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Full-Text Articles in Medicine and Health Sciences
Obesity Promotes Conserved Inflammatory And Metabolic Transcriptional Programs In Colon Tumors: Evidence From Mouse Models And The Colocare Study Patient Cohort, Elaine M Glenny, Adetunji T Toriola, Et Al.
Obesity Promotes Conserved Inflammatory And Metabolic Transcriptional Programs In Colon Tumors: Evidence From Mouse Models And The Colocare Study Patient Cohort, Elaine M Glenny, Adetunji T Toriola, Et Al.
2020-Current year OA Pubs
BACKGROUND: The global prevalence of obesity, an established risk and progression factor for colon cancer, is high and rising. Unfortunately, the mechanisms underlying the obesity-colon cancer association are incompletely understood, and new molecular targets enabling more effective intervention strategies to break the obesity-colon cancer link are urgently needed.
OBJECTIVES: This study integrated RNA sequencing data from mouse and human colon tumor samples, as well as human adipose samples, to rigorously establish obesity-associated transcriptomic signatures conserved between the 2 species.
METHODS: We employed a mouse colon cancer model with colonoscopy-guided orthotopic transplantation of syngeneic Apc
RESULTS: Diet-induced obesity reduced survival in …
Mechanical Explanation For The Hemodynamic Efficacy Of Right Atrial Appendage Autografts Used In Neo-Semilunar Valve Leaflet Reconstruction, Andrew Behrmann, Kate Appleman, Katarina Lettner, Balaji Cherupala, Jessica Cayton, Shamik Bhattacharya, Pirooz Eghtesady
Mechanical Explanation For The Hemodynamic Efficacy Of Right Atrial Appendage Autografts Used In Neo-Semilunar Valve Leaflet Reconstruction, Andrew Behrmann, Kate Appleman, Katarina Lettner, Balaji Cherupala, Jessica Cayton, Shamik Bhattacharya, Pirooz Eghtesady
2020-Current year OA Pubs
BACKGROUND: Pediatric pulmonic and aortic valve insufficiency has recently been treated with novel procedures that use autologous right atrial appendage tissue. Whether atrial tissue's tensile strength correlates with pressures it can withstand to function as a neo-semilunar valve has not been studied. We therefore studied these properties using an ex vivo porcine heart model.
METHODS: Aortic cusps, pulmonic cusps, and right and left atrial appendage tissues were excised from 10 porcine hearts. Native leaflets and atrial appendage samples underwent circumferential and radial stretching by a uniaxial tensile machine. Right atrial appendage tissue from 14 additional porcine hearts was used to …
Proteogenomics In Cerebrospinal Fluid And Plasma Reveals New Biological Fingerprint Of Cerebral Small Vessel Disease, Ilana Caro, Daniel Western, Chengran Yang, Jigyasha Timsina, Laura Ibanez, Carlos Cruchaga, Et Al.
Proteogenomics In Cerebrospinal Fluid And Plasma Reveals New Biological Fingerprint Of Cerebral Small Vessel Disease, Ilana Caro, Daniel Western, Chengran Yang, Jigyasha Timsina, Laura Ibanez, Carlos Cruchaga, Et Al.
2020-Current year OA Pubs
Cerebral small vessel disease (cSVD) is a leading cause of stroke and dementia with no specific treatment, of which molecular mechanisms remain poorly understood. To identify potential biomarkers and therapeutic targets, we applied Mendelian randomization to examine over 2,500 proteins measured in plasma and, uniquely, cerebrospinal fluid, in relation to magnetic resonance imaging (MRI) markers of cSVD in more than 40,000 individuals. Here we show that 49 proteins are associated with MRI markers of cSVD, most prominently in cerebrospinal fluid. We highlight associations that are consistent across platforms and ancestries, and supported by complementary observational analyses, and we explore differences …
Impact Of Silencing Automated Penicillin Cross-Reactivity Alerts On Perioperative Antibiotic Prescribing And Surgical Site Infection Rates, Michael J Durkin, Joshua Nordman, Alice Bewley, Andrew Atkinson, Jonas Marschall, Helen Newland, Kimberly G Blumenthal
Impact Of Silencing Automated Penicillin Cross-Reactivity Alerts On Perioperative Antibiotic Prescribing And Surgical Site Infection Rates, Michael J Durkin, Joshua Nordman, Alice Bewley, Andrew Atkinson, Jonas Marschall, Helen Newland, Kimberly G Blumenthal
2020-Current year OA Pubs
We evaluated the impact of silencing penicillin cross-reactivity alerts on perioperative antibiotic prescribing and surgical site infections (SSIs) in 6 hospitals using an interrupted time series analysis. Silencing the alerts minimally increased cefazolin prescribing among penicillin allergy labeled patients (sensitivity analysis only;
Assessment Of Knowledge And Attitudes Of Undergraduate Students On Trichomoniasis In Ghana, Christopher Yaw Dumevi, Ezekiel Kofi Vicar, Lorie Christla Quansah, Rhoda Oklu, Smith Joshua, Joyce Junior Asiamah, James-Paul Kretchy, George Boateng Kyei, Patience B Tetteh-Quarcoo, Nicholas T K D Dayie, Irene Ayi, Patrick F Ayeh-Kumi
Assessment Of Knowledge And Attitudes Of Undergraduate Students On Trichomoniasis In Ghana, Christopher Yaw Dumevi, Ezekiel Kofi Vicar, Lorie Christla Quansah, Rhoda Oklu, Smith Joshua, Joyce Junior Asiamah, James-Paul Kretchy, George Boateng Kyei, Patience B Tetteh-Quarcoo, Nicholas T K D Dayie, Irene Ayi, Patrick F Ayeh-Kumi
2020-Current year OA Pubs
BACKGROUND: Trichomoniasis is a non-viral neglected sexually transmitted disease of public health importance. Undergraduate students, often experiencing newfound freedom from family oversight, may engage in risky sexual behaviors, predisposing them to trichomoniasis and other sexually transmitted infections (STIs). This study aimed to assess the knowledge, attitudes, and practices towards trichomoniasis and associated factors among the Central University students in the Greater Accra Region of Ghana.
METHODS: An institutional cross-sectional study was conducted between March and July 2024, involving 387 undergraduate students from Central University who were selected using a simple random sampling technique. Data were collected using a structured researcher-led …
A Roadmap To Scale Up Person-Centred Care In The Hiv Response: Recommendations From A Global Consensus-Building Process, Lina Golob, Elvin H Geng, Et Al.
A Roadmap To Scale Up Person-Centred Care In The Hiv Response: Recommendations From A Global Consensus-Building Process, Lina Golob, Elvin H Geng, Et Al.
2020-Current year OA Pubs
INTRODUCTION: World Health Organization global normative guidance recommends person-centred care (PCC) approaches to reduce HIV-related mortality and morbidity and to improve health-related quality of life (HrQoL). However, consensus on the priority PCC elements and guidance on how different stakeholders can realize PCC principles at the health systems, service delivery and individual client-healthcare worker (HCW) levels are lacking. We conducted a global consensus-building process to define core PCC elements and develop recommendations for implementation at scale.
METHODS: We used a multi-phase process to build consensus and prioritize recommendations, consisting of a literature review, five stakeholder consultations (34-43 participants each) between July …
Association Of Area Deprivation Index With Perinatal And Covid-19 Outcomes During The Early Pandemic: A Secondary Analysis Of A Prospective Cohort Study, Abigail Bell, Megan Foeller, Candice Woolfolk, Emily Diveley, Fan Zhang, Amy Scheffer, Ruizhi Huang, Daniel Jackson, Nandini Raghuraman, Ebony Carter, Indira U Mysorekar, Jeannie C Kelly
Association Of Area Deprivation Index With Perinatal And Covid-19 Outcomes During The Early Pandemic: A Secondary Analysis Of A Prospective Cohort Study, Abigail Bell, Megan Foeller, Candice Woolfolk, Emily Diveley, Fan Zhang, Amy Scheffer, Ruizhi Huang, Daniel Jackson, Nandini Raghuraman, Ebony Carter, Indira U Mysorekar, Jeannie C Kelly
2020-Current year OA Pubs
OBJECTIVE: We sought to evaluate the relationship between neighborhood-level deprivation and perinatal outcomes, particularly preterm birth, as well as COVID-19 outcomes among pregnant patients during the early pandemic.
METHODS: We performed a secondary analysis of a prospective longitudinal cohort study that investigated the impact of prenatal COVID-19 exposure on perinatal outcomes. Pregnant patients were recruited 12/23/20-7/18/22 and serially assessed for COVID-19 exposure during pregnancy, with serum antibody testing, electronic medical record review, and patient report. For this secondary analysis, address at the time of delivery was used to categorize patients into low ADI (≤50
RESULTS: 306 patients were included: 124 …
Genetic Predisposition To Persistent Fatigue After A Diagnosis Of Colorectal Cancer, Elham Kazemian, Adetunji T Toriola, Et Al.
Genetic Predisposition To Persistent Fatigue After A Diagnosis Of Colorectal Cancer, Elham Kazemian, Adetunji T Toriola, Et Al.
2020-Current year OA Pubs
BACKGROUND: Cancer-related fatigue (fatigue) is a common and persistent symptom after cancer treatment, yet the role of genetic susceptibility remains unclear.
METHODS: We used data from a prospective cohort study called the ColoCare Study, conducted over 5 US sites and Germany. Fatigue was assessed at 5 time points using the European Organisation for the Research and Treatment of Cancer Core Quality of Life Questionnaire fatigue subscale and analyzed as (1) a binary summary measure of the trajectory from diagnosis into survivorship (defined as severe: yes/no), (2) a mean score across all time points, and (3) the highest (ie, worst) score …
State Of Omics-Based Microbial Diagnostics Of Crc, Jerome Prusa, Mark G Gorelik, Kevin S Blake, Gautam Dantas
State Of Omics-Based Microbial Diagnostics Of Crc, Jerome Prusa, Mark G Gorelik, Kevin S Blake, Gautam Dantas
2020-Current year OA Pubs
Colorectal cancer (CRC) remains a major burden of cancer-related morbidity and mortality globally, especially when detected at later stages. Early detection through improved and more accessible diagnostics is critical for reducing the severity of CRC. As our understanding of CRC and the microbial inhabitants of the gastrointestinal tract continues to improve, it has become increasingly recognized that the bacterial component of the gut microbiome may provide diagnostic utility for detecting CRC. This is because CRC is often accompanied by shifts in bacterial taxa, and the metabolites produced or utilized by the CRC-associated gut bacterial community. Advances in sequencing and metabolite …
Single Cell Viral Tagging Of Faecalibacterium Prausnitzii Reveals Rare Bacteriophages Omitted By Other Techniques, Danielle E Campbell, Xiaofen Wu, Lindsey R Hall, Dylan Lawrence, Jerome M Molleston, Lawrence A Schriefer, Lindsay Droit, James S Weagley, Benjamin S Olson, Joanna Rimmer, Miles Parkes, Scott A Handley, Megan T Baldridge
Single Cell Viral Tagging Of Faecalibacterium Prausnitzii Reveals Rare Bacteriophages Omitted By Other Techniques, Danielle E Campbell, Xiaofen Wu, Lindsey R Hall, Dylan Lawrence, Jerome M Molleston, Lawrence A Schriefer, Lindsay Droit, James S Weagley, Benjamin S Olson, Joanna Rimmer, Miles Parkes, Scott A Handley, Megan T Baldridge
2020-Current year OA Pubs
The associations of the gut microbiome and virome with human health and disease are increasingly numerous and clear. The mechanistic roles of bacteriophages (phages) in the microbiome, however, are especially unclear, as their cultivation is exceedingly difficult and their diversity so immense. We use viral tagging (VT), a technique wherein fluorescently stained uncultivated viruses are allowed to adsorb to host cells and then host cells are singly sorted. This method identifies interacting phage-bacteria pairs to better sample and characterize the phages in human stool samples from healthy and inflammatory bowel disease (IBD)-affected patients. First, we apply VT to uncultivated bacteria …
Implementing And Evaluating Visual Key Information Pages Compared To Text-Based Key Information: Protocol For A Stepped-Wedge Cluster Randomized Trial, Krista E Cooksey, Eliana C Goldstein, Clara N Lee, Jessica Mozersky, Kimberly A Kaphingst, Jingxia Liu, Shuang Wu, Molly Volkmar, Victor Catalan-Gallegos, Mary C Politi
Implementing And Evaluating Visual Key Information Pages Compared To Text-Based Key Information: Protocol For A Stepped-Wedge Cluster Randomized Trial, Krista E Cooksey, Eliana C Goldstein, Clara N Lee, Jessica Mozersky, Kimberly A Kaphingst, Jingxia Liu, Shuang Wu, Molly Volkmar, Victor Catalan-Gallegos, Mary C Politi
2020-Current year OA Pubs
BACKGROUND: Informed consent is a key aspect of conducting research studies, yet many participants do not understand critical study details after reviewing long, complex consent documents. The 2018 Common Rule aimed to address this challenge by requiring a key information section, a "concise and focused" presentation of important and relevant study information. In our ongoing work, we developed a template and toolkit to improve the presentation of key information by incorporating health literacy best practices, including color and visual icons. The goal of this study is to assess the impact of the visual key information (KI) pages at both the …
Development Of Intestinal Tissue-Resident T Cells In Early-Life Mice Before And After Weaning, Catherine Montenegro, Siyuan Ding, Federico Perdomo-Celis, Manuel A Franco
Development Of Intestinal Tissue-Resident T Cells In Early-Life Mice Before And After Weaning, Catherine Montenegro, Siyuan Ding, Federico Perdomo-Celis, Manuel A Franco
2020-Current year OA Pubs
Intestinal tissue-resident T cells have been poorly characterized during early-life. Here, we phenotypically characterized tissue-resident (intravascular staining negative) CD4
Participatory Implementation Science To Enhance Knowledge And Build The Capacity To Increase The Uptake And Sustainability Of Hpv Vaccination Among Girls In Nigeria, Peter Kalulu, Olufunto A Olusanya, Nkiruka Obodoechina, Maria A Afadapa, Temitope Ojo, Priscilla A Kabutey, Caven N Ngoe, Ashley Bardon, Juliet Iwelunmor, Et Al.
Participatory Implementation Science To Enhance Knowledge And Build The Capacity To Increase The Uptake And Sustainability Of Hpv Vaccination Among Girls In Nigeria, Peter Kalulu, Olufunto A Olusanya, Nkiruka Obodoechina, Maria A Afadapa, Temitope Ojo, Priscilla A Kabutey, Caven N Ngoe, Ashley Bardon, Juliet Iwelunmor, Et Al.
2020-Current year OA Pubs
BACKGROUND: Human papillomavirus (HPV) vaccination can prevent cancer in low- and middle-income countries (LMICs), but its uptake remains low, especially in Nigeria. Understanding participatory approaches can help identify local strategies to increase, build capacity for, and sustain vaccine uptake. This study evaluated the effectiveness of an innovation bootcamp in enhancing the knowledge and skills of youth implementers about HPV and cervical cancer as a strategy to increase vaccine uptake among Nigerian girls aged 9-14 years. An innovation bootcamp is an intensive training program that engages end users to build capacity and skills.
METHODS: This was a five-week hybrid bootcamp guided …
So What? Elevating The Impact Of Implementation Science, Ross C Brownson, Juliet Iwelunmor, Thomas A Odeny, Enola K Proctor, Elvin H Geng
So What? Elevating The Impact Of Implementation Science, Ross C Brownson, Juliet Iwelunmor, Thomas A Odeny, Enola K Proctor, Elvin H Geng
2020-Current year OA Pubs
BACKGROUND: Given the substantial public funding of health-related research, tangible benefits of this support must be demonstrated. Implementation science provides actionable methods to enhance population health, reduce health inequities, and guide effective public health and clinical practices and policies. We must elevate the notion of impact (the "so-what gap") and the role of implementation science, particularly in university settings.
MAIN TEXT: We distinguish between scientific output and impacts. Impacts in implementation science are commonly defined as improvements in health outcomes, quality of life, quality of services, or policy change. In contrast, traditional academic outputs, such as citation counts and grant …
Variation In State Policies On Sideline Medical Coverage Of High School Athletic Events, Marcus Allen, Aravind Athiviraham, Darlington Nwaudo, Lutul D Farrow, Aossm Bold Study Group, Matthew Matava
Variation In State Policies On Sideline Medical Coverage Of High School Athletic Events, Marcus Allen, Aravind Athiviraham, Darlington Nwaudo, Lutul D Farrow, Aossm Bold Study Group, Matthew Matava
2020-Current year OA Pubs
BACKGROUND: Certified athletic trainers (ATs) are the primary source of sideline coverage for high school athletic events, providing an essential role in student-athlete health. However, there is a paucity of literature evaluating the existence of state requirements regarding the presence of ATs and mandatory sideline medical coverage of high school athletic events.
HYPOTHESIS: It was hypothesized that there is significant variation among state policies on sideline medical coverage and AT requirements for high school athletic events.
STUDY DESIGN: Cross-sectional study.
METHODS: A 17-question survey was emailed to the executive directors (or analogous position) of the state high school athletic associations …
Maternal Obesogenic Diet Exposure Regulates The Offspring Gut Liver Axis And Fibroinflammatory Liver Disease, Naresh Naik Ramavath, Oğuz Özler, Holly Hinrichs, Francisco R Victorino, Vung Lian, Monica Young, Tarin M Bigley, Michael D Thompson
Maternal Obesogenic Diet Exposure Regulates The Offspring Gut Liver Axis And Fibroinflammatory Liver Disease, Naresh Naik Ramavath, Oğuz Özler, Holly Hinrichs, Francisco R Victorino, Vung Lian, Monica Young, Tarin M Bigley, Michael D Thompson
2020-Current year OA Pubs
Maternal obesogenic diet exposure (MODE) promotes fibroinflammatory liver disease in offspring via vertical transfer of an altered microbiome. The mechanism for how an altered offspring microbiome increases susceptibility to liver disease is not clear. A critical early life event termed the 'weaning reaction' is dependent on the early microbiome and when altered, results in worse pathologic inflammation. MODE attenuates the weaning reaction promoting worse liver disease in mice in an early microbiome-dependent manner. Using our MODE model and cross-fostering approaches we assessed the effect of MODE on neonatal gut-liver axis development. MODE shifts the bile acid (BA) profile, expression of …
Oligomerisation Of Ku From Mycobacterium Tuberculosis Promotes Dna Synapsis, Sayma Zahid, Ankita Chadda, Eric Galburt, Et Al.
Oligomerisation Of Ku From Mycobacterium Tuberculosis Promotes Dna Synapsis, Sayma Zahid, Ankita Chadda, Eric Galburt, Et Al.
2020-Current year OA Pubs
Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), is estimated to infect nearly one-quarter of the global population. A key factor in its resilience and persistence is its robust DNA repair capacity. Non-homologous end joining (NHEJ) is the primary pathway for repairing DNA double-strand breaks (DSBs) in many organisms, including Mtb, where it is mediated by the Ku protein and the multifunctional LigD enzyme. In this study, we demonstrate that Ku is essential for mycobacterial survival under DNA-damaging conditions. Using cryogenic electron microscopy (cryo-EM), we solved high-resolution structures of both the apo and DNA-bound forms of the Ku-Mtb homodimer. …
The Pitfalls Of Multiple-Choice Questions In Generative Ai And Medical Education, Shrutika Singh, Anton Alyakin, Daniel Alexander Alber, Jaden Stryker, Ai Phuong S Tong, Karl Sangwon, Nicolas Goff, Mathew De La Paz, Miguel Hernandez-Rovira, Ki Yun Park, Eric Claude Leuthardt, Eric Karl Oermann
The Pitfalls Of Multiple-Choice Questions In Generative Ai And Medical Education, Shrutika Singh, Anton Alyakin, Daniel Alexander Alber, Jaden Stryker, Ai Phuong S Tong, Karl Sangwon, Nicolas Goff, Mathew De La Paz, Miguel Hernandez-Rovira, Ki Yun Park, Eric Claude Leuthardt, Eric Karl Oermann
2020-Current year OA Pubs
The performance of Large Language Models (LLMs) on multiple-choice question (MCQ) benchmarks is frequently cited as proof of their medical capabilities. We hypothesized that LLM performance on medical MCQs may in part be illusory and driven by factors beyond medical content knowledge and reasoning capabilities. To assess this, we created a novel benchmark of free-response questions with paired MCQs (FreeMedQA). Using this benchmark, we evaluated three state-of-the-art LLMs (GPT-4o, GPT-3.5, and LLama-3-70B-instruct) and found an average absolute deterioration of 39.43% in performance on free-response questions relative to multiple-choice (p = 1.3 * 10
Clinical And Implementation Outcomes Of An Antimicrobial Stewardship Intervention For Rapid Blood Culture Diagnostics, Monica Abdelnour, Christine R Lockowitz, Evan E Facer, Andrew Atkinson, Sara Malone, Virginia R Mckay, Rebekah E Dumm, Alexander S Plattner, Matthew M Sattler, Jason G Newland
Clinical And Implementation Outcomes Of An Antimicrobial Stewardship Intervention For Rapid Blood Culture Diagnostics, Monica Abdelnour, Christine R Lockowitz, Evan E Facer, Andrew Atkinson, Sara Malone, Virginia R Mckay, Rebekah E Dumm, Alexander S Plattner, Matthew M Sattler, Jason G Newland
2020-Current year OA Pubs
OBJECTIVE: To evaluate the clinical and implementation outcomes of an antimicrobial stewardship program (ASP) intervention to improve antibiotic therapy for a rapid diagnostic test (RDT) for bloodstream infections (BSIs).
DESIGN: Retrospective pre and postintervention study.
SETTING: Single pediatric tertiary center from August 2022 to May 2024.
PARTICIPANTS: Patients presenting with a positive blood culture accompanied by the Verigene (VG) Gram-positive Blood Culture Nucleic Acid (BC-GP) assay. Implementation outcomes surveys were completed by infectious diseases (ID) clinicians and non-ID clinicians.
METHODS: We implemented a 24 hours a day, 7 days a week (24/7) ASP intervention to improve response to BC-GP assay …
Implementation Outcomes From The Hypertension Treatment In Nigeria Program: Results From A Type 2 Hybrid Interrupted Time Series Trial, Jiancheng Ye, Erica L Jamro, Guhan Iyer, Mark D Huffman, Et Al.
Implementation Outcomes From The Hypertension Treatment In Nigeria Program: Results From A Type 2 Hybrid Interrupted Time Series Trial, Jiancheng Ye, Erica L Jamro, Guhan Iyer, Mark D Huffman, Et Al.
2020-Current year OA Pubs
BACKGROUND: The Hypertension Treatment in Nigeria Program was implemented across 60 primary healthcare centers (PHCs) in Nigeria to improve hypertension treatment and control using the World Health Organization's HEARTS package. This study reports the program's implementation outcomes.
METHODS: The Hypertension Treatment in Nigeria Program used a type 2 hybrid interrupted time series design, and data were collected from January 2020 to December 2023. The RE-AIM (Reach, Effectiveness, Adoption, Implementation, and Maintenance) framework guided the evaluation, focusing on key metrics such as patients' and clinics' characteristics, prescription rate of fixed dose combination (FDC) drugs, medication availability, and retention.
RESULTS: Among 21,922 …
Successful Implementation Of Stroke Risk Screening For Sickle Cell Anemia In The Displace Study: Results Of A Cluster Randomized Trial, Alyssa M Schlenz, Monica L Hulbert, Et Al.
Successful Implementation Of Stroke Risk Screening For Sickle Cell Anemia In The Displace Study: Results Of A Cluster Randomized Trial, Alyssa M Schlenz, Monica L Hulbert, Et Al.
2020-Current year OA Pubs
BACKGROUND: Stroke risk screening using transcranial Doppler (TCD) is a critical evidence-based tool for children with sickle cell anemia (SCA) that has been poorly implemented in the United States. The Dissemination and Implementation of Stroke Prevention Looking at the Care Environment (DISPLACE) study was designed to improve rates of stroke risk screening for SCA using interventions informed by an extensive multi-level barriers and facilitators assessment. This report describes the final outcomes of a large, randomized implementation trial comparing two intervention arms: 1) an application designed to track TCD implementation, ProviderMinder™, versus 2) ProviderMinder™ plus a single coordinator intervention. All sites …
Prospective Sars-Cov-2 Additional Vaccination In Immunosuppressant-Treated Individuals With Autoimmune Diseases In A Randomized Controlled Trial, Meggan Mackay, Alfred Hj Kim, Et Al.
Prospective Sars-Cov-2 Additional Vaccination In Immunosuppressant-Treated Individuals With Autoimmune Diseases In A Randomized Controlled Trial, Meggan Mackay, Alfred Hj Kim, Et Al.
2020-Current year OA Pubs
BACKGROUND: Individuals with autoimmune diseases (AD) on immunosuppressants often have suboptimal responses to COVID-19 vaccine. We evaluated the efficacy and safety of additional COVID-19 vaccines in those treated with mycophenolate mofetil/mycophenolic acid (MMF/MPA), methotrexate (MTX), and B cell-depleting therapy (BCDT), including the impact of withholding MMF/MPA and MTX.
METHODS: In this open-label, multicenter, randomized trial, 22 participants taking MMF/MPA, 26 taking MTX, and 93 treated with BCDT who had suboptimal antibody responses to initial COVID-19 vaccines (2 doses of BNT162b2 or mRNA-1273 or 1 dose of AD26.COV2.S) received an additional homologous vaccine. Participants taking MMF/MPA and MTX were randomized (1:1) …
Cpx-351 Vs. Conventional Chemotherapy Cardiotoxicity In High-Risk Aml: A Post Hoc Phase Iii Trial Analysis, Joshua D Mitchell, Michael Pfeiffer, John Boehmer, John Gorcsan, Shunsuke Eguchi, Yoshiyuki Orihara, Nalina Dronamraju, Sonja Dhani, Stefan Faderl, Tara L Lin, Geoffrey L Uy, Jeffrey E Lancet, Jorge E Cortes
Cpx-351 Vs. Conventional Chemotherapy Cardiotoxicity In High-Risk Aml: A Post Hoc Phase Iii Trial Analysis, Joshua D Mitchell, Michael Pfeiffer, John Boehmer, John Gorcsan, Shunsuke Eguchi, Yoshiyuki Orihara, Nalina Dronamraju, Sonja Dhani, Stefan Faderl, Tara L Lin, Geoffrey L Uy, Jeffrey E Lancet, Jorge E Cortes
2020-Current year OA Pubs
BACKGROUND: CPX-351, a dual-drug liposomal encapsulation of daunorubicin and cytarabine in a synergistic 1:5 molar ratio, has demonstrated significantly improved overall survival in acute myeloid leukemia (AML) compared with 7 + 3, but its impact on cardiac function remains unclear. In a post hoc analysis of the pivotal clinical trial, we sought to determine the relative cardiotoxicity of CPX-351 vs. 7 + 3 in high-risk AML.
METHODS: We evaluated cardiotoxicity in 102 patients with AML (CPX-351, n = 57; 7 + 3, n = 45) who had normal baseline left ventricular ejection fraction (LVEF) ≥ 53% and at least one …
Deep Learning Reveals How Cells Pull, Buckle, And Navigate Fibrous Environments, Abinash Padhi, Arka Daw, Atharva Agashe, Medha Sawhney, Maahi M Talukder, Mehran M H Pour, Mohammad Jafari, Guy M Genin, Farid Alisafaei, Sohan Kale, Anuj Karpatne, Amrinder S Nain
Deep Learning Reveals How Cells Pull, Buckle, And Navigate Fibrous Environments, Abinash Padhi, Arka Daw, Atharva Agashe, Medha Sawhney, Maahi M Talukder, Mehran M H Pour, Mohammad Jafari, Guy M Genin, Farid Alisafaei, Sohan Kale, Anuj Karpatne, Amrinder S Nain
2020-Current year OA Pubs
Cells in tissues navigate fibrous environments fundamentally differently than they do on flat substrates, but the establishment of cell forces in physiological fibrous settings remains poorly understood. Although factors such as the stiffness of the extracellular matrix (ECM) are known to drive behaviors, including cell motility on flat nonfibrous substrates, the interplay between fiber architecture and stiffness in fibrous ECM is not known. Here, we find that in fibrous environments, the directionality of mechanical forces overrides ECM stiffness as the primary regulator of contractility in migrating cells. Using an approach combining phase microscopy with deep learning to map forces in …
Mitochondrial Iron Transport Via Mfrn1 Is Required For Erythroid Cell Cycle Progression, Mark Perfetto, Aidan Danoff, Muhammad Ishfaq, Heidi Monroe, Aiden Mohideen, Meilin Chen, Jesus Tejero, Amber N Stratman, Satoshi Okawa, Yvette Y Yien
Mitochondrial Iron Transport Via Mfrn1 Is Required For Erythroid Cell Cycle Progression, Mark Perfetto, Aidan Danoff, Muhammad Ishfaq, Heidi Monroe, Aiden Mohideen, Meilin Chen, Jesus Tejero, Amber N Stratman, Satoshi Okawa, Yvette Y Yien
2020-Current year OA Pubs
Iron metabolism drives key erythropoietic processes, including hemoglobinization, survival, and proliferation. Here, we developed in vivo methods to interrogate how iron regulates erythropoiesis and report that mitochondrial iron transport via mitoferrin-1 (MFRN1) is essential for erythroid cell cycle progression. mfrn1 embryos had severely decreased erythroid cell number caused by cell cycle arrest at G2/M. They had enlarged nuclei, suggesting a mitotic defect. Iron supplementation rescued the cell cycle defect, implicating mitochondrial iron deficiency as its cause. In contrast, fpn1 mutants, anemic from systemic iron deficiency, had less severe decreases in erythroid mitochondrial iron than mfrn1 mutants and no proliferative defects. …
Single-Cell Transcriptomic Analysis Of Hpv-Related Multiphenotypic Sinonasal Carcinoma Uncovers Myb-Hpv Association, Avishai Wizel, Matthew D A Spence, Michael Mints, William Britton, Ogoegbunam Okolo, Victoria Yu, Isabel Cioffi, Salvatore Caruana, Scott H Troob, William C Faquin, Derrick T Lin, Itay Tirosh, Sidharth V Puram, Anuraag S Parikh, Yotam Drier
Single-Cell Transcriptomic Analysis Of Hpv-Related Multiphenotypic Sinonasal Carcinoma Uncovers Myb-Hpv Association, Avishai Wizel, Matthew D A Spence, Michael Mints, William Britton, Ogoegbunam Okolo, Victoria Yu, Isabel Cioffi, Salvatore Caruana, Scott H Troob, William C Faquin, Derrick T Lin, Itay Tirosh, Sidharth V Puram, Anuraag S Parikh, Yotam Drier
2020-Current year OA Pubs
Human papillomavirus (HPV)-related multiphenotypic sinonasal carcinoma (HMSC) is a rare tumor that morphologically resembles high-grade adenoid cystic carcinoma (ACC) but exhibits indolent clinical behavior. Both demonstrate MYB proto-oncogene upregulation, though HMSC lacks the MYB translocation characteristic of ACC. We performed single-cell RNA sequencing on an HMSC tumor and compared expression patterns with published ACC and oropharyngeal squamous cell carcinoma (OPSCC) datasets. Malignant HMSC cells clustered separately from ACC and lacked bicellular luminal and myoepithelial differentiation. A greater proportion of HMSC cells expressing HPV-related genes (HPVon) expressed MYB (83% vs. 62%, p = 0.022) and MYB targets (p = 6.4 × …
Cohort Profile: The Pharmacogenomics And Pharmacokinetics Study In Ghanaian Hiv Patients (Genopharm-Gh), Nicholas Ekow Thomford, Oksana Ryabinina, Joel Adu Twum, John Anyimadu, Samuel Badu Nyarko, Akwasi Anyanful, Martins Ekor, George Boateng Kyei
Cohort Profile: The Pharmacogenomics And Pharmacokinetics Study In Ghanaian Hiv Patients (Genopharm-Gh), Nicholas Ekow Thomford, Oksana Ryabinina, Joel Adu Twum, John Anyimadu, Samuel Badu Nyarko, Akwasi Anyanful, Martins Ekor, George Boateng Kyei
2020-Current year OA Pubs
BACKGROUND: The GenoPharm-GH project initiated in 2019, as a longitudinal, multi-site observational cohort study aimed at bridging gaps in understanding the influence of host genetics, pharmacokinetics and comorbidities on treatment outcome among persons living with HIV (PLWH) in Ghana.
METHODS: The study is ongoing prospective, longitudinal, multi-site cohort associated with diverse projects being conducted throughout health facilities across Ghana. So far 2044 persons living with HIV (PLWH) aged ≥ 8 years have been registered. These participants are on treatment with antiretroviral therapies (ART). Viral suppression, treatment adherence (self-reported and pill count), clinical data, genetic variations, coinfections, and comorbidities are being …
Multidomain Therapy For Alzheimer's Disease: A Scoping Review Of Cognitive Decline Trials, Jared C Roach, Cyrus A Raji, Et Al.
Multidomain Therapy For Alzheimer's Disease: A Scoping Review Of Cognitive Decline Trials, Jared C Roach, Cyrus A Raji, Et Al.
2020-Current year OA Pubs
BACKGROUND: Alzheimer’s disease (AD) leading to cognitive decline and dementia results from the interplay of multiple interacting dysfunctional biological systems. These systems can be categorized by domain, such as inflammation, cardiovascular health, proteostasis, or metabolism. Specific causes of AD differ between individuals, but each individual is likely to have causes stemming from multiple domains. Personalized multidomain therapy has been proposed as a standard of care for AD. OBJECTIVES: We sought to enumerate and describe prospective randomized controlled trials (RCTs) for multidomain interventions for AD, and to extract their inclusion criteria, trial design parameters (length, number of participants), and outcome measures. …
A Cluster-Randomized Controlled Trial Assessing The Effectiveness Of A Multifaceted Versus A Discrete Implementation Strategy On Fidelity To An Occupational Guideline For The Prevention Of Mental Health Problems At The Workplace: A Dual Perspective From Swedish Schools, Andreas Rödlund, Anna Toropova, Rebecca Lengnick-Hall, Byron J Powell, Liselotte Schäfer Elinder, Christina Björklund, Lydia Kwak
A Cluster-Randomized Controlled Trial Assessing The Effectiveness Of A Multifaceted Versus A Discrete Implementation Strategy On Fidelity To An Occupational Guideline For The Prevention Of Mental Health Problems At The Workplace: A Dual Perspective From Swedish Schools, Andreas Rödlund, Anna Toropova, Rebecca Lengnick-Hall, Byron J Powell, Liselotte Schäfer Elinder, Christina Björklund, Lydia Kwak
2020-Current year OA Pubs
BACKGROUND: Although the management of psychosocial risks in the work environment represents an evidence-based approach to the prevention of mental health problems, its implementation is limited, including in schools, and knowledge on how to support better implementation is scarce. This study compares the effectiveness of a multifaceted vs. a discrete implementation strategy on fidelity to an occupational guideline for the prevention of mental health problems. Dual perspectives were used to assess fidelity, an important aspect of the measurement agenda.
METHODS: A cluster-randomized controlled trial was conducted among 55 schools in Sweden. A multifaceted strategy (educational meeting, implementation teams, ongoing training, …
Assessing The Usability Of A Novel Toolkit For Creating Visual Key Information Pages For Informed Consent For Research: Mixed Methods Usability Study, Eliana Charlotte Goldstein, Zoe Troubh, Krista E Cooksey, Molly Volkmar, Victor Catalan Gallegos, Kimberly A Kaphingst, Clara N Lee, Ashley J Housten, Jessica Mozersky, Mary C Politi
Assessing The Usability Of A Novel Toolkit For Creating Visual Key Information Pages For Informed Consent For Research: Mixed Methods Usability Study, Eliana Charlotte Goldstein, Zoe Troubh, Krista E Cooksey, Molly Volkmar, Victor Catalan Gallegos, Kimberly A Kaphingst, Clara N Lee, Ashley J Housten, Jessica Mozersky, Mary C Politi
2020-Current year OA Pubs
BACKGROUND: Key information pages for informed consent require a concise summary of information to improve participant understanding but have not widely incorporated health literacy best practices.
OBJECTIVE: We previously developed a visual key information template to improve informed consent. In this study, we conducted usability testing of this customizable one-page key information template.
METHODS: We used the Designing for Accelerated Translation framework to plan for actionable, efficient usability testing. Participants (N=15) were asked to spend about 20 minutes using the visual key information template and engaging in a think-aloud protocol. They then responded to qualitative debrief questions about the template …