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Assessing An Online Patient Decision Aid About Upper Extremity Reconstructive Surgery For Cervical Spinal Cord Injury: Pilot Testing Knowledge, Decisional Conflict, And Acceptability, William Moritz, Amanda M Westman, Mary C Politi, Dod Working Group, Ida K Fox Jan 2023

Assessing An Online Patient Decision Aid About Upper Extremity Reconstructive Surgery For Cervical Spinal Cord Injury: Pilot Testing Knowledge, Decisional Conflict, And Acceptability, William Moritz, Amanda M Westman, Mary C Politi, Dod Working Group, Ida K Fox

2020-Current year OA Pubs

UNLABELLED:

HIGHLIGHTS: People with cervical spinal cord injury prioritize gaining upper extremity function after injury, but few individuals receive information about treatment options.A newly created patient decision aid (PtDA) provides information about recovery after spinal cord injury and the role of traditional tendon and newer nerve transfer surgery to improve upper extremity upper extremity function.The PtDA improved knowledge and decreased decisional conflict in this pilot study.Future work should focus on studying dissemination and implementation of the ptDA into clinical practice.


Unicorn, Hare, Or Tortoise? Using Machine Learning To Predict Working Memory Training Performance, Yi Feng, Anja Pahor, Aaron R Seitz, Dennis L Barbour, Susanne M Jaeggi Jan 2023

Unicorn, Hare, Or Tortoise? Using Machine Learning To Predict Working Memory Training Performance, Yi Feng, Anja Pahor, Aaron R Seitz, Dennis L Barbour, Susanne M Jaeggi

2020-Current year OA Pubs

People differ considerably in the extent to which they benefit from working memory (WM) training. Although there is increasing research focusing on individual differences associated with WM training outcomes, we still lack an understanding of which specific individual differences, and in what combination, contribute to inter-individual variations in training trajectories. In the current study, 568 undergraduates completed one of several N-back intervention variants over the course of two weeks. Participants' training trajectories were clustered into three distinct training patterns (high performers, intermediate performers, and low performers). We applied machine-learning algorithms to train a binary tree model to predict individuals' training …


Preliminary Validation Of A Structural Magnetic Resonance Imaging Metric For Tracking Dementia-Related Neurodegeneration And Future Decline, Gavin T Kress, Emily S Popa, Paul M Thompson, Susan Y Bookheimer, Sophia I Thomopoulos, Christopher R K Ching, Hong Zheng, Daniel A Hirsh, David A Merrill, Stella E Panos, Cyrus A Raji, Prabha Siddarth, Jennifer E Bramen Jan 2023

Preliminary Validation Of A Structural Magnetic Resonance Imaging Metric For Tracking Dementia-Related Neurodegeneration And Future Decline, Gavin T Kress, Emily S Popa, Paul M Thompson, Susan Y Bookheimer, Sophia I Thomopoulos, Christopher R K Ching, Hong Zheng, Daniel A Hirsh, David A Merrill, Stella E Panos, Cyrus A Raji, Prabha Siddarth, Jennifer E Bramen

2020-Current year OA Pubs

Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by cognitive decline and atrophy in the medial temporal lobe (MTL) and subsequent brain regions. Structural magnetic resonance imaging (sMRI) has been widely used in research and clinical care for diagnosis and monitoring AD progression. However, atrophy patterns are complex and vary by patient. To address this issue, researchers have made efforts to develop more concise metrics that can summarize AD-specific atrophy. Many of these methods can be difficult to interpret clinically, hampering adoption. In this study, we introduce a novel index which we call an "AD-NeuroScore," that uses a modified …


Direct Proteomic Detection And Prioritization Of 19 Onchocerciasis Biomarker Candidates In Humans, Bruce A Rosa, Kurt Curtis, Petra Erdmann Gilmore, John Martin, Qiang Zhang, Robert Sprung, Gary J Weil, R Reid Townsend, Peter U Fischer, Makedonka Mitreva Jan 2023

Direct Proteomic Detection And Prioritization Of 19 Onchocerciasis Biomarker Candidates In Humans, Bruce A Rosa, Kurt Curtis, Petra Erdmann Gilmore, John Martin, Qiang Zhang, Robert Sprung, Gary J Weil, R Reid Townsend, Peter U Fischer, Makedonka Mitreva

2020-Current year OA Pubs

Onchocerca volvulus, the causative agent of onchocerciasis, infects over 20 million people and can cause severe dermatitis and ocular conditions including blindness. Current treatments employed in mass drug administration programs do not kill adult female worms, and common diagnostic tests cannot reliably assess viability of adult worms. There is an urgent need for better diagnostic tests to facilitate monitoring the efficacy of new treatments and disease elimination efforts. Here, eight plasma samples collected from individuals infected with O. volvulus and seven from uninfected individuals were analyzed by MS/MS spectrometry to directly identify O. volvulus proteins present in infected but absent …


Changes In Patient-Reported Pain Interference After Surgical Treatment Of Painful Lower Extremity Neuromas, Adam Liebendorfer, Esther Ochoa, Christopher J Dy Jan 2023

Changes In Patient-Reported Pain Interference After Surgical Treatment Of Painful Lower Extremity Neuromas, Adam Liebendorfer, Esther Ochoa, Christopher J Dy

2020-Current year OA Pubs

PURPOSE: Painful neuromas commonly cause neuropathic pain, in up to 1 in 20 cases of traumatic or iatrogenic nerve injury. Despite the multiple surgical treatment types that reduce pain, no type has been universally accepted.

METHODS: We performed a retrospective cohort study by administering follow-up surveys to all surgical patients treated in our department for lower-extremity neuroma from September 1, 2015, to October 22, 2021, that could be contacted, excluding those with Morton neuroma. In addition to the Patient-Reported Outcomes Measurement Information System (PROMIS) Pain Interference (PI) questionnaire, survey questions covered the time to pain reduction, use of physical or …


A Novel Dual Nlrp1 And Nlrp3 Inflammasome Inhibitor For The Treatment Of Inflammatory Diseases, Callum Ah Docherty, Anuruddika J Fernando, Sarah Rosli, Maggie Lam, Roland E Dolle, Manuel A Navia, Ronald Farquhar, Danny La France, Michelle D Tate, Christopher K Murphy, Adriano G Rossi, Ashley Mansell Jan 2023

A Novel Dual Nlrp1 And Nlrp3 Inflammasome Inhibitor For The Treatment Of Inflammatory Diseases, Callum Ah Docherty, Anuruddika J Fernando, Sarah Rosli, Maggie Lam, Roland E Dolle, Manuel A Navia, Ronald Farquhar, Danny La France, Michelle D Tate, Christopher K Murphy, Adriano G Rossi, Ashley Mansell

2020-Current year OA Pubs

OBJECTIVES: Inflammasomes induce maturation of the inflammatory cytokines IL-1β and IL-18, whose activity is associated with the pathophysiology of a wide range of infectious and inflammatory diseases. As validated therapeutic targets for the treatment of acute and chronic inflammatory diseases, there has been intense interest in developing small-molecule inhibitors to target inflammasome activity and reduce disease-associated inflammatory burden.

METHODS: We examined the therapeutic potential of a novel small-molecule inhibitor, and associated derivatives, termed ADS032 to target and reduce inflammasome-mediated inflammation

RESULTS: We describe ADS032 as the first dual NLRP1 and NLRP3 inhibitor. ADS032 is a rapid, reversible and stable inflammasome …


The Perspectives Of General Nephrologists Toward Transitions Of Care And Management Of Failing Kidney Transplants, Tarek Alhamad, Haris Murad, Mengmeng Ji, Omar Alomar, Et Al. Jan 2023

The Perspectives Of General Nephrologists Toward Transitions Of Care And Management Of Failing Kidney Transplants, Tarek Alhamad, Haris Murad, Mengmeng Ji, Omar Alomar, Et Al.

2020-Current year OA Pubs

The management of failing kidney allograft and transition of care to general nephrologists (GN) remain a complex process. The Kidney Pancreas Community of Practice (KPCOP) Failing Allograft Workgroup designed and distributed a survey to GN between May and September 2021. Participants were invited via mail and email invitations. There were 103 respondents with primarily adult nephrology practices, of whom 41% had an academic affiliation. More than 60% reported listing for a second kidney as the most important concern in caring for patients with a failing allograft, followed by immunosuppression management (46%) and risk of mortality (38%), while resistant anemia was …


Proceedings Of The Association For Pathology Informatics Bootcamp 2022, Amrom E Obstfeld, Victor Brodsky, Alexis B Carter, Peter Gershkovich, Shannon Haymond, Bruce Levy, John Sinard, Devereaux Sellers, Michelle Stoffel, Ronald Jackups Jan 2023

Proceedings Of The Association For Pathology Informatics Bootcamp 2022, Amrom E Obstfeld, Victor Brodsky, Alexis B Carter, Peter Gershkovich, Shannon Haymond, Bruce Levy, John Sinard, Devereaux Sellers, Michelle Stoffel, Ronald Jackups

2020-Current year OA Pubs

The Pathology Informatics Bootcamp, held annually at the Pathology Informatics Summit, provides pathology trainees with essential knowledge in the rapidly evolving field of Pathology Informatics. With a focus on data analytics, data science, and data management in 2022, the bootcamp addressed the growing importance of data analysis in pathology and laboratory medicine practice. The expansion of data-related subjects in Pathology Informatics Essentials for Residents (PIER) and the Clinical Informatics fellowship examinations highlights the increasing significance of these skills in pathology practice in particular and medicine in general. The curriculum included lectures on databases, programming, analytics, machine learning basics, and specialized …


Plug Inguinal Hernia Repair Mimicking Nodal Spread Of Prostate Cancer On Psma-Pet/Ct, Genevieve C. Muñoz, Tyler J. Fraum Jan 2023

Plug Inguinal Hernia Repair Mimicking Nodal Spread Of Prostate Cancer On Psma-Pet/Ct, Genevieve C. Muñoz, Tyler J. Fraum

2020-Current year OA Pubs

A variety of non-prostatic or non-malignant findings exhibiting prostate specific membrane antigen (PSMA) tracer uptake and resemble metastatic disease on positron emission tomography (PET) imaging. In this case, a 72-year-old man presenting for initial staging of prostate cancer was found to have PSMA tracer uptake along the left external iliac vessels corresponding to a structure resembling a lymph node on computed tomography (CT). This finding was initially concerning for nodal spread of the patient's primary neoplasm. However, chart review revealed a remote history of left inguinal hernia plug repair with location corresponding to the area of PSMA activity. This case …


The History And Organization Of The Workshop On Population And Speciation Genomics, Julia M I Barth, Scott A Handley, Daniel Kintzl, Guy Leonard, Milan Malinsky, Michael Matschiner, Britta S Meyer, Walter Salzburger, Jan Stefka, Emiliano Trucchi Jan 2023

The History And Organization Of The Workshop On Population And Speciation Genomics, Julia M I Barth, Scott A Handley, Daniel Kintzl, Guy Leonard, Milan Malinsky, Michael Matschiner, Britta S Meyer, Walter Salzburger, Jan Stefka, Emiliano Trucchi

2020-Current year OA Pubs

With the advent of high-throughput genome sequencing, bioinformatics training has become essential for research in evolutionary biology and related fields. However, individual research groups are often not in the position to teach students about the most up-to-date methodology in the field. To fill this gap, extended bioinformatics courses have been developed by various institutions and provide intense training over the course of two or more weeks. Here, we describe our experience with the organization of a course in one of the longest-running extended bioinformatics series of workshops, the Evomics Workshop on Population and Speciation Genomics that takes place biennially in …


Barriers To And Solutions For Representative Inclusion Across The Lifespan And In Life Course Research: The Need For Structural Competency Highlighted By The Covid-19 Pandemic, Madison N Lecroy, Ebony B Carter, Sarah S Farabi, Dominic N Reeds, Et Al. Jan 2023

Barriers To And Solutions For Representative Inclusion Across The Lifespan And In Life Course Research: The Need For Structural Competency Highlighted By The Covid-19 Pandemic, Madison N Lecroy, Ebony B Carter, Sarah S Farabi, Dominic N Reeds, Et Al.

2020-Current year OA Pubs

Exclusion of special populations (older adults; pregnant women, children, and adolescents; individuals of lower socioeconomic status and/or who live in rural communities; people from racial and ethnic minority groups; individuals from sexual or gender minority groups; and individuals with disabilities) in research is a pervasive problem, despite efforts and policy changes by the National Institutes of Health and other organizations. These populations are adversely impacted by social determinants of health (SDOH) that reduce access and ability to participate in biomedical research. In March 2020, the Northwestern University Clinical and Translational Sciences Institute hosted the "Lifespan and Life Course Research: integrating …


Anti-Fibrotic Therapy And Lung Transplant Outcomes In Patients With Idiopathic Pulmonary Fibrosis, Todd L. Astor, Hilary J. Goldberg, Laurie D. Snyder, Andrew Courtwright, Ramsey Hachem, Tahuanty Pena, Lorenzo Zaffiri, Gerard J. Criner, Marie M. Budev, Tany Thaniyavarn, Thomas B. Leonard, Shaun Bender, Aliaa Barakat, Janis L. Breeze, Peter Lacamera Jan 2023

Anti-Fibrotic Therapy And Lung Transplant Outcomes In Patients With Idiopathic Pulmonary Fibrosis, Todd L. Astor, Hilary J. Goldberg, Laurie D. Snyder, Andrew Courtwright, Ramsey Hachem, Tahuanty Pena, Lorenzo Zaffiri, Gerard J. Criner, Marie M. Budev, Tany Thaniyavarn, Thomas B. Leonard, Shaun Bender, Aliaa Barakat, Janis L. Breeze, Peter Lacamera

2020-Current year OA Pubs

BACKGROUND: It is unclear whether continuing anti-fibrotic therapy until the time of lung transplant increases the risk of complications in patients with idiopathic pulmonary fibrosis.

OBJECTIVES: To investigate whether the time between discontinuation of anti-fibrotic therapy and lung transplant in patients with idiopathic pulmonary fibrosis affects the risk of complications.

METHODS: We assessed intra-operative and post-transplant complications among patients with idiopathic pulmonary fibrosis who underwent lung transplant and had been treated with nintedanib or pirfenidone continuously for ⩾ 90 days at listing. Patients were grouped according to whether they had a shorter (⩽ 5 medication half-lives) or longer (> 5 …


Examining Decisional Needs And Contextual Factors Influencing Fertility Status Assessment Among Young Female Survivors Of Childhood Cancer: A Sequential Mixed Methods Study Protocol, Brooke Cherven, Nataliya V. Ivankova, Jessica B. Spencer, Anne M. Fitzpatrick, Karen C. Burns, Jenna Demedis, Holly R Hoefgen, Ann C. Mertens, James L. Klosky Jan 2023

Examining Decisional Needs And Contextual Factors Influencing Fertility Status Assessment Among Young Female Survivors Of Childhood Cancer: A Sequential Mixed Methods Study Protocol, Brooke Cherven, Nataliya V. Ivankova, Jessica B. Spencer, Anne M. Fitzpatrick, Karen C. Burns, Jenna Demedis, Holly R Hoefgen, Ann C. Mertens, James L. Klosky

2020-Current year OA Pubs

INTRODUCTION: Female cancer survivors who received gonadotoxic cancer treatment are at risk for profound diminished ovarian reserve and/or primary ovarian insufficiency with resulting infertility, which can be associated with distress and decreased quality of life.. Despite prioritizing future parenthood, many survivors are unsure of the impact of their treatment on their future fertility, and little is known about the perceived reproductive health needs and factors associated with receipt of a fertility status assessment (FSA). There is a lack of developmentally appropriate reproductive health decisional support interventions available for emerging adult cancer survivors. This study will explore the perceived reproductive health …


The Neurotoxin Dsp-4 Dysregulates The Locus Coeruleus-Norepinephrine System And Recapitulates Molecular And Behavioral Aspects Of Prodromal Neurodegenerative Disease, Alexa F. Iannitelli, Michael A. Kelberman, Daniel J. Lustberg, Anu Korukonda, Katharine E. Mccann, Bernard Mulvey, Arielle Segal, L Cameron Liles, Steven A. Sloan, Joseph D. Dougherty, David Weinshenker Jan 2023

The Neurotoxin Dsp-4 Dysregulates The Locus Coeruleus-Norepinephrine System And Recapitulates Molecular And Behavioral Aspects Of Prodromal Neurodegenerative Disease, Alexa F. Iannitelli, Michael A. Kelberman, Daniel J. Lustberg, Anu Korukonda, Katharine E. Mccann, Bernard Mulvey, Arielle Segal, L Cameron Liles, Steven A. Sloan, Joseph D. Dougherty, David Weinshenker

2020-Current year OA Pubs

The noradrenergic locus coeruleus (LC) is among the earliest sites of tau and α-synuclein pathology in Alzheimer's disease (AD) and Parkinson's disease (PD), respectively. The onset of these pathologies coincides with loss of noradrenergic fibers in LC target regions and the emergence of prodromal symptoms including sleep disturbances and anxiety. Paradoxically, these prodromal symptoms are indicative of a noradrenergic hyperactivity phenotype, rather than the predicted loss of norepinephrine (NE) transmission following LC damage, suggesting the engagement of complex compensatory mechanisms. Because current therapeutic efforts are targeting early disease, interest in the LC has grown, and it is critical to identify …


Cytosolic Epcam Cooperates With H-Ras To Regulate Epithelial To Mesenchymal Transition Through Zeb1, Fatma A. Omar, Taylor C. Brown, William E. Gillanders, Timothy P. Fleming, Michael A. Smith, Ross M. Bremner, Narendra V. Sankpal Jan 2023

Cytosolic Epcam Cooperates With H-Ras To Regulate Epithelial To Mesenchymal Transition Through Zeb1, Fatma A. Omar, Taylor C. Brown, William E. Gillanders, Timothy P. Fleming, Michael A. Smith, Ross M. Bremner, Narendra V. Sankpal

2020-Current year OA Pubs

Next generation sequencing of human cancer mutations has identified novel therapeutic targets. Activating Ras oncogene mutations play a central role in oncogenesis, and Ras-driven tumorigenesis upregulates an array of genes and signaling cascades that can transform normal cells into tumor cells. In this study, we investigated the role of altered localization of epithelial cell adhesion molecule (EpCAM) in Ras-expressing cells. Analysis of microarray data demonstrated that Ras expression induced EpCAM expression in normal breast epithelial cells. Fluorescent and confocal microscopy showed that H-Ras mediated transformation also promoted epithelial-to-mesenchymal transition (EMT) together with EpCAM. To consistently localize EpCAM in the cytosol, …


Rev-Erb Activation As A Novel Pharmacological Approach For Treating Inflammatory Pain, Sangeet Makhija, Joshua D Griffett, Giri Babu Veerakanellore, Thomas P Burris, Bahaa Elgendy, Kristine Griffett Jan 2023

Rev-Erb Activation As A Novel Pharmacological Approach For Treating Inflammatory Pain, Sangeet Makhija, Joshua D Griffett, Giri Babu Veerakanellore, Thomas P Burris, Bahaa Elgendy, Kristine Griffett

2020-Current year OA Pubs

Pain is a complex problem affecting millions of people worldwide. The current therapies to reduce pain are limited as many treatment options inadequately address the causes of pain, lead to tolerance of the drug, or have adverse effects including abuse potential. While there are many causes of pain, one underlying mechanism to the pathogenesis and maintenance of pain conditions is chronic inflammation driven by the NLRP3 inflammasome. Several inflammasome inhibitors are currently under investigation however have the potential to suppress the functioning of the innate immune system, which may cause unwanted affects in patients. Here, we show that the nuclear …


Iron Homeostasis And Post-Hemorrhagic Hydrocephalus: A Review, Shelei Pan, Andrew T Hale, Mackenzie E Lemieux, Dhvanii K Raval, Thomas P Garton, Brooke Sadler, Kelly B Mahaney, Jennifer M Strahle Jan 2023

Iron Homeostasis And Post-Hemorrhagic Hydrocephalus: A Review, Shelei Pan, Andrew T Hale, Mackenzie E Lemieux, Dhvanii K Raval, Thomas P Garton, Brooke Sadler, Kelly B Mahaney, Jennifer M Strahle

2020-Current year OA Pubs

Iron physiology is regulated by a complex interplay of extracellular transport systems, coordinated transcriptional responses, and iron efflux mechanisms. Dysregulation of iron metabolism can result in defects in myelination, neurotransmitter synthesis, and neuronal maturation. In neonates, germinal matrix-intraventricular hemorrhage (GMH-IVH) causes iron overload as a result of blood breakdown in the ventricles and brain parenchyma which can lead to post-hemorrhagic hydrocephalus (PHH). However, the precise mechanisms by which GMH-IVH results in PHH remain elusive. Understanding the molecular determinants of iron homeostasis in the developing brain may lead to improved therapies. This manuscript reviews the various roles iron has in brain …


Prevalence Of Bourbon And Heartland Viruses In Field Collected Ticks At An Environmental Field Station In St. Louis County, Missouri, Usa, Ishmael D. Aziati, Derek Mcfarland Jr., Avan Antia, Astha Joshi, Anahi Aviles-Gamboa, Preston Lee, Houda Harastani, David Wang, Solny A. Adalsteinsson, Adrianus C M Boon Jan 2023

Prevalence Of Bourbon And Heartland Viruses In Field Collected Ticks At An Environmental Field Station In St. Louis County, Missouri, Usa, Ishmael D. Aziati, Derek Mcfarland Jr., Avan Antia, Astha Joshi, Anahi Aviles-Gamboa, Preston Lee, Houda Harastani, David Wang, Solny A. Adalsteinsson, Adrianus C M Boon

2020-Current year OA Pubs

Heartland and Bourbon viruses are pathogenic tick-borne viruses putatively transmitted by Amblyomma americanum, an abundant tick species in Missouri. To assess the prevalence of these viruses in ticks, we collected 2778 ticks from eight sampling sites at Tyson Research Center, an environmental field station within St. Louis County and close to the City of St. Louis, from May - July in 2019 and 2021. Ticks were pooled according to life stage and sex, grouped by year and sampling site to create 355 pools and screened by RT-qPCR for Bourbon and Heartland viruses. Overall, 14 (3.9%) and 27 (7.6%) of the …


Circulatory Arrest For Traumatic Brachiocephalic Artery Pseudoaneurysm Repair, Conor F Hynes, Kunal D Kotkar Jan 2023

Circulatory Arrest For Traumatic Brachiocephalic Artery Pseudoaneurysm Repair, Conor F Hynes, Kunal D Kotkar

2020-Current year OA Pubs

Blunt traumatic injuries to the brachiocephalic artery require surgical management. The operative technique used depends on the location of the injury, the patient's hemodynamic stability, and the surgeon's experience. Perfusion strategy can facilitate vascular control of the aortic arch and branch vessels. This report presents an urgent repair of a proximal posterior blunt traumatic brachiocephalic artery injury under circulatory arrest, with an excellent outcome.


Predictors Of Nonadherence Among Patients With Infectious Complications Of Substance Use Who Are Discharged On Parenteral Antimicrobial Therapy, Shivakumar Narayanan, Patrick R Ching, Edward C Traver, Nivya George, Anthony Amoroso, Shyam Kottilil Jan 2023

Predictors Of Nonadherence Among Patients With Infectious Complications Of Substance Use Who Are Discharged On Parenteral Antimicrobial Therapy, Shivakumar Narayanan, Patrick R Ching, Edward C Traver, Nivya George, Anthony Amoroso, Shyam Kottilil

2020-Current year OA Pubs

BACKGROUND: The management of invasive infections related to substance use disorder (SUD) needing parenteral antimicrobial therapy is challenging and may have poor treatment outcomes including nonadherence and lack of completion of parenteral antimicrobial therapy.

METHODS: In this retrospective cohort of 201 patients with invasive infections related to SUD, we looked at frequency and determinants of unfavorable outcomes including nonadherence.

RESULTS: Seventy-nine percent of patients with SUD-related infection completed parenteral antibiotic therapy in skilled nursing facilities. A total of 21.5% of patient episodes had documentation of nonadherence. Nonadherence was higher in patients with active injection drug use (IDU) (28.5% versus 15% …


Design Of Effisayil™ 2: A Randomized, Double-Blind, Placebo-Controlled Study Of Spesolimab In Preventing Flares In Patients With Generalized Pustular Psoriasis, Akimichi Morita, Siew Eng Choon, Hervé Bachelez, Milan J Anadkat, Slaheddine Marrakchi, Min Zheng, Tsen-Fang Tsai, Hamida Turki, Harry Hua, Sushmita Rajeswari, Christian Thoma, A David Burden Jan 2023

Design Of Effisayil™ 2: A Randomized, Double-Blind, Placebo-Controlled Study Of Spesolimab In Preventing Flares In Patients With Generalized Pustular Psoriasis, Akimichi Morita, Siew Eng Choon, Hervé Bachelez, Milan J Anadkat, Slaheddine Marrakchi, Min Zheng, Tsen-Fang Tsai, Hamida Turki, Harry Hua, Sushmita Rajeswari, Christian Thoma, A David Burden

2020-Current year OA Pubs

INTRODUCTION: Generalized pustular psoriasis (GPP) is a rare autoinflammatory skin disease characterized by flares of widespread erythema with sterile pustules, and can be relapsing with recurrent flares, or persistent with intermittent flares. Spesolimab, a humanized anti-interleukin-36 (IL-36) receptor monoclonal antibody, targets the key IL-36 pathogenetic pathway in GPP. A previous study showed that spesolimab treatment led to rapid pustular and skin clearance in patients with GPP flares, which was sustained for up to 12 weeks. This study investigates the long-term effects of spesolimab on GPP flares, for which no specific treatments are currently available. The Effisayil™ 2 study will assess …


Healthcare-Associated Infections (Hais) During The Coronavirus Disease 2019 (Covid-19) Pandemic: A Time-Series Analysis, John M Sahrmann, Katelin B Nickel, Dustin Stwalley, Erik R Dubberke, Patrick G Lyons, Andrew P Michelson, Kathleen M Mcmullen, Sumanth Gandra, Margaret A Olsen, Jennie H Kwon, Jason P Burnham Jan 2023

Healthcare-Associated Infections (Hais) During The Coronavirus Disease 2019 (Covid-19) Pandemic: A Time-Series Analysis, John M Sahrmann, Katelin B Nickel, Dustin Stwalley, Erik R Dubberke, Patrick G Lyons, Andrew P Michelson, Kathleen M Mcmullen, Sumanth Gandra, Margaret A Olsen, Jennie H Kwon, Jason P Burnham

2020-Current year OA Pubs

OBJECTIVE: To use interrupted time-series analyses to investigate the impact of the coronavirus disease 2019 (COVID-19) pandemic on healthcare-associated infections (HAIs). We hypothesized that the pandemic would be associated with higher rates of HAIs after adjustment for confounders.

DESIGN: We conducted a cross-sectional study of HAIs in 3 hospitals in Missouri from January 1, 2017, through August 31, 2020, using interrupted time-series analysis with 2 counterfactual scenarios.

SETTING: The study was conducted at 1 large quaternary-care referral hospital and 2 community hospitals.

PARTICIPANTS: All adults ≥18 years of age hospitalized at a study hospital for ≥48 hours were included in …


A Single-Molecule Method For Measuring Fluorophore Labeling Yields For The Study Of Membrane Protein Oligomerization In Membranes, Melanie Ernst, Tugba N. Ozturk, Janice L. Robertson Jan 2023

A Single-Molecule Method For Measuring Fluorophore Labeling Yields For The Study Of Membrane Protein Oligomerization In Membranes, Melanie Ernst, Tugba N. Ozturk, Janice L. Robertson

2020-Current year OA Pubs

Membrane proteins are often observed as higher-order oligomers, and in some cases in multiple stoichiometric forms, raising the question of whether dynamic oligomerization can be linked to modulation of function. To better understand this potential regulatory mechanism, there is an ongoing effort to quantify equilibrium reactions of membrane protein oligomerization directly in membranes. Single-molecule photobleaching analysis is particularly useful for this as it provides a binary readout of fluorophores attached to protein subunits at dilute conditions. However, any quantification of stoichiometry also critically requires knowing the probability that a subunit is fluorescently labeled. Since labeling uncertainty is often unavoidable, we …


Autologous T Cell Therapy For Mage-A4+ Solid Cancers In Hla-A*02+ Patients: A Phase 1 Trial, David S Hong, Brian A Van Tine, Armin Ghobadi, Amanda Cashen, Et Al. Jan 2023

Autologous T Cell Therapy For Mage-A4+ Solid Cancers In Hla-A*02+ Patients: A Phase 1 Trial, David S Hong, Brian A Van Tine, Armin Ghobadi, Amanda Cashen, Et Al.

2020-Current year OA Pubs

Affinity-optimized T cell receptors can enhance the potency of adoptive T cell therapy. Afamitresgene autoleucel (afami-cel) is a human leukocyte antigen-restricted autologous T cell therapy targeting melanoma-associated antigen A4 (MAGE-A4), a cancer/testis antigen expressed at varying levels in multiple solid tumors. We conducted a multicenter, dose-escalation, phase 1 trial in patients with relapsed/refractory metastatic solid tumors expressing MAGE-A4, including synovial sarcoma (SS), ovarian cancer and head and neck cancer ( NCT03132922 ). The primary endpoint was safety, and the secondary efficacy endpoints included overall response rate (ORR) and duration of response. All patients (N = 38, nine tumor types) experienced …


Multi-Omic Association Study Identifies Dna Methylation-Mediated Genotype And Smoking Exposure Effects On Lung Function In Children Living In Urban Settings, Matthew Dapas, Michelle A. Gill, Et Al Jan 2023

Multi-Omic Association Study Identifies Dna Methylation-Mediated Genotype And Smoking Exposure Effects On Lung Function In Children Living In Urban Settings, Matthew Dapas, Michelle A. Gill, Et Al

2020-Current year OA Pubs

Impaired lung function in early life is associated with the subsequent development of chronic respiratory disease. Most genetic associations with lung function have been identified in adults of European descent and therefore may not represent those most relevant to pediatric populations and populations of different ancestries. In this study, we performed genome-wide association analyses of lung function in a multiethnic cohort of children (n = 1,035) living in low-income urban neighborhoods. We identified one novel locus at the TDRD9 gene in chromosome 14q32.33 associated with percent predicted forced expiratory volume in one second (FEV1) (p = 2.4x10-9; βz = -0.31, …


Sik3 And Wnk Converge On Fray To Regulate Glial K+ Buffering And Seizure Susceptibility, Lorenzo Lones, Aaron Diantonio Jan 2023

Sik3 And Wnk Converge On Fray To Regulate Glial K+ Buffering And Seizure Susceptibility, Lorenzo Lones, Aaron Diantonio

2020-Current year OA Pubs

Glial cells play a critical role in maintaining homeostatic ion concentration gradients. Salt-inducible kinase 3 (SIK3) regulates a gene expression program that controls K+ buffering in glia, and upregulation of this pathway suppresses seizure behavior in the eag, Shaker hyperexcitability mutant. Here we show that boosting the glial SIK3 K+ buffering pathway suppresses seizures in three additional molecularly diverse hyperexcitable mutants, highlighting the therapeutic potential of upregulating glial K+ buffering. We then explore additional mechanisms regulating glial K+ buffering. Fray, a transcriptional target of the SIK3 K+ buffering program, is a kinase that promotes K+ uptake by activating the Na+/K+/Cl- …


A Novel Biosignature Identifies Patients With Dcis With High Risk Of Local Recurrence After Breast Conserving Surgery And Radiation Therapy, Frank A Vicini, G Bruce Mann, Chirag Shah, Sheila Weinmann, Michael C Leo, Pat Whitworth, Rachel Rabinovitch, Mylin A Torres, Julie A Margenthaler, David Dabbs, Jess Savala, Steven C Shivers, Karuna Mittal, Fredrik Wärnberg, Troy Bremer Jan 2023

A Novel Biosignature Identifies Patients With Dcis With High Risk Of Local Recurrence After Breast Conserving Surgery And Radiation Therapy, Frank A Vicini, G Bruce Mann, Chirag Shah, Sheila Weinmann, Michael C Leo, Pat Whitworth, Rachel Rabinovitch, Mylin A Torres, Julie A Margenthaler, David Dabbs, Jess Savala, Steven C Shivers, Karuna Mittal, Fredrik Wärnberg, Troy Bremer

2020-Current year OA Pubs

PURPOSE: There is an unmet need to identify women diagnosed with ductal carcinoma in situ (DCIS) with a low risk of in-breast recurrence (IBR) after breast conserving surgery (BCS), which could omit radiation therapy (RT), and also to identify those with elevated IBR risk remaining after BCS plus RT. We evaluated a novel biosignature for a residual risk subtype (RRt) to help identify patients with elevated IBR risk after BCS plus RT.

METHODS AND MATERIALS: Women with DCIS treated with BCS with or without RT at centers in the US, Australia, and Sweden (n = 926) were evaluated. Patients were …


The Mutational Landscape In Chronic Myelomonocytic Leukemia And Its Impact On Allogeneic Hematopoietic Cell Transplantation Outcomes: A Center For Blood And Marrow Transplantation Research (Cibmtr) Analysis, Matthew Mei, Ravi Vij, Et Al. Jan 2023

The Mutational Landscape In Chronic Myelomonocytic Leukemia And Its Impact On Allogeneic Hematopoietic Cell Transplantation Outcomes: A Center For Blood And Marrow Transplantation Research (Cibmtr) Analysis, Matthew Mei, Ravi Vij, Et Al.

2020-Current year OA Pubs

Somatic mutations are recognized as an important prognostic factor in chronic myelomonocytic leukemia (CMML). However, limited data are available regarding their impact on outcomes after allogeneic hematopoietic cell transplantation (HCT). In this registry analysis conducted in collaboration with the Center for International Blood and Marrow Transplantation Registry database/sample repository, we identified 313 adult patients with CMML (median age: 64 years, range, 28- 77) who underwent allogeneic HCT during 2001-2017 and had an available biospecimen in the form of a peripheral blood sample obtained prior to the start of conditioning. In multivariate analysis, a CMML-specific prognostic scoring system (CPSS) score of …


Factors Associated With Persistent Postsurgical Pain After Total Knee Or Hip Joint Replacement: A Systematic Review And Meta-Analysis, Arunangshu Ghoshal, Shivam Bhanvadia, Som Singh, Lauren Yaeger, Simon Haroutounian Jan 2023

Factors Associated With Persistent Postsurgical Pain After Total Knee Or Hip Joint Replacement: A Systematic Review And Meta-Analysis, Arunangshu Ghoshal, Shivam Bhanvadia, Som Singh, Lauren Yaeger, Simon Haroutounian

2020-Current year OA Pubs

Studies have identified demographic, clinical, psychosocial, and perioperative variables associated with persistent pain after a variety of surgeries. This study aimed to perform a systematic review and meta-analysis of factors associated with persistent pain after total knee replacement (TKR) and total hip replacement (THR) surgeries. To meet the inclusion criteria, studies were required to assess variables before or at the time of surgery, include a persistent postsurgical pain (PPSP) outcome measure at least 2 months after a TKR or THR surgery, and include a statistical analysis of the effect of the risk factor(s) on the outcome measure. Outcomes from studies …


Imputation Of Missing Values For Cochlear Implant Candidate Audiometric Data And Potential Applications, Cole Pavelchek, Andrew P. Michelson, Amit Walia, Amanda Ortmann, Jacques Herzog, Craig A. Buchman, Matthew A. Shew Jan 2023

Imputation Of Missing Values For Cochlear Implant Candidate Audiometric Data And Potential Applications, Cole Pavelchek, Andrew P. Michelson, Amit Walia, Amanda Ortmann, Jacques Herzog, Craig A. Buchman, Matthew A. Shew

2020-Current year OA Pubs

OBJECTIVE: Assess the real-world performance of popular imputation algorithms on cochlear implant (CI) candidate audiometric data.

METHODS: 7,451 audiograms from patients undergoing CI candidacy evaluation were pooled from 32 institutions with complete case analysis yielding 1,304 audiograms. Imputation model performance was assessed with nested cross-validation on randomly generated sparse datasets with various amounts of missing data, distributions of sparsity, and dataset sizes. A threshold for safe imputation was defined as root mean square error (RMSE) <10dB. Models included univariate imputation, interpolation, multiple imputation by chained equations (MICE), k-nearest neighbors, gradient boosted trees, and neural networks.

RESULTS: Greater quantities of missing data were associated with worse performance. Sparsity in audiometric data is not uniformly distributed, as inter-octave frequencies are less commonly …