Reduced Steroid Use In Juvenile Dermatomyositis, Amir B Orandi, Lampros Fotis, Jamie Lai, Hallie Morris, Andrew J White, Anthony R French, Kevin W Baszis Aug 2021

Favorable Outcomes With Reduced Steroid Use In Juvenile Dermatomyositis, Amir B Orandi, Lampros Fotis, Jamie Lai, Hallie Morris, Andrew J White, Anthony R French, Kevin W Baszis

2020-Current year OA Pubs

BACKGROUND: High-intensity glucocorticoid regimens are commonly used to induce and maintain remission in Juvenile Dermatomyositis but are associated with several adverse side-effects. Evidence-based treatment guidelines from North American and European pediatric rheumatology research societies both advocate induction with intravenous pulse steroids followed by high dose oral steroids (2 mg/kg/day), which are then tapered. This study reports the time to disease control with reduced glucocorticoid dosing.

METHODS: We retrospectively reviewed the records at a single tertiary-care children's hospital of patients diagnosed with Juvenile Dermatomyositis between 2000 and 2014 who had a minimum of 2 years of follow-up. The primary outcome measure …


A Systematic Review And Network Meta-Analyses To Assess The Effectiveness Of Human Immunodeficiency Virus (Hiv) Self-Testing Distribution Strategies, Ingrid Eshun-Wilson, Muhammad S Jamil, T Charles Witzel, David V Glidded, Cheryl Johnson, Noelle Le Trouneau, Nathan Ford, Kathleen Mcgee, Chris Kemp, Stefan Baral, Sheree Schwartz, Elvin H Geng Aug 2021

A Systematic Review And Network Meta-Analyses To Assess The Effectiveness Of Human Immunodeficiency Virus (Hiv) Self-Testing Distribution Strategies, Ingrid Eshun-Wilson, Muhammad S Jamil, T Charles Witzel, David V Glidded, Cheryl Johnson, Noelle Le Trouneau, Nathan Ford, Kathleen Mcgee, Chris Kemp, Stefan Baral, Sheree Schwartz, Elvin H Geng

2020-Current year OA Pubs

BACKGROUND: We conducted a systematic review and network meta-analysis to identify which human immunodeficiency virus (HIV) self-testing (HIVST) distribution strategies are most effective.

METHODS: We abstracted data from randomized controlled trials and observational studies published between 4 June 2006 and 4 June 2019.

RESULTS: We included 33 studies, yielding 6 HIVST distribution strategies. All distribution strategies increased testing uptake compared to standard testing: in sub-Saharan Africa, partner HIVST distribution ranked highest (78% probability); in North America, Asia, and the Pacific regions, web-based distribution ranked highest (93% probability), and facility based distribution ranked second in all settings. Across HIVST distribution strategies …