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Articles 3181 - 3210 of 20238

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Sleep And Circadian Biomarkers Of Postoperative Delirium (Sleep-Pod): Protocol For A Prospective And Observational Cohort Study, Elizabeth Sugg, Elizabeth Gleeson, Sarah N Baker, Peng Li, Chenlu Gao, Ariel Mueller, Hao Deng, Shiqian Shen, Esteban Franco-Garcia, Richa Saxena, Erik S Musiek, Oluwaseun Akeju, Zhongcong Xie, Kun Hu, Lei Gao Apr 2024

Sleep And Circadian Biomarkers Of Postoperative Delirium (Sleep-Pod): Protocol For A Prospective And Observational Cohort Study, Elizabeth Sugg, Elizabeth Gleeson, Sarah N Baker, Peng Li, Chenlu Gao, Ariel Mueller, Hao Deng, Shiqian Shen, Esteban Franco-Garcia, Richa Saxena, Erik S Musiek, Oluwaseun Akeju, Zhongcong Xie, Kun Hu, Lei Gao

2020-Current year OA Pubs

INTRODUCTION: Surgical patients over 70 experience postoperative delirium (POD) complications in up to 50% of procedures. Sleep/circadian disruption has emerged as a potential risk factor for POD in epidemiological studies. This protocol presents a single-site, prospective observational study designed to examine the relationship between sleep/circadian regulation and POD and how this association could be moderated or mediated by Alzheimer's disease (AD) pathology and genetic risk for AD.

METHODS AND ANALYSIS: Study staff members will screen for eligible patients (age ≥70) seeking joint replacement or spinal surgery at Massachusetts General Hospital (MGH). At the inclusion visit, patients will be asked a …


Knowledge Translation Task Force For Core Measures Clinical Practice Guideline: A Short Report On The Process And Utilization, Marghuretta D Bland, Jennifer L Moore, Elizabeth Anderl, Megan Eikenberry, Arlene Mccarthy, Geneviève N Olivier, Tracy Rice, Amelia Siles, Hallie Zeleznik, Wendy Romney Apr 2024

Knowledge Translation Task Force For Core Measures Clinical Practice Guideline: A Short Report On The Process And Utilization, Marghuretta D Bland, Jennifer L Moore, Elizabeth Anderl, Megan Eikenberry, Arlene Mccarthy, Geneviève N Olivier, Tracy Rice, Amelia Siles, Hallie Zeleznik, Wendy Romney

2020-Current year OA Pubs

BACKGROUND: As part of the 2018 Clinical Practice Guideline (CPG): A Core Set of Outcome Measures for Adults with Neurologic Conditions Undergoing Rehabilitation, a Knowledge Translation (KT) Task Force was convened. The purpose of this short report was to (1) demonstrate the potential impact of a CPG KT Task Force through a practical example of efforts to implement a CPG into neurologic physical therapy practice and (2) describe the process to convene a KT Task Force and develop products (KT Toolkit) to facilitate implementation of the CPG.

METHODS: To describe the process used by the KT Task Force to develop …


Bioresorbable, Wireless, Passive Sensors For Continuous Ph Measurements And Early Detection Of Gastric Leakage, Shuo Li, Yameng Xu, Ying Yan, Jorge Zárate Rodriguez, Mitchell A Pet, Chet W Hammill, Matthew R Macewan, Wilson Z Ray, Et Al. Apr 2024

Bioresorbable, Wireless, Passive Sensors For Continuous Ph Measurements And Early Detection Of Gastric Leakage, Shuo Li, Yameng Xu, Ying Yan, Jorge Zárate Rodriguez, Mitchell A Pet, Chet W Hammill, Matthew R Macewan, Wilson Z Ray, Et Al.

2020-Current year OA Pubs

Continuous monitoring of biomarkers at locations adjacent to targeted internal organs can provide actionable information about postoperative status beyond conventional diagnostic methods. As an example, changes in pH in the intra-abdominal space after gastric surgeries can serve as direct indicators of potentially life-threatening leakage events, in contrast to symptomatic reactions that may delay treatment. Here, we report a bioresorbable, wireless, passive sensor that addresses this clinical need, designed to locally monitor pH for early detection of gastric leakage. A pH-responsive hydrogel serves as a transducer that couples to a mechanically optimized inductor-capacitor circuit for wireless readout. This platform enables real-time …


Ipsc-Based Modeling Of Preeclampsia Identifies Epigenetic Defects In Extravillous Trophoblast Differentiation, Robert Morey, Tony Bui, Virginia Chu Cheung, Chen Dong, Joseph E Zemke, Daniela Requena, Harneet Arora, Madeline G Jackson, Donald Pizzo, Thorold W Theunissen, Mariko Horii Apr 2024

Ipsc-Based Modeling Of Preeclampsia Identifies Epigenetic Defects In Extravillous Trophoblast Differentiation, Robert Morey, Tony Bui, Virginia Chu Cheung, Chen Dong, Joseph E Zemke, Daniela Requena, Harneet Arora, Madeline G Jackson, Donald Pizzo, Thorold W Theunissen, Mariko Horii

2020-Current year OA Pubs

Preeclampsia (PE) is a hypertensive pregnancy disorder with increased risk of maternal and fetal morbidity and mortality. Abnormal extravillous trophoblast (EVT) development and function is considered to be the underlying cause of PE, but has not been previously modeled


Antiviral Cellular Therapy For Enhancing T-Cell Reconstitution Before Or After Hematopoietic Stem Cell Transplantation (Aces): A Two-Arm, Open Label Phase Ii Interventional Trial Of Pediatric Patients With Risk Factor Assessment, Michael D Keller, Jeffrey J Bednarski, Et Al. Apr 2024

Antiviral Cellular Therapy For Enhancing T-Cell Reconstitution Before Or After Hematopoietic Stem Cell Transplantation (Aces): A Two-Arm, Open Label Phase Ii Interventional Trial Of Pediatric Patients With Risk Factor Assessment, Michael D Keller, Jeffrey J Bednarski, Et Al.

2020-Current year OA Pubs

Viral infections remain a major risk in immunocompromised pediatric patients, and virus-specific T cell (VST) therapy has been successful for treatment of refractory viral infections in prior studies. We performed a phase II multicenter study (NCT03475212) for the treatment of pediatric patients with inborn errors of immunity and/or post allogeneic hematopoietic stem cell transplant with refractory viral infections using partially-HLA matched VSTs targeting cytomegalovirus, Epstein-Barr virus, or adenovirus. Primary endpoints were feasibility, safety, and clinical responses (>1 log reduction in viremia at 28 days). Secondary endpoints were reconstitution of antiviral immunity and persistence of the infused VSTs. Suitable VST …


Cellular Geometry And Epithelial-Mesenchymal Plasticity Intersect With Piezo1 In Breast Cancer Cells, Choon Leng So, Mélanie Robitaille, Francisco Sadras, Michael H Mccullough, Michael J G Milevskiy, Geoffrey J Goodhill, Sarah J Roberts-Thomson, Gregory R Monteith Apr 2024

Cellular Geometry And Epithelial-Mesenchymal Plasticity Intersect With Piezo1 In Breast Cancer Cells, Choon Leng So, Mélanie Robitaille, Francisco Sadras, Michael H Mccullough, Michael J G Milevskiy, Geoffrey J Goodhill, Sarah J Roberts-Thomson, Gregory R Monteith

2020-Current year OA Pubs

Differences in shape can be a distinguishing feature between different cell types, but the shape of a cell can also be dynamic. Changes in cell shape are critical when cancer cells escape from the primary tumor and undergo major morphological changes that allow them to squeeze between endothelial cells, enter the vasculature, and metastasize to other areas of the body. A shift from rounded to spindly cellular geometry is a consequence of epithelial-mesenchymal plasticity, which is also associated with changes in gene expression, increased invasiveness, and therapeutic resistance. However, the consequences and functional impacts of cell shape changes and the …


Estimated Health Benefits, Costs And Cost-Effectiveness Of Eliminating Industrial Trans-Fatty Acids In Nigeria: Cost-Effectiveness Analysis, Matti Marklund, Leopold N Aminde, Mary Njeri Wanjau, Boni M Ale, Adedayo E Ojo, Clementina E Okoro, Abimbola Adegboye, Liping Huang, J Lennert Veerman, Jason Hy Wu, Mark D Huffman, Dike B Ojji Apr 2024

Estimated Health Benefits, Costs And Cost-Effectiveness Of Eliminating Industrial Trans-Fatty Acids In Nigeria: Cost-Effectiveness Analysis, Matti Marklund, Leopold N Aminde, Mary Njeri Wanjau, Boni M Ale, Adedayo E Ojo, Clementina E Okoro, Abimbola Adegboye, Liping Huang, J Lennert Veerman, Jason Hy Wu, Mark D Huffman, Dike B Ojji

2020-Current year OA Pubs

INTRODUCTION: Nigeria is committed to reducing industrial

METHODS: The effect on ischaemic heart disease (IHD) burden, costs and cost-effectiveness of a mandatory iTFA limit (≤2% of all fats) for foods in Nigeria were estimated using Markov cohort models. Data on demographics, IHD epidemiology and

RESULTS: Over the first 10 years, a mandatory iTFA limit (assumed to eliminate iTFA intake) was estimated to prevent 9996 (95% uncertainty interval: 8870 to 11 118) IHD deaths and 66 569 (58 862 to 74 083) IHD events, and to save US$90 million (78 to 102) in healthcare costs. The corresponding lifetime estimates were 259 …


Characterization Of Early Markers Of Disease In The Mouse Model Of Mucopolysaccharidosis Iiib, Katherine B Mccullough, Amanda Titus, Kate Reardon, Sara Conyers, Joseph D Dougherty, Xia Ge, Joel R Garbow, Patricia Dickson, Carla M Yuede, Susan E Maloney Apr 2024

Characterization Of Early Markers Of Disease In The Mouse Model Of Mucopolysaccharidosis Iiib, Katherine B Mccullough, Amanda Titus, Kate Reardon, Sara Conyers, Joseph D Dougherty, Xia Ge, Joel R Garbow, Patricia Dickson, Carla M Yuede, Susan E Maloney

2020-Current year OA Pubs

BACKGROUND: Mucopolysaccharidosis (MPS) IIIB, also known as Sanfilippo Syndrome B, is a devastating childhood disease. Unfortunately, there are currently no available treatments for MPS IIIB patients. Yet, animal models of lysosomal storage diseases have been valuable tools in identifying promising avenues of treatment. Enzyme replacement therapy, gene therapy, and bone marrow transplant have all shown efficacy in the MPS IIIB model systems. A ubiquitous finding across rodent models of lysosomal storage diseases is that the best treatment outcomes resulted from intervention prior to symptom onset. Therefore, the aim of the current study was to identify early markers of disease in …


The Brain Gene Registry: A Data Snapshot, Dustin Baldridge, Levi Kaster, Catherine Sancimino, Siddharth Srivastava, Sophie Molholm, Aditi Gupta, Inez Oh, Virginia Lanzotti, Daleep Grewal, Erin Rooney Riggs, Juliann M Savatt, Rachel Hauck, Abigail Sveden, Brain Gene Registry Consortium, John N Constantino, Joseph Piven, Christina A Gurnett, Maya Chopra, Heather Hazlett, Philip R O Payne Apr 2024

The Brain Gene Registry: A Data Snapshot, Dustin Baldridge, Levi Kaster, Catherine Sancimino, Siddharth Srivastava, Sophie Molholm, Aditi Gupta, Inez Oh, Virginia Lanzotti, Daleep Grewal, Erin Rooney Riggs, Juliann M Savatt, Rachel Hauck, Abigail Sveden, Brain Gene Registry Consortium, John N Constantino, Joseph Piven, Christina A Gurnett, Maya Chopra, Heather Hazlett, Philip R O Payne

2020-Current year OA Pubs

Monogenic disorders account for a large proportion of population-attributable risk for neurodevelopmental disabilities. However, the data necessary to infer a causal relationship between a given genetic variant and a particular neurodevelopmental disorder is often lacking. Recognizing this scientific roadblock, 13 Intellectual and Developmental Disabilities Research Centers (IDDRCs) formed a consortium to create the Brain Gene Registry (BGR), a repository pairing clinical genetic data with phenotypic data from participants with variants in putative brain genes. Phenotypic profiles are assembled from the electronic health record (EHR) and a battery of remotely administered standardized assessments collectively referred to as the Rapid Neurobehavioral Assessment …


Encoding Of Visual Objects In The Human Medial Temporal Lobe, Yue Wang, Runnan Cao, Shuo Wang Apr 2024

Encoding Of Visual Objects In The Human Medial Temporal Lobe, Yue Wang, Runnan Cao, Shuo Wang

2020-Current year OA Pubs

The human medial temporal lobe (MTL) plays a crucial role in recognizing visual objects, a key cognitive function that relies on the formation of semantic representations. Nonetheless, it remains unknown how visual information of general objects is translated into semantic representations in the MTL. Furthermore, the debate about whether the human MTL is involved in perception has endured for a long time. To address these questions, we investigated three distinct models of neural object coding-semantic coding, axis-based feature coding, and region-based feature coding-in each subregion of the human MTL, using high-resolution fMRI in two male and six female participants. Our …


Topmed Imputed Genomics Enhances Genomic Atlas Of The Human Proteome In Brain, Cerebrospinal Fluid, And Plasma, Heng Yi, Qijun Yang, Charlie Repaci, Cheolmin Matthew Lee, Gyujin Heo, Jigyasha Timsina, Priyanka Gorijala, Chengran Yang, John Budde, Lihua Wang, Carlos Cruchaga, Yun Ju Sung Apr 2024

Topmed Imputed Genomics Enhances Genomic Atlas Of The Human Proteome In Brain, Cerebrospinal Fluid, And Plasma, Heng Yi, Qijun Yang, Charlie Repaci, Cheolmin Matthew Lee, Gyujin Heo, Jigyasha Timsina, Priyanka Gorijala, Chengran Yang, John Budde, Lihua Wang, Carlos Cruchaga, Yun Ju Sung

2020-Current year OA Pubs

Comprehensive expression quantitative trait loci studies have been instrumental for understanding tissue-specific gene regulation and pinpointing functional genes for disease-associated loci in a tissue-specific manner. Compared to gene expressions, proteins more directly affect various biological processes, often dysregulated in disease, and are important drug targets. We previously performed and identified tissue-specific protein quantitative trait loci in brain, cerebrospinal fluid, and plasma. We now enhance this work by analyzing more proteins (1,300 versus 1,079) and an almost twofold increase in high quality imputed genetic variants (8.4 million versus 4.4 million) by using TOPMed reference panel. We identified 38 genomic regions associated …


Recruitment Strategies In The Integration Of Mobile Health Into Sickle Cell Disease Care To Increase Hydroxyurea Utilization Study (Mesh): Multicenter Survey Study, Chinonyelum Nwosu, Hamda Khan, Rita Masese, Judith M Nocek, Siera Gollan, Taniya Varughese, Sarah Bourne, Cindy Clesca, Sara R Jacobs, Ana Baumann, Lisa M Klesges, Nirmish Shah, Jane S Hankins, Matthew P Smeltzer Apr 2024

Recruitment Strategies In The Integration Of Mobile Health Into Sickle Cell Disease Care To Increase Hydroxyurea Utilization Study (Mesh): Multicenter Survey Study, Chinonyelum Nwosu, Hamda Khan, Rita Masese, Judith M Nocek, Siera Gollan, Taniya Varughese, Sarah Bourne, Cindy Clesca, Sara R Jacobs, Ana Baumann, Lisa M Klesges, Nirmish Shah, Jane S Hankins, Matthew P Smeltzer

2020-Current year OA Pubs

BACKGROUND: Hydroxyurea is an evidence-based disease-modifying therapy for sickle cell disease (SCD) but is underutilized. The Integration of Mobile Health into Sickle Cell Disease Care to Increase Hydroxyurea Utilization (meSH) multicenter study leveraged mHealth to deliver targeted interventions to patients and providers. SCD studies often underenroll; and recruitment strategies in the SCD population are not widely studied. Unanticipated events can negatively impact enrollment, making it important to study strategies that ensure adequate study accrual.

OBJECTIVE: The goal of this study was to evaluate enrollment barriers and the impact of modified recruitment strategies among patients and providers in the meSH study …


Novel Jak Inhibitors To Reduce Graft-Versus-Host Disease After Allogeneic Hematopoietic Cell Transplantation In A Preclinical Mouse Model, Sena Kim, Peter Ruminski, Megh Singh, Karl Staser, Kidist Ashami, Julie Ritchey, Sora Lim, John F Dipersio, Jaebok Choi Apr 2024

Novel Jak Inhibitors To Reduce Graft-Versus-Host Disease After Allogeneic Hematopoietic Cell Transplantation In A Preclinical Mouse Model, Sena Kim, Peter Ruminski, Megh Singh, Karl Staser, Kidist Ashami, Julie Ritchey, Sora Lim, John F Dipersio, Jaebok Choi

2020-Current year OA Pubs

Allogeneic hematopoietic cell transplantation (allo-HCT) is a highly effective, well-established treatment for patients with various hematologic malignancies and non-malignant diseases. The therapeutic benefits of allo-HCT are mediated by alloreactive T cells in donor grafts. However, there is a significant risk of graft-versus-host disease (GvHD), in which the donor T cells recognize recipient cells as foreign and attack healthy organs in addition to malignancies. We previously demonstrated that targeting JAK1/JAK2, mediators of interferon-gamma receptor (IFNGR) and IL-6 receptor signaling, in donor T cells using baricitinib and ruxolitinib results in a significant reduction in GvHD after allo-HCT. Furthermore, we showed that balanced …


Host Response During Unresolved Urinary Tract Infection Alters Female Mammary Tissue Homeostasis Through Collagen Deposition And Timp1, Samantha Henry, Xue-Yan He, Et Al. Apr 2024

Host Response During Unresolved Urinary Tract Infection Alters Female Mammary Tissue Homeostasis Through Collagen Deposition And Timp1, Samantha Henry, Xue-Yan He, Et Al.

2020-Current year OA Pubs

Exposure to pathogens throughout a lifetime influences immunity and organ function. Here, we explore how the systemic host-response to bacterial urinary tract infection (UTI) induces tissue-specific alterations to the mammary gland. Utilizing a combination of histological tissue analysis, single cell transcriptomics, and flow cytometry, we identify that mammary tissue from UTI-bearing mice displays collagen deposition, enlarged ductal structures, ductal hyperplasia with atypical epithelial transcriptomes and altered immune composition. Bacterial cells are absent in the mammary tissue and blood of UTI-bearing mice, therefore, alterations to the distal mammary tissue are mediated by the systemic host response to local infection. Furthermore, broad …


Brief Report: Substance Use Care Continuum In Women With And Without Hiv In The Southern United States, Aditi Ramakrishnan, Ayako W. Fujita, C. Christina Mehta, Tracey E. Wilson, Steve Shoptaw, Adam Carrico, Adaora A. Adimora, Ellen F. Eaton, Deborah L. Jones, Aruna Chandran, Anandi N. Sheth Apr 2024

Brief Report: Substance Use Care Continuum In Women With And Without Hiv In The Southern United States, Aditi Ramakrishnan, Ayako W. Fujita, C. Christina Mehta, Tracey E. Wilson, Steve Shoptaw, Adam Carrico, Adaora A. Adimora, Ellen F. Eaton, Deborah L. Jones, Aruna Chandran, Anandi N. Sheth

2020-Current year OA Pubs

BACKGROUND: Substance use (SU) contributes to poor outcomes among persons living with HIV. Women living with HIV (WWH) in the United States are disproportionately affected in the South, and examining SU patterns, treatment, and HIV outcomes in this population is integral to addressing HIV and SU disparities.

METHODS: WWH and comparable women without HIV (WWOH) who enrolled 2013-2015 in the Women's Interagency HIV Study Southern sites (Atlanta, Birmingham/Jackson, Chapel Hill, and Miami) and reported SU (self-reported nonmedical use of drugs) in the past year were included. SU and treatment were described annually from enrollment to the end of follow-up. HIV …


Treating Sex And Gender Differences As A Continuous Variable Can Improve Precision Cancer Treatments, Wei Yang, Joshua B Rubin Apr 2024

Treating Sex And Gender Differences As A Continuous Variable Can Improve Precision Cancer Treatments, Wei Yang, Joshua B Rubin

2020-Current year OA Pubs

BACKGROUND: The significant sex and gender differences that exist in cancer mechanisms, incidence, and survival, have yet to impact clinical practice. One barrier to translation is that cancer phenotypes cannot be segregated into distinct male versus female categories. Instead, within this convenient but contrived dichotomy, male and female cancer phenotypes are highly overlapping and vary between female- and male- skewed extremes. Thus, sex and gender-specific treatments are unrealistic, and our translational goal should be adaptation of treatment to the variable effects of sex and gender on targetable pathways.

METHODS: To overcome this obstacle, we profiled the similarities in 8370 transcriptomes …


Clinical Implications Of Inaccurate Potassium Determination In Hemolyzed Pediatric Blood Specimens, Dennis J Dietzen, Ronald Jackups, Mark A Zaydman Apr 2024

Clinical Implications Of Inaccurate Potassium Determination In Hemolyzed Pediatric Blood Specimens, Dennis J Dietzen, Ronald Jackups, Mark A Zaydman

2020-Current year OA Pubs

BACKGROUND: Analysis of whole blood specimens is rapid and saves blood, but hemolysis may go undetected and compromise the accuracy of potassium measurement. We aimed to define the frequency and magnitude of error in whole blood potassium measurement.

METHODS: 34 months of whole blood and plasma potassium data were extracted from patients aged less than 2 years at the time of sample acquisition. Hemolysis was detected using the plasma "H index." The magnitude of potassium bias was estimated from the difference between paired whole blood and plasma measurement separated by less than 2 h.

RESULTS: 56,000 of the 105,000 data …


Evolution Of The Transforaminal Lumbar Interbody Fusion (Tlif): From Open To Percutaneous To Patient-Specific, Peter N Drossopoulos, Favour C Ononogbu-Uche, Troy Q Tabarestani, Chuan-Ching Huang, Mounica Paturu, Anas Bardeesi, Wilson Z Ray, Christopher I Shaffrey, C Rory Goodwin, Melissa Erickson, John H Chi, Muhammad M Abd-El-Barr Apr 2024

Evolution Of The Transforaminal Lumbar Interbody Fusion (Tlif): From Open To Percutaneous To Patient-Specific, Peter N Drossopoulos, Favour C Ononogbu-Uche, Troy Q Tabarestani, Chuan-Ching Huang, Mounica Paturu, Anas Bardeesi, Wilson Z Ray, Christopher I Shaffrey, C Rory Goodwin, Melissa Erickson, John H Chi, Muhammad M Abd-El-Barr

2020-Current year OA Pubs

The transforaminal lumbar interbody fusion (TLIF) has seen significant evolution since its early inception, reflecting advancements in surgical techniques, patient safety, and outcomes. Originally described as an improvement over the posterior lumbar interbody fusion (PLIF), the TLIF began as an open surgical procedure, that notably reduced the need for the extensive neural retractation that hindered the PLIF. In line with the broader practice of surgery, trending toward minimally invasive access, the TLIF was followed by the development of the minimally invasive TLIF (MIS-TLIF), a technique that further decreased tissue trauma and postoperative complications. Subsequent advancements, including Trans-Kambin's Triangle TLIF (percLIF) …


"In Our Community, We Normalize Pain": Discussions Around Menstruation And Uterine Fibroids With Black Women And Latinas, Minerva Orellana, Karen N Dsouza, Jane Q Yap, Abhirami Sriganeshan, M Elena Jones, Charis Johnson, Megan Allyse, Sateria Venable, Elizabeth A Stewart, Felicity Enders, Joyce E Balls-Berry Apr 2024

"In Our Community, We Normalize Pain": Discussions Around Menstruation And Uterine Fibroids With Black Women And Latinas, Minerva Orellana, Karen N Dsouza, Jane Q Yap, Abhirami Sriganeshan, M Elena Jones, Charis Johnson, Megan Allyse, Sateria Venable, Elizabeth A Stewart, Felicity Enders, Joyce E Balls-Berry

2020-Current year OA Pubs

BACKGROUND: Uterine fibroids are non-cancerous neoplasms that arise from the uterus affecting over 75% of women. However, there is a disparity with Black women having an increased prevalence of nearly 80%. Black women also experience increased symptom burden, including younger age at the time of diagnosis and increased number and volume of fibroids. Less is known about other ethnoracially diverse women such as Latinas and the potential cultural impacts on fibroid burden and treatment.

METHODS: Community engagement studios were conducted to facilitate discussions with stakeholders on their uterine fibroid and menstruation experience. We recruited Black women (n = 6) diagnosed …


Macromolecular Condensation Organizes Nucleolar Sub-Phases To Set Up A Ph Gradient, Matthew R King, Kiersten M Ruff, Andrew Z Lin, Avnika Pant, Mina Farag, Jared M Lalmansingh, Tingting Wu, Martin J Fossat, Wei Ouyang, Matthew D Lew, Emma Lundberg, Michael D Vahey, Rohit V Pappu Apr 2024

Macromolecular Condensation Organizes Nucleolar Sub-Phases To Set Up A Ph Gradient, Matthew R King, Kiersten M Ruff, Andrew Z Lin, Avnika Pant, Mina Farag, Jared M Lalmansingh, Tingting Wu, Martin J Fossat, Wei Ouyang, Matthew D Lew, Emma Lundberg, Michael D Vahey, Rohit V Pappu

2020-Current year OA Pubs

Nucleoli are multicomponent condensates defined by coexisting sub-phases. We identified distinct intrinsically disordered regions (IDRs), including acidic (D/E) tracts and K-blocks interspersed by E-rich regions, as defining features of nucleolar proteins. We show that the localization preferences of nucleolar proteins are determined by their IDRs and the types of RNA or DNA binding domains they encompass. In vitro reconstitutions and studies in cells showed how condensation, which combines binding and complex coacervation of nucleolar components, contributes to nucleolar organization. D/E tracts of nucleolar proteins contribute to lowering the pH of co-condensates formed with nucleolar RNAs in vitro. In cells, this …


Trial Of Early Minimally Invasive Removal Of Intracerebral Hemorrhage, Gustavo Pradilla, Salah G Keyrouz, Et Al. Apr 2024

Trial Of Early Minimally Invasive Removal Of Intracerebral Hemorrhage, Gustavo Pradilla, Salah G Keyrouz, Et Al.

2020-Current year OA Pubs

BACKGROUND: Trials of surgical evacuation of supratentorial intracerebral hemorrhages have generally shown no functional benefit. Whether early minimally invasive surgical removal would result in better outcomes than medical management is not known.

METHODS: In this multicenter, randomized trial involving patients with an acute intracerebral hemorrhage, we assessed surgical removal of the hematoma as compared with medical management. Patients who had a lobar or anterior basal ganglia hemorrhage with a hematoma volume of 30 to 80 ml were assigned, in a 1:1 ratio, within 24 hours after the time that they were last known to be well, to minimally invasive surgical …


Use Of Barium For Diagnosis Of Colonic Perforation Leads To Challenging Barium Peritonitis, Ariana Naaseh, Jorge G Zarate Rodriguez, Matthew J Mchale, Grace M Niziolek, Thoi H Ngo, John P Kirby, Lindsay M Kranker Apr 2024

Use Of Barium For Diagnosis Of Colonic Perforation Leads To Challenging Barium Peritonitis, Ariana Naaseh, Jorge G Zarate Rodriguez, Matthew J Mchale, Grace M Niziolek, Thoi H Ngo, John P Kirby, Lindsay M Kranker

2020-Current year OA Pubs

No abstract provided.


Organizing The Dissemination And Implementation Field: Who Are We, What Are We Doing, And How Should We Do It?, Gretchen J R Buchanan, Lindsey M Filiatreau, Julia E Moore Apr 2024

Organizing The Dissemination And Implementation Field: Who Are We, What Are We Doing, And How Should We Do It?, Gretchen J R Buchanan, Lindsey M Filiatreau, Julia E Moore

2020-Current year OA Pubs

Two decades into its tenure as a field, dissemination and implementation (D&I) scientists have begun a process of self-reflection, illuminating a missed opportunity to bridge the gap between research and practice-one of the field's foundational objectives. In this paper, we, the authors, assert the research-to-practice gap has persisted, in part due to an inadequate characterization of roles, functions, and processes within D&I. We aim to address this issue, and the rising tension between D&I researchers and practitioners, by proposing a community-centered path forward that is grounded in equity.We identify key players within the field and characterize their unique roles using …


Chemotherapy Activates Inflammasomes To Cause Inflammation-Associated Bone Loss, Chun Wang, Khushpreet Kaur, Canxin Xu, Yousef Abu-Amer, Gabriel Mbalaviele Apr 2024

Chemotherapy Activates Inflammasomes To Cause Inflammation-Associated Bone Loss, Chun Wang, Khushpreet Kaur, Canxin Xu, Yousef Abu-Amer, Gabriel Mbalaviele

2020-Current year OA Pubs

Chemotherapy is a widely used treatment for a variety of solid and hematological malignancies. Despite its success in improving the survival rate of cancer patients, chemotherapy causes significant toxicity to multiple organs, including the skeleton, but the underlying mechanisms have yet to be elucidated. Using tumor-free mouse models, which are commonly used to assess direct off-target effects of anti-neoplastic therapies, we found that doxorubicin caused massive bone loss in wild-type mice, a phenotype associated with increased number of osteoclasts, leukopenia, elevated serum levels of danger-associated molecular patterns (DAMPs; e.g. cell-free DNA and ATP) and cytokines (e.g. IL-1β and IL-18). Accordingly, …


Mastigoneme Structure Reveals Insights Into The O-Linked Glycosylation Code Of Native Hydroxyproline-Rich Helices, Jin Dai, Meisheng Ma, Qingwei Niu, Robyn J Eisert, Xiangli Wang, Poulomi Das, Karl F Lechtreck, Susan K Dutcher, Rui Zhang, Alan Brown Apr 2024

Mastigoneme Structure Reveals Insights Into The O-Linked Glycosylation Code Of Native Hydroxyproline-Rich Helices, Jin Dai, Meisheng Ma, Qingwei Niu, Robyn J Eisert, Xiangli Wang, Poulomi Das, Karl F Lechtreck, Susan K Dutcher, Rui Zhang, Alan Brown

2020-Current year OA Pubs

Hydroxyproline-rich glycoproteins (HRGPs) are a ubiquitous class of protein in the extracellular matrices and cell walls of plants and algae, yet little is known of their native structures or interactions. Here, we used electron cryomicroscopy (cryo-EM) to determine the structure of the hydroxyproline-rich mastigoneme, an extracellular filament isolated from the cilia of the alga Chlamydomonas reinhardtii. The structure demonstrates that mastigonemes are formed from two HRGPs (a filament of MST1 wrapped around a single copy of MST3) that both have hyperglycosylated poly(hydroxyproline) helices. Within the helices, O-linked glycosylation of the hydroxyproline residues and O-galactosylation of interspersed serine residues create a …


Impact Of Self-Reported Loss Of Balance And Gait Disturbance On Outcomes Following Adult Spinal Deformity Surgery, Bassel G Diebo, Munish C Gupta, Et Al. Apr 2024

Impact Of Self-Reported Loss Of Balance And Gait Disturbance On Outcomes Following Adult Spinal Deformity Surgery, Bassel G Diebo, Munish C Gupta, Et Al.

2020-Current year OA Pubs

No abstract provided.


Multisensory Flicker Modulates Widespread Brain Networks And Reduces Interictal Epileptiform Discharges, Lou T Blanpain, Eric R Cole, Emily Chen, James K Park, Michael Y Walelign, Robert E Gross, Brian T Cabaniss, Jon T Willie, Annabelle C Singer Apr 2024

Multisensory Flicker Modulates Widespread Brain Networks And Reduces Interictal Epileptiform Discharges, Lou T Blanpain, Eric R Cole, Emily Chen, James K Park, Michael Y Walelign, Robert E Gross, Brian T Cabaniss, Jon T Willie, Annabelle C Singer

2020-Current year OA Pubs

Modulating brain oscillations has strong therapeutic potential. Interventions that both non-invasively modulate deep brain structures and are practical for chronic daily home use are desirable for a variety of therapeutic applications. Repetitive audio-visual stimulation, or sensory flicker, is an accessible approach that modulates hippocampus in mice, but its effects in humans are poorly defined. We therefore quantified the neurophysiological effects of flicker with high spatiotemporal resolution in patients with focal epilepsy who underwent intracranial seizure monitoring. In this interventional trial (NCT04188834) with a cross-over design, subjects underwent different frequencies of flicker stimulation in the same recording session with the effect …


Mechanism Of Antagonist Ligand Binding To Rev-Erbα, Mohammad Homaidur Rahman, Lamees Hegazy Apr 2024

Mechanism Of Antagonist Ligand Binding To Rev-Erbα, Mohammad Homaidur Rahman, Lamees Hegazy

2020-Current year OA Pubs

REV-ERBα, a therapeutically promising nuclear hormone receptor, plays a crucial role in regulating various physiological processes such as the circadian clock, inflammation, and metabolism. However, the availability of chemical probes to investigate the pharmacology of this receptor is limited, with SR8278 being the only identified synthetic antagonist. Moreover, no X-ray crystal structures are currently available that demonstrate the binding of REV-ERBα to antagonist ligands. This lack of structural information impedes the development of targeted therapeutics. To address this issue, we employed Gaussian accelerated molecular dynamics (GaMD) simulations to investigate the binding pathway of SR8278 to REV-ERBα. For comparison, we also …


Vaccine Effectiveness Against Influenza A-Associated Hospitalization, Organ Failure, And Death: United States, 2022-2023, Nathaniel M Lewis, Jennie H Kwon, Et Al. Apr 2024

Vaccine Effectiveness Against Influenza A-Associated Hospitalization, Organ Failure, And Death: United States, 2022-2023, Nathaniel M Lewis, Jennie H Kwon, Et Al.

2020-Current year OA Pubs

BACKGROUND: Influenza circulation during the 2022-2023 season in the United States largely returned to pre-coronavirus disease 2019 (COVID-19)-pandemic patterns and levels. Influenza A(H3N2) viruses were detected most frequently this season, predominately clade 3C.2a1b.2a, a close antigenic match to the vaccine strain.

METHODS: To understand effectiveness of the 2022-2023 influenza vaccine against influenza-associated hospitalization, organ failure, and death, a multicenter sentinel surveillance network in the United States prospectively enrolled adults hospitalized with acute respiratory illness between 1 October 2022, and 28 February 2023. Using the test-negative design, vaccine effectiveness (VE) estimates against influenza-associated hospitalization, organ failures, and death were measured by …


Rare Genetic Variation In Fibronectin 1 (Fn1) Protects Against Apoeε4 In Alzheimer's Disease, Prabesh Bhattarai, Michael E Belloy, Et Al. Apr 2024

Rare Genetic Variation In Fibronectin 1 (Fn1) Protects Against Apoeε4 In Alzheimer's Disease, Prabesh Bhattarai, Michael E Belloy, Et Al.

2020-Current year OA Pubs

The risk of developing Alzheimer's disease (AD) significantly increases in individuals carrying the APOEε4 allele. Elderly cognitively healthy individuals with APOEε4 also exist, suggesting the presence of cellular mechanisms that counteract the pathological effects of APOEε4; however, these mechanisms are unknown. We hypothesized that APOEε4 carriers without dementia might carry genetic variations that could protect them from developing APOEε4-mediated AD pathology. To test this, we leveraged whole-genome sequencing (WGS) data in the National Institute on Aging Alzheimer's Disease Family Based Study (NIA-AD FBS), Washington Heights/Inwood Columbia Aging Project (WHICAP), and Estudio Familiar de Influencia Genetica en Alzheimer (EFIGA) cohorts and …