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Cognition And The Single Neuron: How Cell Types Construct The Dynamic Computations Of Frontal Cortex, Amelia J Christensen, Torben Ott, Adam Kepecs Dec 2022

Cognition And The Single Neuron: How Cell Types Construct The Dynamic Computations Of Frontal Cortex, Amelia J Christensen, Torben Ott, Adam Kepecs

2020-Current year OA Pubs

Frontal cortex is thought to underlie many advanced cognitive capacities, from self-control to long term planning. Reflecting these diverse demands, frontal neural activity is notoriously idiosyncratic, with tuning properties that are correlated with endless numbers of behavioral and task features. This menagerie of tuning has made it difficult to extract organizing principles that govern frontal neural activity. Here, we contrast two successful yet seemingly incompatible approaches that have begun to address this challenge. Inspired by the indecipherability of single-neuron tuning, the first approach casts frontal computations as dynamical trajectories traversed by arbitrary mixtures of neurons. The second approach, by contrast, …


Leflunomide-Induced And Paraneoplastic Ulcers In A Rheumatoid Arthritis Patient, Michael R Vittori, Jonathan Z Tang, William H Mccoy Iv Dec 2022

Leflunomide-Induced And Paraneoplastic Ulcers In A Rheumatoid Arthritis Patient, Michael R Vittori, Jonathan Z Tang, William H Mccoy Iv

2020-Current year OA Pubs

No abstract provided.


Delayed Diagnosis And Recovery Of Fulminant Immune Checkpoint Inhibitor-Associated Myocarditis On Va-Ecmo Support, Tarun Ramayya, Joshua D Mitchell, Justin C Hartupee, Kory Lavine, Clare H Ridley, Kunal D Kotkar, Jesus Jimenez, Chieh-Yu Lin, Jose A Alvarez-Cardona, Ronald K Krone, Courtney M Campbell Dec 2022

Delayed Diagnosis And Recovery Of Fulminant Immune Checkpoint Inhibitor-Associated Myocarditis On Va-Ecmo Support, Tarun Ramayya, Joshua D Mitchell, Justin C Hartupee, Kory Lavine, Clare H Ridley, Kunal D Kotkar, Jesus Jimenez, Chieh-Yu Lin, Jose A Alvarez-Cardona, Ronald K Krone, Courtney M Campbell

2020-Current year OA Pubs

No abstract provided.


Targeting The Autophagy-Lysosome Pathway In A Pathophysiologically Relevant Murine Model Of Reversible Heart Failure, Sarah Evans, Xiucui Ma, Xiqiang Wang, Yana Chen, Chen Zhao, Carla J Weinheimer, Attila Kovacs, Brian Finck, Abhinav Diwan, Douglas L Mann Dec 2022

Targeting The Autophagy-Lysosome Pathway In A Pathophysiologically Relevant Murine Model Of Reversible Heart Failure, Sarah Evans, Xiucui Ma, Xiqiang Wang, Yana Chen, Chen Zhao, Carla J Weinheimer, Attila Kovacs, Brian Finck, Abhinav Diwan, Douglas L Mann

2020-Current year OA Pubs

The key biological "drivers" that are responsible for reverse left ventricle (LV) remodeling are not well understood. To gain an understanding of the role of the autophagy-lysosome pathway in reverse LV remodeling, we used a pathophysiologically relevant murine model of reversible heart failure, wherein pressure overload by transaortic constriction superimposed on acute coronary artery (myocardial infarction) ligation leads to a heart failure phenotype that is reversible by hemodynamic unloading. Here we show transaortic constriction + myocardial infarction leads to decreased flux through the autophagy-lysosome pathway with the accumulation of damaged proteins and organelles in cardiac myocytes, whereas hemodynamic unloading is …


Nosocomial Outbreak Of Vancomycin-Resistant Enterococcus Faecium (Vre) St796, Switzerland, 2017 To 2020, Vanja Piezzi, Nasstasja Wassilew, Andrew Atkinson, Stéphanie D'Incau, Tanja Kaspar, Helena Mb Seth-Smith, Carlo Casanova, Pascal Bittel, Philipp Jent, Rami Sommerstein, Niccolò Buetti, Jonas Marschall Dec 2022

Nosocomial Outbreak Of Vancomycin-Resistant Enterococcus Faecium (Vre) St796, Switzerland, 2017 To 2020, Vanja Piezzi, Nasstasja Wassilew, Andrew Atkinson, Stéphanie D'Incau, Tanja Kaspar, Helena Mb Seth-Smith, Carlo Casanova, Pascal Bittel, Philipp Jent, Rami Sommerstein, Niccolò Buetti, Jonas Marschall

2020-Current year OA Pubs

A large clonal outbreak caused by vancomycin-resistant


Guidelines For Assessment Of Cardiac Electrophysiology And Arrhythmias In Small Animals, Crystal M Ripplinger, Stacey L Rentschler, Et Al. Dec 2022

Guidelines For Assessment Of Cardiac Electrophysiology And Arrhythmias In Small Animals, Crystal M Ripplinger, Stacey L Rentschler, Et Al.

2020-Current year OA Pubs

Cardiac arrhythmias are a major cause of morbidity and mortality worldwide. Although recent advances in cell-based models, including human-induced pluripotent stem cell-derived cardiomyocytes (iPSC-CM), are contributing to our understanding of electrophysiology and arrhythmia mechanisms, preclinical animal studies of cardiovascular disease remain a mainstay. Over the past several decades, animal models of cardiovascular disease have advanced our understanding of pathological remodeling, arrhythmia mechanisms, and drug effects and have led to major improvements in pacing and defibrillation therapies. There exist a variety of methodological approaches for the assessment of cardiac electrophysiology and a plethora of parameters may be assessed with each approach. …


Water T2 Could Predict Functional Decline In Patients With Dysferlinopathy, Ursula Moore, Alan Pestronk, Et Al. Dec 2022

Water T2 Could Predict Functional Decline In Patients With Dysferlinopathy, Ursula Moore, Alan Pestronk, Et Al.

2020-Current year OA Pubs

BACKGROUND: Water T2 (T2

METHODS: Patients with genetically confirmed dysferlinopathy were assessed as part of the Jain Foundation Clinical Outcomes Study in dysferlinopathy. The cohort included 18 patients from two sites, both equipped with 3-tesla magnetic resonance imaging (MRI) systems from the same vendor. T2

RESULTS: A higher T2

CONCLUSIONS: In dysferlinopathy, T2


Cortical Bone Relationships Are Maintained Regardless Of Sex And Diet In A Large Population Of Lgxsm Advanced Intercross Mice, Nicole Migotsky, Michael D Brodt, James M Cheverud, Matthew J Silva Dec 2022

Cortical Bone Relationships Are Maintained Regardless Of Sex And Diet In A Large Population Of Lgxsm Advanced Intercross Mice, Nicole Migotsky, Michael D Brodt, James M Cheverud, Matthew J Silva

2020-Current year OA Pubs

INTRODUCTION: Knowledge of bone structure-function relationships in mice has been based on relatively small sample sets that limit generalizability. We sought to investigate structure-function relationships of long bones from a large population of genetically diverse mice. Therefore, we analyzed previously published data from the femur and radius of male and female mice from the F34 generation of the Large-by-Small advanced intercross line (LGXSM AI), which have over a two-fold continuous spread of bone and body sizes (Silva et al. 2019 JBMR).

METHODS: Morphological traits, mechanical properties, and estimated material properties were collected from the femur and radius from 1113 LGXSM …


Community Prevalence Of Helicobacter Pylori And Dyspepsia And Efficacy Of Triple Therapy In A Rural District Of Eastern Uganda, Yang Jae Lee, Ibrahim Ssekalo, Rauben Kazungu, Timothy S Blackwell Jr, Peter Muwereza, Yuefeng Wu, José B Sáenz Dec 2022

Community Prevalence Of Helicobacter Pylori And Dyspepsia And Efficacy Of Triple Therapy In A Rural District Of Eastern Uganda, Yang Jae Lee, Ibrahim Ssekalo, Rauben Kazungu, Timothy S Blackwell Jr, Peter Muwereza, Yuefeng Wu, José B Sáenz

2020-Current year OA Pubs

BACKGROUND:

OBJECTIVES: We determined the prevalence of

METHODS: Of 400 randomly selected adult residents in eastern Uganda, 376 were administered a validated, chronic dyspepsia questionnaire and provided a stool sample for

RESULTS:

CONCLUSIONS: In our study population, chronic dyspepsia did not predict


Identification Of Patients With Ovarian Cancer Experiencing The Highest Benefit From Bevacizumab In The First-Line Setting On The Basis Of Their Tumor-Intrinsic Chemosensitivity (Kelim): The Gog-0218 Validation Study, Benoit You, David Mutch, Et Al. Dec 2022

Identification Of Patients With Ovarian Cancer Experiencing The Highest Benefit From Bevacizumab In The First-Line Setting On The Basis Of Their Tumor-Intrinsic Chemosensitivity (Kelim): The Gog-0218 Validation Study, Benoit You, David Mutch, Et Al.

2020-Current year OA Pubs

PURPOSE: In patients with high-grade ovarian cancer, predictors of bevacizumab efficacy in first-line setting are needed. In the ICON-7 trial, a poor tumor intrinsic chemosensitivity (defined by unfavorable modeled cancer antigen-125 [CA-125] ELIMination rate constant K [KELIM] score) was a predictive biomarker. Only the patients with high-risk disease (suboptimally resected stage III, or stage IV) exhibiting unfavorable KELIM score < 1.0 had overall survival (OS) benefit from bevacizumab (median: 29.7

METHODS: In GOG-0218, 1,873 patients were treated with carboplatin-paclitaxel ± concurrent-maintenance bevacizumab/placebo. Patient KELIM values were calculated with CA-125 kinetics during the first 100 chemotherapy days by the Lyon University team. The association between KELIM score (favorable ≥ 1.0, or unfavorable …


Hiv Care Experiences And Health Priorities During The First Wave Of Covid-19: Clients' Perspectives - A Qualitative Study In Lusaka, Zambia, Njekwa Mukamba, Anjali Sharma, Chanda Mwamba, Herbert Nyirenda, Marksman Foloko, Kasapo Lumbo, Katerina Christopoulos, Sandra Simbeza, Kombatende Sikombe, Charles B Holmes, Elvin H Geng, Izukanji Sikazwe, Carolyn Bolton-Moore, Laura K Beres Nov 2022

Hiv Care Experiences And Health Priorities During The First Wave Of Covid-19: Clients' Perspectives - A Qualitative Study In Lusaka, Zambia, Njekwa Mukamba, Anjali Sharma, Chanda Mwamba, Herbert Nyirenda, Marksman Foloko, Kasapo Lumbo, Katerina Christopoulos, Sandra Simbeza, Kombatende Sikombe, Charles B Holmes, Elvin H Geng, Izukanji Sikazwe, Carolyn Bolton-Moore, Laura K Beres

2020-Current year OA Pubs

BACKGROUND: The novel COVID-19 pandemic threatened to disrupt access to human immunodeficiency (HIV) treatment for persons living with HIV (PLHIV), two-thirds of whom live in sub-Saharan Africa. To inform a health system response supportive of continuity of care, we sought to understand clients' HIV care experiences and health priorities during the first wave of COVID-19 outbreak in Lusaka, Zambia.

METHODS: Leveraging a study cohort of those who completed periodic SMS surveys on HIV care, we purposefully sampled 25 PLHIV after first confirmed COVID-19 case was reported in Zambia on 18

RESULTS: All participants were aware of COVID-19, and HIV care …


Immune Checkpoint Inhibitor Therapy And Outcomes From Sars-Cov-2 Infection In Patients With Cancer: A Joint Analysis Of Oncovid And Esmo-Cocare Registries, Alessio Cortellini, Gino M Dettorre, Et Al. Nov 2022

Immune Checkpoint Inhibitor Therapy And Outcomes From Sars-Cov-2 Infection In Patients With Cancer: A Joint Analysis Of Oncovid And Esmo-Cocare Registries, Alessio Cortellini, Gino M Dettorre, Et Al.

2020-Current year OA Pubs

BACKGROUND: As management and prevention strategies against COVID-19 evolve, it is still uncertain whether prior exposure to immune checkpoint inhibitors (ICIs) affects COVID-19 severity in patients with cancer.

METHODS: In a joint analysis of ICI recipients from OnCovid (NCT04393974) and European Society for Medical Oncology (ESMO) CoCARE registries, we assessed severity and mortality from SARS-CoV-2 in vaccinated and unvaccinated patients with cancer and explored whether prior immune-related adverse events (irAEs) influenced outcome from COVID-19.

FINDINGS: The study population consisted of 240 patients diagnosed with COVID-19 between January 2020 and February 2022 exposed to ICI within 3 months prior to COVID-19 …


Clinical Management Of Supratentorial Non-Skull Case Meningiomas, Adefisayo Adekanmbi, Mark W Youngblood, Constantine L Karras, Ephraim A Oyetunji, John Kalapurakal, Craig M Horbinski, Hinda Najem, Virginia B Hill, James P Chandler, Amy B Heimberger, Stephen T Magill, Rimas V Lukas Nov 2022

Clinical Management Of Supratentorial Non-Skull Case Meningiomas, Adefisayo Adekanmbi, Mark W Youngblood, Constantine L Karras, Ephraim A Oyetunji, John Kalapurakal, Craig M Horbinski, Hinda Najem, Virginia B Hill, James P Chandler, Amy B Heimberger, Stephen T Magill, Rimas V Lukas

2020-Current year OA Pubs

Supratentorial non-skull base meningiomas are the most common primary central nervous system tumor subtype. An understanding of their pathophysiology, imaging characteristics, and clinical management options will prove of substantial value to the multi-disciplinary team which may be involved in their care. Extensive review of the broad literature on the topic is conducted. Narrowing the scope to meningiomas located in the supratentorial non-skull base anatomic location highlights nuances specific to this tumor subtype. Advances in our understanding of the natural history of the disease and how findings from both molecular pathology and neuroimaging have impacted our understanding are discussed. Clinical management …


Gantenerumab: An Anti-Amyloid Monoclonal Antibody With Potential Disease-Modifying Effects In Early Alzheimer's Disease, Randall J Bateman, Jeffrey Cummings, Scott Schobel, Stephen Salloway, Bruno Vellas, Mercè Boada, Sandra E Black, Kaj Blennow, Paulo Fontoura, Gregory Klein, Sheila Seleri Assunção, Janice Smith, Rachelle S Doody Nov 2022

Gantenerumab: An Anti-Amyloid Monoclonal Antibody With Potential Disease-Modifying Effects In Early Alzheimer's Disease, Randall J Bateman, Jeffrey Cummings, Scott Schobel, Stephen Salloway, Bruno Vellas, Mercè Boada, Sandra E Black, Kaj Blennow, Paulo Fontoura, Gregory Klein, Sheila Seleri Assunção, Janice Smith, Rachelle S Doody

2020-Current year OA Pubs

BACKGROUND: This review describes the research and development process of gantenerumab, a fully human anti-amyloid monoclonal antibody in development to treat early symptomatic and asymptomatic Alzheimer's disease (AD). Anti-amyloid monoclonal antibodies can substantially reverse amyloid plaque pathology and may modify the course of the disease by slowing or stopping its clinical progression. Several molecules targeting amyloid have failed in clinical development due to drug-related factors (e.g., treatment-limiting adverse events, low potency, poor brain penetration), study design/methodological issues (e.g., disease stage, lack of AD pathology confirmation), and other factors. The US Food and Drug Administration's approval of aducanumab, an anti-amyloid monoclonal …


Single-Cell Rna Sequencing Identifies A Paracrine Interaction That May Drive Oncogenic Notch Signaling In Human Adenoid Cystic Carcinoma, Anuraag S. Parikh, Avishai Wizel, Daniel Davis, Armida Lefranc-Torres, Alejandro I. Rodarte-Rascon, Lauren E. Miller, Kevin S. Emerick, Mark A. Varvares, Daniel G. Deschler, William C. Faquin, Jon C. Aster, Derrick T. Lin, Bradley E. Bernstein, Yotam Drier, Sidharth V. Puram Nov 2022

Single-Cell Rna Sequencing Identifies A Paracrine Interaction That May Drive Oncogenic Notch Signaling In Human Adenoid Cystic Carcinoma, Anuraag S. Parikh, Avishai Wizel, Daniel Davis, Armida Lefranc-Torres, Alejandro I. Rodarte-Rascon, Lauren E. Miller, Kevin S. Emerick, Mark A. Varvares, Daniel G. Deschler, William C. Faquin, Jon C. Aster, Derrick T. Lin, Bradley E. Bernstein, Yotam Drier, Sidharth V. Puram

2020-Current year OA Pubs

Salivary adenoid cystic carcinoma (ACC) is a rare, biologically unique biphasic tumor that consists of malignant myoepithelial and luminal cells. MYB and Notch signaling have been implicated in ACC pathophysiology, but in vivo descriptions of these two programs in human tumors and investigation into their active coordination remain incomplete. We utilize single-cell RNA sequencing to profile human head and neck ACC, including a comparison of primary ACC with a matched local recurrence. We define expression heterogeneity in these rare tumors, uncovering diversity in myoepithelial and luminal cell expression. We find differential expression of Notch ligands DLL1, JAG1, and JAG2 in …


Fgfr2b Signalling Restricts Lineage-Flexible Alveolar Progenitors During Mouse Lung Development And Converges In Mature Alveolar Type 2 Cells, Matthew R Jones, Arun Lingampally, Negah Ahmadvand, Lei Chong, Jin Wu, Jochen Wilhem, Ana Ivonne Vazquez-Armendariz, Meshal Ansari, Susanne Herold, David M Ornitz, Herbert B Schiller, Cho-Ming Chao, Jin-San Zhang, Gianni Carraro, Saverio Bellusci Nov 2022

Fgfr2b Signalling Restricts Lineage-Flexible Alveolar Progenitors During Mouse Lung Development And Converges In Mature Alveolar Type 2 Cells, Matthew R Jones, Arun Lingampally, Negah Ahmadvand, Lei Chong, Jin Wu, Jochen Wilhem, Ana Ivonne Vazquez-Armendariz, Meshal Ansari, Susanne Herold, David M Ornitz, Herbert B Schiller, Cho-Ming Chao, Jin-San Zhang, Gianni Carraro, Saverio Bellusci

2020-Current year OA Pubs

The specification, characterization, and fate of alveolar type 1 and type 2 (AT1 and AT2) progenitors during embryonic lung development are poorly defined. Current models of distal epithelial lineage formation fail to capture the heterogeneity and dynamic contribution of progenitor pools present during early development. Furthermore, few studies explore the pathways involved in alveolar progenitor specification and fate. In this paper, we build upon our previously published work on the regulation of airway epithelial progenitors by fibroblast growth factor receptor 2b (FGFR2b) signalling during early (E12.5) and mid (E14.5) pseudoglandular stage lung development. Our results suggest that a significant proportion …


Comprehensive Transcriptomic Analysis Of Vista In Acute Myeloid Leukemia: Insights Into Its Prognostic Value, Simona Pagliuca, Carmelo Gurnari, Keman Zhang, Tariq Kewan, Waled Bahaj, Minako Mori, Ishani Nautiyal, Marie Thérèse Rubio, Francesca Ferraro, Jaroslaw P Maciejewski, Li Wang, Valeria Visconte Nov 2022

Comprehensive Transcriptomic Analysis Of Vista In Acute Myeloid Leukemia: Insights Into Its Prognostic Value, Simona Pagliuca, Carmelo Gurnari, Keman Zhang, Tariq Kewan, Waled Bahaj, Minako Mori, Ishani Nautiyal, Marie Thérèse Rubio, Francesca Ferraro, Jaroslaw P Maciejewski, Li Wang, Valeria Visconte

2020-Current year OA Pubs

The V-domain Ig suppressor of T-cell activation (VISTA) has been recognized as a critical negative regulator of antitumor immune response and is gaining growing interest as a potential pharmacological target in immunotherapy. This molecule is highly expressed in hematopoietic stem cells and myeloid compartment, and it has been found upmodulated in acute myeloid leukemia (AML). However, VISTA-associated immune features are relatively unexplored in myeloid malignancies. Herein, we aimed to explore whether this immune checkpoint regulator could play a role in the generation of an immune escape environment in AML patients. We characterized VISTA mRNA expression levels in leukemia cell lines …


Non-Standard Viral Genome-Derived Rna Activates Tlr3 And Type I Ifn Signaling To Induce Cdc1-Dependent Cd8+ T-Cell Responses During Vaccination In Mice, Devin G Fisher, Victoria Gnazzo, David J Holthausen, Carolina B López Nov 2022

Non-Standard Viral Genome-Derived Rna Activates Tlr3 And Type I Ifn Signaling To Induce Cdc1-Dependent Cd8+ T-Cell Responses During Vaccination In Mice, Devin G Fisher, Victoria Gnazzo, David J Holthausen, Carolina B López

2020-Current year OA Pubs

There is a critical need to develop vaccine adjuvants that induce robust immune responses able to protect against intracellular pathogens, including viruses. Previously, we described defective viral genome-derived oligonucleotides (DDOs) as novel adjuvants that strongly induce type 1 immune responses, including protective Th1 CD4+ T-cells and effector CD8+ T-cells in mice. Here, we unravel the early innate response required for this type 1 immunity induction. Upon DDO subcutaneous injection, type 1 conventional dendritic cells (cDC1s) accumulate rapidly in the draining lymph node in a Toll-like receptor 3 (TLR3)- and type I interferon (IFN)-dependent manner. cDC1 accumulation in the lymph node …


Immune Phenotypes That Are Associated With Subsequent Covid-19 Severity Inferred From Post-Recovery Samples, Thomas Liechti, Yaser Iftikhar, Massimo Mangino, Margaret Beddall, Charles W Goss, Jane A O'Halloran, Philip A Mudd, Mario Roederer Nov 2022

Immune Phenotypes That Are Associated With Subsequent Covid-19 Severity Inferred From Post-Recovery Samples, Thomas Liechti, Yaser Iftikhar, Massimo Mangino, Margaret Beddall, Charles W Goss, Jane A O'Halloran, Philip A Mudd, Mario Roederer

2020-Current year OA Pubs

Severe COVID-19 causes profound immune perturbations, but pre-infection immune signatures contributing to severe COVID-19 remain unknown. Genome-wide association studies (GWAS) identified strong associations between severe disease and several chemokine receptors and molecules from the type I interferon pathway. Here, we define immune signatures associated with severe COVID-19 using high-dimensional flow cytometry. We measure the cells of the peripheral immune system from individuals who recovered from mild, moderate, severe or critical COVID-19 and focused only on those immune signatures returning to steady-state. Individuals that suffered from severe COVID-19 show reduced frequencies of T cell, mucosal-associated invariant T cell (MAIT) and dendritic …


Determining Epigenetic Memory In Kidney Proximal Tubule Cell Derived Induced Pluripotent Stem Cells Using A Quadruple Transgenic Reprogrammable Mouse, Gabriel Khelifi, Theresa Chow, Jennifer Whiteley, Victoire Fort, Benjamin D Humphreys, Samer M I Hussein, Ian M Rogers Nov 2022

Determining Epigenetic Memory In Kidney Proximal Tubule Cell Derived Induced Pluripotent Stem Cells Using A Quadruple Transgenic Reprogrammable Mouse, Gabriel Khelifi, Theresa Chow, Jennifer Whiteley, Victoire Fort, Benjamin D Humphreys, Samer M I Hussein, Ian M Rogers

2020-Current year OA Pubs

The majority of nucleated somatic cells can be reprogrammed to induced pluripotent stem cells (iPSCs). The process of reprogramming involves epigenetic remodelling to turn on pluripotency-associated genes and turn off lineage-specific genes. Some evidence shows that iPSCs retain epigenetic marks of their cell of origin and this "epigenetic memory" influences their differentiation potential, with a preference towards their cell of origin. Here, we reprogrammed proximal tubule cells (PTC) and tail tip fibroblasts (TTF), from a reprogrammable mouse to iPSCs and differentiated the iPSCs to renal progenitors to understand if epigenetic memory plays a role in renal differentiation. This model allowed …


Premature Ovarian Insufficiency In Clpb Deficiency: Transcriptomic, Proteomic And Phenotypic Insights, Elena J Tucker, Julia T Warren, Et Al. Nov 2022

Premature Ovarian Insufficiency In Clpb Deficiency: Transcriptomic, Proteomic And Phenotypic Insights, Elena J Tucker, Julia T Warren, Et Al.

2020-Current year OA Pubs

CONTEXT: Premature ovarian insufficiency (POI) is a common form of female infertility that usually presents as an isolated condition but can be part of various genetic syndromes. Early diagnosis and treatment of POI can minimize comorbidity and improve health outcomes.

OBJECTIVE: We aimed to determine the genetic cause of syndromic POI, intellectual disability, neutropenia, and cataracts.

METHODS: We performed whole-exome sequencing (WES) followed by functional validation via RT-PCR, RNAseq, and quantitative proteomics, as well as clinical update of previously reported patients with variants in the caseinolytic peptidase B (CLPB) gene.

RESULTS: We identified causative variants in CLPB, encoding a mitochondrial …


Mahpic Malaria Systems Biology Data From Plasmodium Cynomolgi Sporozoite Longitudinal Infections In Macaques, Jeremy D Debarry, Xuntian Jiang, Daniel S Ory, Et Al. Nov 2022

Mahpic Malaria Systems Biology Data From Plasmodium Cynomolgi Sporozoite Longitudinal Infections In Macaques, Jeremy D Debarry, Xuntian Jiang, Daniel S Ory, Et Al.

2020-Current year OA Pubs

Plasmodium cynomolgi causes zoonotic malarial infections in Southeast Asia and this parasite species is important as a model for Plasmodium vivax and Plasmodium ovale. Each of these species produces hypnozoites in the liver, which can cause relapsing infections in the blood. Here we present methods and data generated from iterative longitudinal systems biology infection experiments designed and performed by the Malaria Host-Pathogen Interaction Center (MaHPIC) to delve deeper into the biology, pathogenesis, and immune responses of P. cynomolgi in the Macaca mulatta host. Infections were initiated by sporozoite inoculation. Blood and bone marrow samples were collected at defined timepoints for …


Stakeholder Engagement In Eight Comparative Effectiveness Trials In African Americans And Latinos With Asthma, Tiffany Dy, Winifred J Hamilton, C Bradley Kramer, Andrea Apter, Jerry A Krishnan, James W Stout, Stephen J Teach, Alex Federman, John Elder, Tyra Bryant-Stephens, Rebecca J Bruhl, Shawni Jackson, Kaharu Sumino Nov 2022

Stakeholder Engagement In Eight Comparative Effectiveness Trials In African Americans And Latinos With Asthma, Tiffany Dy, Winifred J Hamilton, C Bradley Kramer, Andrea Apter, Jerry A Krishnan, James W Stout, Stephen J Teach, Alex Federman, John Elder, Tyra Bryant-Stephens, Rebecca J Bruhl, Shawni Jackson, Kaharu Sumino

2020-Current year OA Pubs

BACKGROUND: The effects of stakeholder engagement, particularly in comparative effectiveness trials, have not been widely reported. In 2014, eight comparative effectiveness studies targeting African Americans and Hispanics/Latinos with uncontrolled asthma were funded by the Patient-Centered Outcomes Research Institute (PCORI) as part of its Addressing Disparities Program. Awardees were required to meaningfully involve patients and other stakeholders. Using specific examples, we describe how these stakeholders substantially changed the research protocols and in other ways participated meaningfully as full partners in the development and conduct of the eight studies.

METHODS: Using the method content analysis of cases, we identified themes regarding the …


Csf Tau Microtubule-Binding Region Identifies Pathological Changes In Primary Tauopathies, Kanta Horie, Nicolas R Barthélemy, Yingxin He, Albert A Davis, Celeste M Karch, Richard J Perrin, Rama K Koppisetti, Faris Shaikh, Nupur Ghoshal, Randall J Bateman, Chihiro Sato, Et Al. Nov 2022

Csf Tau Microtubule-Binding Region Identifies Pathological Changes In Primary Tauopathies, Kanta Horie, Nicolas R Barthélemy, Yingxin He, Albert A Davis, Celeste M Karch, Richard J Perrin, Rama K Koppisetti, Faris Shaikh, Nupur Ghoshal, Randall J Bateman, Chihiro Sato, Et Al.

2020-Current year OA Pubs

Despite recent advances in fluid biomarker research in Alzheimer's disease (AD), there are no fluid biomarkers or imaging tracers with utility for diagnosis and/or theragnosis available for other tauopathies. Using immunoprecipitation and mass spectrometry, we show that 4 repeat (4R) isoform-specific tau species from microtubule-binding region (MTBR-tau


Wakeful Rest Benefits Recall, But Not Recognition, Of Incidentally Encoded Memory Stimuli In Younger And Older Adults, Peter R Millar, David A Balota Nov 2022

Wakeful Rest Benefits Recall, But Not Recognition, Of Incidentally Encoded Memory Stimuli In Younger And Older Adults, Peter R Millar, David A Balota

2020-Current year OA Pubs

Older adults exhibit deficits in episodic memory tasks, which have often been attributed to encoding or retrieval deficits, with little attention to consolidation mechanisms. More recently, researchers have attempted to measure consolidation in the context of a behavioral experiment using the wakeful rest paradigm (i.e., a brief, quiet period of minimal stimulation, which facilitates memory performance, compared to a distractor task). Critically, older adults might not produce this effect, given established age differences in other episodic memory processes and mind-wandering. In three experiments, we directly compared younger and older adults in modified versions of the wakeful rest paradigm. Critically, we …


Multilevel Correlates Of Domain-Specific Physical Activity Among Rural Adults - A Cross-Sectional Study, Alan M Beck, Natalicio H Serrano, Audrey Toler, Ross C Brownson Nov 2022

Multilevel Correlates Of Domain-Specific Physical Activity Among Rural Adults - A Cross-Sectional Study, Alan M Beck, Natalicio H Serrano, Audrey Toler, Ross C Brownson

2020-Current year OA Pubs

BACKGROUND: Increasing physical activity (PA) in rural communities is a vital prevention tactic in multiple chronic diseases; however, little is known on the multilevel correlates of PA rural areas. A better understanding of domain-specific PA adds context for promoting PA in rural communities. The current study sought to determine factors associated with domain-specific and overall moderate-vigorous physical activity (MVPA) in rural communities.

METHODS: Surveys were conducted across 14 rural mid-Western communities, with the final analytical sample including 1241 adults (ages 19-96, M = 57.0 [SD = 16.7], 67.8% female, 83.8% white). Generalized linear models with negative binomial distributions examined the …


Muscle-Specific Ablation Of Glucose Transporter 1 (Glut1) Does Not Impair Basal Or Overload-Stimulated Skeletal Muscle Glucose Uptake, Shawna L Mcmillin, Parker L Evans, William M Taylor, Luke A Weyrauch, Tyler J Sermersheim, Steven S Welc, Monique R Heitmeier, Richard C Hresko, Paul W Hruz, Francoise Koumanov, Geoffrey D Holman, E Dale Abel, Carol A Witczak Nov 2022

Muscle-Specific Ablation Of Glucose Transporter 1 (Glut1) Does Not Impair Basal Or Overload-Stimulated Skeletal Muscle Glucose Uptake, Shawna L Mcmillin, Parker L Evans, William M Taylor, Luke A Weyrauch, Tyler J Sermersheim, Steven S Welc, Monique R Heitmeier, Richard C Hresko, Paul W Hruz, Francoise Koumanov, Geoffrey D Holman, E Dale Abel, Carol A Witczak

2020-Current year OA Pubs

Glucose transporter 1 (GLUT1) is believed to solely mediate basal (insulin-independent) glucose uptake in skeletal muscle; yet recent work has demonstrated that mechanical overload, a model of resistance exercise training, increases muscle GLUT1 levels. The primary objective of this study was to determine if GLUT1 is necessary for basal or overload-stimulated muscle glucose uptake. Muscle-specific GLUT1 knockout (mGLUT1KO) mice were generated and examined for changes in body weight, body composition, metabolism, systemic glucose regulation, muscle glucose transporters, and muscle [


Cortex-Wide Response Mode Of Vip-Expressing Inhibitory Neurons By Reward And Punishment, Zoltán Szadai, Hyun-Jae Pi, Quentin Chevy, Katalin Ócsai, Dinu F Albeanu, Balázs Chiovini, Gergely Szalay, Gergely Katona, Adam Kepecs, Balázs Rózsa Nov 2022

Cortex-Wide Response Mode Of Vip-Expressing Inhibitory Neurons By Reward And Punishment, Zoltán Szadai, Hyun-Jae Pi, Quentin Chevy, Katalin Ócsai, Dinu F Albeanu, Balázs Chiovini, Gergely Szalay, Gergely Katona, Adam Kepecs, Balázs Rózsa

2020-Current year OA Pubs

Neocortex is classically divided into distinct areas, each specializing in different function, but all could benefit from reinforcement feedback to inform and update local processing. Yet it remains elusive how global signals like reward and punishment are represented in local cortical computations. Previously, we identified a cortical neuron type, vasoactive intestinal polypeptide (VIP)-expressing interneurons, in auditory cortex that is recruited by behavioral reinforcers and mediates disinhibitory control by inhibiting other inhibitory neurons. As the same disinhibitory cortical circuit is present virtually throughout cortex, we wondered whether VIP neurons are likewise recruited by reinforcers throughout cortex. We monitored VIP neural activity …


Myostatin Is A Negative Regulator Of Adult Neurogenesis After Spinal Cord Injury In Zebrafish, Vishnu Muraleedharan Saraswathy, Lili Zhou, Anthony R Mcadow, Brooke Burris, Deepika Dogra, Sven Reischauer, Mayssa H Mokalled Nov 2022

Myostatin Is A Negative Regulator Of Adult Neurogenesis After Spinal Cord Injury In Zebrafish, Vishnu Muraleedharan Saraswathy, Lili Zhou, Anthony R Mcadow, Brooke Burris, Deepika Dogra, Sven Reischauer, Mayssa H Mokalled

2020-Current year OA Pubs

Intrinsic and extrinsic inhibition of neuronal regeneration obstruct spinal cord (SC) repair in mammals. In contrast, adult zebrafish achieve functional recovery after complete SC transection. While studies of innate SC regeneration have focused on axon regrowth as a primary repair mechanism, how local adult neurogenesis affects functional recovery is unknown. Here, we uncover dynamic expression of zebrafish myostatin b (mstnb) in a niche of dorsal SC progenitors after injury. mstnb mutants show impaired functional recovery, normal glial and axonal bridging across the lesion, and an increase in the profiles of newborn neurons. Molecularly, neuron differentiation genes are upregulated, while the …


Chatbot-Delivered Cognitive Behavioral Therapy In Adolescents With Depression And Anxiety During The Covid-19 Pandemic: Feasibility And Acceptability Study, Ginger Nicol, Ruoyun Wang, Sharon Graham, Sherry Dodd, Jane Garbutt Nov 2022

Chatbot-Delivered Cognitive Behavioral Therapy In Adolescents With Depression And Anxiety During The Covid-19 Pandemic: Feasibility And Acceptability Study, Ginger Nicol, Ruoyun Wang, Sharon Graham, Sherry Dodd, Jane Garbutt

2020-Current year OA Pubs

BACKGROUND: Symptoms of depression and anxiety, suicidal ideation, and self-harm have escalated among adolescents to crisis levels during the COVID-19 pandemic. As a result, primary care providers (PCPs) are often called on to provide first-line care for these youth. Digital health interventions can extend mental health specialty care, but few are evidence based. We evaluated the feasibility of delivering an evidence-based mobile health (mHealth) app with an embedded conversational agent to deliver cognitive behavioral therapy (CBT) to symptomatic adolescents presenting in primary care settings during the pandemic.

OBJECTIVE: In this 12-week pilot study, we evaluated the feasibility of delivering the …