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Full-Text Articles in Medicine and Health Sciences
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.
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 …
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
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 …
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
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 …
Predation Without Direction Selectivity, Jenna Krizan, Xiayingfang Song, Michael J Fitzpatrick, Ning Shen, Florentina Soto, Daniel Kerschensteiner
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 …
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.
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 …
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
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 …
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
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 …
The Novel Drug Candidate S2/Iapinh Improves Survival In Models Of Pancreatic And Ovarian Cancer, Takaomi Hagi, Suwanna Vangveravong, Rony Takchi, Qingqing Gong, S Peter Goedegebuure, Herve Tiriac, Brian A Van Tine, Matthew A Powell, William G Hawkins, Dirk Spitzer
The Novel Drug Candidate S2/Iapinh Improves Survival In Models Of Pancreatic And Ovarian Cancer, Takaomi Hagi, Suwanna Vangveravong, Rony Takchi, Qingqing Gong, S Peter Goedegebuure, Herve Tiriac, Brian A Van Tine, Matthew A Powell, William G Hawkins, Dirk Spitzer
2020-Current year OA Pubs
Cancer selective apoptosis remains a therapeutic challenge and off-target toxicity has limited enthusiasm for this target clinically. Sigma-2 ligands (S2) have been shown to enhance the cancer selectivity of small molecule drug candidates by improving internalization. Here, we report the synthesis of a novel drug conjugate, which was created by linking a clinically underperforming SMAC mimetic (second mitochondria-derived activator of caspases; LCL161), an inhibitor (antagonist) of inhibitor of apoptosis proteins (IAPinh) with the sigma-2 ligand SW43, resulting in the new chemical entity S2/IAPinh. Drug potency was assessed via cell viability assays across several pancreatic and ovarian cancer cell lines in …
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
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 …
Simulation-Based Analysis Of Trial Design In Regional Anesthesia, Melisa Pasli, Dmitry Tumin, Ryan Guffey
Simulation-Based Analysis Of Trial Design In Regional Anesthesia, Melisa Pasli, Dmitry Tumin, Ryan Guffey
2020-Current year OA Pubs
BACKGROUND: In regional anesthesia, the efficacy of novel blocks is typically evaluated using randomized controlled trials (RCTs), the findings of which are aggregated in systematic reviews and meta-analyses. Systematic review authors frequently point out the small sample size of RCTs as limiting conclusions from this literature. We sought to determine via statistical simulation if small sample size could be an expected property of RCTs focusing on novel blocks with typical effect sizes.
METHODS: We simulated the conduct of a series of RCTs comparing a novel block versus placebo on a single continuous outcome measure. Simulation analysis inputs were obtained from …
Defining Clinical Endpoints In Limb Girdle Muscular Dystrophy: A Grasp-Lgmd Study, Amy Doody, Lindsay Alfano, Jordi Diaz-Manera, Linda Lowes, Tahseen Mozaffar, Katherine D Mathews, Conrad C Weihl, Matthew Wicklund, Man Hung, Jeffrey Statland, Nicholas E Johnson, Grasp-Lgmd Consortium
Defining Clinical Endpoints In Limb Girdle Muscular Dystrophy: A Grasp-Lgmd Study, Amy Doody, Lindsay Alfano, Jordi Diaz-Manera, Linda Lowes, Tahseen Mozaffar, Katherine D Mathews, Conrad C Weihl, Matthew Wicklund, Man Hung, Jeffrey Statland, Nicholas E Johnson, Grasp-Lgmd Consortium
2020-Current year OA Pubs
BACKGROUND: The Limb Girdle Muscular Dystrophies (LGMDs) are characterized by progressive weakness of the shoulder and hip girdle muscles as a result of over 30 different genetic mutations. This study is designed to develop clinical outcome assessments across the group of disorders.
METHODS/DESIGN: The primary goal of this study is to evaluate the utility of a set of outcome measures on a wide range of LGMD phenotypes and ability levels to determine if it would be possible to use similar outcomes between individuals with different phenotypes. We will perform a multi-center, 12-month study of 188 LGMD patients within the established …
Effects Of A Liquefied Petroleum Gas Stove Intervention On Stillbirth, Congenital Anomalies And Neonatal Mortality: A Multi-Country Household Air Pollution Intervention Network Trial, Ashley Younger, Ashley Toenjes, Lindsay J Underhill, Et Al.
Effects Of A Liquefied Petroleum Gas Stove Intervention On Stillbirth, Congenital Anomalies And Neonatal Mortality: A Multi-Country Household Air Pollution Intervention Network Trial, Ashley Younger, Ashley Toenjes, Lindsay J Underhill, Et Al.
2020-Current year OA Pubs
Household air pollution (HAP) from cooking with solid fuels used during pregnancy has been associated with adverse pregnancy outcomes. The Household Air Pollution Intervention Network (HAPIN) trial was a randomized controlled trial that assessed the impact of a liquefied petroleum gas (LPG) stove and fuel intervention on health in Guatemala, India, Peru, and Rwanda. Here we investigated the effects of the LPG stove and fuel intervention on stillbirth, congenital anomalies and neonatal mortality and characterized exposure-response relationships between personal exposures to fine particulate matter (PM
Calpain-2 Mediates Sars-Cov-2 Entry Via Regulating Ace2 Levels, Qiru Zeng, Avan Antia, Luis Alberto Casorla-Perez, Maritza Puray-Chavez, Sebla B Kutluay, Matthew A Ciorba, Siyuan Ding
Calpain-2 Mediates Sars-Cov-2 Entry Via Regulating Ace2 Levels, Qiru Zeng, Avan Antia, Luis Alberto Casorla-Perez, Maritza Puray-Chavez, Sebla B Kutluay, Matthew A Ciorba, Siyuan Ding
2020-Current year OA Pubs
UNLABELLED: Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic, much effort has been dedicated to identifying effective antivirals against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A number of calpain inhibitors show excellent antiviral activities against SARS-CoV-2 by targeting the viral main protease (M
IMPORTANCE: Many efforts in small-molecule screens have been made to counter SARS-CoV-2 infection by targeting the viral main protease, the major element that processes viral proteins after translation. Here, we discovered that calpain inhibitors further block SARS-CoV-2 infection in a main protease-independent manner. We identified the host cysteine protease calpain-2 as an important positive …
A Phase I Trial Of Pevonedistat In Combination With Ruxolitinib For The Treatment Of Myelofibrosis, Tim Kong, Nicole Gaudin, Karyn Gordon, Maggie J Cox, Amy W Zhou, Stephen T Oh
A Phase I Trial Of Pevonedistat In Combination With Ruxolitinib For The Treatment Of Myelofibrosis, Tim Kong, Nicole Gaudin, Karyn Gordon, Maggie J Cox, Amy W Zhou, Stephen T Oh
2020-Current year OA Pubs
Janus kinase 2 (JAK2) inhibitors such as ruxolitinib have become standard-of-care therapy for patients with myeloproliferative neoplasms (MPNs); however, activation of alternate oncogenic pathways including nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) has limited durable response as single-agent therapy. With the rationale of targeting both pathways, we conducted a phase I dose escalation trial of pevonedistat in combination with ruxolitinib for the treatment of patients with myelofibrosis (NCT03386214). The primary objective was to assess the safety and tolerability of combination therapy with additional objectives of treatment efficacy and alterations of biomarkers. There were no dose-limiting toxicities observed with most …
The Identification Of Small Molecule Inhibitors With Anthelmintic Activities That Target Conserved Proteins Among Ruminant Gastrointestinal Nematodes, Hyeim Jung, Dante Zarlenga, John C Martin, Peter Geldhof, Kymberlie Hallsworth-Pepin, Makedonka Mitreva
The Identification Of Small Molecule Inhibitors With Anthelmintic Activities That Target Conserved Proteins Among Ruminant Gastrointestinal Nematodes, Hyeim Jung, Dante Zarlenga, John C Martin, Peter Geldhof, Kymberlie Hallsworth-Pepin, Makedonka Mitreva
2020-Current year OA Pubs
Gastrointestinal nematode (GIN) infections are a major concern for the ruminant industry worldwide and result in significant production losses. Naturally occurring polyparasitism and increasing drug resistance that potentiate disease outcomes are observed among the most prevalent GINs of veterinary importance. Within the five major taxonomic clades, clade Va represents a group of GINs that predominantly affect the abomasum or small intestine of ruminants. However, the development of effective broad-spectrum anthelmintics against ruminant clade Va GINs has been challenged by a lack of comprehensive druggable genome resources. Here, we first assembled draft genomes for three clade Va species (
Inducing Vulnerability To Inha Inhibition Restores Isoniazid Susceptibility In Drug-Resistant Mycobacterium Tuberculosis, Gregory A Harrison, Erin R Wang, Kevin Cho, Yassin Mreyoud, Souvik Sarkar, Fredrik Almqvist, Gary J Patti, Christina L Stallings
Inducing Vulnerability To Inha Inhibition Restores Isoniazid Susceptibility In Drug-Resistant Mycobacterium Tuberculosis, Gregory A Harrison, Erin R Wang, Kevin Cho, Yassin Mreyoud, Souvik Sarkar, Fredrik Almqvist, Gary J Patti, Christina L Stallings
2020-Current year OA Pubs
Of the approximately 10 million cases of
Genomic Surveillance Of Clostridioides Difficile Transmission And Virulence In A Healthcare Setting, Erin P Newcomer, Skye R S Fishbein, Kailun Zhang, Tiffany Hink, Kimberly A Reske, Candice Cass, Zainab H Iqbal, Emily L Struttmann, Carey-Ann D Burnham, Erik R Dubberke, Gautam Dantas
Genomic Surveillance Of Clostridioides Difficile Transmission And Virulence In A Healthcare Setting, Erin P Newcomer, Skye R S Fishbein, Kailun Zhang, Tiffany Hink, Kimberly A Reske, Candice Cass, Zainab H Iqbal, Emily L Struttmann, Carey-Ann D Burnham, Erik R Dubberke, Gautam Dantas
2020-Current year OA Pubs
UNLABELLED:
IMPORTANCE:
Als-Related P97 R155h Mutation Disrupts Lysophagy In Ipsc-Derived Motor Neurons, Jacob A Klickstein, Michelle A Johnson, Pantelis Antonoudiou, Jamie Maguire, Joao A Paulo, Steve P Gygi, Chris Weihl, Malavika Raman
Als-Related P97 R155h Mutation Disrupts Lysophagy In Ipsc-Derived Motor Neurons, Jacob A Klickstein, Michelle A Johnson, Pantelis Antonoudiou, Jamie Maguire, Joao A Paulo, Steve P Gygi, Chris Weihl, Malavika Raman
2020-Current year OA Pubs
Mutations in the AAA+ ATPase p97 cause multisystem proteinopathy 1, which includes amyotrophic lateral sclerosis; however, the pathogenic mechanisms that contribute to motor neuron loss remain obscure. Here, we use two induced pluripotent stem cell models differentiated into spinal motor neurons to investigate how p97 mutations perturb the motor neuron proteome. Using quantitative proteomics, we find that motor neurons harboring the p97 R155H mutation have deficits in the selective autophagy of lysosomes (lysophagy). p97 R155H motor neurons are unable to clear damaged lysosomes and have reduced viability. Lysosomes in mutant motor neurons have increased pH compared with wild-type cells. The …
Use Of Lcp-Tacrolimus (Lcpt) In Kidney Transplantation: A Delphi Consensus Survey Of Expert Clinicians, Alexander Wiseman, Tarek Alhamad, Rita R Alloway, Beatrice P Concepcion, Matthew Cooper, Richard Formica, Christina L Klein, Vineeta Kumar, Nicolae Leca, Fuad Shihab, David J Taber, Sarah Mulnick, Donald M Bushnell, Monica Hadi, Suphamai Bunnapradist
Use Of Lcp-Tacrolimus (Lcpt) In Kidney Transplantation: A Delphi Consensus Survey Of Expert Clinicians, Alexander Wiseman, Tarek Alhamad, Rita R Alloway, Beatrice P Concepcion, Matthew Cooper, Richard Formica, Christina L Klein, Vineeta Kumar, Nicolae Leca, Fuad Shihab, David J Taber, Sarah Mulnick, Donald M Bushnell, Monica Hadi, Suphamai Bunnapradist
2020-Current year OA Pubs
BACKGROUND LCPT (Envarsus XR®) is a common once-daily, extended-release oral tacrolimus formulation used in kidney transplantation. However, there are minimal evidence-based recommendations regarding optimal dosing and treatment in the de novo and conversion settings. MATERIAL AND METHODS Using Delphi methodology, 12 kidney transplantation experts with LCPT experience reviewed available data to determine potential consensus topics. Key statements regarding LCPT use were generated and disseminated to the panel in an online Delphi survey. Statements were either accepted, revised, or rejected based on the level of consensus, perceived strength of evidence, and alignment with clinical practice. Consensus was defined a priori as …
Durable Immunity To Ebv After Rituximab And Third-Party Lmp-Specific T Cells: A Children's Oncology Group Study, Birte Wistinghausen, Robert J Hayashi, Et Al.
Durable Immunity To Ebv After Rituximab And Third-Party Lmp-Specific T Cells: A Children's Oncology Group Study, Birte Wistinghausen, Robert J Hayashi, Et Al.
2020-Current year OA Pubs
Posttransplant lymphoproliferative disease (PTLD) in pediatric solid organ transplant (SOT) recipients is characterized by uncontrolled proliferation of Epstein-Barr virus-infected (EBV+) B cells due to decreased immune function. This study evaluated the feasibility, safety, clinical and immunobiological outcomes in pediatric SOT recipients with PTLD treated with rituximab and third-party latent membrane protein-specific T cells (LMP-TCs). Newly diagnosed (ND) patients without complete response to rituximab and all patients with relapsed/refractory (R/R) disease received LMP-TCs. Suitable LMP-TC products were available for all eligible subjects. Thirteen of 15 patients who received LMP-TCs were treated within the prescribed 14-day time frame. LMP-TC therapy was generally …
Germline Knockout Of Nr2e3 Protects Photoreceptors In Three Distinct Mouse Models Of Retinal Degeneration, Alexander V Kolesnikov, Daniel P Murphy, Joseph C Corbo, Vladimir J Kefalov
Germline Knockout Of Nr2e3 Protects Photoreceptors In Three Distinct Mouse Models Of Retinal Degeneration, Alexander V Kolesnikov, Daniel P Murphy, Joseph C Corbo, Vladimir J Kefalov
2020-Current year OA Pubs
Retinitis pigmentosa (RP) is a common form of retinal dystrophy that can be caused by mutations in any one of dozens of rod photoreceptor genes. The genetic heterogeneity of RP represents a significant challenge for the development of effective therapies. Here, we present evidence for a potential gene-independent therapeutic strategy based on targeting
Guiding Principles For Adolescent Web-Based Portal Access Policies: Interviews With Informatics Administrators, Bryan Sisk, Alison L Antes, Christine Bereitschaft, Madi Enloe, Fabienne Bourgeois, James Dubois
Guiding Principles For Adolescent Web-Based Portal Access Policies: Interviews With Informatics Administrators, Bryan Sisk, Alison L Antes, Christine Bereitschaft, Madi Enloe, Fabienne Bourgeois, James Dubois
2020-Current year OA Pubs
BACKGROUND: Web-based patient portals are tools that could support adolescents in managing their health and developing autonomy. However, informatics administrators must navigate competing interests when developing portal access policies for adolescents and their parents.
OBJECTIVE: We aimed to assess the perspectives of informatics administrators on guiding principles for the development of web-based health care portal access policies in adolescent health care.
METHODS: We interviewed informatics administrators from US hospitals with ≥50 dedicated pediatric beds. We performed a thematic analysis of guiding principles for developing and implementing adolescent portal access policies.
RESULTS: We interviewed 65 informatics leaders who represented 63 pediatric …
Comprehensive Proteomics Of Csf, Plasma, And Urine Identify Ddc And Other Biomarkers Of Early Parkinson's Disease., Jarod Rutledge, Dan Western, Priyanka Gorijala, Carlos Cruchaga, Et Al.
Comprehensive Proteomics Of Csf, Plasma, And Urine Identify Ddc And Other Biomarkers Of Early Parkinson's Disease., Jarod Rutledge, Dan Western, Priyanka Gorijala, Carlos Cruchaga, Et Al.
2020-Current year OA Pubs
Parkinson's disease (PD) starts at the molecular and cellular level long before motor symptoms appear, yet there are no early-stage molecular biomarkers for diagnosis, prognosis prediction, or monitoring therapeutic response. This lack of biomarkers greatly impedes patient care and translational research-L-DOPA remains the standard of care more than 50 years after its introduction. Here, we performed a large-scale, multi-tissue, and multi-platform proteomics study to identify new biomarkers for early diagnosis and disease monitoring in PD. We analyzed 4877 cerebrospinal fluid, blood plasma, and urine samples from participants across seven cohorts using three orthogonal proteomics methods: Olink proximity extension assay, SomaScan …
Serum Soluble Alpha-Klotho Klotho And Cognitive Functioning In Older Adults Aged 60 And 79: An Analysis Of Cross-Sectional Data Of The National Health And Nutrition Examination Survey 2011 To 2014, Song Ge, Fanghong Dong, Chong Tian, Chih-Hsiang Yang, Minhui Liu, Jingkai Wei
Serum Soluble Alpha-Klotho Klotho And Cognitive Functioning In Older Adults Aged 60 And 79: An Analysis Of Cross-Sectional Data Of The National Health And Nutrition Examination Survey 2011 To 2014, Song Ge, Fanghong Dong, Chong Tian, Chih-Hsiang Yang, Minhui Liu, Jingkai Wei
2020-Current year OA Pubs
OBJECTIVES: Klotho, consisting of membrane klotho and soluble alpha-klotho, is found to be associated with better cognitive outcomes in small samples of the aged population. We aimed to examine the association of serum soluble alpha-klotho with cognitive functioning among older adults using a nationally representative sample of U.S. older adults.
METHOD: A total of 2,173 U.S. older adults aged 60-79 years in the National Health and Nutrition Examination Survey from 2011 to 2014 were included in this cross-sectional analysis. Serum soluble alpha-klotho was measured in the laboratory and analyzed with an ELISA kit. Cognitive function was measured using the Consortium …
Dark Adaptometry And Optical Coherence Tomography-Angiography In Huntington Disease, Aaditya Shah, Spencer Fuller, Susan Criswell, Rajendra S. Apte
Dark Adaptometry And Optical Coherence Tomography-Angiography In Huntington Disease, Aaditya Shah, Spencer Fuller, Susan Criswell, Rajendra S. Apte
2020-Current year OA Pubs
No abstract provided.
Activator Protein Transcription Factors Coordinate Human Il-33 Expression From Noncanonical Promoters In Chronic Airway Disease, Heather E. Raphael, Ghandi F. Hassan, Omar A. Osorio, Lucy S. Cohen, Morgan D. Payne, Ella Katz-Kiriakos, Ishana Tata, Jamie Hicks, Derek E. Byers, Bo Zhang, Jen Alexander-Brett
Activator Protein Transcription Factors Coordinate Human Il-33 Expression From Noncanonical Promoters In Chronic Airway Disease, Heather E. Raphael, Ghandi F. Hassan, Omar A. Osorio, Lucy S. Cohen, Morgan D. Payne, Ella Katz-Kiriakos, Ishana Tata, Jamie Hicks, Derek E. Byers, Bo Zhang, Jen Alexander-Brett
2020-Current year OA Pubs
IL-33 is a cytokine central to type 2 immune pathology in chronic airway disease. This cytokine is abundantly expressed in the respiratory epithelium and increased in disease, but how expression is regulated is undefined. Here we show that increased IL33 expression occurs from multiple noncanonical promoters in human chronic obstructive pulmonary disease (COPD), and it facilitates production of alternatively spliced isoforms in airway cells. We found that phorbol 12-myristate 13-acetate (PMA) can activate IL33 promoters through protein kinase C in primary airway cells and lines. Transcription factor (TF) binding arrays combined with RNA interference identified activator protein (AP) TFs as …
Graduate Medical Education Well-Being Directors In The United States: Who Are They, And What Does The Role Entail?, Larissa R Thomas, Jonathan A Ripp, Jennifer G Duncan
Graduate Medical Education Well-Being Directors In The United States: Who Are They, And What Does The Role Entail?, Larissa R Thomas, Jonathan A Ripp, Jennifer G Duncan
2020-Current year OA Pubs
BACKGROUND: Institutional Graduate Medical Education (GME) Well-being Director (WBD) roles have recently emerged in the United States to support resident and fellow well-being. However, with a standard position description lacking, the current scope and responsibilities of such roles is unknown. This study describes the scope of work, salary support, and opportunities for role definition for those holding institutional leadership positions for GME well-being.
METHODS: In November 2021, 43 members of a national network of GME WBDs in the United States were invited to complete a cross-sectional survey that included questions about job responsibilities, percent effort, and dedicated budget, and a …
An Mhealth Intervention To Address Depression And Improve Antiretroviral Therapy Adherence Among Youths Living With Hiv In Uganda: Protocol For A Pilot Randomized Controlled Trial, Proscovia Nabunya, Patricia Cavazos-Rehg, James Mugisha, Erin Kasson, Olive Imelda Namuyaba, Claire Najjuuko, Edward Nsubuga, Lindsey M Filiatreau, Abel Mwebembezi, Fred M Ssewamala
An Mhealth Intervention To Address Depression And Improve Antiretroviral Therapy Adherence Among Youths Living With Hiv In Uganda: Protocol For A Pilot Randomized Controlled Trial, Proscovia Nabunya, Patricia Cavazos-Rehg, James Mugisha, Erin Kasson, Olive Imelda Namuyaba, Claire Najjuuko, Edward Nsubuga, Lindsey M Filiatreau, Abel Mwebembezi, Fred M Ssewamala
2020-Current year OA Pubs
BACKGROUND: People living with HIV often struggle with mental health comorbidities that lower their antiretroviral therapy (ART) adherence. There is growing evidence that depression treatment may improve ART adherence and result in improved HIV outcomes. Given that mental health services are severely underequipped in low-resource settings, including in Uganda, new solutions to increase access to mental health care and close the treatment gap are urgently needed. This protocol paper presents the Suubi-Mhealth study, which proposed to develop a mobile health (mHealth) intervention for use among Ugandan youths (14-17 years) with comorbid HIV and depression, taking into account their unique contextual, …
How Does Weight Gain Since The Age Of 18 Years Affect Breast Cancer Risk In Later Life? A Meta-Analysis, Yunan Han, Ebunoluwa E Otegbeye, Carrie Stoll, Angela Hardi, Graham A Colditz, Adetunji T Toriola
How Does Weight Gain Since The Age Of 18 Years Affect Breast Cancer Risk In Later Life? A Meta-Analysis, Yunan Han, Ebunoluwa E Otegbeye, Carrie Stoll, Angela Hardi, Graham A Colditz, Adetunji T Toriola
2020-Current year OA Pubs
Early life factors are important risk factors for breast cancer. The association between weight gain after age 18 and breast cancer risk is inconsistent across previous epidemiologic studies. To evaluate this association, we conducted a meta-analysis according to PRISMA guidelines and the established inclusion criteria. We performed a comprehensive literature search using Medline (Ovid), Embase, Scopus, Cochrane Library, and ClinicalTrials.gov to identify relevant studies published before June 3, 2022. Two reviewers independently reviewed the articles for final inclusion. Seventeen out of 4,725 unique studies met the selection criteria. The quality of studies was assessed using the Newcastle-Ottawa Scale (NOS), and …
Radiological Outcomes Of Magnetically Controlled Growing Rods For The Treatment Of Children With Various Etiologies Of Early-Onset Scoliosis-A Multicenter Study, Pawel Grabala, Munish C Gupta, Daniel E Pereira, Michal Latalski, Anna Danielewicz, Pawel Glowka, Michal Grabala
Radiological Outcomes Of Magnetically Controlled Growing Rods For The Treatment Of Children With Various Etiologies Of Early-Onset Scoliosis-A Multicenter Study, Pawel Grabala, Munish C Gupta, Daniel E Pereira, Michal Latalski, Anna Danielewicz, Pawel Glowka, Michal Grabala
2020-Current year OA Pubs
No abstract provided.