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Articles 4861 - 4890 of 10568

Full-Text Articles in Medicine and Health Sciences

Factor Xa Cleaves Sars-Cov-2 Spike Protein To Block Viral Entry And Infection, Wenjuan Dong, Sean P J Whelan, Et Al. Apr 2023

Factor Xa Cleaves Sars-Cov-2 Spike Protein To Block Viral Entry And Infection, Wenjuan Dong, Sean P J Whelan, Et Al.

2020-Current year OA Pubs

Serine proteases (SP), including furin, trypsin, and TMPRSS2 cleave the SARS-CoV-2 spike (S) protein, enabling the virus to enter cells. Here, we show that factor (F) Xa, an SP involved in blood coagulation, is upregulated in COVID-19 patients. In contrast to other SPs, FXa exerts antiviral activity. Mechanistically, FXa cleaves S protein, preventing its binding to ACE2, and thus blocking viral entry and infection. However, FXa is less effective against variants carrying the D614G mutation common in all pandemic variants. The anticoagulant rivaroxaban, a direct FXa inhibitor, inhibits FXa-mediated S protein cleavage and facilitates viral entry, whereas the indirect FXa …


Sphingomyelin 16:0 Is A Therapeutic Target For Neuronal Death In Acid Sphingomyelinase Deficiency, Ángel Gaudioso, Xuntian Jiang, Josefina Casas, Edward H Schuchman, María Dolores Ledesma Apr 2023

Sphingomyelin 16:0 Is A Therapeutic Target For Neuronal Death In Acid Sphingomyelinase Deficiency, Ángel Gaudioso, Xuntian Jiang, Josefina Casas, Edward H Schuchman, María Dolores Ledesma

2020-Current year OA Pubs

Acid sphingomyelinase deficiency (ASMD) is a lysosomal storage disorder caused by mutations in the SMPD1 gene encoding for the acid sphingomyelinase (ASM). While intravenous infusion of recombinant ASM is an effective treatment for the peripheral disease, the neurological complications of ASMD remain unaddressed. It has been shown that aberrantly high level of total brain sphingomyelin (SM) is a key pathological event leading to neurodegeneration. Using mice lacking ASM (ASMko), which mimic the disease, we here demonstrate that among the SM species, SM16:0 shows the highest accumulation and toxicity in ASMko neurons. By targeting lysosomes, SM16:0 causes permeabilization and exocytosis of …


Cross-Sectional Study To Assess Depression Among Healthcare Workers In Lusaka, Zambia During The Covid-19 Pandemic, Sandra Simbeza, Jacob Mutale, Musunge Mulabe, Lazarus Jere, Chama Bukankala, Kombatende Sikombe, Izukanji Sikazwe, Carolyn Bolton-Moore, Aaloke Mody, Elvin H. Geng, Anjali Sharma, Laura K. Beres, Jake M. Pry Apr 2023

Cross-Sectional Study To Assess Depression Among Healthcare Workers In Lusaka, Zambia During The Covid-19 Pandemic, Sandra Simbeza, Jacob Mutale, Musunge Mulabe, Lazarus Jere, Chama Bukankala, Kombatende Sikombe, Izukanji Sikazwe, Carolyn Bolton-Moore, Aaloke Mody, Elvin H. Geng, Anjali Sharma, Laura K. Beres, Jake M. Pry

2020-Current year OA Pubs

OBJECTIVES: We sought to assess depression among healthcare workers (HCWs) in the context of COVID-19 in Lusaka Province, Zambia.

DESIGN: This cross-sectional study is nested within a larger study, the Person-Centred Public Health for HIV Treatment in Zambia (PCPH), a cluster-randomised trial to assess HIV care and outcomes.

SETTING: The research was conducted in 24 government-run health facilities from 11 August to 15 October 2020 during the first wave of the COVID-19 pandemic in Lusaka, Zambia.

PARTICIPANTS: We used convenience sampling to recruit HCW participants who were previously enrolled in the PCPH study, had more than 6 months' experience working …


Extended Dna Threading Through A Dual-Engine Motor Module Of The Activating Signal Co-Integrator 1 Complex, Junqiao Jia, Tarek Hilal, Katherine E Bohnsack, Aleksandar Chernev, Ning Tsao, Juliane Bethmann, Aruna Arumugam, Lane Parmely, Nicole Holton, Bernhard Loll, Nima Mosammaparast, Markus T Bohnsack, Henning Urlaub, Markus C Wahl Apr 2023

Extended Dna Threading Through A Dual-Engine Motor Module Of The Activating Signal Co-Integrator 1 Complex, Junqiao Jia, Tarek Hilal, Katherine E Bohnsack, Aleksandar Chernev, Ning Tsao, Juliane Bethmann, Aruna Arumugam, Lane Parmely, Nicole Holton, Bernhard Loll, Nima Mosammaparast, Markus T Bohnsack, Henning Urlaub, Markus C Wahl

2020-Current year OA Pubs

Activating signal co-integrator 1 complex (ASCC) subunit 3 (ASCC3) supports diverse genome maintenance and gene expression processes, and contains tandem Ski2-like NTPase/helicase cassettes crucial for these functions. Presently, the molecular mechanisms underlying ASCC3 helicase activity and regulation remain unresolved. We present cryogenic electron microscopy, DNA-protein cross-linking/mass spectrometry as well as in vitro and cellular functional analyses of the ASCC3-TRIP4 sub-module of ASCC. Unlike the related spliceosomal SNRNP200 RNA helicase, ASCC3 can thread substrates through both helicase cassettes. TRIP4 docks on ASCC3 via a zinc finger domain and stimulates the helicase by positioning an ASC-1 homology domain next to the C-terminal …


The F-Pilus Biomechanical Adaptability Accelerates Conjugative Dissemination Of Antimicrobial Resistance And Biofilm Formation, Jonasz B Patkowski, Tobias Dahlberg, Himani Amin, Dharmender K Gahlot, Sukhithasri Vijayrajratnam, Joseph P Vogel, Matthew S Francis, Joseph L Baker, Magnus Andersson, Tiago R D Costa Apr 2023

The F-Pilus Biomechanical Adaptability Accelerates Conjugative Dissemination Of Antimicrobial Resistance And Biofilm Formation, Jonasz B Patkowski, Tobias Dahlberg, Himani Amin, Dharmender K Gahlot, Sukhithasri Vijayrajratnam, Joseph P Vogel, Matthew S Francis, Joseph L Baker, Magnus Andersson, Tiago R D Costa

2020-Current year OA Pubs

Conjugation is used by bacteria to propagate antimicrobial resistance (AMR) in the environment. Central to this process are widespread conjugative F-pili that establish the connection between donor and recipient cells, thereby facilitating the spread of IncF plasmids among enteropathogenic bacteria. Here, we show that the F-pilus is highly flexible but robust at the same time, properties that increase its resistance to thermochemical and mechanical stresses. By a combination of biophysical and molecular dynamics methods, we establish that the presence of phosphatidylglycerol molecules in the F-pilus contributes to the structural stability of the polymer. Moreover, this structural stability is important for …


Statins Enhance The Efficacy Of Her2-Targeting Radioligand Therapy In Drug-Resistant Gastric Cancers, Yi Rao, Zachary Samuels, Lukas M Carter, Sebastien Monette, Sandeep Surendra Panikar, Patricia M R Pereira, Jason S Lewis Apr 2023

Statins Enhance The Efficacy Of Her2-Targeting Radioligand Therapy In Drug-Resistant Gastric Cancers, Yi Rao, Zachary Samuels, Lukas M Carter, Sebastien Monette, Sandeep Surendra Panikar, Patricia M R Pereira, Jason S Lewis

2020-Current year OA Pubs

Human epidermal growth factor receptor 2 (HER2) is overexpressed in various cancer types. HER2-targeting trastuzumab plus chemotherapy is used as first-line therapy for HER2-positive recurrent or primary metastatic gastric cancer, but intrinsic and acquired trastuzumab resistance inevitably develop over time. To overcome gastric cancer resistance to HER2-targeted therapies, we have conjugated trastuzumab with a beta-emitting therapeutic isotope, lutetium-177, to deliver radiation locally to gastric tumors with minimal toxicity. Because trastuzumab-based targeted radioligand therapy (RLT) requires only the extramembrane domain binding of membrane-bound HER2 receptors, HER2-targeting RLT can bypass any resistance mechanisms that occur downstream of HER2 binding. Leveraging our previous …


A Dna Damage-Induced Phosphorylation Circuit Enhances Mec1atr Ddc2atrip Recruitment To Replication Protein A, Luke A Yates, Elias A Tannous, R Marc Morgan, Peter M Burgers, Xiaodong Zhang Apr 2023

A Dna Damage-Induced Phosphorylation Circuit Enhances Mec1atr Ddc2atrip Recruitment To Replication Protein A, Luke A Yates, Elias A Tannous, R Marc Morgan, Peter M Burgers, Xiaodong Zhang

2020-Current year OA Pubs

The cell cycle checkpoint kinase Mec1


On-The-Go Adaptation Of Implementation Approaches And Strategies In Health: Emerging Perspectives And Research Opportunities, Elvin H Geng, Aaloke Mody, Byron J Powell Apr 2023

On-The-Go Adaptation Of Implementation Approaches And Strategies In Health: Emerging Perspectives And Research Opportunities, Elvin H Geng, Aaloke Mody, Byron J Powell

2020-Current year OA Pubs

In many cases, implementation approaches (composed of one or more strategies) may need to change over time to work optimally. We use a literature review to inform a mechanistic analysis of such on-the-go adaptations. We suggest that such adaptations of implementation strategies consist of three necessary steps. The first component is the initial effect of the implementation approach on intended implementation, service delivery, or clinical outcomes. Second, these initial effects must in turn be used to modify, alter, intensify, or otherwise change the implementation approach. Third, the modified approach itself has effects. Conceiving of adaptation as all three steps implies …


Estimated Clinical Outcomes And Cost-Effectiveness Associated With Provision Of Addiction Treatment In Us Primary Care Clinics, Raagini Jawa, Yjuliana Tin, Samantha Nall, Susan L Calcaterra, Alexandra Savinkina, Laura R Marks, Simeon D Kimmel, Benjamin P Linas, Joshua A Barocas Apr 2023

Estimated Clinical Outcomes And Cost-Effectiveness Associated With Provision Of Addiction Treatment In Us Primary Care Clinics, Raagini Jawa, Yjuliana Tin, Samantha Nall, Susan L Calcaterra, Alexandra Savinkina, Laura R Marks, Simeon D Kimmel, Benjamin P Linas, Joshua A Barocas

2020-Current year OA Pubs

IMPORTANCE: US primary care practitioners (PCPs) are the largest clinical workforce, but few provide addiction care. Primary care is a practical place to expand addiction services, including buprenorphine and harm reduction kits, yet the clinical outcomes and health care sector costs are unknown.

OBJECTIVE: To estimate the long-term clinical outcomes, costs, and cost-effectiveness of integrated buprenorphine and harm reduction kits in primary care for people who inject opioids.

DESIGN, SETTING, AND PARTICIPANTS: In this modeling study, the Reducing Infections Related to Drug Use Cost-Effectiveness (REDUCE) microsimulation model, which tracks serious injection-related infections, overdose, hospitalization, and death, was used to examine …


Monocyte Depletion Enhances Neutrophil Influx And Proneural To Mesenchymal Transition In Glioblastoma, Zhihong Chen, David H Gutmann, Et Al. Apr 2023

Monocyte Depletion Enhances Neutrophil Influx And Proneural To Mesenchymal Transition In Glioblastoma, Zhihong Chen, David H Gutmann, Et Al.

2020-Current year OA Pubs

Myeloid cells comprise the majority of immune cells in tumors, contributing to tumor growth and therapeutic resistance. Incomplete understanding of myeloid cells response to tumor driver mutation and therapeutic intervention impedes effective therapeutic design. Here, by leveraging CRISPR/Cas9-based genome editing, we generate a mouse model that is deficient of all monocyte chemoattractant proteins. Using this strain, we effectively abolish monocyte infiltration in genetically engineered murine models of de novo glioblastoma (GBM) and hepatocellular carcinoma (HCC), which show differential enrichment patterns for monocytes and neutrophils. Eliminating monocyte chemoattraction in monocyte enriched PDGFB-driven GBM invokes a compensatory neutrophil influx, while having no …


Associations Of Combined Physical Activity And Body Mass Index Groups With Colorectal Cancer Survival Outcomes, Caroline Himbert, Matthew G Mutch, Corey Bernadt, Adetunji T Toriola, Et Al. Apr 2023

Associations Of Combined Physical Activity And Body Mass Index Groups With Colorectal Cancer Survival Outcomes, Caroline Himbert, Matthew G Mutch, Corey Bernadt, Adetunji T Toriola, Et Al.

2020-Current year OA Pubs

BACKGROUND: Physical activity and BMI have been individually associated with cancer survivorship but have not yet been studied in combinations in colorectal cancer patients. Here, we investigate individual and combined associations of physical activity and BMI groups with colorectal cancer survival outcomes.

METHODS: Self-reported physical activity levels (MET hrs/wk) were assessed using an adapted version of the International Physical Activity Questionnaire (IPAQ) at baseline in 931 patients with stage I-III colorectal cancer and classified into 'highly active' and'not-highly active'(≥ / < 18 MET hrs/wk). BMI (kg/m

RESULTS: 'Not-highly active' compared to 'highly active' and 'overweight'/ 'obese' compared to 'normal weight' patients had a 40-50% increased risk …


Rapid Profiling Of Dna Replication Dynamics Using Mass Spectrometry-Based Analysis Of Nascent Dna, Mohamed E Ashour, Andrea K Byrum, Alice Meroni, Jun Xia, Saurabh Singh, Roberto Galletto, Susan M Rosenberg, Alessandro Vindigni, Nima Mosammaparast Apr 2023

Rapid Profiling Of Dna Replication Dynamics Using Mass Spectrometry-Based Analysis Of Nascent Dna, Mohamed E Ashour, Andrea K Byrum, Alice Meroni, Jun Xia, Saurabh Singh, Roberto Galletto, Susan M Rosenberg, Alessandro Vindigni, Nima Mosammaparast

2020-Current year OA Pubs

The primary method for probing DNA replication dynamics is DNA fiber analysis, which utilizes thymidine analog incorporation into nascent DNA, followed by immunofluorescent microscopy of DNA fibers. Besides being time-consuming and prone to experimenter bias, it is not suitable for studying DNA replication dynamics in mitochondria or bacteria, nor is it adaptable for higher-throughput analysis. Here, we present mass spectrometry-based analysis of nascent DNA (MS-BAND) as a rapid, unbiased, quantitative alternative to DNA fiber analysis. In this method, incorporation of thymidine analogs is quantified from DNA using triple quadrupole tandem mass spectrometry. MS-BAND accurately detects DNA replication alterations in both …


Advanced Care Planning For Hospitalized Patients Following Clinician Notification Of Patient Mortality By A Machine Learning Algorithm, Stephen Chi, Seunghwan Kim, Matthew Reuter, Katharine Ponzillo, Debra Parker Oliver, Randi Foraker, Kevin Heard, Jingxia Liu, Kyle Pitzer, Patrick White, Nathan Moore Apr 2023

Advanced Care Planning For Hospitalized Patients Following Clinician Notification Of Patient Mortality By A Machine Learning Algorithm, Stephen Chi, Seunghwan Kim, Matthew Reuter, Katharine Ponzillo, Debra Parker Oliver, Randi Foraker, Kevin Heard, Jingxia Liu, Kyle Pitzer, Patrick White, Nathan Moore

2020-Current year OA Pubs

IMPORTANCE: Goal-concordant care is an ongoing challenge in hospital settings. Identification of high mortality risk within 30 days may call attention to the need to have serious illness conversations, including the documentation of patient goals of care.

OBJECTIVE: To examine goals of care discussions (GOCDs) in a community hospital setting with patients identified as having a high risk of mortality by a machine learning mortality prediction algorithm.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study took place at community hospitals within 1 health care system. Participants included adult patients with a high risk of 30-day mortality who were admitted to 1 …


Evaluation Of Birth By Cesarean Delivery And Development Of Early-Onset Colorectal Cancer, Yin Cao, Long H Nguyen, Stefani Tica, Ebunoluwa Otegbeye, Xiaoyu Zong, Bjorn Roelstraete, Andrew T Chan, Barbara B Warner, Olof Stephansson, Jonas F Ludvigsson Apr 2023

Evaluation Of Birth By Cesarean Delivery And Development Of Early-Onset Colorectal Cancer, Yin Cao, Long H Nguyen, Stefani Tica, Ebunoluwa Otegbeye, Xiaoyu Zong, Bjorn Roelstraete, Andrew T Chan, Barbara B Warner, Olof Stephansson, Jonas F Ludvigsson

2020-Current year OA Pubs

IMPORTANCE: The incidence of early-onset colorectal cancer (CRC), diagnosed younger than 50 years of age, has increased worldwide. Gut dysbiosis throughout the life course is hypothesized as a leading mechanism, yet epidemiologic data are limited.

OBJECTIVE: To prospectively examine the association between birth by cesarean delivery and early-onset CRC among offspring.

DESIGN, SETTING, AND PARTICIPANTS: In this population-based, nationwide case-control study in Sweden, adults diagnosed with CRC between 18 and 49 years of age from 1991 to 2017 were identified through the Epidemiology Strengthened by Histopathology Reports in Sweden (ESPRESSO) cohort. Up to 5 general population control individuals without CRC …


Association Of Radiotherapy Duration With Clinical Outcomes In Patients With Esophageal Cancer Treated In Nrg Oncology Trials: A Secondary Analysis Of Nrg Oncology Randomized Clinical Trials, Christopher L Hallemeier, Hyun Kim, Et Al. Apr 2023

Association Of Radiotherapy Duration With Clinical Outcomes In Patients With Esophageal Cancer Treated In Nrg Oncology Trials: A Secondary Analysis Of Nrg Oncology Randomized Clinical Trials, Christopher L Hallemeier, Hyun Kim, Et Al.

2020-Current year OA Pubs

IMPORTANCE: For many types of epithelial malignant neoplasms that are treated with definitive radiotherapy (RT), treatment prolongation and interruptions have an adverse effect on outcomes.

OBJECTIVE: To analyze the association between RT duration and outcomes in patients with esophageal cancer who were treated with definitive chemoradiotherapy (CRT).

DESIGN, SETTING, AND PARTICIPANTS: This study was an unplanned, post hoc secondary analysis of 3 prospective, multi-institutional phase 3 randomized clinical trials (Radiation Therapy Oncology Group [RTOG] 8501, RTOG 9405, and RTOG 0436) of the National Cancer Institute-sponsored NRG Oncology (formerly the National Surgical Adjuvant Breast and Bowel Project, RTOG, and Gynecologic Oncology …


Priorities To Promote Participant Engagement In The Participant Engagement And Cancer Genome Sequencing (Pe-Cgs) Network, Anne Lr Schuster, Graham A Colditz, Li Ding, Bettina F Drake, Ryan C Fields, Et Al. Apr 2023

Priorities To Promote Participant Engagement In The Participant Engagement And Cancer Genome Sequencing (Pe-Cgs) Network, Anne Lr Schuster, Graham A Colditz, Li Ding, Bettina F Drake, Ryan C Fields, Et Al.

2020-Current year OA Pubs

BACKGROUND: Engaging diverse populations in cancer genomics research is of critical importance and is a fundamental goal of the NCI Participant Engagement and Cancer Genome Sequencing (PE-CGS) Network. Established as part of the Cancer Moonshot, PE-CGS is a consortium of stakeholders including clinicians, scientists, genetic counselors, and representatives of potential study participants and their communities. Participant engagement is an ongoing, bidirectional, and mutually beneficial interaction between study participants and researchers. PE-CGS sought to set priorities in participant engagement for conducting the network's research.

METHODS: PE-CGS deliberatively engaged its stakeholders in the following four-phase process to set the network's research priorities …


The Value And Impacts Of Academic Public Health Departments, Paul C Erwin, Julie H Grubaugh, Stephanie Mazzucca-Ragan, Ross C Brownson Apr 2023

The Value And Impacts Of Academic Public Health Departments, Paul C Erwin, Julie H Grubaugh, Stephanie Mazzucca-Ragan, Ross C Brownson

2020-Current year OA Pubs

The academic health department (AHD) is a partnership between an academic institution and a governmental health agency. These partnerships are meant to provide mutual benefits that include opportunities for student field placements and internships, practice-informed curriculum, and practice-based research. The term academic health department dates back only to 2000, although there are several examples of academic-practice partnerships prior to that date. In addition to AHDs that have been established over the past two decades, other forms of academic-practice engagement provide similar mutual benefits, such as prevention research centers and public health training centers. Current research on AHDs explores how these …


Social Disadvantage During Pregnancy: Effects On Gestational Age And Birthweight, Joan L Luby, Sarah K England, Deanna M Barch, Barbara B Warner, Cynthia Rogers, Christopher D Smyser, Regina Triplett, Jyoti Arora, Tara A Smyser, George M Slavich, Peinan Zhao, Molly Stout, Erik Herzog, J Philip Miller Apr 2023

Social Disadvantage During Pregnancy: Effects On Gestational Age And Birthweight, Joan L Luby, Sarah K England, Deanna M Barch, Barbara B Warner, Cynthia Rogers, Christopher D Smyser, Regina Triplett, Jyoti Arora, Tara A Smyser, George M Slavich, Peinan Zhao, Molly Stout, Erik Herzog, J Philip Miller

2020-Current year OA Pubs

OBJECTIVE: Whether psychosocial adversity during pregnancy impacts fetal health outcomes at birth remains underexplored. This is a critical issue given significant social disadvantage and psychosocial stress faced by pregnant women worldwide.

STUDY DESIGN: Measures of social disadvantage and psychological factors, and medical/reproductive and nutritional health status in pregnant women were obtained at each trimester. Using Structural Equation Modeling (SEM), we investigated the relationship of forms of adversity to each other and to infant gestational age, and birthweight.

RESULTS: Among 399 singletons, Social Disadvantage significantly predicted gestational age (p = 0.003), and residual birthweight (p = 0.006). There was a 0.4 …


Charged Multivesicular Body Protein 4b Forms Complexes With Gap Junction Proteins During Lens Fiber Cell Differentiation, Yuefang Zhou, Thomas M Bennett, Thomas W White, Alan Shiels Apr 2023

Charged Multivesicular Body Protein 4b Forms Complexes With Gap Junction Proteins During Lens Fiber Cell Differentiation, Yuefang Zhou, Thomas M Bennett, Thomas W White, Alan Shiels

2020-Current year OA Pubs

Charged multivesicular body protein 4b (CHMP4B) is a core sub-unit of the endosomal sorting complex required for transport III (ESCRT-III) machinery that serves myriad remodeling and scission processes of biological membranes. Mutation of the human CHMP4B gene underlies rare forms of early-onset lens opacities or cataracts, and CHMP4B is required for lens growth and differentiation in mice. Here, we determine the sub-cellular distribution of CHMP4B in the lens and uncover a novel association with gap junction alpha-3 protein (GJA3) or connexin 46 (Cx46) and GJA8 or Cx50. Immunofluorescence confocal microscopy revealed that CHMP4B localized to cell membranes of elongated fiber …


Ultrasmall, Elementary And Highly Translational Nanoparticle X-Ray Contrast Media From Amphiphilic Iodinated Statistical Copolymers, Lu Su, Kellie S Dalby, Hannah Luehmann, Sussana A Elkassih, Sangho Cho, Xun He, Lisa Detering, Yen-Nan Lin, Nari Kang, Dennis A Moore, Richard Laforest, Guorong Sun, Yongjian Liu, Karen L Wooley Apr 2023

Ultrasmall, Elementary And Highly Translational Nanoparticle X-Ray Contrast Media From Amphiphilic Iodinated Statistical Copolymers, Lu Su, Kellie S Dalby, Hannah Luehmann, Sussana A Elkassih, Sangho Cho, Xun He, Lisa Detering, Yen-Nan Lin, Nari Kang, Dennis A Moore, Richard Laforest, Guorong Sun, Yongjian Liu, Karen L Wooley

2020-Current year OA Pubs

To expand the single-dose duration over which noninvasive clinical and preclinical cancer imaging can be conducted with high sensitivity, and well-defined spatial and temporal resolutions, a facile strategy to prepare ultrasmall nanoparticulate X-ray contrast media (nano-XRCM) as dual-modality imaging agents for positron emission tomography (PET) and computed tomography (CT) has been established. Synthesized from controlled copolymerization of triiodobenzoyl ethyl acrylate and oligo(ethylene oxide) acrylate monomers, the amphiphilic statistical iodocopolymers (ICPs) could directly dissolve in water to afford thermodynamically stable solutions with high aqueous iodine concentrations (>140 mg iodine/mL water) and comparable viscosities to conventional small molecule XRCM. The formation …


Insights Into The Pathogenesis Of Hereditary Angioedema Using Genetic Sequencing And Recombinant Protein Expression Analyses, Zhen Ren, Shuangxia Zhao, Tiandao Li, H James Wedner, John P Atkinson Apr 2023

Insights Into The Pathogenesis Of Hereditary Angioedema Using Genetic Sequencing And Recombinant Protein Expression Analyses, Zhen Ren, Shuangxia Zhao, Tiandao Li, H James Wedner, John P Atkinson

2020-Current year OA Pubs

BACKGROUND: The pathogenesis of hereditary angioedema (HAE) type I and type II is linked to defective C1 esterase inhibitor (C1-INH) encoded by the SERPING1 gene. There are substantial variabilities in the clinical presentations of patients with HAE that are not directly correlated to the serum levels of C1-INH. The impact of SERPING1 variants on C1-INH expression, structure, and function is incompletely understood.

OBJECTIVE: To investigate the influence of SERPING1 variants on the C1-INH expression, structure, and function of 20 patients with HAE from 14 families with no prior genetic diagnosis.

METHODS: Patients underwent whole-exome sequencing (WES). If no variants were …


Translingual Neurostimulation Combined With Physical Therapy To Improve Walking And Balance In Multiple Sclerosis (Neuromstrals): Study Protocol For A Randomized Controlled Trial, Michelle Ploughman, Ganeswara Rao Melam, Syamala Buragadda, Keith R Lohse, Fraser Clift, Mark Stefanelli, Michael Levin, Sarah J Donkers Apr 2023

Translingual Neurostimulation Combined With Physical Therapy To Improve Walking And Balance In Multiple Sclerosis (Neuromstrals): Study Protocol For A Randomized Controlled Trial, Michelle Ploughman, Ganeswara Rao Melam, Syamala Buragadda, Keith R Lohse, Fraser Clift, Mark Stefanelli, Michael Levin, Sarah J Donkers

2020-Current year OA Pubs

INTRODUCTION: Physical rehabilitation restores lost function and promotes brain plasticity in people with Multiple Sclerosis (MS). Research groups worldwide are testing the therapeutic effects of combining non-invasive neuromodulation with physical therapy (PT) to further improve functional outcomes in neurological disorders but with mixed results. Whether such devices enhance function is not clear. We present the rationale and study design for a randomized controlled trial evaluating if there is additional benefit to the synergistic pairing of translingual neurostimulation (TLNS) with PT to improve walking and balance in MS.

METHODS AND ANALYSIS: A parallel group [PT + TLNS or PT + Sham], …


Potential Uses Of Ai For Perioperative Nursing Handoffs: A Qualitative Study, Christopher Ryan King, Ayanna Shambe, Joanna Abraham Apr 2023

Potential Uses Of Ai For Perioperative Nursing Handoffs: A Qualitative Study, Christopher Ryan King, Ayanna Shambe, Joanna Abraham

2020-Current year OA Pubs

OBJECTIVE: Situational awareness and anticipatory guidance for nurses receiving a patient after surgery are keys to patient safety. Little work has defined the role of artificial intelligence (AI) to support these functions during nursing handoff communication or patient assessment. We used interviews to better understand how AI could work in this context.

MATERIALS AND METHODS: Eleven nurses participated in semistructured interviews. Mixed inductive-deductive thematic analysis was used to extract major themes and subthemes around roles for AI supporting postoperative nursing.

RESULTS: Five themes were generated from the interviews: (1) nurse understanding of patient condition guides care decisions, (2) handoffs are …


Circadian Rhythm Disrupting Behaviours And Cancer Outcomes In Breast Cancer Survivors: A Systematic Review, Kelly D'Cunha, Yikyung Park, Melinda M Protani, Marina M Reeves Apr 2023

Circadian Rhythm Disrupting Behaviours And Cancer Outcomes In Breast Cancer Survivors: A Systematic Review, Kelly D'Cunha, Yikyung Park, Melinda M Protani, Marina M Reeves

2020-Current year OA Pubs

PURPOSE: Circadian rhythm disruptors (e.g., night-shift work) are risk factors for breast cancer, however studies on their association with prognosis is limited. A small but growing body of research suggests that altered sleep patterns and eating behaviours are potential mechanistic links between circadian rhythm disruptors and breast cancer. We therefore systematically summarised literature examining the influence of circadian rhythm disrupting behaviours on cancer outcomes in women with breast cancer.

METHODS: A systematic search of five databases from inception to January 2021 was conducted. Original research published in English, assessing the relationship between post-diagnosis sleep patters and eating behaviours, and breast …


Melanoma In A Patient With Dnmt3a Overgrowth Syndrome, David Y Chen, Leslie A Sutton, Sai Mukund Ramakrishnan, Eric J Duncavage, Sharon E Heath, Leigh A Compton, Christopher A Miller, Timothy J Ley Apr 2023

Melanoma In A Patient With Dnmt3a Overgrowth Syndrome, David Y Chen, Leslie A Sutton, Sai Mukund Ramakrishnan, Eric J Duncavage, Sharon E Heath, Leigh A Compton, Christopher A Miller, Timothy J Ley

2020-Current year OA Pubs

Alterations in epigenetic regulators are increasingly recognized as early events in tumorigenesis; thus, patients with acquired or inherited variants in epigenetic regulators may be at increased risk for developing multiple types of cancer. DNMT3A overgrowth syndrome (DOS), caused by germline pathogenic variants in the DNA methyltransferase gene


Myt1l Is Required For Suppressing Earlier Neuronal Development Programs In The Adult Mouse Brain, Jiayang Chen, Nicole A Fuhler, Kevin K Noguchi, Joseph D Dougherty Apr 2023

Myt1l Is Required For Suppressing Earlier Neuronal Development Programs In The Adult Mouse Brain, Jiayang Chen, Nicole A Fuhler, Kevin K Noguchi, Joseph D Dougherty

2020-Current year OA Pubs

In vitro studies indicate the neurodevelopmental disorder gene myelin transcription factor 1-like (MYT1L) suppresses non-neuronal lineage genes during fibroblast-to-neuron direct differentiation. However, MYT1L's molecular and cellular functions in the adult mammalian brain have not been fully characterized. Here, we found that MYT1L loss leads to up-regulated deep layer (DL) gene expression, corresponding to an increased ratio of DL/UL neurons in the adult mouse cortex. To define potential mechanisms, we conducted Cleavage Under Targets & Release Using Nuclease (CUT&RUN) to map MYT1L binding targets and epigenetic changes following MYT1L loss in mouse developing cortex and adult prefrontal cortex (PFC). We found …


Delayed Ipsilateral Intestinal Perforation After Endoscopic Gastrojejunostomy: A Perspective On Underlying Mechanisms, Juan Reyes Genere, Zoilo K Suarez, Vladimir Kushnir Apr 2023

Delayed Ipsilateral Intestinal Perforation After Endoscopic Gastrojejunostomy: A Perspective On Underlying Mechanisms, Juan Reyes Genere, Zoilo K Suarez, Vladimir Kushnir

2020-Current year OA Pubs

The endoscopic management for malignant gastric outlet obstruction has expanded with the advent of endoscopic ultrasound-guided gastrojejunostomy. Delayed perforation after endoscopic ultrasound-guided gastrojejunostomy is an important yet rarely reported adverse event, and it is unclear why some patients may suffer this complication. We present a case of intestinal perforation occurring one month after endoscopic ultrasound-guided gastrojejunostomy and discuss potential mechanisms which may contribute to this outcome.


The Next Phase In Patient Safety Education: Towards A Standardized, Tools-Based Pathology Patient Safety Curriculum: A Call To Action From The Association Of Pathology Chairs' Residency Program Directors Section Training Residents In Patient Safety Workgroup, Cynthia K Harris, Ronald Jackups Jr, Et Al. Apr 2023

The Next Phase In Patient Safety Education: Towards A Standardized, Tools-Based Pathology Patient Safety Curriculum: A Call To Action From The Association Of Pathology Chairs' Residency Program Directors Section Training Residents In Patient Safety Workgroup, Cynthia K Harris, Ronald Jackups Jr, Et Al.

2020-Current year OA Pubs

Patient safety education is a mandated Common Program Requirement of the Accreditation Council for Graduate Medical Education and for the Royal College of Physicians and Surgeons of Canada in all medical residency and fellowship programs. Although many hospitals and healthcare environments have general patient safety education tools for trainees, few to none focus on the unique training milieu of pathologists, including a mix of highly automated and manual error-prone processes, frequent multiplicity of events, and lack of direct patient relationships for error disclosure. We established a national Association of Pathology Chairs-Program Directors Section Workgroup focused on patient safety education for …


Lrp6 High Bone Mass Characterized In Two Generations Harboring A Unique Mutation Of Low-Density Lipoprotein Receptor-Related Protein 6, Michael P Whyte, Steven Mumm, Jonathan C Baker, Fan Zhang, Homer Sedighi, Shenghui Duan, Tim Cundy Apr 2023

Lrp6 High Bone Mass Characterized In Two Generations Harboring A Unique Mutation Of Low-Density Lipoprotein Receptor-Related Protein 6, Michael P Whyte, Steven Mumm, Jonathan C Baker, Fan Zhang, Homer Sedighi, Shenghui Duan, Tim Cundy

2020-Current year OA Pubs

Osteoblast Wnt/


Cis Interactions In The Irf8 Locus Regulate Stage-Dependent Enhancer Activation, Tian-Tian Liu, Feiya Ou, Julia A Belk, Prachi Bagadia, David A Anderson Iii, Vivek Durai, Winnie Yao, Ansuman T Satpathy, Theresa L Murphy, Kenneth M Murphy Apr 2023

Cis Interactions In The Irf8 Locus Regulate Stage-Dependent Enhancer Activation, Tian-Tian Liu, Feiya Ou, Julia A Belk, Prachi Bagadia, David A Anderson Iii, Vivek Durai, Winnie Yao, Ansuman T Satpathy, Theresa L Murphy, Kenneth M Murphy

2020-Current year OA Pubs

Individual elements within a superenhancer can act in a cooperative or temporal manner, but the underlying mechanisms remain obscure. We recently identified an