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Mitochondrial Phenotypes In Genetically Diverse Neurodegenerative Diseases And Their Response To Mitofusin Activation, Xiawei Dang, Emily K Walton, Barbara Zablocka, Robert H Baloh, Michael E Shy, Gerald W Dorn Ii
Mitochondrial Phenotypes In Genetically Diverse Neurodegenerative Diseases And Their Response To Mitofusin Activation, Xiawei Dang, Emily K Walton, Barbara Zablocka, Robert H Baloh, Michael E Shy, Gerald W Dorn Ii
Open Access Publications
Mitochondrial fusion is essential to mitochondrial fitness and cellular health. Neurons of patients with genetic neurodegenerative diseases often exhibit mitochondrial fragmentation, reflecting an imbalance in mitochondrial fusion and fission (mitochondrial dysdynamism). Charcot-Marie-Tooth (CMT) disease type 2A is the prototypical disorder of impaired mitochondrial fusion caused by mutations in the fusion protein mitofusin (MFN)2. Yet, cultured CMT2A patient fibroblast mitochondria are often reported as morphologically normal. Metabolic stress might evoke pathological mitochondrial phenotypes in cultured patient fibroblasts, providing a platform for the pre-clinical individualized evaluation of investigational therapeutics. Here, substitution of galactose for glucose in culture media was used to redirect …
Predicting Mitochondrial Dynamic Behavior In Genetically Defined Neurodegenerative Diseases, Gerald W Dorn Ii, Xiawei Dang
Predicting Mitochondrial Dynamic Behavior In Genetically Defined Neurodegenerative Diseases, Gerald W Dorn Ii, Xiawei Dang
Open Access Publications
Mitochondrial dynamics encompass mitochondrial fusion, fission, and movement. Mitochondrial fission and fusion are seemingly ubiquitous, whereas mitochondrial movement is especially important for organelle transport through neuronal axons. Here, we review the roles of different mitochondrial dynamic processes in mitochondrial quantity and quality control, emphasizing their impact on the neurological system in Charcot-Marie-Tooth disease type 2A, amyotrophic lateral sclerosis, Friedrich's ataxia, dominant optic atrophy, and Alzheimer's, Huntington's, and Parkinson's diseases. In addition to mechanisms and concepts, we explore in detail different technical approaches for measuring mitochondrial dynamic dysfunction in vitro, describe how results from tissue culture studies may be applied to …
Infection-Related And Lifestyle-Related Cancer Burden In Kampala, Uganda: Projection Of The Future Cancer Incidence Up To 2030, Judith Asasira, Sanghee Lee, Thi Xuan Mai Tran, Collins Mpamani, Henry Wabinga, So-Youn Jung, Yoon Jung Chang, Yikyung Park, Hyunsoon Cho
Infection-Related And Lifestyle-Related Cancer Burden In Kampala, Uganda: Projection Of The Future Cancer Incidence Up To 2030, Judith Asasira, Sanghee Lee, Thi Xuan Mai Tran, Collins Mpamani, Henry Wabinga, So-Youn Jung, Yoon Jung Chang, Yikyung Park, Hyunsoon Cho
Open Access Publications
OBJECTIVES: In Uganda, infection-related cancers have made the greatest contribution to cancer burden in the past; however, burden from lifestyle-related cancers has increased recently. Using the Kampala Cancer Registry data, we projected incidence of top five cancers, namely, Kaposi sarcoma (KS), cervical, breast and prostate cancer, and non-Hodgkin's lymphoma (NHL) in Uganda.
DESIGN: Trend analysis of cancer registry data.
SETTING: Kampala Cancer Registry, Uganda.
MAIN OUTCOME MEASURE: Cancer incidence data from 2001 to 2015 were used and projected to 2030. Population data were obtained from the Uganda Bureau of Statistics. Age-standardised incidence rates (ASRs) and their trends over the observed …
Principles And Applications Of Crispr Toolkit In Virus Manipulation, Diagnosis, And Virus-Host Interactions, Saleh Jamehdor, Sara Pajouhanfar, Sadaf Saba, Georges Uzan, Ali Teimoori, Sina Naserian
Principles And Applications Of Crispr Toolkit In Virus Manipulation, Diagnosis, And Virus-Host Interactions, Saleh Jamehdor, Sara Pajouhanfar, Sadaf Saba, Georges Uzan, Ali Teimoori, Sina Naserian
Open Access Publications
Viruses are one of the most important concerns for human health, and overcoming viral infections is a worldwide challenge. However, researchers have been trying to manipulate viral genomes to overcome various disorders, including cancer, for vaccine development purposes. CRISPR (clustered regularly interspaced short palindromic repeats) is becoming one of the most functional and widely used tools for RNA and DNA manipulation in multiple organisms. This approach has provided an unprecedented opportunity for creating simple, inexpensive, specific, targeted, accurate, and practical manipulations of viruses, such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), human immunodeficiency virus-1 (HIV-1), and vaccinia virus. Furthermore, …
Cd4/Cd8 Double-Negative Mycosis Fungoides With Large Cell Transformation And Involvement Of The Lungs And Leptomeninges, Kelly M Wilmas, Alexander B Aria, Laura N Landis, Sri Krishna Chaitanya, Victor G Prieto, Madeleine Duvic
Cd4/Cd8 Double-Negative Mycosis Fungoides With Large Cell Transformation And Involvement Of The Lungs And Leptomeninges, Kelly M Wilmas, Alexander B Aria, Laura N Landis, Sri Krishna Chaitanya, Victor G Prieto, Madeleine Duvic
Open Access Publications
Mycosis fungoides (MF), the most common cutaneous T-cell lymphoma, classically has an indolent clinical course, with lesions slowly progressing from patch to plaque to tumor stage. In some cases, the late stages of disease involve extra-cutaneous dissemination to lymph nodes or viscera. Although this "Alibert-Bazin" type is the prototypic MF, there are several variants and subtypes of MF that may have different clinical implications for treatment and prognosis. We describe a woman whose disease course involved a variety of histopathologic and immunophenotypic variants including folliculotropic MF, granulomatous MF with loss of CD8, and then finally CD4/CD8 double-negative MF with large …
Feasibility And Efficacy Of Telehealth-Based Resistance Exercise Training In Adolescents With Cystic Fibrosis And Glucose Intolerance, Clifton J Holmes, Susan B Racette, Leslie Symonds, Ana Maria Arbeláez, Chao Cao, Andrea Granados
Feasibility And Efficacy Of Telehealth-Based Resistance Exercise Training In Adolescents With Cystic Fibrosis And Glucose Intolerance, Clifton J Holmes, Susan B Racette, Leslie Symonds, Ana Maria Arbeláez, Chao Cao, Andrea Granados
Open Access Publications
The aims of this study were to (1) determine the feasibility of a home-based resistance exercise training (RET) program in patients with cystic fibrosis and impaired glucose tolerance using virtual personal training and (2) observe the effects completion of the RET program had on glucose metabolism, pulmonary function, body composition, and physical fitness. The feasibility of the program was defined as 80% compliance. Ten participants (15.80 ± 2.20 yr, 25.1 ± 7.4 kg/m
Exploiting Radiation Induction Of Antigens In Cancer: Targeted Drug Delivery, Vaishali Kapoor, Abhay K Singh, Calvin D Lewis, Sapna Deore, Dennis E Hallahan
Exploiting Radiation Induction Of Antigens In Cancer: Targeted Drug Delivery, Vaishali Kapoor, Abhay K Singh, Calvin D Lewis, Sapna Deore, Dennis E Hallahan
Open Access Publications
Therapeutic antibodies used to treat cancer are effective in patients with advanced-stage disease. For example, antibodies that activate T-lymphocytes improve survival in many cancer subtypes. In addition, antibody-drug conjugates effectively target cytotoxic agents that are specific to cancer. This review discusses radiation-inducible antigens, which are stress-regulated proteins that are over-expressed in cancer. These inducible cell surface proteins become accessible to antibody binding during the cellular response to genotoxic stress. The lead antigens are induced in all histologic subtypes and nearly all advanced-stage cancers, but show little to no expression in normal tissues. Inducible antigens are exploited by using therapeutic antibodies …
Pftaire Kinase L63 Interactor 1a (Pif1a Protein) Is Required For Actin Cone Movement During Spermatid Individualization In Drosophila Melanogaster, Harrison D Pravder, Dorota Grabowska, Kaushik Roychoudhury, Betty Zhang, Deborah Frank, Przemysław Zakrzewski, Marta Lenartowska, Kathryn G Miller
Pftaire Kinase L63 Interactor 1a (Pif1a Protein) Is Required For Actin Cone Movement During Spermatid Individualization In Drosophila Melanogaster, Harrison D Pravder, Dorota Grabowska, Kaushik Roychoudhury, Betty Zhang, Deborah Frank, Przemysław Zakrzewski, Marta Lenartowska, Kathryn G Miller
Open Access Publications
A useful model for determining the mechanisms by which actin and actin binding proteins control cellular architecture is the
Clinical Severity Of, And Effectiveness Of Mrna Vaccines Against, Covid-19 From Omicron, Delta, And Alpha Sars-Cov-2 Variants In The United States: Prospective Observational Study, Adam S Lauring, Hilary M Babcock, Jennie H Kwon, Et Al
Clinical Severity Of, And Effectiveness Of Mrna Vaccines Against, Covid-19 From Omicron, Delta, And Alpha Sars-Cov-2 Variants In The United States: Prospective Observational Study, Adam S Lauring, Hilary M Babcock, Jennie H Kwon, Et Al
Open Access Publications
OBJECTIVES: To characterize the clinical severity of covid-19 associated with the alpha, delta, and omicron SARS-CoV-2 variants among adults admitted to hospital and to compare the effectiveness of mRNA vaccines to prevent hospital admissions related to each variant.
DESIGN: Case-control study.
SETTING: 21 hospitals across the United States.
PARTICIPANTS: 11 690 adults (≥18 years) admitted to hospital: 5728 with covid-19 (cases) and 5962 without covid-19 (controls). Patients were classified into SARS-CoV-2 variant groups based on viral whole genome sequencing, and, if sequencing did not reveal a lineage, by the predominant circulating variant at the time of hospital admission: alpha (11 …
Jagged1/Notch3 Activation Promotes Aortic Hypermuscularization And Stenosis In Elastin Deficiency, Jui M. Dave, Robert Mecham, Et Al
Jagged1/Notch3 Activation Promotes Aortic Hypermuscularization And Stenosis In Elastin Deficiency, Jui M. Dave, Robert Mecham, Et Al
Open Access Publications
Obstructive arterial diseases, including supravalvular aortic stenosis (SVAS), atherosclerosis, and restenosis, share 2 important features: an abnormal or disrupted elastic lamellae structure and excessive smooth muscle cells (SMCs). However, the relationship between these pathological features is poorly delineated. SVAS is caused by heterozygous loss-of-function, hypomorphic, or deletion mutations in the elastin gene (ELN), and SVAS patients and elastin-mutant mice display increased arterial wall cellularity and luminal obstructions. Pharmacological treatments for SVAS are lacking, as the underlying pathobiology is inadequately defined. Herein, using human aortic vascular cells, mouse models, and aortic samples and SMCs derived from induced pluripotent stem cells of …
Evaluation Of Hiv Treatment Outcomes With Reduced Frequency Of Clinical Encounters And Antiretroviral Treatment Refills: A Systematic Review And Meta-Analysis, Noelle Le Tourneau, Ashley Germann, Ryan R. Thompson, Nathan Ford, Sheree Schwartz, Laura Beres, Aaloke Mody, Stefan Baral, Elvin H. Geng, Ingrid Eshun-Wilson
Evaluation Of Hiv Treatment Outcomes With Reduced Frequency Of Clinical Encounters And Antiretroviral Treatment Refills: A Systematic Review And Meta-Analysis, Noelle Le Tourneau, Ashley Germann, Ryan R. Thompson, Nathan Ford, Sheree Schwartz, Laura Beres, Aaloke Mody, Stefan Baral, Elvin H. Geng, Ingrid Eshun-Wilson
Open Access Publications
BACKGROUND: Global HIV treatment programs have sought to lengthen the interval between clinical encounters for people living with HIV (PLWH) who are established on antiretroviral treatment (ART) to reduce the burden of seeking care and to decongest health facilities. The overall effect of reduced visit frequency on HIV treatment outcomes is however unknown. We conducted a systematic review and meta-analysis to evaluate the effect of implementation strategies that reduce the frequency of clinical appointments and ART refills for PLWH established on ART.
METHODS AND FINDINGS: We searched databases between 1 January 2010 and 9 November 2021 to identify randomized controlled …
Fk506-Binding Protein-Like And Fk506-Binding Protein 8 Regulate Dual Leucine Zipper Kinase Degradation And Neuronal Responses To Axon Injury, Bohm Lee, Yeonsoo Oh, Eunhye Cho, Aaron Diantonio, Valeria Cavalli, Jung Eun Shin, Hae Woong Choi, Yongcheol Cho
Fk506-Binding Protein-Like And Fk506-Binding Protein 8 Regulate Dual Leucine Zipper Kinase Degradation And Neuronal Responses To Axon Injury, Bohm Lee, Yeonsoo Oh, Eunhye Cho, Aaron Diantonio, Valeria Cavalli, Jung Eun Shin, Hae Woong Choi, Yongcheol Cho
Open Access Publications
The dual leucine zipper kinase (DLK) is a key regulator of axon regeneration and degeneration in response to neuronal injury; however, regulatory mechanisms of the DLK function via its interacting proteins are largely unknown. To better understand the molecular mechanism of DLK function, we performed yeast two-hybrid screening analysis and identified FK506-binding protein-like (FKBPL, also known as WAF-1/CIP1 stabilizing protein 39) as a DLK-binding protein. FKBPL binds to the kinase domain of DLK and inhibits its kinase activity. In addition, FKBPL induces DLK protein degradation through ubiquitin-dependent pathways. We further assessed other members in the FKBP protein family and found …
Social Isolation And Incident Heart Failure Hospitalization In Older Women: Women's Health Initiative Study Findings, Crystal W Cené, Xiaoyan Iris Leng, Khushnood Faraz, Matthew Allison, Khadijah Breathett, Chloe Bird, Mace Coday, Giselle Corbie-Smith, Randi Foraker, Nkechinyere N Ijioma, Milagros C Rosal, Shawnita Sealy-Jefferson, Tetyana P Shippee, Candyce H Kroenke
Social Isolation And Incident Heart Failure Hospitalization In Older Women: Women's Health Initiative Study Findings, Crystal W Cené, Xiaoyan Iris Leng, Khushnood Faraz, Matthew Allison, Khadijah Breathett, Chloe Bird, Mace Coday, Giselle Corbie-Smith, Randi Foraker, Nkechinyere N Ijioma, Milagros C Rosal, Shawnita Sealy-Jefferson, Tetyana P Shippee, Candyce H Kroenke
Open Access Publications
Background The association of social isolation or lack of social network ties in older adults is unknown. This knowledge gap is important since the risk of heart failure (HF) and social isolation increase with age. The study examines whether social isolation is associated with incident HF in older women, and examines depressive symptoms as a potential mediator and age and race and ethnicity as effect modifiers. Methods and Results This study included 44 174 postmenopausal women of diverse race and ethnicity from the WHI (Women's Health Initiative) study who underwent annual assessment for HF adjudication from baseline enrollment (1993-1998) through …
Transcriptomic Profile Investigations Highlight A Putative Role For Nudt16 In Sepsis, Susie Shih Yin Huang, Darawan Rinchai, Mohammed Toufiq, Basirudeen Syed Ahamed Kabeer, Jessica Roelands, Wouter Hendrickx, Sabri Boughorbel, Davide Bedognetti, Nicholas Van Panhuys, Damien Chaussabel, Mathieu Garand
Transcriptomic Profile Investigations Highlight A Putative Role For Nudt16 In Sepsis, Susie Shih Yin Huang, Darawan Rinchai, Mohammed Toufiq, Basirudeen Syed Ahamed Kabeer, Jessica Roelands, Wouter Hendrickx, Sabri Boughorbel, Davide Bedognetti, Nicholas Van Panhuys, Damien Chaussabel, Mathieu Garand
Open Access Publications
Sepsis is an aberrant systemic inflammatory response mediated by the acute activation of the innate immune system. Neutrophils are important contributors to the innate immune response that controls the infection, but harbour the risk of collateral tissue damage such as thrombosis and organ dysfunction. A better understanding of the modulations of cellular processes in neutrophils and other blood cells during sepsis is needed and can be initiated via transcriptomic profile investigations. To that point, the growing repertoire of publicly accessible transcriptomic datasets serves as a valuable resource for discovering and/or assessing the robustness of biomarkers. We employed systematic literature mining, …
Commissioning A Secondary Dose Calculation Software For A 0.35 T Mr-Linac, Alex T Price, Nels C Knutson, Taeho Kim, Olga L Green
Commissioning A Secondary Dose Calculation Software For A 0.35 T Mr-Linac, Alex T Price, Nels C Knutson, Taeho Kim, Olga L Green
Open Access Publications
Secondary external dose calculations for a 0.35 T magnetic resonance image-guided radiation therapy (MRgRT) are needed within the radiation oncology community to follow safety standards set forth within the field. We evaluate the commercially available software, RadCalc, in its ability to accurately perform monitor unit dose calculations within a magnetic field. We also evaluate the potential effects of a 0.35 T magnetic field upon point dose calculations. Monitor unit calculations were evaluated with (wMag) and without (noMag) a magnetic field considerations in RadCalc for the ViewRay MRIdian. The magnetic field is indirectly accounted for by using asymmetric profiles for calculation. …
Translational Randomized Phase Ii Trial Of Cabozantinib In Combination With Nivolumab In Advanced, Recurrent, Or Metastatic Endometrial Cancer, Stephanie Lheureux, Carolyn Mccourt, Et Al
Translational Randomized Phase Ii Trial Of Cabozantinib In Combination With Nivolumab In Advanced, Recurrent, Or Metastatic Endometrial Cancer, Stephanie Lheureux, Carolyn Mccourt, Et Al
Open Access Publications
BACKGROUND: Combining immunotherapy and antiangiogenic agents is a promising treatment strategy in endometrial cancer. To date, no biomarkers for response have been identified and data on post-immunotherapy progression are lacking. We explored the combination of a checkpoint inhibitor (nivolumab) and an antiangiogenic agent (cabozantinib) in immunotherapy-naïve endometrial cancer and in patients whose disease progressed on previous immunotherapy with baseline biopsy for immune profiling.
PATIENTS AND METHODS: In this phase II trial (ClinicalTrials.gov NCT03367741, registered December 11, 2017), women with recurrent endometrial cancer were randomized 2:1 to nivolumab with cabozantinib (Arm A) or nivolumab alone (Arm B). The primary endpoint was …
Fragile X Mental Retardation Protein And Cerebral Expression Of Metabotropic Glutamate Receptor Subtype 5 In Men With Fragile X Syndrome: A Pilot Study, James Robert Brašić, Jack Alexander Goodman, Ayon Nandi, David S Russell, Danna Jennings, Olivier Barret, Samuel D Martin, Keith Slifer, Thomas Sedlak, Anil Kumar Mathur, John P Seibyl, Elizabeth M Berry-Kravis, Dean F Wong, Dejan B Budimirovic
Fragile X Mental Retardation Protein And Cerebral Expression Of Metabotropic Glutamate Receptor Subtype 5 In Men With Fragile X Syndrome: A Pilot Study, James Robert Brašić, Jack Alexander Goodman, Ayon Nandi, David S Russell, Danna Jennings, Olivier Barret, Samuel D Martin, Keith Slifer, Thomas Sedlak, Anil Kumar Mathur, John P Seibyl, Elizabeth M Berry-Kravis, Dean F Wong, Dejan B Budimirovic
Open Access Publications
Multiple lines of evidence suggest that a deficiency of Fragile X Mental Retardation Protein (FMRP) mediates dysfunction of the metabotropic glutamate receptor subtype 5 (mGluR
Synthesis And Structure-Activity Relationship Of Thioacetamide-Triazoles Against Escherichia Coli, Suresh Dharuman, Miranda J Wallace, Stephanie M Reeve, Jürgen B Bulitta, Richard E Lee
Synthesis And Structure-Activity Relationship Of Thioacetamide-Triazoles Against Escherichia Coli, Suresh Dharuman, Miranda J Wallace, Stephanie M Reeve, Jürgen B Bulitta, Richard E Lee
Open Access Publications
Infections due to Gram-negative bacteria are increasingly dangerous due to the spread of multi-drug resistant strains, emphasizing the urgent need for new antibiotics with alternative modes of action. We have previously identified a novel class of antibacterial agents, thioacetamide-triazoles, using an antifolate targeted screen and determined their mode of action which is dependent on activation by cysteine synthase A. Herein, we report a detailed examination of the anti-
Current And Future Approaches To Classify Vuss In Lgmd-Related Genes, Chengcheng Li, Gabe Haller, Conrad C Weihl
Current And Future Approaches To Classify Vuss In Lgmd-Related Genes, Chengcheng Li, Gabe Haller, Conrad C Weihl
Open Access Publications
Next-generation sequencing (NGS) has revealed large numbers of genetic variants in LGMD-related genes, with most of them classified as variants of uncertain significance (VUSs). VUSs are genetic changes with unknown pathological impact and present a major challenge in genetic test interpretation and disease diagnosis. Understanding the phenotypic consequences of VUSs can provide clinical guidance regarding LGMD risk and therapy. In this review, we provide a brief overview of the subtypes of LGMD, disease diagnosis, current classification systems for investigating VUSs, and a potential deep mutational scanning approach to classify VUSs in LGMD-related genes.
Assessing Infant Cognition In Field Settings Using Eye-Tracking: A Pilot Cohort Trial In Sierra Leone, Jukka Leppänen, Julius Butcher, Claire Godbout, Kevin Stephenson, D. Taylor Hendrixson, Stacy Griswold, Beatrice Rogers, Patrick Webb, Aminata Koroma, Mark Manary
Assessing Infant Cognition In Field Settings Using Eye-Tracking: A Pilot Cohort Trial In Sierra Leone, Jukka Leppänen, Julius Butcher, Claire Godbout, Kevin Stephenson, D. Taylor Hendrixson, Stacy Griswold, Beatrice Rogers, Patrick Webb, Aminata Koroma, Mark Manary
Open Access Publications
OBJECTIVES: To investigate the feasibility of eye-tracking-based testing of the speed of visual orienting in malnourished young children at rural clinics in Sierra Leone.
DESIGN: Prospective dual cohort study nested in a cluster-randomised trial.
SETTING: 8 sites participating in a cluster-randomised trial of supplementary feeding for moderate acute malnutrition (MAM).
PARTICIPANTS: For the MAM cohort, all infants aged 7-11 months at the eight sites were enrolled, 138 altogether. For controls, a convenience sample of all non-malnourished infants aged 7-11 months at the same sites were eligible, 60 altogether. A sample of 30 adults at the sites also underwent eye-tracking tests …
Unilateral Cleft Lip Repair: Technical Maneuvers To Achieve Vermilion And Mucosal Height, Sarah N Chiang, Ema Zubovic, Gary B Skolnick, Kamlesh B Patel
Unilateral Cleft Lip Repair: Technical Maneuvers To Achieve Vermilion And Mucosal Height, Sarah N Chiang, Ema Zubovic, Gary B Skolnick, Kamlesh B Patel
Open Access Publications
Patients with unilateral cleft lip often require secondary procedures due to asymmetric fullness or deficiencies along the mucosal free margin of the upper lip. Here, we describe our technique for mucosal advancement and repair to attain symmetry.
Methods: Maneuvers to obtain vermilion and mucosal height include (1) use of a tailored vermilion flap; (2) supraperiosteal release of the lesser segment; (3) backcut "poker incision" to mobilize the mucosal flap on the lesser segment; (4) transverse release of mucosa across the greater segment; (5) accurate reduction along vermilion-mucosal junction; and (6) bilateral medial mucosal advancement. To examine postoperative outcomes, photographic data …
The History And Innovations Of Blood Vessel Anastomosis, William R Moritz, Shreya Raman, Sydney Pessin, Cameron Martin, Xiaowei Li, Amanda Westman, Justin M Sacks
The History And Innovations Of Blood Vessel Anastomosis, William R Moritz, Shreya Raman, Sydney Pessin, Cameron Martin, Xiaowei Li, Amanda Westman, Justin M Sacks
Open Access Publications
Surgical technique and technology frequently coevolve. The brief history of blood vessel anastomosis is full of famous names. While the techniques pioneered by these surgeons have been well described, the technology that facilitated their advancements and their inventors deserve recognition. The mass production of laboratory microscopes in the mid-1800s allowed for an explosion of interest in tissue histology. This improved understanding of vascular physiology and thrombosis laid the groundwork for Carrel and Guthrie to report some of the first successful vascular anastomoses. In 1916, McLean discovered heparin. Twenty-four years later, Gordon Murray found that it could prevent thrombosis when performing …
Health-Related Quality Of Life In Older Patients With Advanced Heart Failure: Findings From The Sustain-It Study, Kathleen L Grady, Justin Hartupee, Et Al
Health-Related Quality Of Life In Older Patients With Advanced Heart Failure: Findings From The Sustain-It Study, Kathleen L Grady, Justin Hartupee, Et Al
Open Access Publications
Background There is a paucity of research describing health-related quality of life (HRQOL) in older adults considered for advanced heart failure surgical therapies. Using data from our SUSTAIN-IT (Sustaining Quality of Life of the Aged: Heart Transplant or Mechanical Support) study, we aimed to compare HRQOL among 3 groups of older (60-80 years) patients with heart failure before heart transplantation (HT) or long-term mechanical circulatory support (MCS) and identify factors associated with HRQOL: (1) HT candidates with MCS, (2) HT candidates without MCS, or (3) candidates ineligible for HT and scheduled for long-term MCS. Methods and Results Patients from 13 …
Two-Tier Care Pathways For Liver Fibrosis Associated To Non-Alcoholic Fatty Liver Disease In Hiv Mono-Infected Patients, Giada Sebastiani, Jovana Milic, Adriana Cervo, Sahar Saeed, Thomas Krahn, Dana Kablawi, Al Shaima Al Hinai, Bertrand Lebouché, Philip Wong, Marc Deschenes, Claudia Gioè, Antonio Cascio, Giovanni Mazzola, Giovanni Guaraldi
Two-Tier Care Pathways For Liver Fibrosis Associated To Non-Alcoholic Fatty Liver Disease In Hiv Mono-Infected Patients, Giada Sebastiani, Jovana Milic, Adriana Cervo, Sahar Saeed, Thomas Krahn, Dana Kablawi, Al Shaima Al Hinai, Bertrand Lebouché, Philip Wong, Marc Deschenes, Claudia Gioè, Antonio Cascio, Giovanni Mazzola, Giovanni Guaraldi
Open Access Publications
(1) Background: Developing strategies to identify significant liver fibrosis in people with HIV (PWH) is crucial to prevent complications of non-alcoholic fatty liver disease (NAFLD). We aim to investigate if five simple serum biomarkers applied to PWH can optimize a care pathway to identify significant liver fibrosis defined by transient elastography (TE). (2) Methods: A two-tier fibrosis pathway was applied to three prospective cohorts of PWH undergoing TE with CAP. NAFLD was diagnosed as a controlled attenuation parameter ≥ 248 dB/m. Five simple fibrosis biomarkers (FIB-4 < 1.3, BARD score 0-1, NAFLD fibrosis score < -1.455, AST:ALT ratio < 0.8 and APRI < 0.5) were applied as first-tiers to exclude significant liver fibrosis. We determined the decrease in referral for TE that would have occurred based on biomarker assessment and the discordance between low simple fibrosis biomarkers and high TE (≥7.1 kPa), indicating significant liver fibrosis. (3) Results: Of the 1749 consecutive PWH, 15.1% had significant liver fibrosis by TE and 39.1% had NAFLD. The application of the fibrosis biomarkers as first tiers would have resulted in a decrease in TE referrals between 24.9% (BARD score) and 86.3% (APRI). The lowest discordance rate was with NAFLD fibrosis score (8.5%). After adjustments, BMI (odds ratio (OR) 1.12, 95% CI: 1.08-1.17) and triglycerides (OR 1.26, 95% CI: 1.11-1.44) were independent predictors of discordance for APRI < 0.5 and TE ≥ 7.1. The performance of the two-tier pathways was similar in PWH with and without NAFLD. (4) Conclusions: Implementing a two-tier pathway could save a substantial proportion up of TE examinations, reducing costs and helping resource optimization in HIV care. Patients with metabolic risk factors for NAFLD and low fibrosis biomarker may still be considered for TE referral.
Small Molecule Swell1 Complex Induction Improves Glycemic Control And Nonalcoholic Fatty Liver Disease In Murine Type 2 Diabetes, Susheel K Gunasekar, Litao Xie, Ashutosh Kumar, Juan Hong, Chen Kang, Joshua Maurer, John Heebink, Phillip Key, Joseph W Beals, Gordon I Smith, Samuel Klein, Rajan Sah, Et Al
Small Molecule Swell1 Complex Induction Improves Glycemic Control And Nonalcoholic Fatty Liver Disease In Murine Type 2 Diabetes, Susheel K Gunasekar, Litao Xie, Ashutosh Kumar, Juan Hong, Chen Kang, Joshua Maurer, John Heebink, Phillip Key, Joseph W Beals, Gordon I Smith, Samuel Klein, Rajan Sah, Et Al
Open Access Publications
Type 2 diabetes is associated with insulin resistance, impaired pancreatic β-cell insulin secretion, and nonalcoholic fatty liver disease. Tissue-specific SWELL1 ablation impairs insulin signaling in adipose, skeletal muscle, and endothelium, and impairs β-cell insulin secretion and glycemic control. Here, we show that I
The Association Between Hiv Status, Estradiol, And Sex Hormone Binding Globulin Among Premenopausal Women In The Women's Interagency Hiv Study, Sally B Coburn, Jodie Dionne-Odom, Maria L Alcaide, Caitlin A Moran, Lisa Rahangdale, Elizabeth T Golub, Leslie Stewart Massad, Dominika Seidman, Katherine G Michel, Howard Minkoff, Kerry Murphy, Todd T Brown, Kala Visvanathan, Bryan Lau, Keri N Althoff
The Association Between Hiv Status, Estradiol, And Sex Hormone Binding Globulin Among Premenopausal Women In The Women's Interagency Hiv Study, Sally B Coburn, Jodie Dionne-Odom, Maria L Alcaide, Caitlin A Moran, Lisa Rahangdale, Elizabeth T Golub, Leslie Stewart Massad, Dominika Seidman, Katherine G Michel, Howard Minkoff, Kerry Murphy, Todd T Brown, Kala Visvanathan, Bryan Lau, Keri N Althoff
Open Access Publications
No abstract provided.
Spatiotemporal Expression Of Regulatory Kinases Directs The Transition From Mitosis To Cellular Morphogenesis In Drosophila, Shuo Yang, Jennifer Mcadow, Yingqiu Du, Jennifer Trigg, Paul H Taghert, Aaron N Johnson
Spatiotemporal Expression Of Regulatory Kinases Directs The Transition From Mitosis To Cellular Morphogenesis In Drosophila, Shuo Yang, Jennifer Mcadow, Yingqiu Du, Jennifer Trigg, Paul H Taghert, Aaron N Johnson
Open Access Publications
Embryogenesis depends on a tightly regulated balance between mitosis, differentiation, and morphogenesis. Understanding how the embryo uses a relatively small number of proteins to transition between growth and morphogenesis is a central question of developmental biology, but the mechanisms controlling mitosis and differentiation are considered to be fundamentally distinct. Here we show the mitotic kinase Polo, which regulates all steps of mitosis in Drosophila, also directs cellular morphogenesis after cell cycle exit. In mitotic cells, the Aurora kinases activate Polo to control a cytoskeletal regulatory module that directs cytokinesis. We show that in the post-mitotic mesoderm, the control of Polo …
Live-Dead Assay On Unlabeled Cells Using Phase Imaging With Computational Specificity, Chenfei Hu, Shenghua He, Young Jae Lee, Yuchen He, Edward M Kong, Hua Li, Mark A Anastasio, Gabriel Popescu
Live-Dead Assay On Unlabeled Cells Using Phase Imaging With Computational Specificity, Chenfei Hu, Shenghua He, Young Jae Lee, Yuchen He, Edward M Kong, Hua Li, Mark A Anastasio, Gabriel Popescu
Open Access Publications
Existing approaches to evaluate cell viability involve cell staining with chemical reagents. However, the step of exogenous staining makes these methods undesirable for rapid, nondestructive, and long-term investigation. Here, we present an instantaneous viability assessment of unlabeled cells using phase imaging with computation specificity. This concept utilizes deep learning techniques to compute viability markers associated with the specimen measured by label-free quantitative phase imaging. Demonstrated on different live cell cultures, the proposed method reports approximately 95% accuracy in identifying live and dead cells. The evolution of the cell dry mass and nucleus area for the labeled and unlabeled populations reveal …
Protocol For Development Of A Core Outcome Set For Clinical Trials In Melasma, Sarah Ibrahim, Bianca Kang, Daniel Schlessinger, Sarah Chiren, Jennifer Tang, Jamie Kirkham, Jochen Schmitt, Emily Poon, Ian Maher, Joseph Sobanko, Todd Cartee, Murad Alam
Protocol For Development Of A Core Outcome Set For Clinical Trials In Melasma, Sarah Ibrahim, Bianca Kang, Daniel Schlessinger, Sarah Chiren, Jennifer Tang, Jamie Kirkham, Jochen Schmitt, Emily Poon, Ian Maher, Joseph Sobanko, Todd Cartee, Murad Alam
Open Access Publications
INTRODUCTION: Melasma is a pigmentation disorder of the skin. Characterised by brown to gray-brown patches on the face and neck, the condition predominantly affects women and has been associated with pregnancy, hormonal variation and sun exposure. Melasma can be disfiguring and anxiety-provoking, and quality of life is often adversely impacted. Management includes sun protection, laser and energy device therapy, topical and oral skin-bleaching agents and chemical peels. While clinical trials of melasma exist, there is a lack of consistency in reported outcomes, which has been a barrier to the aggregation of data in systematic reviews and meta-analyses. This protocol describes …
Coronavirus Disease 2019 (Covid-19) Research Agenda For Healthcare Epidemiology, Lona Mody, Hilary M Babcock, Jennie H Kwon, Et Al
Coronavirus Disease 2019 (Covid-19) Research Agenda For Healthcare Epidemiology, Lona Mody, Hilary M Babcock, Jennie H Kwon, Et Al
Open Access Publications
This SHEA white paper identifies knowledge gaps and challenges in healthcare epidemiology research related to coronavirus disease 2019 (COVID-19) with a focus on core principles of healthcare epidemiology. These gaps, revealed during the worst phases of the COVID-19 pandemic, are described in 10 sections: epidemiology, outbreak investigation, surveillance, isolation precaution practices, personal protective equipment (PPE), environmental contamination and disinfection, drug and supply shortages, antimicrobial stewardship, healthcare personnel (HCP) occupational safety, and return to work policies. Each section highlights three critical healthcare epidemiology research questions with detailed description provided in supplementary materials. This research agenda calls for translational studies from laboratory-based …