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Open Access Publications

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2020

Humans

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Clip And Massively Parallel Functional Analysis Of Celf6 Reveal A Role In Destabilizing Synaptic Gene Mrnas Through Interaction With 3' Utr Elements, Michael A Rieger, Dana M King, Haley Crosby, Yating Liu, Barak A Cohen, Joseph D Dougherty Dec 2020

Clip And Massively Parallel Functional Analysis Of Celf6 Reveal A Role In Destabilizing Synaptic Gene Mrnas Through Interaction With 3' Utr Elements, Michael A Rieger, Dana M King, Haley Crosby, Yating Liu, Barak A Cohen, Joseph D Dougherty

Open Access Publications

CELF6 is a CELF-RNA-binding protein, and thus part of a protein family with roles in human disease; however, its mRNA targets in the brain are largely unknown. Using cross-linking immunoprecipitation and sequencing (CLIP-seq), we define its CNS targets, which are enriched for 3' UTRs in synaptic protein-coding genes. Using a massively parallel reporter assay framework, we test the consequence of CELF6 expression on target sequences, with and without mutating putative binding motifs. Where CELF6 exerts an effect on sequences, it is largely to decrease RNA abundance, which is reversed by mutating UGU-rich motifs. This is also the case for CELF3-5, …


Comparison Of Upper Respiratory Viral Load Distributions In Asymptomatic And Symptomatic Children Diagnosed With Sars-Cov-2 Infection In Pediatric Hospital Testing Programs, Larry K Kociolek, Bijal A Parikh, Ariel Hernandez-Leyva, Et Al Dec 2020

Comparison Of Upper Respiratory Viral Load Distributions In Asymptomatic And Symptomatic Children Diagnosed With Sars-Cov-2 Infection In Pediatric Hospital Testing Programs, Larry K Kociolek, Bijal A Parikh, Ariel Hernandez-Leyva, Et Al

Open Access Publications

The distribution of upper respiratory viral loads (VL) in asymptomatic children infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is unknown. We assessed PCR cycle threshold (Ct) values and estimated VL in infected asymptomatic children diagnosed in nine pediatric hospital testing programs. Records for asymptomatic and symptomatic patients with positive clinical SARS-CoV-2 tests were reviewed. Ct values were (i) adjusted by centering each value around the institutional median Ct value from symptomatic children tested with that assay and (ii) converted to estimated VL (numbers of copies per milliliter) using internal or manufacturer data. Adjusted Ct values and estimated VL …


A Study Protocol For A Multicentre, Prospective, Before-And-After Trial Evaluating The Feasibility Of Implementing Targeted Sedation After Initiation Of Mechanical Ventilation In The Emergency Department (The Ed-Sed Pilot Trial), Brian M Fuller, Brian W Roberts, Nicholas M Mohr, Ryan D Pappal, Robert J Stephens, Yan Yan, Chris Carpenter, Marin H Kollef, Michael Simon Avidan Dec 2020

A Study Protocol For A Multicentre, Prospective, Before-And-After Trial Evaluating The Feasibility Of Implementing Targeted Sedation After Initiation Of Mechanical Ventilation In The Emergency Department (The Ed-Sed Pilot Trial), Brian M Fuller, Brian W Roberts, Nicholas M Mohr, Ryan D Pappal, Robert J Stephens, Yan Yan, Chris Carpenter, Marin H Kollef, Michael Simon Avidan

Open Access Publications

INTRODUCTION: Sedation is a cornerstone therapy in the management of patients receiving mechanical ventilation and is highly influential on outcome. Early sedation depth appears especially influential, as early deep sedation is associated with worse outcome when compared with light sedation. Our research group has shown that patients receiving mechanical ventilation in the emergency department (ED) are exposed to deep sedation commonly, and ED sedation depth is impactful on intensive care unit (ICU) care and clinical outcomes. While extensive investigation has occurred for patients in the ICU, comparatively little data exist from the ED. Given the influence that ED sedation seems …


Associations Between Atrial Cardiopathy And Cerebral Amyloid: The Aric-Pet Study, Michelle C Johansen, Thomas H Mosley, David S Knopman, Dean F Wong, Chiadi Ndumele, Amil M Shah, Scott D Solomon, Rebecca F Gottesman Dec 2020

Associations Between Atrial Cardiopathy And Cerebral Amyloid: The Aric-Pet Study, Michelle C Johansen, Thomas H Mosley, David S Knopman, Dean F Wong, Chiadi Ndumele, Amil M Shah, Scott D Solomon, Rebecca F Gottesman

Open Access Publications

Background Atrial fibrillation (AF) is a risk factor for cognitive decline, possibly from silent brain infarction. Left atrial changes in structure or function (atrial cardiopathy) can lead to AF but may impact cognition independently. It is unknown if AF or atrial cardiopathy also acts on Alzheimer disease-specific mechanisms, such as deposition of β-amyloid. Methods and Results A total of 316 dementia-free participants from the ARIC (Atherosclerosis Risk in Communities) study underwent florbetapir positron emission tomography, electrocardiography, and 2-dimensional echocardiography. Atrial cardiopathy was defined as ≥1: (1) left atrial volume index >34 mL/m


Coronary Computed Tomography Angiography Compared With Single Photon Emission Computed Tomography Myocardial Perfusion Imaging As A Guide To Optimal Medical Therapy In Patients Presenting With Stable Angina: The Rescue Trial, Arthur E Stillman, Constantine Gatsonis, Joao A C Lima, Tao Liu, Bradley S Snyder, Jean Cormack, Vinay Malholtra, Mitchell D Schnall, James E Udelson, Udo Hoffmann, Pamela K Woodard, Rescue Investigators Dec 2020

Coronary Computed Tomography Angiography Compared With Single Photon Emission Computed Tomography Myocardial Perfusion Imaging As A Guide To Optimal Medical Therapy In Patients Presenting With Stable Angina: The Rescue Trial, Arthur E Stillman, Constantine Gatsonis, Joao A C Lima, Tao Liu, Bradley S Snyder, Jean Cormack, Vinay Malholtra, Mitchell D Schnall, James E Udelson, Udo Hoffmann, Pamela K Woodard, Rescue Investigators

Open Access Publications

Background The RESCUE (Randomized Evaluation of Patients with Stable Angina Comparing Utilization of Noninvasive Examinations) trial was a randomized, controlled, multicenter, comparative efficacy outcomes trial designed to assess whether initial testing with coronary computed tomographic angiography (CCTA) is noninferior to single photon emission computed tomography (SPECT) myocardial perfusion imaging in directing patients with stable angina to optimal medical therapy alone or optimal medical therapy with revascularization. Methods and Results The end point was first major adverse cardiovascular event (MACE) (cardiac death or myocardial infarction), or revascularization. Noninferiority margin for CCTA was set a priori as a hazard ratio (HR) of …


Comparative Evaluation Of Clinical Manifestations And Risk Of Death In Patients Admitted To Hospital With Covid-19 And Seasonal Influenza: Cohort Study, Yan Xie, Benjamin Bowe, Geetha Maddukuri, Ziyad Al-Aly Dec 2020

Comparative Evaluation Of Clinical Manifestations And Risk Of Death In Patients Admitted To Hospital With Covid-19 And Seasonal Influenza: Cohort Study, Yan Xie, Benjamin Bowe, Geetha Maddukuri, Ziyad Al-Aly

Open Access Publications

No abstract provided.


Human Pluripotent Stem Cell-Derived Kidney Organoids With Improved Collecting Duct Maturation And Injury Modeling, Kohei Uchimura, Haojia Wu, Yasuhiro Yoshimura, Benjamin D Humphreys Dec 2020

Human Pluripotent Stem Cell-Derived Kidney Organoids With Improved Collecting Duct Maturation And Injury Modeling, Kohei Uchimura, Haojia Wu, Yasuhiro Yoshimura, Benjamin D Humphreys

Open Access Publications

Maximizing the potential of human kidney organoids for drug testing and regenerative medicine and to model development and disease requires addressing cell immaturity, the lack of a mature collecting system, and off-target cell types. By independently generating two kidney progenitor cell populations-metanephric mesenchyme and ureteric bud (UB)-like cells-we could generate kidney organoids with a collecting system. We also identify the hormones aldosterone and arginine vasopressin (AVP) as critical to promote differentiation of collecting duct cell types including both principal cells (PCs) and intercalated cells (ICs). The resulting PCs express aquaporin-2 (AQP2) protein, which undergoes translocation to the apical membrane after …


Neonatal Mouse Gut Metabolites Influence Cryptosporidium Parvum Infection In Intestinal Epithelial Cells, Kelli L Vandussen, Lisa J Funkhouser-Jones, Marianna E Akey, Deborah A Schaefer, Kevin Ackman, Michael W Riggs, Thaddeus S Stappenbeck, L David Sibley Dec 2020

Neonatal Mouse Gut Metabolites Influence Cryptosporidium Parvum Infection In Intestinal Epithelial Cells, Kelli L Vandussen, Lisa J Funkhouser-Jones, Marianna E Akey, Deborah A Schaefer, Kevin Ackman, Michael W Riggs, Thaddeus S Stappenbeck, L David Sibley

Open Access Publications

The protozoan parasite


Yap And Taz Maintain Prox1 Expression In The Developing Lymphatic And Lymphovenous Valves In Response To Vegf-C Signaling, Boksik Cha, Yen-Chun Ho, Xin Geng, Md Riaj Mahamud, Lijuan Chen, Yeunhee Kim, Dongwon Choi, Tae Hoon Kim, Gwendalyn J Randolph, Xinwei Cao, Hong Chen, R Sathish Srinivasan Dec 2020

Yap And Taz Maintain Prox1 Expression In The Developing Lymphatic And Lymphovenous Valves In Response To Vegf-C Signaling, Boksik Cha, Yen-Chun Ho, Xin Geng, Md Riaj Mahamud, Lijuan Chen, Yeunhee Kim, Dongwon Choi, Tae Hoon Kim, Gwendalyn J Randolph, Xinwei Cao, Hong Chen, R Sathish Srinivasan

Open Access Publications

Lymphatic vasculature is an integral part of digestive, immune and circulatory systems. The homeobox transcription factor PROX1 is necessary for the development of lymphatic vessels, lymphatic valves (LVs) and lymphovenous valves (LVVs). We and others previously reported a feedback loop between PROX1 and vascular endothelial growth factor-C (VEGF-C) signaling. PROX1 promotes the expression of the VEGF-C receptor VEGFR3 in lymphatic endothelial cells (LECs). In turn, VEGF-C signaling maintains PROX1 expression in LECs. However, the mechanisms of PROX1/VEGF-C feedback loop remain poorly understood. Whether VEGF-C signaling is necessary for LV and LVV development is also unknown. Here, we report for the …


Protocol For The Prognosticating Delirium Recovery Outcomes Using Wakefulness And Sleep Electroencephalography (P-Drows-E) Study: A Prospective Observational Study Of Delirium In Elderly Cardiac Surgical Patients, S Kendall Smith, Thomas Nguyen, Alyssa K Labonte, Mohammadmehdi Kafashan, Orlandrea Hyche, Christian S Guay, Elizabeth Wilson, Courtney W Chan, Anhthi Luong, L Brian Hickman, Bradley A Fritz, Daniel Emmert, Thomas J Graetz, Spencer J Melby, Brendan P Lucey, Yo-El S Ju, Troy S Wildes, Michael S Avidan, Ben J A Palanca Dec 2020

Protocol For The Prognosticating Delirium Recovery Outcomes Using Wakefulness And Sleep Electroencephalography (P-Drows-E) Study: A Prospective Observational Study Of Delirium In Elderly Cardiac Surgical Patients, S Kendall Smith, Thomas Nguyen, Alyssa K Labonte, Mohammadmehdi Kafashan, Orlandrea Hyche, Christian S Guay, Elizabeth Wilson, Courtney W Chan, Anhthi Luong, L Brian Hickman, Bradley A Fritz, Daniel Emmert, Thomas J Graetz, Spencer J Melby, Brendan P Lucey, Yo-El S Ju, Troy S Wildes, Michael S Avidan, Ben J A Palanca

Open Access Publications

INTRODUCTION: Delirium is a potentially preventable disorder characterised by acute disturbances in attention and cognition with fluctuating severity. Postoperative delirium is associated with prolonged intensive care unit and hospital stay, cognitive decline and mortality. The development of biomarkers for tracking delirium could potentially aid in the early detection, mitigation and assessment of response to interventions. Because sleep disruption has been posited as a contributor to the development of this syndrome, expression of abnormal electroencephalography (EEG) patterns during sleep and wakefulness may be informative. Here we hypothesise that abnormal EEG patterns of sleep and wakefulness may serve as predictive and diagnostic …


Single-Arm Prospective Interventional Study Assessing Feasibility Of Using Gallium-68 Ventilation And Perfusion Pet/Ct To Avoid Functional Lung In Patients With Stage Iii Non-Small Cell Lung Cancer, Nicholas Bucknell, Amir Iravani, Et Al Dec 2020

Single-Arm Prospective Interventional Study Assessing Feasibility Of Using Gallium-68 Ventilation And Perfusion Pet/Ct To Avoid Functional Lung In Patients With Stage Iii Non-Small Cell Lung Cancer, Nicholas Bucknell, Amir Iravani, Et Al

Open Access Publications

BACKGROUND: In the curative-intent treatment of locally advanced lung cancer, significant morbidity and mortality can result from thoracic radiation therapy. Symptomatic radiation pneumonitis occurs in one in three patients and can lead to radiation-induced fibrosis. Local failure occurs in one in three patients due to the lungs being a dose-limiting organ, conventionally restricting tumour doses to around 60 Gy. Functional lung imaging using positron emission tomography (PET)/CT provides a geographic map of regional lung function and preclinical studies suggest this enables personalised lung radiotherapy. This map of lung function can be integrated into Volumetric Modulated Arc Therapy (VMAT) radiotherapy planning …


Impact Of A 2-Year Trial Of Nutritional Ketosis On Indices Of Cardiovascular Disease Risk In Patients With Type 2 Diabetes, Shaminie J Athinarayanan, Sarah J Hallberg, Amy L Mckenzie, Katharina Lechner, Sarah King, James P Mccarter, Jeff S Volek, Stephen D Phinney, Ronald M Krauss Dec 2020

Impact Of A 2-Year Trial Of Nutritional Ketosis On Indices Of Cardiovascular Disease Risk In Patients With Type 2 Diabetes, Shaminie J Athinarayanan, Sarah J Hallberg, Amy L Mckenzie, Katharina Lechner, Sarah King, James P Mccarter, Jeff S Volek, Stephen D Phinney, Ronald M Krauss

Open Access Publications

BACKGROUND: We have previously reported that in patients with type 2 diabetes (T2D) consumption of a very low carbohydrate diet capable of inducing nutritional ketosis over 2 years (continuous care intervention, CCI) resulted in improved body weight, glycemic control, and multiple risk factors for cardiovascular disease (CVD) with the exception of an increase in low density lipoprotein cholesterol (LDL-C). In the present study, we report the impact of this intervention on markers of risk for atherosclerotic cardiovascular disease (CVD), with a focus on lipoprotein subfraction particle concentrations as well as carotid-artery intima-media thickness (CIMT).

METHODS: Analyses were performed in patients …


Stem Cell And Niche Regulation In Human Short Bowel Syndrome, Vered A Gazit, Elzbieta A Swietlicki, Miranda U Liang, Adam Surti, Raechel Mcdaniel, Mackenzie Geisman, David M Alvarado, Matthew A Ciorba, Grant Bochicchio, Obeid Ilahi, John Kirby, William J Symons, Nicholas O Davidson, Marc S. Levin, Deborah C Rubin Dec 2020

Stem Cell And Niche Regulation In Human Short Bowel Syndrome, Vered A Gazit, Elzbieta A Swietlicki, Miranda U Liang, Adam Surti, Raechel Mcdaniel, Mackenzie Geisman, David M Alvarado, Matthew A Ciorba, Grant Bochicchio, Obeid Ilahi, John Kirby, William J Symons, Nicholas O Davidson, Marc S. Levin, Deborah C Rubin

Open Access Publications

Loss of functional small bowel surface area following surgical resection for disorders such as Crohn's disease, intestinal ischemic injury, radiation enteritis, and in children, necrotizing enterocolitis, atresia, and gastroschisis, may result in short bowel syndrome, with attendant high morbidity, mortality, and health care costs in the United States. Following resection, the remaining small bowel epithelium mounts an adaptive response, resulting in increased crypt cell proliferation, increased villus height, increased crypt depth, and enhanced nutrient and electrolyte absorption. Although these morphologic and functional changes are well described in animal models, the adaptive response in humans is less well understood. Clinically the …


Positive Information Facilitates Response Inhibition In Older Adults Only When Emotion Is Task-Relevant, Samantha E Williams, Eric J Lenze, Jill D Waring Dec 2020

Positive Information Facilitates Response Inhibition In Older Adults Only When Emotion Is Task-Relevant, Samantha E Williams, Eric J Lenze, Jill D Waring

Open Access Publications

Emotional information is integral to everyday life and impacts a variety of cognitive abilities including response inhibition, a critical skill for maintaining appropriate and flexible behaviour. However, reported effects of emotion on response inhibition are inconsistent in younger adults, and very limited in older adults. Effects of aging are especially relevant because emotion regulation improves with aging despite declining inhibitory control over neutral information. Across three studies, we assessed the impact of emotional facial expressions on response inhibition in younger and older adults while manipulating attention to task stimuli. Emotional faces (versus neutral faces) altered response inhibition only when task …


Full-Length Trkb Variant In Nsclc Is Associated With Brain Metastasis, Mariangela Lombardi, Michela D'Ascanio, Stefania Scarpino, Davide Scozzi, Marco Giordano, Leopoldo Costarelli, Enrico Rathina Raj, Rita Mancini, Giuseppe Cardillo, Vittorio Cardaci, Marta Innammorato, Andrea Vecchione, Alberto Ricci Nov 2020

Full-Length Trkb Variant In Nsclc Is Associated With Brain Metastasis, Mariangela Lombardi, Michela D'Ascanio, Stefania Scarpino, Davide Scozzi, Marco Giordano, Leopoldo Costarelli, Enrico Rathina Raj, Rita Mancini, Giuseppe Cardillo, Vittorio Cardaci, Marta Innammorato, Andrea Vecchione, Alberto Ricci

Open Access Publications

Despite remarkable therapeutic advances have been made in the last few decades, non-small cell lung cancer (NSCLC) is still one of the leading causes of death worldwide. Brain metastases are a common complication of a wide range of human malignancies and in particular NSCLC. Brain-derived neurotrophic factor (BDNF), binding its high-affinity tyrosine kinase B receptor, has been shown to promote cancer progression and metastasis. We hereby investigated the expression of the BDNF and its TrkB receptor in its full-length and truncated isoform T1, in samples from primary adenocarcinomas (ADKs) of the lung and in their metastasis to evaluate if their …


Hsv-1 And Zika Virus But Not Sars-Cov-2 Replicate In The Human Cornea And Are Restricted By Corneal Type Iii Interferon, Jonathan J Miner, Derek J Platt, Cyrus M Ghaznavi, Pallavi Chandra, Andrea Santeford, Amber M Menos, Zhenyu Dong, Erin R Wang, Wei Qian, Elysse S Karozichian, Jennifer A Philips, Rajendra S Apte Nov 2020

Hsv-1 And Zika Virus But Not Sars-Cov-2 Replicate In The Human Cornea And Are Restricted By Corneal Type Iii Interferon, Jonathan J Miner, Derek J Platt, Cyrus M Ghaznavi, Pallavi Chandra, Andrea Santeford, Amber M Menos, Zhenyu Dong, Erin R Wang, Wei Qian, Elysse S Karozichian, Jennifer A Philips, Rajendra S Apte

Open Access Publications

Here, we report our studies of immune-mediated regulation of Zika virus (ZIKV), herpes simplex virus 1 (HSV-1), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the human cornea. We find that ZIKV can be transmitted via corneal transplantation in mice. However, in human corneal explants, we report that ZIKV does not replicate efficiently and that SARS-CoV-2 does not replicate at all. Additionally, we demonstrate that type III interferon (IFN-λ) and its receptor (IFNλR1) are expressed in the corneal epithelium. Treatment of human corneal explants with IFN-λ, and treatment of mice with IFN-λ eye drops, upregulates antiviral interferon-stimulated genes. …


The Perceived Challenge Of Everyday Technologies In Sweden, The United States And England: Exploring Differential Item Functioning In The Everyday Technology Use Questionnaire, Sarah Wallcook, Camilla Malinowsky, Louise Nygård, Georgina Charlesworth, Jenica Lee, Ryan Walsh, Sophie Gaber, Anders Kottorp Nov 2020

The Perceived Challenge Of Everyday Technologies In Sweden, The United States And England: Exploring Differential Item Functioning In The Everyday Technology Use Questionnaire, Sarah Wallcook, Camilla Malinowsky, Louise Nygård, Georgina Charlesworth, Jenica Lee, Ryan Walsh, Sophie Gaber, Anders Kottorp

Open Access Publications

No abstract provided.


Prospective, Randomized, Double-Blind, Placebo-Controlled Evaluation Of The Pharmacokinetics, Safety And Efficacy Of Recombinant Antithrombin Versus Placebo In Preterm Preeclampsia, Michael J Paidas, George A Macones, Et Al Nov 2020

Prospective, Randomized, Double-Blind, Placebo-Controlled Evaluation Of The Pharmacokinetics, Safety And Efficacy Of Recombinant Antithrombin Versus Placebo In Preterm Preeclampsia, Michael J Paidas, George A Macones, Et Al

Open Access Publications

BACKGROUND: Despite expectant management, preeclampsia remote from term usually results in preterm delivery. Antithrombin, which displays antiinflammatory and anticoagulant properties, may have a therapeutic role in treating preterm preeclampsia, a disorder characterized by endothelial dysfunction, inflammation, and activation of the coagulation system.

OBJECTIVE: This randomized, placebo-controlled clinical trial aimed to evaluate whether intravenous recombinant human antithrombin could prolong gestation and therefore improve maternal and fetal outcomes.

STUDY DESIGN: We performed a double-blind, placebo-controlled trial at 23 hospitals. Women were eligible if they had a singleton pregnancy, early-onset or superimposed preeclampsia at 23 0/7 to 30 0/7 weeks' gestation, and planned …


Beyond Just A Tight Fortress: Contribution Of Stroma To Epithelial-Mesenchymal Transition In Pancreatic Cancer, Ashenafi Bulle, Kian-Huat Lim Oct 2020

Beyond Just A Tight Fortress: Contribution Of Stroma To Epithelial-Mesenchymal Transition In Pancreatic Cancer, Ashenafi Bulle, Kian-Huat Lim

Open Access Publications

Novel effective treatment is direly needed for patients with pancreatic ductal adenocarcinoma (PDAC). Therapeutics that target the driver mutations, especially the KRAS oncoprotein and its effector cascades, have been ineffective. It is increasing clear that the extensive fibro-inflammatory stroma (or desmoplasia) of PDAC plays an active role in the progression and therapeutic resistance of PDAC. The desmoplastic stroma is composed of dense extracellular matrix (ECM) deposited mainly by the cancer-associated-fibroblasts (CAFs) and infiltrated with various types of immune cells. The dense ECM functions as a physical barrier that limits tumor vasculatures and distribution of therapeutics to PDAC cells. In addition, …


Covid-19-Associated Acute Kidney Injury: Consensus Report Of The 25th Acute Disease Quality Initiative (Adqi) Workgroup, Mitra K Nadim, Anitha Vijayan, Et Al Oct 2020

Covid-19-Associated Acute Kidney Injury: Consensus Report Of The 25th Acute Disease Quality Initiative (Adqi) Workgroup, Mitra K Nadim, Anitha Vijayan, Et Al

Open Access Publications

Kidney involvement in patients with coronavirus disease 2019 (COVID-19) is common, and can range from the presence of proteinuria and haematuria to acute kidney injury (AKI) requiring renal replacement therapy (RRT; also known as kidney replacement therapy). COVID-19-associated AKI (COVID-19 AKI) is associated with high mortality and serves as an independent risk factor for all-cause in-hospital death in patients with COVID-19. The pathophysiology and mechanisms of AKI in patients with COVID-19 have not been fully elucidated and seem to be multifactorial, in keeping with the pathophysiology of AKI in other patients who are critically ill. Little is known about the …


Zanubrutinib Monotherapy For Patients With Treatment Naïve Chronic Lymphocytic Leukemia And 17p Deletion, Constantine S. Tam, Brad S. Kahl, Et Al Oct 2020

Zanubrutinib Monotherapy For Patients With Treatment Naïve Chronic Lymphocytic Leukemia And 17p Deletion, Constantine S. Tam, Brad S. Kahl, Et Al

Open Access Publications

Patients with chronic lymphocytic leukemia or small lymphocytic lymphoma whose tumors carry deletion of chromosome 17p13.1 [del(17p)] have an unfavorable prognosis and respond poorly to standard chemoimmunotherapy. Zanubrutinib is a selective next-generation Bruton tyrosine kinase inhibitor. We evaluated the safety and efficacy of zanubrutinib 160 mg twice daily in treatment-naïve patients with del(17p) disease enrolled in a dedicated, nonrandomized cohort (Arm C) of the phase 3 SEQUOIA trial. A total of 109 patients (median age, 70 years; range, 42 - 86) with centrally confirmed del(17p) were enrolled and treated. After a median of 18.2 months (range, 5.0 - 26.3), seven …


It's Complicated: The Relationship Between Sleep And Alzheimer's Disease In Humans, Brendan P Lucey Oct 2020

It's Complicated: The Relationship Between Sleep And Alzheimer's Disease In Humans, Brendan P Lucey

Open Access Publications

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by an asymptomatic period of amyloid-β (Aβ) deposition as insoluble extracellular plaque, intracellular tau aggregation, neuronal and synaptic loss, and subsequent cognitive dysfunction and dementia. A growing public health crisis, the worldwide prevalence of AD is expected to rise from 46.8 million individuals affected in 2015 to 131.5 million in 2050. Sleep disturbances have been associated with increased future risk of AD. A bi-directional relationship is hypothesized between sleep and AD with sleep disturbances as either markers for AD pathology and/or a mechanism mediating increased risk of AD. In this review, …


Identifying And Validating Subtypes Within Major Psychiatric Disorders Based On Frontal-Posterior Functional Imbalance Via Deep Learning, Miao Chang, Fay Y Womer, Xiaohong Gong, Weixiong Zhang, Et Al Oct 2020

Identifying And Validating Subtypes Within Major Psychiatric Disorders Based On Frontal-Posterior Functional Imbalance Via Deep Learning, Miao Chang, Fay Y Womer, Xiaohong Gong, Weixiong Zhang, Et Al

Open Access Publications

Converging evidence increasingly implicates shared etiologic and pathophysiological characteristics among major psychiatric disorders (MPDs), such as schizophrenia (SZ), bipolar disorder (BD), and major depressive disorder (MDD). Examining the neurobiology of the psychotic-affective spectrum may greatly advance biological determination of psychiatric diagnosis, which is critical for the development of more effective treatments. In this study, ensemble clustering was developed to identify subtypes within a trans-diagnostic sample of MPDs. Whole brain amplitude of low-frequency fluctuations (ALFF) was used to extract the low-dimensional features for clustering in a total of 944 participants: 581 psychiatric patients (193 with SZ, 171 with BD, and 217 …


Five Years Of Ocrelizumab In Relapsing Multiple Sclerosis: Opera Studies Open-Label Extension, Stephen L Hauser, Robert T Naismith, Et Al Sep 2020

Five Years Of Ocrelizumab In Relapsing Multiple Sclerosis: Opera Studies Open-Label Extension, Stephen L Hauser, Robert T Naismith, Et Al

Open Access Publications

OBJECTIVE: To assess over 3 years of follow-up the effects of maintaining or switching to ocrelizumab (OCR) therapy on clinical and MRI outcomes and safety measures in the open-label extension (OLE) phase of the pooled OPERA: I/II studies in relapsing multiple sclerosis.

METHODS: After 2 years of double-blind, controlled treatment, patients continued OCR (600 mg infusions every 24 weeks) or switched from interferon (IFN)-β-1a (44 μg 3 times weekly) to OCR when entering the OLE phase (3 years). Adjusted annualized relapse rate, time to onset of 24-week confirmed disability progression (CDP)/improvement (CDP), brain MRI activity (gadolinium-enhanced and new/enlarging T2 lesions), …


Severe Immunosuppression And Not A Cytokine Storm Characterizes Covid-19 Infections, Kenneth E Remy, Monty Mazer, David A Striker, Ali H Ellebedy, Andrew H Walton, Jacqueline Unsinger, Teresa M Blood, Philip A Mudd, Daehan J Yi, Daniel A Mannion, Dale F Osborne, R Scott Martin, Nitin J Anand, James P Bosanquet, Jane Blood, Anne M Drewry, Charles C Caldwell, Isaiah R Turnbull, Scott C Brakenridge, Lyle L Moldwawer, Richard S Hotchkiss Sep 2020

Severe Immunosuppression And Not A Cytokine Storm Characterizes Covid-19 Infections, Kenneth E Remy, Monty Mazer, David A Striker, Ali H Ellebedy, Andrew H Walton, Jacqueline Unsinger, Teresa M Blood, Philip A Mudd, Daehan J Yi, Daniel A Mannion, Dale F Osborne, R Scott Martin, Nitin J Anand, James P Bosanquet, Jane Blood, Anne M Drewry, Charles C Caldwell, Isaiah R Turnbull, Scott C Brakenridge, Lyle L Moldwawer, Richard S Hotchkiss

Open Access Publications

COVID-19-associated morbidity and mortality have been attributed to a pathologic host response. Two divergent hypotheses have been proposed: hyperinflammatory cytokine storm; and failure of host protective immunity that results in unrestrained viral dissemination and organ injury. A key explanation for the inability to address this controversy has been the lack of diagnostic tools to evaluate immune function in COVID-19 infections. ELISpot, a highly sensitive, functional immunoassay, was employed in 27 patients with COVID-19, 51 patients with sepsis, 18 critically ill nonseptic (CINS) patients, and 27 healthy control volunteers to evaluate adaptive and innate immune status by quantitating T cell IFN-ɣ …


Impact Of Annual And Semi-Annual Mass Drug Administration For Lymphatic Filariasis And Onchocerciasis On Hookworm Infection In Côte D'Ivoire, Agodio Loukouri, Aboulaye Méité, Benjamin G. Koudou, Charles W. Goss, Daphne Lew, Gary J. Weil, Eliezer K. N'Goran, Peter U. Fischer Sep 2020

Impact Of Annual And Semi-Annual Mass Drug Administration For Lymphatic Filariasis And Onchocerciasis On Hookworm Infection In Côte D'Ivoire, Agodio Loukouri, Aboulaye Méité, Benjamin G. Koudou, Charles W. Goss, Daphne Lew, Gary J. Weil, Eliezer K. N'Goran, Peter U. Fischer

Open Access Publications

Mass Drug Administration (MDA) programs to eliminate Lymphatic Filariasis (LF) in western Africa use the anthelminthics ivermectin plus albendazole. These drugs have the potential to impact also Soil-Transmitted Helminth (STH) infections, since the drugs have a broad range of anthelminthic activity. Integration of preventive chemotherapy efforts for LF, onchocerciasis and STH is recommended by the World Health Organization (WHO) in order to avoid duplication of MDA and to reduce costs. The objective of the current study was to determine whether five semi-annual rounds of community-wide MDA to eliminate LF and onchocerciasis have a greater impact on STH than three annual …


The Effect Of Exposure To Long Working Hours On Stroke: A Systematic Review And Meta-Analysis From The Who/Ilo Joint Estimates Of The Work-Related Burden Of Disease And Injury, Alexis Descatha, Bradley A Evanoff, Et Al Sep 2020

The Effect Of Exposure To Long Working Hours On Stroke: A Systematic Review And Meta-Analysis From The Who/Ilo Joint Estimates Of The Work-Related Burden Of Disease And Injury, Alexis Descatha, Bradley A Evanoff, Et Al

Open Access Publications

BACKGROUND: The World Health Organization (WHO) and the International Labour Organization (ILO) are developing joint estimates of the work-related burden of disease and injury (WHO/ILO Joint Estimates), with contributions from a large network of individual experts. Evidence from mechanistic data and prior studies suggests that exposure to long working hours may cause stroke. In this paper, we present a systematic review and meta-analysis of parameters for estimating the number of deaths and disability-adjusted life years from stroke that are attributable to exposure to long working hours, for the development of the WHO/ILO Joint Estimates.

OBJECTIVES: We aimed to systematically review …


Malignant Cell-Specific Cxcl14 Promotes Tumor Lymphocyte Infiltration In Oral Cavity Squamous Cell Carcinoma, Anuraag Parikh, Juneho Shin, William Faquin, Derrick T Lin, Itay Tirosh, John B Sunwoo, Sidharth V Puram Sep 2020

Malignant Cell-Specific Cxcl14 Promotes Tumor Lymphocyte Infiltration In Oral Cavity Squamous Cell Carcinoma, Anuraag Parikh, Juneho Shin, William Faquin, Derrick T Lin, Itay Tirosh, John B Sunwoo, Sidharth V Puram

Open Access Publications

OBJECTIVES: To explore lymphocyte infiltration as a potential mechanism behind CXCL14-mediated tumor growth suppression in oral cavity squamous cell carcinoma (OSCC).

METHODS: We analyzed single cell RNA-sequencing (scRNA-seq) data from OSCC to identify expression changes among malignant cells in lymph nodes (LN) versus primary tumors. CXCL14 expression in murine OSCC cell lines was quantified using qRT-PCR. Short hairpin RNA knockdown of CXCL14 was performed in mouse oral cavity (MOC)1 cells, and CXCL14 overexpression was performed in MOC2 cells. Cells in each condition were injected into C57BL/6 mice with and without T cell depletion, and tumor volume was measured. At 30 …


Association Of Guideline Publication And Delays To Treatment In Pediatric Status Epilepticus, Iván Sánchez Fernández, Réjean M Guerriero, Et Al Sep 2020

Association Of Guideline Publication And Delays To Treatment In Pediatric Status Epilepticus, Iván Sánchez Fernández, Réjean M Guerriero, Et Al

Open Access Publications

OBJECTIVE: To determine whether publication of evidence on delays in time to treatment shortens time to treatment in pediatric refractory convulsive status epilepticus (rSE), we compared time to treatment before (2011-2014) and after (2015-2019) publication of evidence of delays in treatment of rSE in the Pediatric Status Epilepticus Research Group (pSERG) as assessed by patient interviews and record review.

METHODS: We performed a retrospective analysis of a prospectively collected dataset from June 2011 to September 2019 on pediatric patients (1 month-21 years of age) with rSE.

RESULTS: We studied 328 patients (56% male) with median (25th-75th percentile [p

CONCLUSION: Publication …


Reducing Antibiotic Prescribing And Addressing The Global Problem Of Antibiotic Resistance By Targeted Hygiene In The Home And Everyday Life Settings: A Position Paper, Jean-Yves Maillard, Sally F Bloomfield, Patrice Courvalin, Sabiha Y Essack, Sumanth Gandra, Charles P Gerba, Joseph R Rubino, Elizabeth A Scott Sep 2020

Reducing Antibiotic Prescribing And Addressing The Global Problem Of Antibiotic Resistance By Targeted Hygiene In The Home And Everyday Life Settings: A Position Paper, Jean-Yves Maillard, Sally F Bloomfield, Patrice Courvalin, Sabiha Y Essack, Sumanth Gandra, Charles P Gerba, Joseph R Rubino, Elizabeth A Scott

Open Access Publications

Antimicrobial resistance (AMR) continues to threaten global health. Although global and national AMR action plans are in place, infection prevention and control is primarily discussed in the context of health care facilities with home and everyday life settings barely addressed. As seen with the recent global SARS-CoV-2 pandemic, everyday hygiene measures can play an important role in containing the threat from infectious microorganisms. This position paper has been developed following a meeting of global experts in London, 2019. It presents evidence that home and community settings are important for infection transmission and also the acquisition and spread of AMR. It …