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Full-Text Articles in Medicine and Health Sciences

2024 European Heart Rhythm Association/Heart Rhythm Society/Asia Pacific Heart Rhythm Society/Latin American Heart Rhythm Society Expert Consensus Statement On Catheter And Surgical Ablation Of Atrial Fibrillation, Stylianos Tzeis, Ralph J Damiano, Et Al. Mar 2024

2024 European Heart Rhythm Association/Heart Rhythm Society/Asia Pacific Heart Rhythm Society/Latin American Heart Rhythm Society Expert Consensus Statement On Catheter And Surgical Ablation Of Atrial Fibrillation, Stylianos Tzeis, Ralph J Damiano, Et Al.

2020-Current year OA Pubs

In the last three decades, ablation of atrial fibrillation (AF) has become an evidence-based safe and efficacious treatment for managing the most common cardiac arrhythmia. In 2007, the first joint expert consensus document was issued, guiding healthcare professionals involved in catheter or surgical AF ablation. Mounting research evidence and technological advances have resulted in a rapidly changing landscape in the field of catheter and surgical AF ablation, thus stressing the need for regularly updated versions of this partnership which were issued in 2012 and 2017. Seven years after the last consensus, an updated document was considered necessary to define a …


Arch: Improving The Performance Of Clonal Hematopoiesis Variant Calling And Interpretation, Irenaeus C C Chan, Alex Panchot, Evelyn Schmidt, Brian J Wiley, Jie Liu, Kimberly Turner, Duc Tran, J Scott Beeler, Armel Landry Batchi-Bouyou, Daniel C Link, Kelly L Bolton, Et Al. Mar 2024

Arch: Improving The Performance Of Clonal Hematopoiesis Variant Calling And Interpretation, Irenaeus C C Chan, Alex Panchot, Evelyn Schmidt, Brian J Wiley, Jie Liu, Kimberly Turner, Duc Tran, J Scott Beeler, Armel Landry Batchi-Bouyou, Daniel C Link, Kelly L Bolton, Et Al.

2020-Current year OA Pubs

MOTIVATION: The acquisition of somatic mutations in hematopoietic stem and progenitor stem cells with resultant clonal expansion, termed clonal hematopoiesis (CH), is associated with increased risk of hematologic malignancies and other adverse outcomes. CH is generally present at low allelic fractions, but clonal expansion and acquisition of additional mutations leads to hematologic cancers in a small proportion of individuals. With high depth and high sensitivity sequencing, CH can be detected in most adults and its clonal trajectory mapped over time. However, accurate CH variant calling is challenging due to the difficulty in distinguishing low frequency CH mutations from sequencing artifacts. …


Structure Of Alpha-Synuclein Fibrils Derived From Human Lewy Body Dementia Tissue, Dhruva D Dhavale, Katherine Basore, Isabelle R Gordon, Jialu Liu, Jennifer Y O'Shea, Michael J Rau, Zachary Smith, Brock Summers, Richard J Perrin, Joel S Perlmutter, James A J Fitzpatrick, Paul T Kotzbauer, Et Al. Mar 2024

Structure Of Alpha-Synuclein Fibrils Derived From Human Lewy Body Dementia Tissue, Dhruva D Dhavale, Katherine Basore, Isabelle R Gordon, Jialu Liu, Jennifer Y O'Shea, Michael J Rau, Zachary Smith, Brock Summers, Richard J Perrin, Joel S Perlmutter, James A J Fitzpatrick, Paul T Kotzbauer, Et Al.

2020-Current year OA Pubs

The defining feature of Parkinson disease (PD) and Lewy body dementia (LBD) is the accumulation of alpha-synuclein (Asyn) fibrils in Lewy bodies and Lewy neurites. Here we develop and validate a method to amplify Asyn fibrils extracted from LBD postmortem tissue samples and use solid state nuclear magnetic resonance (SSNMR) studies to determine atomic resolution structure. Amplified LBD Asyn fibrils comprise a mixture of single protofilament and two protofilament fibrils with very low twist. The protofilament fold is highly similar to the fold determined by a recent cryo-electron microscopy study for a minority population of twisted single protofilament fibrils extracted …


Using Stated Preference Methods To Facilitate Knowledge Translation In Implementation Science, Whitney C Irie, Andrew Kerkhoff, Hae-Young Kim, Elvin Geng, Ingrid Eshun-Wilson Mar 2024

Using Stated Preference Methods To Facilitate Knowledge Translation In Implementation Science, Whitney C Irie, Andrew Kerkhoff, Hae-Young Kim, Elvin Geng, Ingrid Eshun-Wilson

2020-Current year OA Pubs

Enhancing the arsenal of methods available to shape implementation strategies and bolster knowledge translation is imperative. Stated preference methods, including discrete choice experiments (DCE) and best-worst scaling (BWS), rooted in economics, emerge as robust, theory-driven tools for understanding and influencing the behaviors of both recipients and providers of innovation. This commentary outlines the wide-ranging application of stated preference methods across the implementation continuum, ushering in effective knowledge translation. The prospects for utilizing these methods within implementation science encompass (1) refining and tailoring intervention and implementation strategies, (2) exploring the relative importance of implementation determinants, (3) identifying critical outcomes for key …


Comparative Lipidome Study Of Maternal Plasma, Milk, And Lamb Plasma In Sheep, Soundara Viveka Thangaraj, Adel Ghnenis, Brooke Pallas, Arpita Kalla Vyas, Brigid Gregg, Vasantha Padmanabhan Mar 2024

Comparative Lipidome Study Of Maternal Plasma, Milk, And Lamb Plasma In Sheep, Soundara Viveka Thangaraj, Adel Ghnenis, Brooke Pallas, Arpita Kalla Vyas, Brigid Gregg, Vasantha Padmanabhan

2020-Current year OA Pubs

Lipids play a critical role in neonate development and breastmilk is the newborn's major source of lipids. Milk lipids directly influence the neonate plasma lipid profile. The milk lipidome is dynamic, influenced by maternal factors and related to the maternal plasma lipidome. The close inter-relationship between the maternal plasma, milk and neonate plasma lipidomes is critical to understanding maternal-child health and nutrition. In this exploratory study, lipidomes of blood and breast milk from Suffolk sheep and matched lamb blood (n = 13), were profiled on day 34 post birth by untargeted mass spectrometry. Comparative multivariate analysis of the three matrices …


Fibrinolytic-Deficiencies Predispose Hosts To Septicemia From A Catheter-Associated Uti, Jonathan J Molina, Wei Xu, Karla Bergeron, Aleksandra Klim, Michael G Caparon, Scott J Hultgren, Alana Desai, Et Al. Mar 2024

Fibrinolytic-Deficiencies Predispose Hosts To Septicemia From A Catheter-Associated Uti, Jonathan J Molina, Wei Xu, Karla Bergeron, Aleksandra Klim, Michael G Caparon, Scott J Hultgren, Alana Desai, Et Al.

2020-Current year OA Pubs

Catheter-associated urinary tract infections (CAUTIs) are amongst the most common nosocomial infections worldwide and are difficult to treat partly due to development of multidrug-resistance from CAUTI-related pathogens. Importantly, CAUTI often leads to secondary bloodstream infections and death. A major challenge is to predict when patients will develop CAUTIs and which populations are at-risk for bloodstream infections. Catheter-induced inflammation promotes fibrinogen (Fg) and fibrin accumulation in the bladder which are exploited as a biofilm formation platform by CAUTI pathogens. Using our established mouse model of CAUTI, here we identified that host populations exhibiting either genetic or acquired fibrinolytic-deficiencies, inducing fibrin deposition …


Next Generation Microfluidics: Fulfilling The Promise Of Lab-On-A-Chip Technologies, Umut A Gurkan, Jorge Di Paola, Et Al. Mar 2024

Next Generation Microfluidics: Fulfilling The Promise Of Lab-On-A-Chip Technologies, Umut A Gurkan, Jorge Di Paola, Et Al.

2020-Current year OA Pubs

Microfluidic lab-on-a-chip technologies enable the analysis and manipulation of small fluid volumes and particles at small scales and the control of fluid flow and transport processes at the microscale, leading to the development of new methods to address a broad range of scientific and medical challenges. Microfluidic and lab-on-a-chip technologies have made a noteworthy impact in basic, preclinical, and clinical research, especially in hematology and vascular biology due to the inherent ability of microfluidics to mimic physiologic flow conditions in blood vessels and capillaries. With the potential to significantly impact translational research and clinical diagnostics, technical issues and incentive mismatches …


Efficacy And Feasibility Of Short-Stretch Compression Therapy For Filarial Lymphedema In Sri Lanka, Jaimee M Hall, Nirmitha Lalindi De Silva, Janaka Ruben, Sandani S Thilakarathne, Thishan Channa Yahathugoda, Philip J Budge Mar 2024

Efficacy And Feasibility Of Short-Stretch Compression Therapy For Filarial Lymphedema In Sri Lanka, Jaimee M Hall, Nirmitha Lalindi De Silva, Janaka Ruben, Sandani S Thilakarathne, Thishan Channa Yahathugoda, Philip J Budge

2020-Current year OA Pubs

The WHO-recommended essential package of care (EPC) for filarial limb lymphedema consists of daily limb washing, entry lesion management, limb protection, exercises, and elevation. Decongestive therapy (DT) with compression bandaging by trained lymphedema therapists adds additional benefit but is unavailable for most in low- and middle-income countries (LMICs). To determine whether DT using self-adjustable, short-stretch compression garments (SSCG), prefitted using portable, three-dimensional infrared imaging (3DII), would be effective and feasible in LMIC settings, we conducted a pilot 6-week, interventional, single-group, open-label pilot study in Galle, Sri Lanka. Ten participants with Dreyer stage 3 lymphedema used SSCG for 2 weeks after …


Ly6c+ Monocytes In The Skin Promote Systemic Alphavirus Dissemination, Autumn C Holmes, Cormac J Lucas, Morgan E Brisse, Brian C Ware, Heather D Hickman, Thomas E Morrison, Michael S Diamond Mar 2024

Ly6c+ Monocytes In The Skin Promote Systemic Alphavirus Dissemination, Autumn C Holmes, Cormac J Lucas, Morgan E Brisse, Brian C Ware, Heather D Hickman, Thomas E Morrison, Michael S Diamond

2020-Current year OA Pubs

Alphaviruses are mosquito-transmitted pathogens that induce high levels of viremia, which facilitates dissemination and vector transmission. One prevailing paradigm is that, after skin inoculation, alphavirus-infected resident dendritic cells migrate to the draining lymph node (DLN), facilitating further rounds of infection and dissemination. Here, we assess the contribution of infiltrating myeloid cells to alphavirus spread. We observe two phases of virus transport to the DLN, one that occurs starting at 1 h post infection and precedes viral replication, and a second that requires replication in the skin, enabling transit to the bloodstream. Depletion of Ly6C


Targeting Cxcr4, Vla-4, And Cxcr2 For Hematopoietic Stem Cell Mobilization, Daniel Cancilla, Michael P Rettig, Darja Karpova, Haresh Thakellapalli, Megh Singh, Marvin J Meyers, Peter G Ruminski, Stephanie Christ, Ezhilarasi Chendamarai, Feng Gao, Leah Gehrs, Julie K Ritchey, Michael Prinsen, John F Dipersio Mar 2024

Targeting Cxcr4, Vla-4, And Cxcr2 For Hematopoietic Stem Cell Mobilization, Daniel Cancilla, Michael P Rettig, Darja Karpova, Haresh Thakellapalli, Megh Singh, Marvin J Meyers, Peter G Ruminski, Stephanie Christ, Ezhilarasi Chendamarai, Feng Gao, Leah Gehrs, Julie K Ritchey, Michael Prinsen, John F Dipersio

2020-Current year OA Pubs

No abstract provided.


Phase 2 Study Of Add-On Parsaclisib For Patients With Myelofibrosis And Suboptimal Response To Ruxolitinib: Final Results, Abdulraheem Yacoub, Stephen T Oh, Et Al. Mar 2024

Phase 2 Study Of Add-On Parsaclisib For Patients With Myelofibrosis And Suboptimal Response To Ruxolitinib: Final Results, Abdulraheem Yacoub, Stephen T Oh, Et Al.

2020-Current year OA Pubs

Ruxolitinib reduces spleen volume, improves symptoms, and increases survival in patients with intermediate- or high-risk myelofibrosis. However, suboptimal response may occur, potentially because of signaling via the phosphoinositide 3-kinase (PI3K)/protein kinase B pathway. This phase 2 study evaluated dosing, efficacy, and safety of add-on PI3Kδ inhibitor parsaclisib for patients with primary or secondary myelofibrosis with suboptimal response to ruxolitinib. Eligible patients remained on a stable ruxolitinib dose and received add-on parsaclisib 10 or 20 mg, once daily for 8 weeks, and once weekly thereafter (daily-to-weekly dosing; n = 32); or parsaclisib 5 or 20 mg, once daily for 8 weeks, …


Impact Of Imaging Frequency On Progression-Free Survival In Alliance Trials Enrolling Patients With Follicular Lymphoma, Sarah C Rutherford, Jun Yin, Levi D Pederson, Kristie A Blum, Peter Martin, Sin-Ho Jung, Barbara Grant, Cara Rosenbaum, Bruce D Cheson, Nancy L Bartlett, Sumithra J Mandrekar, John P Leonard Mar 2024

Impact Of Imaging Frequency On Progression-Free Survival In Alliance Trials Enrolling Patients With Follicular Lymphoma, Sarah C Rutherford, Jun Yin, Levi D Pederson, Kristie A Blum, Peter Martin, Sin-Ho Jung, Barbara Grant, Cara Rosenbaum, Bruce D Cheson, Nancy L Bartlett, Sumithra J Mandrekar, John P Leonard

2020-Current year OA Pubs

No abstract provided.


Intergenerational Protective Anti-Gut Commensal Immunoglobulin G Originates In Early Life, Brigida Rusconi, Adina K Bard, Ryan Mcdonough, Angel M Kindsvogel, Jacqueline D Wang, Sreeram Udayan, Keely G Mcdonald, Rodney D Newberry, Phillip I Tarr Mar 2024

Intergenerational Protective Anti-Gut Commensal Immunoglobulin G Originates In Early Life, Brigida Rusconi, Adina K Bard, Ryan Mcdonough, Angel M Kindsvogel, Jacqueline D Wang, Sreeram Udayan, Keely G Mcdonald, Rodney D Newberry, Phillip I Tarr

2020-Current year OA Pubs

Maternal immunoglobulins of the class G (IgGs) protect offspring from enteric infection, but when, where, and how these antibodies are physiologically generated and confer protection remains enigmatic. We found that circulating IgGs in adult mice preferentially bind early-life gut commensal bacteria over their own adult gut commensal bacteria. IgG-secreting plasma cells specific for early-life gut bacteria appear in the intestine soon after weaning, where they remain into adulthood. Manipulating exposure to gut bacteria or plasma cell development before, but not after, weaning reduced IgG-secreting plasma cells targeting early-life gut bacteria throughout life. Further, the development of this anti-gut commensal IgG …


The Disordered N-Terminal Tail Of Sars-Cov-2 Nucleocapsid Protein Forms A Dynamic Complex With Rna, Jasmine Cubuk, Jhullian J Alston, J Jeremías Incicco, Alex S Holehouse, Kathleen B Hall, Melissa D Stuchell-Brereton, Andrea Soranno Mar 2024

The Disordered N-Terminal Tail Of Sars-Cov-2 Nucleocapsid Protein Forms A Dynamic Complex With Rna, Jasmine Cubuk, Jhullian J Alston, J Jeremías Incicco, Alex S Holehouse, Kathleen B Hall, Melissa D Stuchell-Brereton, Andrea Soranno

2020-Current year OA Pubs

The SARS-CoV-2 Nucleocapsid (N) protein is responsible for condensation of the viral genome. Characterizing the mechanisms controlling nucleic acid binding is a key step in understanding how condensation is realized. Here, we focus on the role of the RNA binding domain (RBD) and its flanking disordered N-terminal domain (NTD) tail, using single-molecule Förster Resonance Energy Transfer and coarse-grained simulations. We quantified contact site size and binding affinity for nucleic acids and concomitant conformational changes occurring in the disordered region. We found that the disordered NTD increases the affinity of the RBD for RNA by about 50-fold. Binding of both nonspecific …


Distal Extent Of Resection In Type A Dissection: Keeping It Simple, Marc R Moon, Puja Kachroo Mar 2024

Distal Extent Of Resection In Type A Dissection: Keeping It Simple, Marc R Moon, Puja Kachroo

2020-Current year OA Pubs

No abstract provided.


The Latissimus Dorsi Creates A Dynamic Track For The Inferior Angle Of The Scapula During Arm Abduction In Humans, Alp Paksoy, Doruk Akgün, Henry Gebauer, Daniel Karczewski, Lucca Lacheta, John M Tokish, Aaron Chamberlain, Philipp Moroder Mar 2024

The Latissimus Dorsi Creates A Dynamic Track For The Inferior Angle Of The Scapula During Arm Abduction In Humans, Alp Paksoy, Doruk Akgün, Henry Gebauer, Daniel Karczewski, Lucca Lacheta, John M Tokish, Aaron Chamberlain, Philipp Moroder

2020-Current year OA Pubs

BACKGROUND: The importance of several scapulothoracic muscles, including trapezius and serratus anterior, in maintaining physiological scapula kinematics has been highlighted in the past. However, the relationship between the scapula and the latissimus dorsi muscle remains unclear. Our clinical surgical observation is that the latissimus dorsi does not directly attach but rather runs superficial to the inferior angle of the scapula. Based on this observation, we hypothesise that the latissimus dorsi creates a dynamic track on which the scapula glides under the muscle belly during elevation of the arm, creating the latissimus-scapula overlap (LSO).

METHODS: All consecutive patients who had a …


Epitope Mapping Of Japanese Encephalitis Virus Neutralizing Antibodies By Native Mass Spectrometry And Hydrogen/Deuterium Exchange, Jagat Adhikari, James Heffernan, Melissa Edeling, Estefania Fernandez, Prashant N Jethva, Michael S Diamond, Daved H Fremont, Michael L Gross Mar 2024

Epitope Mapping Of Japanese Encephalitis Virus Neutralizing Antibodies By Native Mass Spectrometry And Hydrogen/Deuterium Exchange, Jagat Adhikari, James Heffernan, Melissa Edeling, Estefania Fernandez, Prashant N Jethva, Michael S Diamond, Daved H Fremont, Michael L Gross

2020-Current year OA Pubs

Japanese encephalitis virus (JEV) remains a global public health concern due to its epidemiological distribution and the existence of multiple strains. Neutralizing antibodies against this infection have shown efficacy in in vivo studies. Thus, elucidation of the epitopes of neutralizing antibodies can aid in the design and development of effective vaccines against different strains of JEV. Here, we describe a combination of native mass spectrometry (native-MS) and hydrogen/deuterium exchange mass spectrometry (HDX-MS) to complete screening of eight mouse monoclonal antibodies (MAbs) against JEV E-DIII to identify epitope regions. Native-MS was used as a first pass to identify the antibodies that …


Mapping Human Tissues With Highly Multiplexed Rna In Situ Hybridization, Kian Kalhor, Amanda Knoten, Joseph P Gaut, Sanjay Jain, Et Al. Mar 2024

Mapping Human Tissues With Highly Multiplexed Rna In Situ Hybridization, Kian Kalhor, Amanda Knoten, Joseph P Gaut, Sanjay Jain, Et Al.

2020-Current year OA Pubs

In situ transcriptomic techniques promise a holistic view of tissue organization and cell-cell interactions. There has been a surge of multiplexed RNA in situ mapping techniques but their application to human tissues has been limited due to their large size, general lower tissue quality and high autofluorescence. Here we report DART-FISH, a padlock probe-based technology capable of profiling hundreds to thousands of genes in centimeter-sized human tissue sections. We introduce an omni-cell type cytoplasmic stain that substantially improves the segmentation of cell bodies. Our enzyme-free isothermal decoding procedure allows us to image 121 genes in large sections from the human …


Combined Kras-Mapk Pathway Inhibitors And Her2-Directed Drug Conjugate Is Efficacious In Pancreatic Cancer, Ashenafi Bulle, Peng Liu, Kuljeet Seehra, Sapana Bansod, Yali Chen, Kiran Zahra, Vikas Somani, Iftikhar Ali Khawar, Hung-Po Chen, Paarth B Dodhiawala, Lin Li, Yutong Geng, Chia-Kuei Mo, Jay Mahsl, Li Ding, Ramaswamy Govindan, Sherri Davies, Jacqueline Mudd, William G Hawkins, Ryan C Fields, David G Denardo, Jason M Held, Patrick M Grierson, Andrea Wang-Gillam, Marianna B Ruzinova, Kian-Huat Lim, Et Al. Mar 2024

Combined Kras-Mapk Pathway Inhibitors And Her2-Directed Drug Conjugate Is Efficacious In Pancreatic Cancer, Ashenafi Bulle, Peng Liu, Kuljeet Seehra, Sapana Bansod, Yali Chen, Kiran Zahra, Vikas Somani, Iftikhar Ali Khawar, Hung-Po Chen, Paarth B Dodhiawala, Lin Li, Yutong Geng, Chia-Kuei Mo, Jay Mahsl, Li Ding, Ramaswamy Govindan, Sherri Davies, Jacqueline Mudd, William G Hawkins, Ryan C Fields, David G Denardo, Jason M Held, Patrick M Grierson, Andrea Wang-Gillam, Marianna B Ruzinova, Kian-Huat Lim, Et Al.

2020-Current year OA Pubs

Targeting the mitogen-activated protein kinase (MAPK) cascade in pancreatic ductal adenocarcinoma (PDAC) remains clinically unsuccessful. We aim to develop a MAPK inhibitor-based therapeutic combination with strong preclinical efficacy. Utilizing a reverse-phase protein array, we observe rapid phospho-activation of human epidermal growth factor receptor 2 (HER2) in PDAC cells upon pharmacological MAPK inhibition. Mechanistically, MAPK inhibitors lead to swift proteasomal degradation of dual-specificity phosphatase 6 (DUSP6). The carboxy terminus of HER2, containing a TEY motif also present in extracellular signal-regulated kinase 1/2 (ERK1/2), facilitates binding with DUSP6, enhancing its phosphatase activity to dephosphorylate HER2. In the presence of MAPK inhibitors, DUSP6 …


Application Of Learned Ideal Observers For Estimating Task-Based Performance Bounds For Computed Imaging Systems, Kaiyan Li, Umberto Villa, Hua Li, Mark A. Anastasio Mar 2024

Application Of Learned Ideal Observers For Estimating Task-Based Performance Bounds For Computed Imaging Systems, Kaiyan Li, Umberto Villa, Hua Li, Mark A. Anastasio

2020-Current year OA Pubs

No abstract provided.


Differential Cognitive And Behavioral Development From 6 To 24 Months In Autism And Fragile X Syndrome, Lindsay J Mullin, Lisa Flake, Kelly N Botteron, Et Al. Mar 2024

Differential Cognitive And Behavioral Development From 6 To 24 Months In Autism And Fragile X Syndrome, Lindsay J Mullin, Lisa Flake, Kelly N Botteron, Et Al.

2020-Current year OA Pubs

BACKGROUND: Specifying early developmental differences among neurodevelopmental disorders with distinct etiologies is critical to improving early identification and tailored intervention during the first years of life. Recent studies have uncovered important differences between infants with fragile X syndrome (FXS) and infants with familial history of autism spectrum disorder who go on to develop autism themselves (FH-ASD), including differences in brain development and behavior. Thus far, there have been no studies longitudinally investigating differential developmental skill profiles in FXS and FH-ASD infants.

METHODS: The current study contrasted longitudinal trajectories of verbal (expressive and receptive language) and nonverbal (gross and fine motor, …


Pathogenic Variants In Crx Have Distinct Cis-Regulatory Effects On Enhancers And Silencers In Photoreceptors, James L Shepherdson, Ryan Z Friedman, Yiqiao Zheng, Chi Sun, Inez Y Oh, David M Granas, Barak A Cohen, Shiming Chen, Michael A White Mar 2024

Pathogenic Variants In Crx Have Distinct Cis-Regulatory Effects On Enhancers And Silencers In Photoreceptors, James L Shepherdson, Ryan Z Friedman, Yiqiao Zheng, Chi Sun, Inez Y Oh, David M Granas, Barak A Cohen, Shiming Chen, Michael A White

2020-Current year OA Pubs

Dozens of variants in the gene for the homeodomain transcription factor (TF) cone-rod homeobox (


Two Dot1 Enzymes Cooperatively Mediate Efficient Ubiquitin-Independent Histone H3 Lysine 76 Tri-Methylation In Kinetoplastids, Victoria S Frisbie, Hideharu Hashimoto, Yixuan Xie, Francisca N De Luna Vitorino, Josue Baeza, Tam Nguyen, Zhangerjiao Yuan, Janna Kiselar, Benjamin A Garcia, Erik W Debler Mar 2024

Two Dot1 Enzymes Cooperatively Mediate Efficient Ubiquitin-Independent Histone H3 Lysine 76 Tri-Methylation In Kinetoplastids, Victoria S Frisbie, Hideharu Hashimoto, Yixuan Xie, Francisca N De Luna Vitorino, Josue Baeza, Tam Nguyen, Zhangerjiao Yuan, Janna Kiselar, Benjamin A Garcia, Erik W Debler

2020-Current year OA Pubs

In higher eukaryotes, a single DOT1 histone H3 lysine 79 (H3K79) methyltransferase processively produces H3K79me2/me3 through histone H2B mono-ubiquitin interaction, while the kinetoplastid Trypanosoma brucei di-methyltransferase DOT1A and tri-methyltransferase DOT1B efficiently methylate the homologous H3K76 without H2B mono-ubiquitination. Based on structural and biochemical analyses of DOT1A, we identify key residues in the methyltransferase motifs VI and X for efficient ubiquitin-independent H3K76 methylation in kinetoplastids. Substitution of a basic to an acidic residue within motif VI (Gx


Predation Without Direction Selectivity, Jenna Krizan, Xiayingfang Song, Michael J Fitzpatrick, Ning Shen, Florentina Soto, Daniel Kerschensteiner Mar 2024

Predation Without Direction Selectivity, Jenna Krizan, Xiayingfang Song, Michael J Fitzpatrick, Ning Shen, Florentina Soto, Daniel Kerschensteiner

2020-Current year OA Pubs

Across the animal kingdom, visual predation relies on motion-sensing neurons in the superior colliculus (SC) and its orthologs. These neurons exhibit complex stimulus preferences, including direction selectivity, which is thought to be critical for tracking the unpredictable escape routes of prey. The source of direction selectivity in the SC is contested, and its contributions to predation have not been tested experimentally. Here, we use type-specific cell removal to show that narrow-field (NF) neurons in the mouse SC guide predation. In vivo recordings demonstrate that direction-selective responses of NF cells are independent of recently reported stimulus-edge effects. Monosynaptic retrograde tracing reveals …


Prediction Of 3-Dimensional Coverage Surface Area Of The Femoral Head In Hip Dysplasia Through Conventional Computed Tomography, Tomoyuki Kamenaga, Lucas Ritacco, Pablo A Slullitel, Chadi Nahal, Jeffrey J Nepple, John C Clohisy, Cecilia Pascual-Garrido Mar 2024

Prediction Of 3-Dimensional Coverage Surface Area Of The Femoral Head In Hip Dysplasia Through Conventional Computed Tomography, Tomoyuki Kamenaga, Lucas Ritacco, Pablo A Slullitel, Chadi Nahal, Jeffrey J Nepple, John C Clohisy, Cecilia Pascual-Garrido

2020-Current year OA Pubs

BACKGROUND: Assessment of 3-dimensional (3D) femoral head coverage is critical in evaluating, preoperative planning, and treating hip dysplasia.

PURPOSE: To (1) propose a mathematical model to establish 3D femoral head coverage using conventional computed tomography (CT), (2) determine the correlation of 2D parameters with 3D coverage, and (3) characterize the patterns of dysplasia based on 3D morphology.

STUDY DESIGN: Cross-sectional study; Level of evidence, 3.

METHODS: We identified 30 patients (n = hips) with symptomatic dysplasia and 30 patients (n = hips) without dysplasia. Patients with dysplastic hips were matched with regard to sex, age, and body mass index to …


Therapeutic Benefit Of Idebenone In Patients With Leber Hereditary Optic Neuropathy: The Leros Nonrandomized Controlled Trial, Patrick Yu-Wai-Man, Gregory Van Stavern, Et Al. Mar 2024

Therapeutic Benefit Of Idebenone In Patients With Leber Hereditary Optic Neuropathy: The Leros Nonrandomized Controlled Trial, Patrick Yu-Wai-Man, Gregory Van Stavern, Et Al.

2020-Current year OA Pubs

Leber hereditary optic neuropathy (LHON) is a mitochondrial disease leading to rapid and severe bilateral vision loss. Idebenone has been shown to be effective in stabilizing and restoring vision in patients treated within 1 year of onset of vision loss. The open-label, international, multicenter, natural history-controlled LEROS study (ClinicalTrials.gov NCT02774005) assesses the efficacy and safety of idebenone treatment (900 mg/day) in patients with LHON up to 5 years after symptom onset (N = 199) and over a treatment period of 24 months, compared to an external natural history control cohort (N = 372), matched by time since symptom onset. LEROS …


Prophylactic Defunctioning Stomas Improve Clinical Outcomes Of Anastomotic Leak Following Rectal Cancer Resections: An Analysis Of The Us Rectal Cancer Consortium, Katherine Hrebinko, Vincent P Anto, Katherine M Reitz, Adriana C Gamboa, Scott E Regenbogen, Alexander T Hawkins, M Benjamin Hopkins, Aslam Ejaz, Philip S Bauer, Paul E Wise, Glen C Balch, Jennifer Holder-Murray Mar 2024

Prophylactic Defunctioning Stomas Improve Clinical Outcomes Of Anastomotic Leak Following Rectal Cancer Resections: An Analysis Of The Us Rectal Cancer Consortium, Katherine Hrebinko, Vincent P Anto, Katherine M Reitz, Adriana C Gamboa, Scott E Regenbogen, Alexander T Hawkins, M Benjamin Hopkins, Aslam Ejaz, Philip S Bauer, Paul E Wise, Glen C Balch, Jennifer Holder-Murray

2020-Current year OA Pubs

PURPOSE: Anastomotic leak (AL) is a complication of low anterior resection (LAR) that results in substantial morbidity. There is immense interest in evaluating immediate postoperative and long-term oncologic outcomes in patients who undergo diverting loop ileostomies (DLI). The purpose of this study is to understand the relationship between fecal diversion, AL, and oncologic outcomes.

METHODS: This is a retrospective multicenter cohort study using patient data obtained from the US Rectal Cancer Consortium database compiled from six academic institutions. The study population included patients with rectal adenocarcinoma undergoing LAR. The primary outcome was the incidence of AL among patients who did …


Htra1 Disaggregates Α-Synuclein Amyloid Fibrils And Converts Them Into Non-Toxic And Seeding Incompetent Species, Sheng Chen, Anuradhika Puri, Braxton Bell, Joseph Fritsche, Hector H Palacios, Maurie Balch, Macy L Sprunger, Matthew K Howard, Jeremy J Ryan, Jessica N Haines, Gary J Patti, Albert A Davis, Meredith E Jackrel Mar 2024

Htra1 Disaggregates Α-Synuclein Amyloid Fibrils And Converts Them Into Non-Toxic And Seeding Incompetent Species, Sheng Chen, Anuradhika Puri, Braxton Bell, Joseph Fritsche, Hector H Palacios, Maurie Balch, Macy L Sprunger, Matthew K Howard, Jeremy J Ryan, Jessica N Haines, Gary J Patti, Albert A Davis, Meredith E Jackrel

2020-Current year OA Pubs

Parkinson's disease (PD) is closely linked to α-synuclein (α-syn) misfolding and accumulation in Lewy bodies. The PDZ serine protease HTRA1 degrades fibrillar tau, which is associated with Alzheimer's disease, and inactivating mutations to mitochondrial HTRA2 are implicated in PD. Here, we report that HTRA1 inhibits aggregation of α-syn as well as FUS and TDP-43, which are implicated in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. The protease domain of HTRA1 is necessary and sufficient for inhibiting aggregation, yet this activity is proteolytically-independent. Further, HTRA1 disaggregates preformed α-syn fibrils, rendering them incapable of seeding aggregation of endogenous α-syn, while reducing HTRA1 …


Sequence-Structure-Function Characterization Of The Emerging Tetracycline Destructase Family Of Antibiotic Resistance Enzymes, Kevin S Blake, Hirdesh Kumar, Anisha Loganathan, Emily E Williford, Luke Diorio-Toth, Yao-Peng Xue, Wai Kwan Tang, Tayte P Campbell, David D Chong, Steven Angtuaco, Timothy A Wencewicz, Niraj H Tolia, Gautam Dantas Mar 2024

Sequence-Structure-Function Characterization Of The Emerging Tetracycline Destructase Family Of Antibiotic Resistance Enzymes, Kevin S Blake, Hirdesh Kumar, Anisha Loganathan, Emily E Williford, Luke Diorio-Toth, Yao-Peng Xue, Wai Kwan Tang, Tayte P Campbell, David D Chong, Steven Angtuaco, Timothy A Wencewicz, Niraj H Tolia, Gautam Dantas

2020-Current year OA Pubs

Tetracycline destructases (TDases) are flavin monooxygenases which can confer resistance to all generations of tetracycline antibiotics. The recent increase in the number and diversity of reported TDase sequences enables a deep investigation of the TDase sequence-structure-function landscape. Here, we evaluate the sequence determinants of TDase function through two complementary approaches: (1) constructing profile hidden Markov models to predict new TDases, and (2) using multiple sequence alignments to identify conserved positions important to protein function. Using the HMM-based approach we screened 50 high-scoring candidate sequences in Escherichia coli, leading to the discovery of 13 new TDases. The X-ray crystal structures of …


Treatment Setting And Buprenorphine Discontinuation: An Analysis Of Multi-State Insurance Claims, Kevin Y Xu, Alex K Gertner, Shelly F Greenfield, Arthur Robin Williams, Richard A Grucza Mar 2024

Treatment Setting And Buprenorphine Discontinuation: An Analysis Of Multi-State Insurance Claims, Kevin Y Xu, Alex K Gertner, Shelly F Greenfield, Arthur Robin Williams, Richard A Grucza

2020-Current year OA Pubs

BACKGROUND: Potential differences in buprenorphine treatment outcomes across various treatment settings are poorly characterized in multi-state administrative data. We thus evaluated the association of opioid use disorder (OUD) treatment setting and insurance type with risk of buprenorphine discontinuation among commercial insurance and Medicaid enrollees initiated on buprenorphine.

METHODS: In this observational, retrospective cohort study using the Merative MarketScan databases (2006-2016), we analyzed buprenorphine retention in 58,200 US adults with OUD. Predictor variables included insurance status (Medicaid vs commercial) and treatment setting, operationalized as substance use disorder (SUD) specialty treatment facility versus outpatient primary care physicians (PCPs) versus outpatient psychiatry, ascertained …