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Full-Text Articles in Medicine and Health Sciences
Dna Combing Versus Dna Spreading And The Separation Of Sister Chromatids, Alice Meroni, Sophie E Wells, Carmen Fonseca, Arnab Ray Chaudhuri, Keith W Caldecott, Alessandro Vindigni
Dna Combing Versus Dna Spreading And The Separation Of Sister Chromatids, Alice Meroni, Sophie E Wells, Carmen Fonseca, Arnab Ray Chaudhuri, Keith W Caldecott, Alessandro Vindigni
2020-Current year OA Pubs
DNA combing and DNA spreading are two central approaches for studying DNA replication fork dynamics genome-wide at single-molecule resolution by distributing labeled genomic DNA on coverslips or slides for immunodetection. Perturbations in DNA replication fork dynamics can differentially affect either leading or lagging strand synthesis, for example, in instances where replication is blocked by a lesion or obstacle on only one of the two strands. Thus, we sought to investigate whether the DNA combing and/or spreading approaches are suitable for resolving adjacent sister chromatids during DNA replication, thereby enabling the detection of DNA replication dynamics within individual nascent strands. To …
Cognitive Flexibility Training For Chronic Pain: A Randomized Clinical Study, Katherine J. Holzer, Marko S. Todorovic, Elizabeth A. Wilson, Aaron Steinberg, Michael S. Avidan, Simon Haroutounian
Cognitive Flexibility Training For Chronic Pain: A Randomized Clinical Study, Katherine J. Holzer, Marko S. Todorovic, Elizabeth A. Wilson, Aaron Steinberg, Michael S. Avidan, Simon Haroutounian
2020-Current year OA Pubs
INTRODUCTION: Previous studies suggest an association between cognitive flexibility and development of chronic pain after surgery. It is not known whether cognitive flexibility can be improved in patients with chronic pain.
OBJECTIVES: This study tested whether a neurocognitive training program results in improved cognitive flexibility and pain in patients with chronic pain.
METHODS: We conducted a single-center, prospective, randomized study investigating 5-week daily neurocognitive training in patients with chronic pain. Participants (n = 145) were randomized into neurocognitive training or care as usual, and they completed assessments at baseline, posttreatment, and 3 months. The treatment group was asked to spend …
Reliability And Validity Of Smartphone Cognitive Testing For Frontotemporal Lobar Degeneration, Adam M Staffaroni, Nupur Ghoshal, Jason Hassenstab, Et Al.
Reliability And Validity Of Smartphone Cognitive Testing For Frontotemporal Lobar Degeneration, Adam M Staffaroni, Nupur Ghoshal, Jason Hassenstab, Et Al.
2020-Current year OA Pubs
IMPORTANCE: Frontotemporal lobar degeneration (FTLD) is relatively rare, behavioral and motor symptoms increase travel burden, and standard neuropsychological tests are not sensitive to early-stage disease. Remote smartphone-based cognitive assessments could mitigate these barriers to trial recruitment and success, but no such tools are validated for FTLD.
OBJECTIVE: To evaluate the reliability and validity of smartphone-based cognitive measures for remote FTLD evaluations.
DESIGN, SETTING, AND PARTICIPANTS: In this cohort study conducted from January 10, 2019, to July 31, 2023, controls and participants with FTLD performed smartphone application (app)-based executive functioning tasks and an associative memory task 3 times over 2 weeks. …
Sensitive Mrd Detection From Lymphatic Fluid After Surgery In Hpv-Associated Oropharyngeal Cancer, Noah Earland, Nicholas P Semenkovich, Ricardo J Ramirez, Peter K Harris, Andrew I Hearn, Matthew Inkman, Jeffrey J Szymanski, Benjamin M Wahle, Kevin Chen, Irfan Alahi, Gabris Ni, Andrew Chen, Jin Zhang, Aadel A Chaudhuri, Et Al.
Sensitive Mrd Detection From Lymphatic Fluid After Surgery In Hpv-Associated Oropharyngeal Cancer, Noah Earland, Nicholas P Semenkovich, Ricardo J Ramirez, Peter K Harris, Andrew I Hearn, Matthew Inkman, Jeffrey J Szymanski, Benjamin M Wahle, Kevin Chen, Irfan Alahi, Gabris Ni, Andrew Chen, Jin Zhang, Aadel A Chaudhuri, Et Al.
2020-Current year OA Pubs
PURPOSE: Our goal was to demonstrate that lymphatic drainage fluid (lymph) has improved sensitivity in quantifying postoperative minimal residual disease (MRD) in locally advanced human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) compared with plasma, and leverage this novel biofluid for patient risk stratification.
EXPERIMENTAL DESIGN: We prospectively collected lymph samples from neck drains of 106 patients with HPV (+) OPSCC, along with 67 matched plasma samples, 24 hours after surgery. PCR and next-generation sequencing were used to quantify cancer-associated cell-free HPV (cf-HPV) and tumor-informed variants in lymph and plasma. Next, lymph cf-HPV and variants were compared with TNM stage, …
Prevotella Copri And Microbiota Members Mediate The Beneficial Effects Of A Therapeutic Food For Malnutrition, Hao-Wei Chang, Evan M Lee, Yi Wang, Cyrus Zhou, Kali M Pruss, Suzanne Henrissat, Robert Y Chen, Clara Kao, Matthew C Hibberd, Hannah M Lynn, Daniel M Webber, Marie Crane, Jiye Cheng, Ye Chen, Jeffrey I Gordon, Et Al.
Prevotella Copri And Microbiota Members Mediate The Beneficial Effects Of A Therapeutic Food For Malnutrition, Hao-Wei Chang, Evan M Lee, Yi Wang, Cyrus Zhou, Kali M Pruss, Suzanne Henrissat, Robert Y Chen, Clara Kao, Matthew C Hibberd, Hannah M Lynn, Daniel M Webber, Marie Crane, Jiye Cheng, Ye Chen, Jeffrey I Gordon, Et Al.
2020-Current year OA Pubs
Microbiota-directed complementary food (MDCF) formulations have been designed to repair the gut communities of malnourished children. A randomized controlled trial demonstrated that one formulation, MDCF-2, improved weight gain in malnourished Bangladeshi children compared to a more calorically dense standard nutritional intervention. Metagenome-assembled genomes from study participants revealed a correlation between ponderal growth and expression of MDCF-2 glycan utilization pathways by Prevotella copri strains. To test this correlation, here we use gnotobiotic mice colonized with defined consortia of age- and ponderal growth-associated gut bacterial strains, with or without P. copri isolates closely matching the metagenome-assembled genomes. Combining gut metagenomics and metatranscriptomics …
Exploring The Association Between Weight Loss-Inducing Medications And Multiple Sclerosis: Insights From The Fda Adverse Event Reporting System Database, Afsaneh Shirani, Anne H Cross, Olaf Stuve
Exploring The Association Between Weight Loss-Inducing Medications And Multiple Sclerosis: Insights From The Fda Adverse Event Reporting System Database, Afsaneh Shirani, Anne H Cross, Olaf Stuve
2020-Current year OA Pubs
BACKGROUND: Several studies have demonstrated that early childhood and adolescent obesity are risk factors for multiple sclerosis (MS) susceptibility. Obesity is thought to share inflammatory components with MS through overproduction of pro-inflammatory adipokines (e.g., leptin) and reduction of anti-inflammatory adipokines (e.g, adiponectin). Recently, drug repurposing (i.e. identifying new indications for existing drugs) has garnered significant attention. The US Food and Drug Administration Adverse Event Reporting System (FAERS) database serves not only as a resource for mining adverse drug reactions and safety signals but also for identifying inverse associations and potential medication repurposing opportunities.
OBJECTIVE: We aimed to explore the association …
Incidence And Mortality Of Covid-19-Associated Invasive Fungal Infections Among Critically Ill Intubated Patients: A Multicenter Retrospective Cohort Analysis, Julio C Zuniga-Moya, Benjamin Papadopoulos, Armaghan-E-Rehman Mansoor, Patrick B Mazi, Adriana M Rauseo, Andrej Spec
Incidence And Mortality Of Covid-19-Associated Invasive Fungal Infections Among Critically Ill Intubated Patients: A Multicenter Retrospective Cohort Analysis, Julio C Zuniga-Moya, Benjamin Papadopoulos, Armaghan-E-Rehman Mansoor, Patrick B Mazi, Adriana M Rauseo, Andrej Spec
2020-Current year OA Pubs
BACKGROUND: An association between coronavirus disease 2019 (COVID-19)-associated invasive fungal infections (CAIFIs) and high mortality among intubated patients has been suggested in previous research. However, some of the current evidence was derived from small case series and multicenter studies conducted during different waves of the COVID-19 pandemic. We examined the incidence of CAIFIs and their associated mortality using a large, multicenter COVID-19 database built throughout the pandemic.
METHODS: We conducted a retrospective analysis of the National COVID Cohort Collaborative (N3C) database collected from 76 medical centers in the United States between January 2020 and August 2022. Patients were 18 years …
Pyridoxine Challenge Reflects Pediatric Hypophosphatasia Severity And Thereby Examines Tissue-Nonspecific Alkaline Phosphatase's Role In Vitamin B6 Metabolism, Michael P Whyte, Fan Zhang, Karen E Mack, Deborah Wenkert, Gary S Gottesman, Karen L Ericson, Jeffrey T Cole, Stephen P Coburn
Pyridoxine Challenge Reflects Pediatric Hypophosphatasia Severity And Thereby Examines Tissue-Nonspecific Alkaline Phosphatase's Role In Vitamin B6 Metabolism, Michael P Whyte, Fan Zhang, Karen E Mack, Deborah Wenkert, Gary S Gottesman, Karen L Ericson, Jeffrey T Cole, Stephen P Coburn
2020-Current year OA Pubs
Alkaline phosphatase (ALP) is detected in most human tissues. However, ALP activity is routinely assayed using high concentrations of artificial colorimetric substrates in phosphate-free laboratory buffers at lethal pH. Hypophosphatasia (HPP) is the inborn-error-of-metabolism caused by loss-of-function mutation(s) of the ALPL gene that encodes the ALP isoenzyme expressed in bone, liver, kidney, and elsewhere and is therefore designated "tissue-nonspecific" ALP (TNSALP). Consequently, HPP harbors clues concerning the biological function of this phosphohydrolase that is anchored onto the surface of cells. The biochemical signature of HPP features low serum ALP activity (hypophosphatasemia) together with elevated plasma levels of three natural substrates …
The Impact Of Individual-Level Income Predicted From The Brfss On The Association Between Insurance Status And Overall Survival Among Adults With Cancer From The Seer Program, Justin M Barnes, Kimberly J Johnson, Nosayaba Osazuwa-Peters, Matthew B Spraker
The Impact Of Individual-Level Income Predicted From The Brfss On The Association Between Insurance Status And Overall Survival Among Adults With Cancer From The Seer Program, Justin M Barnes, Kimberly J Johnson, Nosayaba Osazuwa-Peters, Matthew B Spraker
2020-Current year OA Pubs
INTRODUCTION: Among patients with cancer in the United States, Medicaid insurance is associated with worse outcomes than private insurance and with similar outcomes as being uninsured. However, prior studies have not addressed the impact of individual-level socioeconomic status, which determines Medicaid eligibility, on the associations of Medicaid status and cancer outcomes. Our objective was to determine whether differences in cancer outcomes by insurance status persist after accounting for individual-level income.
METHODS: The Surveillance, Epidemiology, and End Results (SEER) database was queried for 18-64 year-old individuals with cancer from 2014-2016. Individual-level income was imputed using a model trained on Behavioral Risk …
Who's Essential Medicines And Aware: Recommendations On First- And Second-Choice Antibiotics For Empiric Treatment Of Clinical Infections, Lorenzo Moja, Sumanth Gandra, Et Al.
Who's Essential Medicines And Aware: Recommendations On First- And Second-Choice Antibiotics For Empiric Treatment Of Clinical Infections, Lorenzo Moja, Sumanth Gandra, Et Al.
2020-Current year OA Pubs
The WHO Model List of Essential Medicines (EML) prioritizes medicines that have significant global public health value. The EML can also deliver important messages on appropriate medicine use. Since 2017, in response to the growing challenge of antimicrobial resistance, antibiotics on the EML have been reviewed and categorized into three groups: Access, Watch, and Reserve, leading to a new categorization called AWaRe. These categories were developed taking into account the impact of different antibiotics and classes on antimicrobial resistance and the implications for their appropriate use. The 2023 AWaRe classification provides empirical guidance on 41 essential antibiotics for over 30 …
Early Treatment With Fluvoxamine, Bromhexine, Cyproheptadine, And Niclosamide To Prevent Clinical Deterioration In Patients With Symptomatic Covid-19: A Randomized Clinical Trial, Dhammika Leshan Wannigama, Angela M Reiersen, Et Al.
Early Treatment With Fluvoxamine, Bromhexine, Cyproheptadine, And Niclosamide To Prevent Clinical Deterioration In Patients With Symptomatic Covid-19: A Randomized Clinical Trial, Dhammika Leshan Wannigama, Angela M Reiersen, Et Al.
2020-Current year OA Pubs
BACKGROUND: Repurposed drugs with host-directed antiviral and immunomodulatory properties have shown promise in the treatment of COVID-19, but few trials have studied combinations of these agents. The aim of this trial was to assess the effectiveness of affordable, widely available, repurposed drugs used in combination for treatment of COVID-19, which may be particularly relevant to low-resource countries.
METHODS: We conducted an open-label, randomized, outpatient, controlled trial in Thailand from October 1, 2021, to June 21, 2022, to assess whether early treatment within 48-h of symptoms onset with combinations of fluvoxamine, bromhexine, cyproheptadine, and niclosamide, given to adults with confirmed mild …
The Performance Of 11 Fingertip Pulse Oximeters During Hypoxemia In Healthy Human Participants With Varied, Quantified Skin Pigment, Gregory Leeb, Leonid Shmuylovich, Et Al.
The Performance Of 11 Fingertip Pulse Oximeters During Hypoxemia In Healthy Human Participants With Varied, Quantified Skin Pigment, Gregory Leeb, Leonid Shmuylovich, Et Al.
2020-Current year OA Pubs
BACKGROUND: Fingertip pulse oximeters are widely available, inexpensive, and commonly used to make clinical decisions in many settings. Device performance is largely unregulated and poorly characterised, especially in people with dark skin pigmentation.
METHODS: Eleven popular fingertip pulse oximeters were evaluated using the US Food and Drug Administration (FDA) Guidance (2013) and International Organization for Standardization Standards (ISO, 2017) in 34 healthy humans with diverse skin pigmentation utilising a controlled desaturation study with arterial oxygen saturation (SaO 2) plateaus between 70% and 100%. Skin pigmentation was assessed subjectively using a perceived Fitzpatrick Scale (pFP) and objectively using the individual typology …
Epigenetic Underpinnings Of Tumor-Immune Dynamics In Prostate Cancer Immune Suppression, Duminduni Hewa Angappulige, Nupam P Mahajan, Kiran Mahajan
Epigenetic Underpinnings Of Tumor-Immune Dynamics In Prostate Cancer Immune Suppression, Duminduni Hewa Angappulige, Nupam P Mahajan, Kiran Mahajan
2020-Current year OA Pubs
Prostate cancer (PC) is immunosuppressive and refractory to immunotherapy. Infiltration of myeloid-derived suppressor cells (MDSCs) and senescent-like neutrophils and T cell exhaustion are observed in the tumor microenvironment (TME) following androgen receptor (AR) antagonism with antiandrogens or androgen ablation. De novo post-translational acetylation of the AR, HOXB13, and H2A at K609, K13, and K130, respectively, and phosphorylation of H4 at Y88 have emerged as key epigenetic modifications associated with castration-resistant PC (CRPC). The resulting chromatin changes are integrated into cellular processes via phosphorylation of the AR, ACK1, ATPF1A, and SREBP1 at Y267, Y284, Y243/Y246, and Y673/Y951, respectively. In this review, …
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.
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.
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.
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
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 …
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.
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 …
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
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
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
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.
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, …
Next Generation Microfluidics: Fulfilling The Promise Of Lab-On-A-Chip Technologies, Umut A Gurkan, Jorge Di Paola, Et Al.
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 …
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
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
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 …
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
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 (
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
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.
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 …
Application Of Learned Ideal Observers For Estimating Task-Based Performance Bounds For Computed Imaging Systems, Kaiyan Li, Umberto Villa, Hua Li, Mark A. Anastasio
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.
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, …