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Advances And Gaps In Sars-Cov-2 Infection Models, César Muñoz-Fontela, Michael S. Diamond, Et Al Jan 2022

Advances And Gaps In Sars-Cov-2 Infection Models, César Muñoz-Fontela, Michael S. Diamond, Et Al

Open Access Publications

The global response to Coronavirus Disease 2019 (COVID-19) is now facing new challenges such as vaccine inequity and the emergence of SARS-CoV-2 variants of concern (VOCs). Preclinical models of disease, in particular animal models, are essential to investigate VOC pathogenesis, vaccine correlates of protection and postexposure therapies. Here, we provide an update from the World Health Organization (WHO) COVID-19 modeling expert group (WHO-COM) assembled by WHO, regarding advances in preclinical models. In particular, we discuss how animal model research is playing a key role to evaluate VOC virulence, transmission and immune escape, and how animal models are being refined to …


Perceptions Of Risk Of Sars-Cov-2 Transmission In Social And Educational Activities By Infectious Diseases And General Pediatric Healthcare Providers, A Pre-Vaccine Risk Perception Cross-Sectional Survey, Andrew B. Janowski, Philip M. Polgreen, Susan E. Beekmann, Jason G. Newland Jan 2022

Perceptions Of Risk Of Sars-Cov-2 Transmission In Social And Educational Activities By Infectious Diseases And General Pediatric Healthcare Providers, A Pre-Vaccine Risk Perception Cross-Sectional Survey, Andrew B. Janowski, Philip M. Polgreen, Susan E. Beekmann, Jason G. Newland

Open Access Publications

BACKGROUND: The perception of the transmission risks of SARS-CoV-2 in social and educational settings by US healthcare providers have not been previously quantified.

METHODS: Respondents completed an online survey between September and October 2020 to estimate the risk of SARS-CoV-2 transmission on a scale of 0-10 for different social and educational activities prior to the availability of the SARS-CoV-2 vaccines. Demographic information and experiences during the pandemic were also collected. The risk assessment was emailed to three listservs of healthcare providers, including national listservs of pediatric (PID) and adult infectious diseases (AID) providers, and a listserv of general pediatric practitioners …


Ultrasound-Guided Thrombin Injection For The Treatment Of Bleeding Following Kidney And Liver Biopsies, Mark J Hoegger, William D Middleton Jan 2022

Ultrasound-Guided Thrombin Injection For The Treatment Of Bleeding Following Kidney And Liver Biopsies, Mark J Hoegger, William D Middleton

Open Access Publications

The purpose of this study was to describe the technique and outcomes of percutaneous thrombin injection into the superficial aspect of actively bleeding liver and kidney biopsy tracks identified with color Doppler ultrasound with the aim of hemorrhage termination. After percutaneous thrombin injection, 15/16 (94%) patients did not require further intervention. Ultrasound-guided thrombin injection into the superficial site of active bleeding is an effective technique for terminating bleeding in the immediate post-procedure period following kidney and liver biopsies and should be considered if active bleeding persists on color Doppler after ≥30 minutes of compression and observation.


Ethical, Regulatory, And Practical Barriers To Covid-19 Research: A Stakeholder-Informed Inventory Of Concerns, Bryan A. Sisk, Kari Baldwin, Meredith Parsons, James M. Dubois Jan 2022

Ethical, Regulatory, And Practical Barriers To Covid-19 Research: A Stakeholder-Informed Inventory Of Concerns, Bryan A. Sisk, Kari Baldwin, Meredith Parsons, James M. Dubois

Open Access Publications

INTRODUCTION: SARS-CoV-2 (COVID-19) has caused death and economic injury around the globe. The urgent need for COVID-19 research created new ethical, regulatory, and practical challenges. The next public health emergency could be worse than COVID-19. We must learn about these challenges from the experiences of researchers and Research Ethics Committee professionals responsible for these COVID-19 studies to prepare for the next emergency.

MATERIALS AND METHODS: We conducted an online survey to identify the ethical, oversight, and regulatory challenges of conducting COVID-19 research during the early pandemic, and proposed solutions for overcoming these barriers. Using criterion-based, convenience sampling, we invited researchers …


Hemodynamic Profiles By Non-Invasive Monitoring Of Cardiac Index And Vascular Tone In Acute Heart Failure Patients In The Emergency Department: External Validation And Clinical Outcomes, Nicholas Eric Harrison, Sarah Meram, Xiangrui Li, Morgan B. White, Sarah Henry, Sushane Gupta, Dongxiao Zhu, Peter Pang, Phillip Levy Jan 2022

Hemodynamic Profiles By Non-Invasive Monitoring Of Cardiac Index And Vascular Tone In Acute Heart Failure Patients In The Emergency Department: External Validation And Clinical Outcomes, Nicholas Eric Harrison, Sarah Meram, Xiangrui Li, Morgan B. White, Sarah Henry, Sushane Gupta, Dongxiao Zhu, Peter Pang, Phillip Levy

Open Access Publications

BACKGROUND: Non-invasive finger-cuff monitors measuring cardiac index and vascular tone (SVRI) classify emergency department (ED) patients with acute heart failure (AHF) into three otherwise-indistinguishable subgroups. Our goals were to validate these "hemodynamic profiles" in an external cohort and assess their association with clinical outcomes.

METHODS: AHF patients (n = 257) from five EDs were prospectively enrolled in the validation cohort (VC). Cardiac index and SVRI were measured with a ClearSight finger-cuff monitor (formerly NexFin, Edwards Lifesciences) as in a previous study (derivation cohort, DC, n = 127). A control cohort (CC, n = 127) of ED patients with sepsis was …


Association Of A Perioperative Multicomponent Fall Prevention Intervention With Falls And Quality Of Life After Elective Inpatient Surgical Procedures, Bradley A. Fritz, Christopher R. King, Divya Mehta, Emily Somerville, Alex Kronzer, Arbi Ben Abdallah, Troy Wildes, Michael S. Avidan, Eric J. Lenze, Susan Stark Jan 2022

Association Of A Perioperative Multicomponent Fall Prevention Intervention With Falls And Quality Of Life After Elective Inpatient Surgical Procedures, Bradley A. Fritz, Christopher R. King, Divya Mehta, Emily Somerville, Alex Kronzer, Arbi Ben Abdallah, Troy Wildes, Michael S. Avidan, Eric J. Lenze, Susan Stark

Open Access Publications

Importance: Falls after elective inpatient surgical procedures are common and have physical, emotional, and financial consequences. Close interactions between patients and health care teams before and after surgical procedures may offer opportunities to address modifiable risk factors associated with falls.

Objective: To assess whether a multicomponent intervention that incorporates education, home medication review, and home safety assessment is associated with reductions in the incidence of falls after elective inpatient surgical procedures.

Design, Setting, and Participants: This prospective propensity score-matched cohort study was a prespecified secondary analysis of data from the Electroencephalography Guidance of Anesthesia to Alleviate Geriatric Syndromes (ENGAGES) randomized …


Association Of Multidimensional Poverty With Dementia In Adults Aged 50 Years Or Older In South Africa, Jean-Francois Trani, Jacqueline Moodley, May Thu Thu Maw, Ganesh M. Babulal Jan 2022

Association Of Multidimensional Poverty With Dementia In Adults Aged 50 Years Or Older In South Africa, Jean-Francois Trani, Jacqueline Moodley, May Thu Thu Maw, Ganesh M. Babulal

Open Access Publications

Importance: Limited research exists investigating the association between multidimensional poverty and dementia in low-and middle-income countries (LMICs).

Objective: To investigate the association between multidimensional poverty and dementia among adults aged 50 years or older living in South Africa.

Design, Setting, and Participants: This cross-sectional study was conducted in Soweto, Johannesburg, South Africa, between November 11, 2019, and February 28, 2020. Participants included 227 adults aged 50 years or older. Data analysis was concluded from August 1 to 30, 2021.

Exposures: Multidimensional poverty included 7 dimensions that are central to well-being (education, health, economic activity, living standards, social participation, fair treatment, …


De Novo Missense Variants In Fbxo11 Alter Its Protein Expression And Subcellular Localization, Anne Gregor, Marwan Shinawi, Et Al Jan 2022

De Novo Missense Variants In Fbxo11 Alter Its Protein Expression And Subcellular Localization, Anne Gregor, Marwan Shinawi, Et Al

Open Access Publications

Recently, others and we identified de novo FBXO11 (F-Box only protein 11) variants as causative for a variable neurodevelopmental disorder (NDD). We now assembled clinical and mutational information on 23 additional individuals. The phenotypic spectrum remains highly variable, with developmental delay and/or intellectual disability as the core feature and behavioral anomalies, hypotonia and various facial dysmorphism as frequent aspects. The mutational spectrum includes intragenic deletions, likely gene disrupting and missense variants distributed across the protein. To further characterize the functional consequences of FBXO11 missense variants, we analyzed their effects on protein expression and localization by overexpression of 17 different mutant …


Nia Long Life Family Study: Objectives, Design, And Heritability Of Cross-Sectional And Longitudinal Phenotypes, Mary K. Wojczynski, Shiow Jiuan Lin, Paola Sebastiani, Thomas T. Perls, Joseph Lee, Alexander Kulminski, Anne Newman, Joe M. Zmuda, Kaare Christensen, Michael A. Province Jan 2022

Nia Long Life Family Study: Objectives, Design, And Heritability Of Cross-Sectional And Longitudinal Phenotypes, Mary K. Wojczynski, Shiow Jiuan Lin, Paola Sebastiani, Thomas T. Perls, Joseph Lee, Alexander Kulminski, Anne Newman, Joe M. Zmuda, Kaare Christensen, Michael A. Province

Open Access Publications

The NIA Long Life Family Study (LLFS) is a longitudinal, multicenter, multinational, population-based multigenerational family study of the genetic and nongenetic determinants of exceptional longevity and healthy aging. The Visit 1 in-person evaluation (2006-2009) recruited 4 953 individuals from 539 two-generation families, selected from the upper 1% tail of the Family Longevity Selection Score (FLoSS, which quantifies the degree of familial clustering of longevity). Demographic, anthropometric, cognitive, activities of daily living, ankle-brachial index, blood pressure, physical performance, and pulmonary function, along with serum, plasma, lymphocytes, red cells, and DNA, were collected. A Genome Wide Association Scan (GWAS) (Ilumina Omni 2.5M …


Exposure To Family Planning Messages And Teenage Pregnancy: Results From The 2017 Philippine National Demographic And Health Survey, Veincent Christian F. Pepito, Arianna Maever L. Amit, Clinton S. Tang, Luis Miguel B. Co, Neil Andrew K. Aliazas, Sarah J. De Los Reyes, Raymundo S. Baquiran, Lourdes Bernadette S. Tanchanco Jan 2022

Exposure To Family Planning Messages And Teenage Pregnancy: Results From The 2017 Philippine National Demographic And Health Survey, Veincent Christian F. Pepito, Arianna Maever L. Amit, Clinton S. Tang, Luis Miguel B. Co, Neil Andrew K. Aliazas, Sarah J. De Los Reyes, Raymundo S. Baquiran, Lourdes Bernadette S. Tanchanco

Ateneo School of Medicine and Public Health Publications

Background

Teenage pregnancy is known to have physical, emotional, and psychosocial effects. Because of these risks, family planning and contraception messages have been disseminated in various forms of media, but their association with teenage pregnancy has not been studied previously in the Philippines. This study aims to examine the association between exposure to various family planning and contraception messages disseminated in various media channels and pregnancy among Filipino women aged 15–19. The study also intended to examine interactions between the different media channels where these family planning and contraception messages are being disseminated on their effect on teenage pregnancy.

Methods …


Pulmonary Capillary Recruitment And Distention In Mammalian Lungs: Species Similarities, David Langleben, Benjamin D. Fox, Stylianos E. Orfanos, Michele Giovinazzo, John D. Catravas Jan 2022

Pulmonary Capillary Recruitment And Distention In Mammalian Lungs: Species Similarities, David Langleben, Benjamin D. Fox, Stylianos E. Orfanos, Michele Giovinazzo, John D. Catravas

Bioelectrics Publications

Pulmonary arterial pressure rises minimally during exercise. The pulmonary microcirculation accommodates increasing blood flow via recruitment of pulmonary capillaries and, at higher flows, by distention of already perfused capillaries. The flow transition range between recruitment and distention has not been studied or compared across mammalian species, including humans. We hypothesised that the range would be similar. Functional pulmonary capillary surface area (FCSA) can be estimated using validated metabolic techniques. We reviewed data from previous studies in three mammalian species (perfused rabbit lungs and dog lung lobes, and exercising humans) and generated blood flow-FCSA curves over a range of flows. We …


Mothers' Perceptions Of Their Children's Weight: Opportunity For Health Promotion In Kuwait, Abdullah Al-Taiar, Nawal Alqaoud, Reem Sharaf-Alddin, Muge Akpinar-Elci Jan 2022

Mothers' Perceptions Of Their Children's Weight: Opportunity For Health Promotion In Kuwait, Abdullah Al-Taiar, Nawal Alqaoud, Reem Sharaf-Alddin, Muge Akpinar-Elci

Community & Environmental Health Faculty Publications

Background: Mothers’ perceptions of their children’s weight remain mostly unknown in oil-rich countries of the Middle East.

Aims: To compare maternal perceptions of their children’s weight with actual body weight.

Methods: We used the Kuwait nutritional surveillance data for 5 consecutive years (2015-2019) (N = 5119), which were collected through face-to-face interviews with mothers of children aged 2-5 years attending vaccination centres.

Results: Of the 5119 mothers in the study, 163 (3.18%) and 332 (6.48%) had obese or overweight children, respectively. Among 4624 mothers who had normal weight children, 1350 (29.20%) perceived their children’s weight as …


Prevalence Versus Evidence: A Closer Look At The Research Available For Serving Children Exposed To Maltreatment And A Response To Hyter's Call For Trauma-Informed Care, Savanah Gayaldo, Allison Gladfelter Jan 2022

Prevalence Versus Evidence: A Closer Look At The Research Available For Serving Children Exposed To Maltreatment And A Response To Hyter's Call For Trauma-Informed Care, Savanah Gayaldo, Allison Gladfelter

Faculty Articles, Papers, and Other Scholarship

Purpose:

In an October 2021 post of The ASHA LeaderLive, Dr. Yvette Hyter emphasized the need for trauma-informed services for children exposed to maltreatment in the wake of the COVID-19 pandemic. Inspired by her call, we discuss how the pandemic created a high-risk context for maltreatment, the speech-language pathologists' (SLPs') role in prevention and intervention, reflect on the gap in evidence for maltreatment within empirical journals aimed at the speech-language pathology audience, and reiterate Hyter's call for trauma-informed care as a guide for clinicians serving children exposed to maltreatment.

Method:

We searched for empirical evidence within journals aimed at …


One-Year Post-Operative Comparison Of Visual Function And Patient Satisfaction With Trifocal And Extended Depth Of Focus Intraocular Lenses, Elizabeth M. Law, Rajesh K. Aggarwal, Hetal Buckhurst, Hosam E. Kasaby, Jonathan Marsden, Gary Shum, Phillip J. Buckhust Jan 2022

One-Year Post-Operative Comparison Of Visual Function And Patient Satisfaction With Trifocal And Extended Depth Of Focus Intraocular Lenses, Elizabeth M. Law, Rajesh K. Aggarwal, Hetal Buckhurst, Hosam E. Kasaby, Jonathan Marsden, Gary Shum, Phillip J. Buckhust

School of Health Professions

PURPOSE: To evaluate visual performance with trifocal and extended depth of focus IOL at 1 year post-operatively.

SETTING: BMI Southend Hospital.

DESIGN: Cohort study.

METHODS: An age-matched cohort of forty subjects bilaterally implanted with the AT LISA 839MP trifocal IOL (20 patients, 40 eyes) and the Tecnis Symfony extended depth of focus IOL (20 patients, 40 eyes) were assessed at 3-6 months and 12-18 months post-operatively. Primary outcome measures were distance (6 m), intermediate (70 cm), near visual acuity (40 cm), and analysis of defocus profiles. Secondary outcomes included contrast sensitivity, Radner reading performance, quality of vision and assessment of …


Edge-Centric Analysis Of Stroke Patients: An Alternative Approach For Biomarkers Of Lesion Recovery, Sebastian Idesis, Joshua Faskowitz, Richard F Betzel, Maurizio Corbetta, Olaf Sporns, Gustavo Deco Jan 2022

Edge-Centric Analysis Of Stroke Patients: An Alternative Approach For Biomarkers Of Lesion Recovery, Sebastian Idesis, Joshua Faskowitz, Richard F Betzel, Maurizio Corbetta, Olaf Sporns, Gustavo Deco

2020-Current year OA Pubs

Most neuroimaging studies of post-stroke recovery rely on analyses derived from standard node-centric functional connectivity to map the distributed effects in stroke patients. Here, given the importance of nonlocal and diffuse damage, we use an edge-centric approach to functional connectivity in order to provide an alternative description of the effects of this disorder. These techniques allow for the rendering of metrics such as normalized entropy, which describes the diversity of edge communities at each node. Moreover, the approach enables the identification of high amplitude co-fluctuations in fMRI time series. We found that normalized entropy is associated with stroke lesion severity …


Neonatal Motor Functional Connectivity And Motor Outcomes At Age Two Years In Very Preterm Children With And Without High-Grade Brain Injury, Peppar E P Cyr, Rachel E Lean, Jeanette K Kenley, Sydney Kaplan, Dominique E Meyer, Jeffery J Neil, Dimitrios Alexopoulos, Rebecca G Brady, Joshua S Shimony, Thomas L Rodebaugh, Cynthia E Rogers, Christopher D Smyser Jan 2022

Neonatal Motor Functional Connectivity And Motor Outcomes At Age Two Years In Very Preterm Children With And Without High-Grade Brain Injury, Peppar E P Cyr, Rachel E Lean, Jeanette K Kenley, Sydney Kaplan, Dominique E Meyer, Jeffery J Neil, Dimitrios Alexopoulos, Rebecca G Brady, Joshua S Shimony, Thomas L Rodebaugh, Cynthia E Rogers, Christopher D Smyser

2020-Current year OA Pubs

Preterm-born children have high rates of motor impairments, but mechanisms for early identification remain limited. We hypothesized that neonatal motor system functional connectivity (FC) would relate to motor outcomes at age two years; currently, this relationship is not yet well-described in very preterm (VPT; born <32 weeks' gestation) infants with and without brain injury. We recruited 107 VPT infants - including 55 with brain injury (grade III-IV intraventricular hemorrhage, cystic periventricular leukomalacia, post-hemorrhagic hydrocephalus) - and collected FC data at/near term-equivalent age (35-45 weeks postmenstrual age). Correlation coefficients were used to calculate the FC between bilateral motor and visual cortices and thalami. At two years corrected-age, motor outcomes were assessed with the Bayley Scales of Infant and Toddler Development, 3rd edition. Multiple imputation was used to estimate missing data, and regression models related FC measures to motor outcomes. Within the brain-injured group only, interhemispheric motor cortex FC was positively related to gross motor outcomes. Thalamocortical and visual FC were not related to motor scores. This suggests neonatal alterations in motor system FC may provide prognostic information about impairments in children with brain injury.


Inferring The Dynamical Effects Of Stroke Lesions Through Whole-Brain Modeling, Sebastian Idesis, Chiara Favaretto, Nicholas V Metcalf, Joseph C Griffis, Gordon L Shulman, Maurizio Corbetta, Gustavo Deco Jan 2022

Inferring The Dynamical Effects Of Stroke Lesions Through Whole-Brain Modeling, Sebastian Idesis, Chiara Favaretto, Nicholas V Metcalf, Joseph C Griffis, Gordon L Shulman, Maurizio Corbetta, Gustavo Deco

2020-Current year OA Pubs

Understanding the effect of focal lesions (stroke) on brain structure-function traditionally relies on behavioral analyses and correlation with neuroimaging data. Here we use structural disconnection maps from individual lesions to derive a causal mechanistic generative whole-brain model able to explain both functional connectivity alterations and behavioral deficits induced by stroke. As compared to other models that use only the local lesion information, the similarity to the empirical fMRI connectivity increases when the widespread structural disconnection information is considered. The presented model classifies behavioral impairment severity with higher accuracy than other types of information (e.g.: functional connectivity). We assessed topological measures …


Cost And Value In Contemporary Heart Failure Clinical Guidance Documents, John W. Ostrominski, Sameer Hirji, Ankeet S. Bhatt, Javed Butler, Mona Fiuzat, Gregg C. Fonarow, Paul A. Heidenreich, James L. Januzzi, Carolyn S. P. Lam, Thomas M. Maddox, Christopher M. O'Connor, Muthiah Vaduganathan Jan 2022

Cost And Value In Contemporary Heart Failure Clinical Guidance Documents, John W. Ostrominski, Sameer Hirji, Ankeet S. Bhatt, Javed Butler, Mona Fiuzat, Gregg C. Fonarow, Paul A. Heidenreich, James L. Januzzi, Carolyn S. P. Lam, Thomas M. Maddox, Christopher M. O'Connor, Muthiah Vaduganathan

2020-Current year OA Pubs

OBJECTIVES: This study sought to evaluate the frequency and nature of cost/value statements in contemporary heart failure (HF) clinical guidance documents (CGDs).

BACKGROUND: In an era of rising health care costs and expanding therapeutic options, there is an increasing need for formal consideration of cost and value in the development of HF CGDs.

METHODS: HF CGDs published by major professional cardiovascular organizations between January 2010 and February 2021 were reviewed for the inclusion of cost/value statements.

RESULTS: Overall, 33 documents were identified, including 5 (15%) appropriate use criteria, 7 (21%) clinical practice guidelines, and 21 (64%) expert consensus documents. Most …


Creation Of Philadelphia Chromosome By Crispr/Cas9-Mediated Double Cleavages On Bcr And Abl1 Genes As A Model For Initial Event In Leukemogenesis, Minori Tamai, Kenji Kamimoto, Kohei Omachi, Et Al. Jan 2022

Creation Of Philadelphia Chromosome By Crispr/Cas9-Mediated Double Cleavages On Bcr And Abl1 Genes As A Model For Initial Event In Leukemogenesis, Minori Tamai, Kenji Kamimoto, Kohei Omachi, Et Al.

2020-Current year OA Pubs

The Philadelphia (Ph) chromosome was the first translocation identified in leukemia. It is supposed to be generated by aberrant ligation between two DNA double-strand breaks (DSBs) at the BCR gene located on chromosome 9q34 and the ABL1 gene located on chromosome 22q11. Thus, mimicking the initiation process of translocation, we induced CRISPR/Cas9-mediated DSBs simultaneously at the breakpoints of the BCR and ABL1 genes in a granulocyte-macrophage colony-stimulating factor (GM-CSF) dependent human leukemia cell line. After transfection of two single guide RNAs (sgRNAs) targeting intron 13 of the BCR gene and intron 1 of the ABL1 gene, a factor-independent subline was …


Estimation Of Intrafamilial Dna Contamination In Family Trio Genome Sequencing Using Deviation From Mendelian Inheritance, Christopher J Yoon, Brian Wiley, Malachi Griffith, Obi L Griffith, Et Al. Jan 2022

Estimation Of Intrafamilial Dna Contamination In Family Trio Genome Sequencing Using Deviation From Mendelian Inheritance, Christopher J Yoon, Brian Wiley, Malachi Griffith, Obi L Griffith, Et Al.

2020-Current year OA Pubs

With the increasing number of sequencing projects involving families, quality control tools optimized for family genome sequencing are needed. However, accurately quantifying contamination in a DNA mixture is particularly difficult when genetically related family members are the sources. We developed TrioMix, a maximum likelihood estimation (MLE) framework based on Mendel's law of inheritance, to quantify DNA mixture between family members in genome sequencing data of parent-offspring trios. TrioMix can accurately deconvolute any intrafamilial DNA contamination, including parent-offspring, sibling-sibling, parent-parent, and even multiple familial sources. In addition, TrioMix can be applied to detect genomic abnormalities that deviate from Mendelian inheritance patterns, …


Induction Egfr Tyrosine Kinase Inhibitors Prior To Definitive Chemoradiotherapy In Unresectable Stage Iii Egfr-Mutated Non-Small Cell Lung Cancer, Jacqueline V Aredo, Heather A Wakelee, Angela Bik-Yu Hui, Sukhmani K Padda, Nitin D Joshi, H Henry Guo, Aadel Chaudhuri, Maximilian Diehn, Billy W Loo Jr, Joel W Neal Jan 2022

Induction Egfr Tyrosine Kinase Inhibitors Prior To Definitive Chemoradiotherapy In Unresectable Stage Iii Egfr-Mutated Non-Small Cell Lung Cancer, Jacqueline V Aredo, Heather A Wakelee, Angela Bik-Yu Hui, Sukhmani K Padda, Nitin D Joshi, H Henry Guo, Aadel Chaudhuri, Maximilian Diehn, Billy W Loo Jr, Joel W Neal

2020-Current year OA Pubs

INTRODUCTION: Increasing evidence suggests that consolidation durvalumab confers limited benefits for patients with stage III EGFR-mutated NSCLC. Induction or maintenance EGFR tyrosine kinase inhibitors (TKIs) added to concurrent chemoradiotherapy (CRT) may optimize definitive treatment, but there are limited data supporting an induction TKI strategy.

METHODS: We evaluated the efficacy and safety of induction EGFR TKIs administered before concurrent CRT in a retrospective series of patients with unresectable locally advanced EGFR-mutated NSCLC. Circulating tumor DNA (ctDNA) analysis was performed on a patient subset using CAPP-seq and correlated with outcomes.

RESULTS: Of six patients, three received erlotinib and three osimertinib as induction …


Detection Of Emerging Neurodegeneration Using Bayesian Linear Mixed-Effect Modeling, Yann Cobigo, Richard J Perrin, Et Al. Jan 2022

Detection Of Emerging Neurodegeneration Using Bayesian Linear Mixed-Effect Modeling, Yann Cobigo, Richard J Perrin, Et Al.

2020-Current year OA Pubs

Early detection of neurodegeneration, and prediction of when neurodegenerative diseases will lead to symptoms, are critical for developing and initiating disease modifying treatments for these disorders. While each neurodegenerative disease has a typical pattern of early changes in the brain, these disorders are heterogeneous, and early manifestations can vary greatly across people. Methods for detecting emerging neurodegeneration in any part of the brain are therefore needed. Prior publications have described the use of Bayesian linear mixed-effects (BLME) modeling for characterizing the trajectory of change across the brain in healthy controls and patients with neurodegenerative disease. Here, we use an extension …


Cgas-Sting Pathway Targeted Therapies And Their Applications In The Treatment Of High-Grade Glioma, Shashwat Tripathi, Hinda Najem, Akanksha Sanjay Mahajan, Peng Zhang, Justin T Low, Alexander H Stegh, Michael A Curran, David M Ashley, Charles David James, Amy B Heimberger Jan 2022

Cgas-Sting Pathway Targeted Therapies And Their Applications In The Treatment Of High-Grade Glioma, Shashwat Tripathi, Hinda Najem, Akanksha Sanjay Mahajan, Peng Zhang, Justin T Low, Alexander H Stegh, Michael A Curran, David M Ashley, Charles David James, Amy B Heimberger

2020-Current year OA Pubs

Median survival of patients with glioblastoma (GBM) treated with standard of care which consists of maximal safe resection of the contrast-enhancing portion of the tumor followed by radiation therapy with concomitant adjuvant temozolomide (TMZ) remains 15 months. The tumor microenvironment (TME) is known to contain immune suppressive myeloid cells with minimal effector T cell infiltration. Stimulator of interferon genes (STING) is an important activator of immune response and results in production of Type 1 interferon and antigen presentation by myeloid cells. This review will discuss important developments in STING agonists, potential biomarkers for STING response, and new combinatorial therapeutic approaches …


Understanding The Contribution Of Metabolism To Mycobacterium Tuberculosis Drug Tolerance, Amanda N Samuels, Erin R Wang, Gregory A Harrison, Joy C Valenta, Christina L Stallings Jan 2022

Understanding The Contribution Of Metabolism To Mycobacterium Tuberculosis Drug Tolerance, Amanda N Samuels, Erin R Wang, Gregory A Harrison, Joy C Valenta, Christina L Stallings

2020-Current year OA Pubs

Treatment of


A Role For An Htlv-1 Vaccine?, Lee Ratner Jan 2022

A Role For An Htlv-1 Vaccine?, Lee Ratner

2020-Current year OA Pubs

HTLV-1 is a global infection with 5-20 million infected individuals. Although only a minority of infected individuals develop myelopathy, lymphoproliferative malignancy, or inflammatory disorders, infection is associated with immunosuppression and shorter survival. Transmission of HTLV-1 is through contaminated blood or needles, mother-to-child exposure through breast-feeding, and sexual intercourse. HTLV-1 is a delta retrovirus that expresses immunogenic Gag, Envelope, TAX, and Hbz proteins. Neutralizing antibodies have been identified directed against the surface envelope protein, and cytotoxic T-cell epitopes within TAX have been characterized. Thus far, there have been few investigations of vaccines directed against each of these proteins, with limited responses, …


Program Adaptation By Health Departments, Louise Farah Saliba, Peg Allen, Stephanie L Mazzucca, Emily Rodriguez Weno, Sarah Moreland-Russell, Margaret Padek, Ross C Brownson Jan 2022

Program Adaptation By Health Departments, Louise Farah Saliba, Peg Allen, Stephanie L Mazzucca, Emily Rodriguez Weno, Sarah Moreland-Russell, Margaret Padek, Ross C Brownson

2020-Current year OA Pubs

INTRODUCTION: The dissemination of evidence-based interventions (i.e., programs, practices, and policies) is a core function of US state health departments (SHDs). However, interventions are originally designed and tested with a specific population and context. Hence, adapting the intervention to meet the real-world circumstances and population's needs can increase the likelihood of achieving the expected health outcomes for the target population from the implemented intervention. This study identified how SHD employees decide to adapt public health programs and what influences decisions on how to adapt them.

MATERIALS AND METHODS: SHD employees (

RESULTS: Data, outcomes, and health department evaluations influenced decisions …


Survival After Simultaneous Pancreas-Kidney Transplantation In Type 1 Diabetes: The Critical Role Of Early Pancreas Allograft Function, Mengmeng Ji, Mei Wang, Wenjun Hu, Mohamed Ibrahim, Krista L. Lentine, Massini Merzkani, Haris Murad, Yazen Al-Hosni, Ronald Parsons, Jason Wellen, Su-Hsin Chang, Tarek Alhamad Jan 2022

Survival After Simultaneous Pancreas-Kidney Transplantation In Type 1 Diabetes: The Critical Role Of Early Pancreas Allograft Function, Mengmeng Ji, Mei Wang, Wenjun Hu, Mohamed Ibrahim, Krista L. Lentine, Massini Merzkani, Haris Murad, Yazen Al-Hosni, Ronald Parsons, Jason Wellen, Su-Hsin Chang, Tarek Alhamad

2020-Current year OA Pubs

Simultaneous pancreas-kidney transplantation (SPK) carries about a 7%-22% risk of technical failure, but the impact of early pancreas allograft loss on subsequent kidney graft and patient survival is not well-defined. We examined national transplant registry data for type 1 diabetic patients who received SPK between 2000 and 2021. Associations of transplant type (i.e., SPK, deceased-donor kidney transplant [DDKA], living-donor kidney transplant [LDKA]) with kidney graft failure and patient survival were estimated by multivariable inverse probability of treatment-weighted accelerated failure-time models. Compared to SPK recipients with a functioning pancreas graft 3 months posttransplant (SPK,P+), LDKA had 18% (Time Ratio [TR] 0.82, …


In And Out: Leishmania Metastasis By Hijacking Lymphatic System And Migrating Immune Cells, Baijayanti Jha, Marta Reverte, Catherine Ronet, Florence Prevel, Florence D Morgenthaler, Chantal Desponds, Lon-Fye Lye, Katherine L Owens, Leonardo Scarpellino, Lalit Kumar Dubey, Amélie Sabine, Tatiana V Petrova, Sanjiv A Luther, Stephen M Beverley, Nicolas Fasel Jan 2022

In And Out: Leishmania Metastasis By Hijacking Lymphatic System And Migrating Immune Cells, Baijayanti Jha, Marta Reverte, Catherine Ronet, Florence Prevel, Florence D Morgenthaler, Chantal Desponds, Lon-Fye Lye, Katherine L Owens, Leonardo Scarpellino, Lalit Kumar Dubey, Amélie Sabine, Tatiana V Petrova, Sanjiv A Luther, Stephen M Beverley, Nicolas Fasel

2020-Current year OA Pubs

The lymphatic system plays a crucial role in mounting immune response against intracellular pathogens, and recent studies have documented its role in facilitating tumor dissemination linked largely with cancer cells. However, in mucocutaneous leishmaniasis (MCL) caused by


Apoe Mediated Neuroinflammation And Neurodegeneration In Alzheimer's Disease, Samira Parhizkar, David M Holtzman Jan 2022

Apoe Mediated Neuroinflammation And Neurodegeneration In Alzheimer's Disease, Samira Parhizkar, David M Holtzman

2020-Current year OA Pubs

Neuroinflammation is a central mechanism involved in neurodegeneration as observed in Alzheimer's disease (AD), the most prevalent form of neurodegenerative disease. Apolipoprotein E4 (APOE4), the strongest genetic risk factor for AD, directly influences disease onset and progression by interacting with the major pathological hallmarks of AD including amyloid-β plaques, neurofibrillary tau tangles, as well as neuroinflammation. Microglia and astrocytes, the two major immune cells in the brain, exist in an immune-vigilant state providing immunological defense as well as housekeeping functions that promote neuronal well-being. It is becoming increasingly evident that under disease conditions, these immune cells become progressively dysfunctional in …


Silver Jubilee: 25 Years Of The First Demonstration Of The Direct Effect Of Phosphate On The Parathyroid Cell, Jordi Bover, Adriana Dusso, Et Al. Jan 2022

Silver Jubilee: 25 Years Of The First Demonstration Of The Direct Effect Of Phosphate On The Parathyroid Cell, Jordi Bover, Adriana Dusso, Et Al.

2020-Current year OA Pubs

Although phosphorus is an essential element for life, it is not found in nature in its native state but rather combined in the form of inorganic phosphates (PO