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Full-Text Articles in Medicine and Health Sciences
A Bistable Inhibitory Optogpcr For Multiplexed Optogenetic Control Of Neural Circuits, Jonas Wietek, Bobbie J Brown, Bryan A Copits, Et Al.
A Bistable Inhibitory Optogpcr For Multiplexed Optogenetic Control Of Neural Circuits, Jonas Wietek, Bobbie J Brown, Bryan A Copits, Et Al.
2020-Current year OA Pubs
Information is transmitted between brain regions through the release of neurotransmitters from long-range projecting axons. Understanding how the activity of such long-range connections contributes to behavior requires efficient methods for reversibly manipulating their function. Chemogenetic and optogenetic tools, acting through endogenous G-protein-coupled receptor pathways, can be used to modulate synaptic transmission, but existing tools are limited in sensitivity, spatiotemporal precision or spectral multiplexing capabilities. Here we systematically evaluated multiple bistable opsins for optogenetic applications and found that the Platynereis dumerilii ciliary opsin (PdCO) is an efficient, versatile, light-activated bistable G-protein-coupled receptor that can suppress synaptic transmission in mammalian neurons with …
Gene Expression Networks Regulated By Human Personality, Coral Del Val, Elisa Díaz De La Guardia-Bolívar, Igor Zwir, Pashupati P Mishra, Alberto Mesa, Ramiro Salas, Guillermo F Poblete, Gabriel De Erausquin, Emma Raitoharju, Mika Kähönen, Olli Raitakari, Liisa Keltikangas-Järvinen, Terho Lehtimäki, Claude Robert Cloninger
Gene Expression Networks Regulated By Human Personality, Coral Del Val, Elisa Díaz De La Guardia-Bolívar, Igor Zwir, Pashupati P Mishra, Alberto Mesa, Ramiro Salas, Guillermo F Poblete, Gabriel De Erausquin, Emma Raitoharju, Mika Kähönen, Olli Raitakari, Liisa Keltikangas-Järvinen, Terho Lehtimäki, Claude Robert Cloninger
2020-Current year OA Pubs
Genome-wide association studies of human personality have been carried out, but transcription of the whole genome has not been studied in relation to personality in humans. We collected genome-wide expression profiles of adults to characterize the regulation of expression and function in genes related to human personality. We devised an innovative multi-omic approach to network analysis to identify the key control elements and interactions in multi-modular networks. We identified sets of transcribed genes that were co-expressed in specific brain regions with genes known to be associated with personality. Then we identified the minimum networks for the co-localized genes using bioinformatic …
Alcohol Milestones And Internalizing, Externalizing, And Executive Function: Longitudinal And Polygenic Score Associations, Sarah E Paul, David A A Baranger, Joshua J Jackson, Aaron J Gorelik, Alexander S Hatoum, Michael Strube, Andrey P Anokhin, Arpana Agrawal, Kathleen K Bucholz, Ryan Bogdan, Et Al.
Alcohol Milestones And Internalizing, Externalizing, And Executive Function: Longitudinal And Polygenic Score Associations, Sarah E Paul, David A A Baranger, Joshua J Jackson, Aaron J Gorelik, Alexander S Hatoum, Michael Strube, Andrey P Anokhin, Arpana Agrawal, Kathleen K Bucholz, Ryan Bogdan, Et Al.
2020-Current year OA Pubs
BACKGROUND: Although the link between alcohol involvement and behavioral phenotypes (e.g. impulsivity, negative affect, executive function [EF]) is well-established, the directionality of these associations, specificity to stages of alcohol involvement, and extent of shared genetic liability remain unclear. We estimate longitudinal associations between transitions among alcohol milestones, behavioral phenotypes, and indices of genetic risk.
METHODS: Data came from the Collaborative Study on the Genetics of Alcoholism (
RESULTS: Externalizing phenotypes (e.g. conduct disorder symptoms) were associated with future initiation and drinking problems (hazard ratio (HR)⩾1.16). Internalizing (e.g. social anxiety) was associated with hazards for progression from first drink to severe …
Origins Of Cancer: Ain't It Just Mature Cells Misbehaving?, Charles J Cho, Jeffrey W Brown, Jason C Mills
Origins Of Cancer: Ain't It Just Mature Cells Misbehaving?, Charles J Cho, Jeffrey W Brown, Jason C Mills
2020-Current year OA Pubs
A pervasive view is that undifferentiated stem cells are alone responsible for generating all other cells and are the origins of cancer. However, emerging evidence demonstrates fully differentiated cells are plastic, can be coaxed to proliferate, and also play essential roles in tissue maintenance, regeneration, and tumorigenesis. Here, we review the mechanisms governing how differentiated cells become cancer cells. First, we examine the unique characteristics of differentiated cell division, focusing on why differentiated cells are more susceptible than stem cells to accumulating mutations. Next, we investigate why the evolution of multicellularity in animals likely required plastic differentiated cells that maintain …
Feasibility Of Simulation Free Abdominal Stereotactic Adaptive Radiotherapy Using An Expedited Pre-Plan Workflow, Alex T Price, Joshua P Schiff, Alice Silberstein, Robbie Beckert, Tianyu Zhao, Geoffrey D Hugo, Pamela P Samson, Eric Laugeman, Lauren E Henke
Feasibility Of Simulation Free Abdominal Stereotactic Adaptive Radiotherapy Using An Expedited Pre-Plan Workflow, Alex T Price, Joshua P Schiff, Alice Silberstein, Robbie Beckert, Tianyu Zhao, Geoffrey D Hugo, Pamela P Samson, Eric Laugeman, Lauren E Henke
2020-Current year OA Pubs
BACKGROUND AND PURPOSE: Improved hounsfield-unit accuracy of on-board imaging may lead to direct-to-unit treatment approaches We aimed to demonstrate the feasibility of using only a diagnostic (dx) computed tomography (CT)-defined target pre-plan in an
MATERIALS AND METHODS: Eight patients with abdominal treatment sites (five pancreatic cancer, three oligometastases) were treated using an integrated adaptive O-Ring gantry system. Each patient's target was delineated on a dxCT. The target only pre-plan served primarily to seed the ART process. During the ART session, all structures were delineated. All simulated cases were treated to 50 Gy in 5 fractions to a planning target optimization …
Dlg1 Functions Upstream Of Sdccag3 And Ift20 To Control Ciliary Targeting Of Polycystin-2, Csenge K Rezi, Tao Cheng, Jeffrey H Miner, Moe R Mahjoub, Et Al.
Dlg1 Functions Upstream Of Sdccag3 And Ift20 To Control Ciliary Targeting Of Polycystin-2, Csenge K Rezi, Tao Cheng, Jeffrey H Miner, Moe R Mahjoub, Et Al.
2020-Current year OA Pubs
Polarized vesicular trafficking directs specific receptors and ion channels to cilia, but the underlying mechanisms are poorly understood. Here we describe a role for DLG1, a core component of the Scribble polarity complex, in regulating ciliary protein trafficking in kidney epithelial cells. Conditional knockout of Dlg1 in mouse kidney causes ciliary elongation and cystogenesis, and cell-based proximity labeling proteomics and fluorescence microscopy show alterations in the ciliary proteome upon loss of DLG1. Specifically, the retromer-associated protein SDCCAG3, IFT20, and polycystin-2 (PC2) are reduced in the cilia of DLG1-deficient cells compared to control cells. This phenotype is recapitulated in vivo and …
Evaluation Of Markers Of Immunity In Different Metastatic Immune Microenvironments Suggests More Suppression Within Breast To Liver Metastases In Breast Cancer, Robert Hsu, Foluso O Ademuyiwa, Et Al.
Evaluation Of Markers Of Immunity In Different Metastatic Immune Microenvironments Suggests More Suppression Within Breast To Liver Metastases In Breast Cancer, Robert Hsu, Foluso O Ademuyiwa, Et Al.
2020-Current year OA Pubs
PURPOSE: Programmed death receptor ligand-1 (PD-L1) expression and tumor mutational burden (TMB) are approved screening biomarkers for immune checkpoint inhibition (ICI) in advanced triple negative breast cancer. We examined these biomarkers along with characterization of the tumor microenvironment (TME) between breast tumors (BrTs), axillary metastases (AxMs), liver metastases (LvMs), non-axillary lymph node metastases, and non-liver metastases to determine differences related to site of metastatic disease.
METHODS: 3076 unpaired biopsies from breast cancer patients were analyzed using whole transcriptome sequencing and NextGen DNA depicting TMB within tumor sites. The PD-L1 positivity was determined with VENTANA PD-L1 (SP142) assay. The immune cell …
Spinal Calcifying Pseudoneoplasms Of The Neuraxis: A Case Report And Review Of The Literature, Ajay Chatrath, Mackenzie Lemieux, Rujvee P Patel, Kaleigh F Roberts, Sonika Dahiya, Brenton Pennicooke
Spinal Calcifying Pseudoneoplasms Of The Neuraxis: A Case Report And Review Of The Literature, Ajay Chatrath, Mackenzie Lemieux, Rujvee P Patel, Kaleigh F Roberts, Sonika Dahiya, Brenton Pennicooke
2020-Current year OA Pubs
Calcifying pseudoneoplasms of the neuraxis (CAPNON) are rare, non-neoplastic, slow-growing tumors that can present anywhere throughout the central nervous system. While the etiology of these lesions remains unknown, the mainstay of treatment is surgical excision. We describe a case of CAPNON at our institution in a 66 year-old female patient who presented with 5 months of pain and burning sensation in her thigh. On MRI, an intradural extramedullary lesion was identified at the level of T11-T12. The mass was surgically excised and the patient reported resolution of her symptoms by her six week follow-up appointment. We reviewed 79 spinal CAPNON …
Vaso-Lock For Sutureless Anastomosis In A Pig Arteriovenous Loop Model, Xiaowei Li, Emma R Young, Cameron Martin, Joseph G Ribaudo, Mohamed Zaghloul, Sophia Roberts, Rodrigo Meade, Batool Arif, William R Moritz, Sarah Madira, Jonathon B Schofield, Mohamed A Zayed, Justin M Sacks, Et Al.
Vaso-Lock For Sutureless Anastomosis In A Pig Arteriovenous Loop Model, Xiaowei Li, Emma R Young, Cameron Martin, Joseph G Ribaudo, Mohamed Zaghloul, Sophia Roberts, Rodrigo Meade, Batool Arif, William R Moritz, Sarah Madira, Jonathon B Schofield, Mohamed A Zayed, Justin M Sacks, Et Al.
2020-Current year OA Pubs
A vascular anastomosis is a critical surgical skill that involves connecting blood vessels. Traditional handsewn techniques can be challenging and resource intensive. To address these issues, we have developed a unique sutureless anastomotic device called Vaso-Lock. This intraluminal device connects free vascular ends using anchors to maintain traction and enable a rapid anastomosis. We tested the anastomotic capability of Vaso-Locks in a pig common carotid-internal jugular arteriovenous model. The use of Vaso-Lock allowed us to accomplish this procedure in less than 10 min, in contrast to the approximately 40 min required for a handsewn anastomosis. The Vaso-Lock effectively maintained patency …
Aqueous Macrophages Contribute To Conserved Ccl2 And Cxcl10 Gradients In Uveitis, Joseph B Lin, Kathryn L Pepple, Christian Concepcion, Yulia Korshunova, Michael A Paley, Grace L Paley, Jennifer Laurent, Rajendra S Apte, Lynn M Hassman
Aqueous Macrophages Contribute To Conserved Ccl2 And Cxcl10 Gradients In Uveitis, Joseph B Lin, Kathryn L Pepple, Christian Concepcion, Yulia Korshunova, Michael A Paley, Grace L Paley, Jennifer Laurent, Rajendra S Apte, Lynn M Hassman
2020-Current year OA Pubs
PURPOSE: Uveitis is a heterogenous group of inflammatory eye disease for which current cytokine-targeted immune therapies are effective for only a subset of patients. We hypothesized that despite pathophysiologic nuances that differentiate individual disease states, all forms of eye inflammation might share common mechanisms for immune cell recruitment. Identifying these mechanisms is critical for developing novel, broadly acting therapeutic strategies.
DESIGN: Experimental study.
SUBJECTS: Biospecimens from patients with active or inactive uveitis and healthy controls.
METHODS: Protein concentration and single cell gene expression were assessed in aqueous fluid biopsies and plasma samples from deidentified patients with uveitis or healthy controls. …
Clinical Mycology Today: Emerging Challenges And Opportunities, Jessica Little, Adriana M Rauseo, Julio C Zuniga-Moya, Andrej Spec, Peter Pappas, John Perfect, Todd Mccarthy, Ilan S Schwartz
Clinical Mycology Today: Emerging Challenges And Opportunities, Jessica Little, Adriana M Rauseo, Julio C Zuniga-Moya, Andrej Spec, Peter Pappas, John Perfect, Todd Mccarthy, Ilan S Schwartz
2020-Current year OA Pubs
The Mycoses Study Group Education and Research Consortium is a collective of clinicians, researchers, and educators with the common goal to advance awareness, diagnosis, and management of invasive fungal diseases. Clinical Mycology Today, the Mycoses Study Group Education and Research Consortium's biennial meeting, is dedicated to discussing the most pressing contemporary issues facing the field of clinical mycology, promoting clinical, translational, and basic science collaborations, and mentoring the next generation of clinical mycologists. Here, we review the current opportunities and challenges facing the field of mycology that arose from discussions at the 2022 meeting, with emphasis on novel host risk …
Tumor-Immune Signatures Of Treatment Resistance To Brentuximab Vedotin With Ipilimumab And/Or Nivolumab In Hodgkin Lymphoma, Edgar Gonzalez-Kozlova, Brad S Kahl, Et Al.
Tumor-Immune Signatures Of Treatment Resistance To Brentuximab Vedotin With Ipilimumab And/Or Nivolumab In Hodgkin Lymphoma, Edgar Gonzalez-Kozlova, Brad S Kahl, Et Al.
2020-Current year OA Pubs
UNLABELLED: To investigate the cellular and molecular mechanisms associated with targeting CD30-expressing Hodgkin lymphoma (HL) and immune checkpoint modulation induced by combination therapies of CTLA4 and PD1, we leveraged Phase 1/2 multicenter open-label trial NCT01896999 that enrolled patients with refractory or relapsed HL (R/R HL). Using peripheral blood, we assessed soluble proteins, cell composition, T-cell clonality, and tumor antigen-specific antibodies in 54 patients enrolled in the phase 1 component of the trial. NCT01896999 reported high (>75%) overall objective response rates with brentuximab vedotin (BV) in combination with ipilimumab (I) and/or nivolumab (N) in patients with R/R HL. We observed …
Suicide In Us Preteens Aged 8 To 12 Years, 2001 To 2022, Donna A Ruch, Lisa M Horowitz, Jennifer L Hughes, Katherine Sarkisian, Joan L Luby, Cynthia A Fontanella, Jeffrey A Bridge
Suicide In Us Preteens Aged 8 To 12 Years, 2001 To 2022, Donna A Ruch, Lisa M Horowitz, Jennifer L Hughes, Katherine Sarkisian, Joan L Luby, Cynthia A Fontanella, Jeffrey A Bridge
2020-Current year OA Pubs
No abstract provided.
Matching-Adjusted Indirect Comparison From The Lymphoma Epidemiology Of Outcomes Consortium For Real World Evidence (Leo Crewe) Study To A Clinical Trial Of Mosunetuzumab In Relapsed Or Refractory Follicular Lymphoma, Matthew J. Maurer, Brad S. Kahl, Et Al.
Matching-Adjusted Indirect Comparison From The Lymphoma Epidemiology Of Outcomes Consortium For Real World Evidence (Leo Crewe) Study To A Clinical Trial Of Mosunetuzumab In Relapsed Or Refractory Follicular Lymphoma, Matthew J. Maurer, Brad S. Kahl, Et Al.
2020-Current year OA Pubs
Mosunetuzumab is a novel bispecific antibody targeting epitopes on CD3 on T cells and CD20 on B cells with the goal of inducing T-cell mediated elimination of malignant B cells. A recent pivotal phase I/II clinical trial (GO29781) demonstrated that mosunetuzumab induced an overall response rate (ORR) of 80%, complete response (CR) rate of 60%, and a median progression-free survival (PFS) of 17.9 months in patients with relapsed/refractory (R/R) follicular lymphoma (FL) following at least two prior lines of systemic therapy, including alkylator and anti-CD20 antibody-based therapy. Historical data from cohorts receiving therapy for R/R FL can provide some context …
A Phase Ii Trial Of The Wee1 Inhibitor Adavosertib In Setd2-Altered Advanced Solid Tumor Malignancies (Nci 10170), Edward Maldonado, Nikolaos A Trikalinos, Et Al.
A Phase Ii Trial Of The Wee1 Inhibitor Adavosertib In Setd2-Altered Advanced Solid Tumor Malignancies (Nci 10170), Edward Maldonado, Nikolaos A Trikalinos, Et Al.
2020-Current year OA Pubs
UNLABELLED: We sought to evaluate the efficacy of WEE1 inhibitor adavosertib in patients with solid tumor malignancies (cohort A) and clear cell renal cell carcinoma (ccRCC; cohort B). NCT03284385 was a parallel cohort, Simon two-stage, phase II study of adavosertib (300 mg QDAY by mouth on days 1-5 and 8-12 of each 21-day cycle) in patients with solid tumor malignancies harboring a pathogenic SETD2 mutation. The primary endpoint was the objective response rate. Correlative assays evaluated the loss of H3K36me3 by IHC, a downstream consequence of SETD2 loss, in archival tumor tissue. Eighteen patients were enrolled (9/cohort). The median age …
Distinguishing Recrudescence From Reinfection In Lymphatic Filariasis, Young-Jun Choi, Kerstin Fischer, Aboulaye Méité, Benjamin G Koudou, Peter U Fischer, Makedonka Mitreva
Distinguishing Recrudescence From Reinfection In Lymphatic Filariasis, Young-Jun Choi, Kerstin Fischer, Aboulaye Méité, Benjamin G Koudou, Peter U Fischer, Makedonka Mitreva
2020-Current year OA Pubs
BACKGROUND: The Global Program to Eliminate Lymphatic Filariasis (GPELF) is the largest public health program based on mass drug administration (MDA). Despite decades of MDA, ongoing transmission in some countries remains a challenge. To optimise interventions, it is critical to differentiate between recrudescence and new infections. Since adult filariae are inaccessible in humans, deriving a method that relies on the offspring microfilariae (mf) is necessary.
METHODS: We developed a genome amplification and kinship analysis-based approach using Brugia malayi samples from gerbils, and applied it to analyse Wuchereria bancrofti mf from humans in Côte d'Ivoire. We examined the pre-treatment genetic diversity …
Modulation Of Tmem16b Channel Activity By The Calcium-Activated Chloride Channel Regulator 4 (Clca4) In Human Cells, Monica Sala-Rabanal, Zeynep Yurtsever, Kayla N Berry, Conor Mcclenaghan, Alyssa J Foy, Alex Hanson, Deborah F Steinberg, Jessica A Greven, Colin E Kluender, Jennifer M Alexander-Brett, Colin G Nichols, Tom J Brett
Modulation Of Tmem16b Channel Activity By The Calcium-Activated Chloride Channel Regulator 4 (Clca4) In Human Cells, Monica Sala-Rabanal, Zeynep Yurtsever, Kayla N Berry, Conor Mcclenaghan, Alyssa J Foy, Alex Hanson, Deborah F Steinberg, Jessica A Greven, Colin E Kluender, Jennifer M Alexander-Brett, Colin G Nichols, Tom J Brett
2020-Current year OA Pubs
The Ca
Diagnostic Efficacy And Clinical Impact Of Image-Guided Core Needle Biopsy Of Suspected Vertebral Osteomyelitis, Winston L Winkler, Ige A George, Sumanth Gandra, Jonathan C Baker, Anderanik Tomasian, Benjamin Northrup, Theodore L Vander Velde, Travis J Hillen, Chongliang Luo, Resten Imaoka, Gino M Dettorre, Jack W Jennings
Diagnostic Efficacy And Clinical Impact Of Image-Guided Core Needle Biopsy Of Suspected Vertebral Osteomyelitis, Winston L Winkler, Ige A George, Sumanth Gandra, Jonathan C Baker, Anderanik Tomasian, Benjamin Northrup, Theodore L Vander Velde, Travis J Hillen, Chongliang Luo, Resten Imaoka, Gino M Dettorre, Jack W Jennings
2020-Current year OA Pubs
OBJECTIVES: The diagnostic yield and clinical impact of image-guided core needle biopsy (ICNB) of suspected vertebral osteomyelitis in adults is heterogenous in published studies owing to small sample sizes, indicating the need for large cohort studies.
METHODS: A retrospective analysis of ICNBs was performed from 2010 to 2021 for patients with imaging findings consistent with vertebral osteomyelitis. For each biopsy, a series of factors were analyzed, as well as if histopathology was diagnostic of osteomyelitis and if microbiological cultures were positive. In addition, it was recorded in what way biopsy influenced clinical management regarding antimicrobial treatment. A multivariate statistical analysis …
Integrating Multisector Molecular Characterization Into Personalized Peptide Vaccine Design For Patients With Newly Diagnosed Glioblastoma, Tanner M Johanns, Elizabeth A R Garfinkle, Katherine E Miller, Alexandra J Livingstone, Kaleigh F Roberts, Lakshmi P Rao Venkata, Joshua L Dowling, Michael R Chicoine, Ralph G Dacey, Gregory J Zipfel, Albert H Kim, Elaine R Mardis, Gavin P Dunn
Integrating Multisector Molecular Characterization Into Personalized Peptide Vaccine Design For Patients With Newly Diagnosed Glioblastoma, Tanner M Johanns, Elizabeth A R Garfinkle, Katherine E Miller, Alexandra J Livingstone, Kaleigh F Roberts, Lakshmi P Rao Venkata, Joshua L Dowling, Michael R Chicoine, Ralph G Dacey, Gregory J Zipfel, Albert H Kim, Elaine R Mardis, Gavin P Dunn
2020-Current year OA Pubs
PURPOSE: Outcomes for patients with glioblastoma (GBM) remain poor despite multimodality treatment with surgery, radiation, and chemotherapy. There are few immunotherapy options due to the lack of tumor immunogenicity. Several clinical trials have reported promising results with cancer vaccines. To date, studies have used data from a single tumor site to identify targetable antigens, but this approach limits the antigen pool and is antithetical to the heterogeneity of GBM. We have implemented multisector sequencing to increase the pool of neoantigens across the GBM genomic landscape that can be incorporated into personalized peptide vaccines called NeoVax.
PATIENTS AND METHODS: In this …
Il2 Targeted To Cd8+ T Cells Promotes Robust Effector T-Cell Responses And Potent Antitumor Immunity, Kelly D Moynihan, Hussein Sultan, Robert D Schreiber, Et Al.
Il2 Targeted To Cd8+ T Cells Promotes Robust Effector T-Cell Responses And Potent Antitumor Immunity, Kelly D Moynihan, Hussein Sultan, Robert D Schreiber, Et Al.
2020-Current year OA Pubs
IL2 signals pleiotropically on diverse cell types, some of which contribute to therapeutic activity against tumors, whereas others drive undesired activity, such as immunosuppression or toxicity. We explored the theory that targeting of IL2 to CD8+ T cells, which are key antitumor effectors, could enhance its therapeutic index. To this aim, we developed AB248, a CD8 cis-targeted IL2 that demonstrates over 500-fold preference for CD8+ T cells over natural killer and regulatory T cells (Tregs), which may contribute to toxicity and immunosuppression, respectively. AB248 recapitulated IL2's effects on CD8+ T cells in vitro and induced selective expansion of CD8+T cells …
Epigenetic Developmental Mechanisms Underlying Sex Differences In Cancer, Joshua B. Rubin, Tamara Abou-Antoun, Joseph E. Ippolito, Lorida Llaci, Camryn T. Marquez, Jason P. Wong, Lihua Yang
Epigenetic Developmental Mechanisms Underlying Sex Differences In Cancer, Joshua B. Rubin, Tamara Abou-Antoun, Joseph E. Ippolito, Lorida Llaci, Camryn T. Marquez, Jason P. Wong, Lihua Yang
2020-Current year OA Pubs
Cancer risk is modulated by hereditary and somatic mutations, exposures, age, sex, and gender. The mechanisms by which sex and gender work alone and in combination with other cancer risk factors remain underexplored. In general, cancers that occur in both the male and female sexes occur more commonly in XY compared with XX individuals, regardless of genetic ancestry, geographic location, and age. Moreover, XY individuals are less frequently cured of their cancers, highlighting the need for a greater understanding of sex and gender effects in oncology. This will be necessary for optimal laboratory and clinical cancer investigations. To that end, …
A Survey Of Availability And Affordability Of Polypills For Cardiovascular Disease In Selected Countries, Gautam Satheesh, Bishal Gyawali, Marie France Chan Sun, Mark D Huffman, Amitava Banerjee, Pablo Perel, Adrianna Murphy
A Survey Of Availability And Affordability Of Polypills For Cardiovascular Disease In Selected Countries, Gautam Satheesh, Bishal Gyawali, Marie France Chan Sun, Mark D Huffman, Amitava Banerjee, Pablo Perel, Adrianna Murphy
2020-Current year OA Pubs
BACKGROUND: The recent inclusion of polypills-fixed-dose combinations of antihypertensive medicines and a statin with or without aspirin-in the World Health Organization's Essential Medicines List (EML) reiterates the potential of this approach to improve global treatment coverage for cardiovascular diseases (CVDs). Although there exists extensive evidence on the effectiveness, safety and acceptability of polypills, there has been no research to date assessing the real-world availability and affordability of polypills globally.
METHODS: We conducted a cross-sectional survey, based on the WHO/Health Action International methodology, in 13 countries around the world. In the surveyed countries, we first ascertained whether any polypill was authorised …
Replication And Reliability Of Parkinson's Disease Clinical Subtypes, Therese V Cash, Christina N Lessov-Schlaggar, Erin R Foster, Peter S Myers, Joshua J Jackson, Baijayanta Maiti, Paul T Kotzbauer, Joel S Perlmutter, Meghan C Campbell
Replication And Reliability Of Parkinson's Disease Clinical Subtypes, Therese V Cash, Christina N Lessov-Schlaggar, Erin R Foster, Peter S Myers, Joshua J Jackson, Baijayanta Maiti, Paul T Kotzbauer, Joel S Perlmutter, Meghan C Campbell
2020-Current year OA Pubs
BACKGROUND: We recently identified three distinct Parkinson's disease subtypes: "motor only" (predominant motor deficits with intact cognition and psychiatric function); "psychiatric & motor" (prominent psychiatric symptoms and moderate motor deficits); "cognitive & motor" (cognitive and motor deficits).
OBJECTIVE: We used an independent cohort to replicate and assess reliability of these Parkinson's disease subtypes.
METHODS: We tested our original subtype classification with an independent cohort (N = 100) of Parkinson's disease participants without dementia and the same comprehensive evaluations assessing motor, cognitive, and psychiatric function. Next, we combined the original (N = 162) and replication (N = 100) datasets to test …
Pharmacokinetic Modeling Of The Effect Of Tariquidar On Ondansetron Disposition Into The Central Nervous System, Manting Chiang, Hyunmoon Back, Jong Bong Lee, Sarah Oh, Tiffany Guo, Simone Girgis, Celine Park, Simon Haroutounian, Leonid Kagan
Pharmacokinetic Modeling Of The Effect Of Tariquidar On Ondansetron Disposition Into The Central Nervous System, Manting Chiang, Hyunmoon Back, Jong Bong Lee, Sarah Oh, Tiffany Guo, Simone Girgis, Celine Park, Simon Haroutounian, Leonid Kagan
2020-Current year OA Pubs
PURPOSE: Serotonin (5-HT
METHODS: Ondansetron (10 mg/kg) and tariquidar (7.5 mg/kg) were administered intravenously, plasma and tissue samples were collected and analyzed by HPLC. A mathematical model with brain, spinal cord, cerebrospinal fluid and two systemic disposition compartments was developed to describe the data.
RESULTS: The results demonstrate that tariquidar at 7.5 mg/kg resulted in a complete inhibition of Pgp efflux of ondansetron in the brain and spinal cord. The compartmental model successfully captured pharmacokinetics of ondansetron in wild type and Pgp knockout (KO) animals receiving the drug alone or in wild type animals receiving the ondansetron and tariquidar combination. …
Phase 1b Study To Assess The Safety, Tolerability, And Clinical Activity Of Pamiparib In Combination With Temozolomide In Patients With Locally Advanced Or Metastatic Solid Tumors, Agostina Stradella, Haeseong Park, Et Al.
Phase 1b Study To Assess The Safety, Tolerability, And Clinical Activity Of Pamiparib In Combination With Temozolomide In Patients With Locally Advanced Or Metastatic Solid Tumors, Agostina Stradella, Haeseong Park, Et Al.
2020-Current year OA Pubs
BACKGROUND: Pamiparib is a potent, selective, poly (ADP-ribose) polymerase 1/2 inhibitor that demonstrates synthetic lethality in cells with breast cancer susceptibility gene mutations or other homologous recombination deficiency. This two-stage phase 1b study (NCT03150810) assessed pamiparib in combination with temozolomide (TMZ) in adult patients with histologically confirmed locally advanced and metastatic solid tumors.
METHODS: Oral pamiparib 60 mg was administered twice daily. During the dose-escalation stage, increasing doses of TMZ (40-120 mg once daily pulsed or 20-40 mg once daily continuous) were administered to determine the recommended dose to be administered in the dose-expansion stage. The primary objectives were to …
Implementation Strategies To Improve Hiv Care Cascade Outcomes In Low- And Middle-Income Countries: A Systematic Review From 2014 To 2021, Sita Lujintanon, Ingrid Eshun-Wilson, Noelle Le Tourneau, Laura Beres, Sheree Schwartz, Stefan Baral, Ryan Thompson, Ashley Underwood, Branson Fox, Elvin H Geng, Christopher G Kemp
Implementation Strategies To Improve Hiv Care Cascade Outcomes In Low- And Middle-Income Countries: A Systematic Review From 2014 To 2021, Sita Lujintanon, Ingrid Eshun-Wilson, Noelle Le Tourneau, Laura Beres, Sheree Schwartz, Stefan Baral, Ryan Thompson, Ashley Underwood, Branson Fox, Elvin H Geng, Christopher G Kemp
2020-Current year OA Pubs
INTRODUCTION: In low- and middle-income countries (LMICs), which are disproportionately affected by the HIV epidemic and manage limited resources, optimized implementation strategies are needed to enhance the efficiency of the HIV response. Assessing strategy usage to date could identify research gaps and inform future implementation efforts. We conducted a systematic review to describe the features and distributions of published implementation strategies attempting to improve HIV treatment service delivery and outcomes.
METHODS: We searched PubMed, Embase, and CINAHL and screened abstracts and full texts published between 1 January 2014 and 27 August 2021, for English-language studies conducted in LMICs that described …
A Pilot Study Of Nintedanib In Molecularly Selected Patients With Advanced Non-Small Cell Lung Cancer, Christine Auberle, Feng Gao, Mark Sloan, Daniel Morgensztern, Linda Winkler, Jeffrey P. Ward, Siddhartha Devarakonda, Timothy P. Rearden, Ramaswamy Govindan, Saiama N. Waqar
A Pilot Study Of Nintedanib In Molecularly Selected Patients With Advanced Non-Small Cell Lung Cancer, Christine Auberle, Feng Gao, Mark Sloan, Daniel Morgensztern, Linda Winkler, Jeffrey P. Ward, Siddhartha Devarakonda, Timothy P. Rearden, Ramaswamy Govindan, Saiama N. Waqar
2020-Current year OA Pubs
BACKGROUND: Nintedanib is a small molecule tyrosine kinase inhibitor (TKI) targeting vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor (PDGFR), and fibroblast growth factor receptor (FGFR). The purpose of the study was to evaluate the response rate for patients with advanced non-small cell lung cancer (NSCLC) with mutations in
METHODS: Patients with advanced NSCLC previously treated with platinum-doublet chemotherapy with the above mutations were enrolled. Exclusion criteria included necrotic tumors with invasion of blood vessels, history of recent thromboembolic events, increased risk of bleeding or thrombosis, myocardial infarction, and weight loss >10% within past 6 months. Nintedanib was …
Motor Competence Is Related To Acquisition Of Error-Based But Not Reinforcement Learning In Children Ages 6 To 12, Jeffrey D Konrad, Natasha Marrus, Keith R Lohse, Kayla M Thuet, Catherine E Lang
Motor Competence Is Related To Acquisition Of Error-Based But Not Reinforcement Learning In Children Ages 6 To 12, Jeffrey D Konrad, Natasha Marrus, Keith R Lohse, Kayla M Thuet, Catherine E Lang
2020-Current year OA Pubs
BACKGROUND: An essential component of childhood development is increasing motor competence. Poor motor learning is often thought to underlie impaired motor competence, but this link is unclear in previous studies.
AIMS: Our aim was to test the relationship between motor competence and motor learning in the acquisition phase. Both reinforcement learning (RL) and error-based learning (EBL) were tested. We hypothesized that slower RL and slower EBL acquisition rates would relate to lower motor competence.
METHODS AND PROCEDURES: Eighty-six participants ages 6-12 performed a target throwing task under RL and EBL conditions. The Movement Assessment Battery for Children - 2nd edition …
Python Tooth-Inspired Fixation Device For Enhanced Rotator Cuff Repair, Iden Kurtaliaj, Ethan D Hoppe, Yuxuan Huang, David Ju, Jacob A Sandler, Donghwan Yoon, Guy M Genin
Python Tooth-Inspired Fixation Device For Enhanced Rotator Cuff Repair, Iden Kurtaliaj, Ethan D Hoppe, Yuxuan Huang, David Ju, Jacob A Sandler, Donghwan Yoon, Guy M Genin
2020-Current year OA Pubs
Rotator cuff repair surgeries fail frequently, with 20 to 94% of the 600,000 repairs performed annually in the United States resulting in retearing of the rotator cuff. The most common cause of failure is sutures tearing through tendons at grasping points. To address this issue, we drew inspiration from the specialized teeth of snakes of the Pythonoidea superfamily, which grasp soft tissues without tearing. To apply this nondamaging gripping approach to the surgical repair of tendon, we developed and optimized a python tooth-inspired device as an adjunct to current rotator cuff suture repair and found that it nearly doubled repair …
Extracorporeal Membrane Oxygenation For Respiratory Failure: A Narrative Review, John C Grotberg, Daniel Reynolds, Bryan D Kraft
Extracorporeal Membrane Oxygenation For Respiratory Failure: A Narrative Review, John C Grotberg, Daniel Reynolds, Bryan D Kraft
2020-Current year OA Pubs
Extracorporeal membrane oxygenation support for respiratory failure in the intensive care unit continues to have an expanded role in select patients. While acute respiratory distress syndrome remains the most common indication, extracorporeal membrane oxygenation may be used in other causes of refractory hypoxemia and/or hypercapnia. The most common configuration is veno-venous extracorporeal membrane oxygenation; however, in specific cases of refractory hypoxemia or right ventricular failure, some patients may benefit from veno-pulmonary extracorporeal membrane oxygenation or veno-venoarterial extracorporeal membrane oxygenation. Patient selection and extracorporeal circuit management are essential to successful outcomes. This narrative review explores the physiology of extracorporeal membrane oxygenation, …