Medicine and Health Sciences Commons^™

"Brain Age" Predicts Disability Accumulation In Multiple Sclerosis, Matthew R Brier, Zhuocheng Li, Maria Ly, Helmet T Karim, Leda Liang, Weixin Du, John E Mccarthy, Anne H Cross, Tammie L S Benzinger, Robert T Naismith, Salim Chahin

2020-Current year OA Pubs

OBJECTIVE: Neurodegenerative conditions often manifest radiologically with the appearance of premature aging. Multiple sclerosis (MS) biomarkers related to lesion burden are well developed, but measures of neurodegeneration are less well-developed. The appearance of premature aging quantified by machine learning applied to structural MRI assesses neurodegenerative pathology. We assess the explanatory and predictive power of "brain age" analysis on disability in MS using a large, real-world dataset.

METHODS: Brain age analysis is predicated on the over-estimation of predicted brain age in patients with more advanced pathology. We compared the performance of three brain age algorithms in a large, longitudinal dataset ( …

The Mitophagy Receptor Bnip3 Is Critical For The Regulation Of Metabolic Homeostasis And Mitochondrial Function In The Nucleus Pulposus Cells Of The Intervertebral Disc, Vedavathi Madhu, Miriam Hernandez-Meadows, Paige K Boneski, Yunping Qiu, Anyonya R Guntur, Irwin J Kurland, Ruteja A Barve, Makarand V Risbud

2020-Current year OA Pubs

The contribution of mitochondria to the metabolic function of hypoxic NP cells has been overlooked. We have shown that NP cells contain networked mitochondria and that mitochondrial translocation of BNIP3 mediates hypoxia-induced mitophagy. However, whether BNIP3 also plays a role in governing mitochondrial function and metabolism in hypoxic NP cells is not known. BNIP3 knockdown altered mitochondrial morphology, and number, and increased mitophagy. Interestingly, BNIP3 deficiency in NP cells reduced glycolytic capacity reflected by lower production of lactate/H

Mri Findings Associated With Anterior Cruciate Ligament Tears In National Football League Athletes, Robert H. Brophy, Jon C. Baker, Jana M. Crain, Mackenzie M. Herzog, Ben Stollberg, Edward M. Wojtys, Christina D. Mack

2020-Current year OA Pubs

BACKGROUND: Anterior cruciate ligament (ACL) tears are a high-frequency injury requiring a lengthy recovery in professional American football players. Concomitant pathology associated with ACL tears as identified on magnetic resonance imaging (MRI) is not well understood in these athletes.

PURPOSE: To describe the MRI findings of concomitant injuries associated with ACL tears among athletes in the National Football League (NFL).

STUDY DESIGN: Cross-sectional study; Level of evidence, 3.

METHODS: Of 314 ACL injuries in NFL athletes from 2015 through 2019, 191 complete MRI scans from the time of primary ACL injury were identified and reviewed by 2 fellowship-trained musculoskeletal radiologists. …

Autophagy Prevents Early Proinflammatory Responses And Neutrophil Recruitment During Mycobacterium Tuberculosis Infection Without Affecting Pathogen Burden In Macrophages, Rachel L. Kinsella, Jacqueline M. Kimmey, Asya Smirnov, Reilly Woodson, Margaret R. Gaggioli, Sthefany M. Chavez, Darren Kreamalmeyer, Christina L. Stallings

2020-Current year OA Pubs

The immune response to Mycobacterium tuberculosis infection determines tuberculosis disease outcomes, yet we have an incomplete understanding of what immune factors contribute to a protective immune response. Neutrophilic inflammation has been associated with poor disease prognosis in humans and in animal models during M. tuberculosis infection and, therefore, must be tightly regulated. ATG5 is an essential autophagy protein that is required in innate immune cells to control neutrophil-dominated inflammation and promote survival during M. tuberculosis infection; however, the mechanistic basis for how ATG5 regulates neutrophil recruitment is unknown. To interrogate what innate immune cells require ATG5 to control neutrophil recruitment …

Replicative Acinetobacter Baumannii Strains Interfere With Phagosomal Maturation By Modulating The Vacuolar Ph, Jesus S. Distel, Gisela Di Venanzio, Joseph J. Mackel, David A. Rosen, Mario F. Feldman

2020-Current year OA Pubs

Bacterial pneumonia is a common infection of the lower respiratory tract that can afflict patients of all ages. Multidrug-resistant strains of Acinetobacter baumannii are increasingly responsible for causing nosocomial pneumonias, thus posing an urgent threat. Alveolar macrophages play a critical role in overcoming respiratory infections caused by this pathogen. Recently, we and others have shown that new clinical isolates of A. baumannii, but not the common lab strain ATCC 19606 (19606), can persist and replicate in macrophages within spacious vacuoles that we called Acinetobacter Containing Vacuoles (ACV). In this work, we demonstrate that the modern A. baumannii clinical isolate 398, …

Finding Motifs Using Dna Images Derived From Sparse Representations, Shane K Chu, Gary D Stormo

2020-Current year OA Pubs

MOTIVATION: Motifs play a crucial role in computational biology, as they provide valuable information about the binding specificity of proteins. However, conventional motif discovery methods typically rely on simple combinatoric or probabilistic approaches, which can be biased by heuristics such as substring-masking for multiple motif discovery. In recent years, deep neural networks have become increasingly popular for motif discovery, as they are capable of capturing complex patterns in data. Nonetheless, inferring motifs from neural networks remains a challenging problem, both from a modeling and computational standpoint, despite the success of these networks in supervised learning tasks.

RESULTS: We present a …

Participant- And Disease-Related Factors As Independent Predictors Of Treatment Outcomes In The Restore-Imi 2 Clinical Trial: A Multivariable Regression Analysis, Ignacio Martin-Loeches, Andrew F Shorr, Marin H Kollef, Jiejun Du, Maria C Losada, Amanda Paschke, C Andrew Deryke, Michael Wong, Erin H Jensen, Luke F Chen

2020-Current year OA Pubs

BACKGROUND: In the RESTORE-IMI 2 trial, imipenem/cilastatin/relebactam (IMI/REL) was noninferior to piperacillin/tazobactam in treating hospital-acquired bacterial pneumonia/ventilator-associated bacterial pneumonia. This post hoc analysis was conducted to determine independent predictors of efficacy outcomes in the RESTORE-IMI 2 trial, to assist in treatment decision making.

METHODS: A stepwise multivariable regression analysis was conducted to identify variables that were independently associated with day 28 all-cause mortality (ACM), favorable clinical response at early follow-up (EFU), and favorable microbiologic response at end of treatment (EOT). The analysis accounted for the number of baseline infecting pathogens and in vitro susceptibility to randomized treatment.

RESULTS: Vasopressor use, …

Terrorist Attacks Against Sports Venues: Emerging Trends And Characteristics Spanning 50 Years, Grace R Rahman, Gregory N Jasani, Stephen Y Liang

2020-Current year OA Pubs

INTRODUCTION: Sports venues foster community and support local economies. Due to their capacity to host hundreds to thousands of spectators, sports venues are vulnerable to becoming targets of terrorism. Types of venues targeted, regional trends, and methods of attack employed world-wide have not been well-described.

METHODS: A search of the Global Terrorism Database (GTD) was conducted from 1970 through the end of 2019. Pre-coded variables for target type "business" and target subtype "entertainment/cultural/stadium/casino" were used to identify attacks involving venues where sports events might be viewed by spectators as part of an audience. Sports venues were specifically identified using the …

Tarlatamab, A First-In-Class Dll3-Targeted Bispecific T-Cell Engager, In Recurrent Small-Cell Lung Cancer: An Open-Label, Phase I Study, Luis Paz-Ares, Ramaswamy Govindan, Et Al.

2020-Current year OA Pubs

PURPOSE: Small-cell lung cancer (SCLC) is an aggressive malignancy with limited treatments. Delta-like ligand 3 (DLL3) is aberrantly expressed in most SCLC. Tarlatamab (AMG 757), a bispecific T-cell engager molecule, binds both DLL3 and CD3 leading to T-cellb-mediated tumor lysis. Herein, we report phase I results of tarlatamab in patients with SCLC.

PATIENTS AND METHODS: This study evaluated tarlatamab in patients with relapsed/refractory SCLC. The primary end point was safety. Secondary end points included antitumor activity by modified RECIST 1.1, overall survival, and pharmacokinetics.

RESULTS: By July 19, 2022, 107 patients received tarlatamab in dose exploration (0.003 to 100 mg; …

Associations Between Socioeconomic Status, Obesity, Cognition, And White Matter Microstructure In Children, Zhaolong Adrian Li, Yuqi Cai, Rita L Taylor, Sarah A Eisenstein, Deanna M Barch, Scott Marek, Tamara Hershey

2020-Current year OA Pubs

IMPORTANCE: Lower neighborhood and household socioeconomic status (SES) are associated with negative health outcomes and altered brain structure in children. It is unclear whether such findings extend to white matter and via what mechanisms.

OBJECTIVE: To assess whether and how neighborhood and household SES are independently associated with children's white matter microstructure and examine whether obesity and cognitive performance (reflecting environmental cognitive and sensory stimulation) are plausible mediators.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used baseline data from participants in the Adolescent Brain Cognitive Development (ABCD) study. Data were collected at 21 US sites, and school-based recruitment was used …

Cochlear Implantation And Audiological Findings In A Child With Zellweger Spectrum Disorder, Amit Walia, Amy Lynn Birath, Craig A. Buchman

2020-Current year OA Pubs

No abstract provided.

A Pentasaccharide For Monitoring Pharmacodynamic Response To Gene Therapy In Gm1 Gangliosidosis, Pamela Kell, Rohini Sidhu, Mingxing Qian, Sonali Mishra, Dennis J Dietzen, Jingqin Luo, Jean E Schaffer, Daniel S Ory, Xuntian Jiang, Et Al.

2020-Current year OA Pubs

BACKGROUND: GM1 gangliosidosis is a rare, fatal, neurodegenerative disease caused by mutations in the GLB1 gene and deficiency in β-galactosidase. Delay of symptom onset and increase in lifespan in a GM1 gangliosidosis cat model after adeno-associated viral (AAV) gene therapy treatment provide the basis for AAV gene therapy trials. The availability of validated biomarkers would greatly improve assessment of therapeutic efficacy.

METHODS: The liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to screen oligosaccharides as potential biomarkers for GM1 gangliosidosis. The structures of pentasaccharide biomarkers were determined with mass spectrometry, as well as chemical and enzymatic degradations. Comparison of LC-MS/MS data …

Cortical Adaptation Of The Night Monkey To A Nocturnal Niche Environment: A Comparative Non-Invasive T1w/T2w Myelin Study, Takuro Ikeda, Joonas A Autio, Akihiro Kawasaki, Chiho Takeda, Takayuki Ose, Masahiko Takada, David C Van Essen, Matthew F Glasser, Takuya Hayashi

2020-Current year OA Pubs

Night monkeys (Aotus) are the only genus of monkeys within the Simian lineage that successfully occupy a nocturnal environmental niche. Their behavior is supported by their sensory organs' distinctive morphological features; however, little is known about their evolutionary adaptations in sensory regions of the cerebral cortex. Here, we investigate this question by exploring the cortical organization of night monkeys using high-resolution in-vivo brain MRI and comparative cortical-surface T1w/T2w myeloarchitectonic mapping. Our results show that the night monkey cerebral cortex has a qualitatively similar but quantitatively different pattern of cortical myelin compared to the diurnal macaque and marmoset monkeys. T1w/T2w myelin …

Toward Blood-Based Precision Medicine: Identifying Age-Sex-Specific Vascular Biomarker Quantities On Circulating Vascular Cells, Yingye Fang, Ling Chen, P I Imoukhuede

2020-Current year OA Pubs

INTRODUCTION: Abnormal angiogenesis is central to vascular disease and cancer, and noninvasive biomarkers of vascular origin are needed to evaluate patients and therapies. Vascular endothelial growth factor receptors (VEGFRs) are often dysregulated in these diseases, making them promising biomarkers, but the need for an invasive biopsy has limited biomarker research on VEGFRs. Here, we pioneer a blood biopsy approach to quantify VEGFR plasma membrane localization on two circulating vascular proxies: circulating endothelial cells (cECs) and circulating progenitor cells (cPCs).

METHODS: Using quantitative flow cytometry, we examined VEGFR expression on cECs and cPCs in four age-sex groups: peri/premenopausal females (aged < 50 years), menopausal/postmenopausal females (≥ 50 years), and younger and older males with the same age cut-off (50 years).

RESULTS: …

Irritability Moderates The Association Between Cognitive Flexibility Task Performance And Related Prefrontal Cortex Activation In Young Children, Yanwei Li, Adam S Grabell, Susan B Perlman

2020-Current year OA Pubs

The association between cognitive flexibility and related neural functioning has been inconsistent. This is particularly true in young children, where previous studies have found heterogenous results linking behavior and neural function, raising the possibility of unexplored moderators. The current study explored the moderating role of dimensional irritability in the association between cognitive flexibility task performance and prefrontal activation in young children. A total of 106 3- to 7-year-old children were recruited to complete a custom-designed, child-adapted, cognitive flexibility task, and 98 of them were included in the data analysis. The children's dorsolateral prefrontal cortex activation was monitored using functional near-infrared …

Neuron-Associated Macrophage Proliferation In The Sensory Ganglia Is Associated With Peripheral Nerve Injury-Induced Neuropathic Pain Involving Cx3cr1 Signaling, Rafaela M Guimarães, Conceição E Aníbal-Silva, Marcela Davoli-Ferreira, Francisco Isaac F Gomes, Atlante Mendes, Maria C M Cavallini, Miriam M Fonseca, Samara Damasceno, Larissa P Andrade, Marco Colonna, Cyril Rivat, Fernando Q Cunha, José C Alves-Filho, Thiago M Cunha

2020-Current year OA Pubs

Resident macrophages are distributed across all tissues and are highly heterogeneous due to adaptation to different tissue-specific environments. The resident macrophages of the sensory ganglia (sensory neuron-associated macrophages, sNAMs) are in close contact with the cell body of primary sensory neurons and might play physiological and pathophysiological roles. After peripheral nerve injury, there is an increase in the population of macrophages in the sensory ganglia, which have been implicated in different conditions, including neuropathic pain development. However, it is still under debate whether macrophage accumulation in the sensory ganglia after peripheral nerve injury is due to the local proliferation of …

Leukemia Relapse Via Genetic Immune Escape After Allogeneic Hematopoietic Cell Transplantation, Simona Pagliuca, Francesca Ferraro, Et Al.

2020-Current year OA Pubs

Graft-versus-leukemia (GvL) reactions are responsible for the effectiveness of allogeneic hematopoietic cell transplantation as a treatment modality for myeloid neoplasia, whereby donor T- effector cells recognize leukemia neoantigens. However, a substantial fraction of patients experiences relapses because of the failure of the immunological responses to control leukemic outgrowth. Here, through a broad immunogenetic study, we demonstrate that germline and somatic reduction of human leucocyte antigen (HLA) heterogeneity enhances the risk of leukemic recurrence. We show that preexistent germline-encoded low evolutionary divergence of class II HLA genotypes constitutes an independent factor associated with disease relapse and that acquisition of clonal somatic …

Healthcare Provider Perspectives On Hiv Cure Research In Ghana, Helena Lamptey, Benjamin Newcomb, Evelyn Y Bonney, James O Aboagye, Peter Puplampu, Vincent J Ganu, Gloria Ansa, Joseph Oliver-Commey, George B Kyei

2020-Current year OA Pubs

INTRODUCTION: Antiretroviral therapy (ART) has reduced mortality and improved life expectancy among HIV patients but does not provide a cure. Patients must remain on lifelong medications and deal with drug resistance and side effects. This underscores the need for HIV cure research. However, participation in HIV cure research has risks without guaranteed benefits. We determined what HIV healthcare providers know about HIV cure research trials, the risks involved, and what kind of cure interventions they are likely to recommend for their patients.

METHODS: We conducted in-depth qualitative interviews with 39 HIV care providers consisting of 12 physicians, 8 counsellors, 14 …

Starvation Sensing By Mycobacterial Rela/Spot Homologue Through Constitutive Surveillance Of Translation, Yunlong Li, Soneya Majumdar, Ryan Treen, Manjuli R Sharma, Jamie Corro, Howard B Gamper, Swati R Manjari, Jerome Prusa, Nilesh K Banavali, Christina L Stallings, Ya-Ming Hou, Rajendra K Agrawal, Anil K Ojha

2020-Current year OA Pubs

The stringent response, which leads to persistence of nutrient-starved mycobacteria, is induced by activation of the RelA/SpoT homolog (Rsh) upon entry of a deacylated-tRNA in a translating ribosome. However, the mechanism by which Rsh identifies such ribosomes in vivo remains unclear. Here, we show that conditions inducing ribosome hibernation result in loss of intracellular Rsh in a Clp protease-dependent manner. This loss is also observed in nonstarved cells using mutations in Rsh that block its interaction with the ribosome, indicating that Rsh association with the ribosome is important for Rsh stability. The cryo-EM structure of the Rsh-bound 70S ribosome in …

Architecture Of Androgen Receptor Pathways Amplifying Glucagon-Like Peptide-1 Insulinotropic Action In Male Pancreatic Β Cells, Weiwei Xu, Wandy Beatty, Et Al.

2020-Current year OA Pubs

Male mice lacking the androgen receptor (AR) in pancreatic β cells exhibit blunted glucose-stimulated insulin secretion (GSIS), leading to hyperglycemia. Testosterone activates an extranuclear AR in β cells to amplify glucagon-like peptide-1 (GLP-1) insulinotropic action. Here, we examined the architecture of AR targets that regulate GLP-1 insulinotropic action in male β cells. Testosterone cooperates with GLP-1 to enhance cAMP production at the plasma membrane and endosomes via: (1) increased mitochondrial production of CO

Resting-State Cortical Hubs In Youth Organize Into Four Categories, Damion V Demeter, Evan M Gordon, Tehila Nugiel, Annacarolina Garza, Tyler L Larguinho, Jessica A Church

2020-Current year OA Pubs

During childhood, neural systems supporting high-level cognitive processes undergo periods of rapid growth and refinement, which rely on the successful coordination of activation across the brain. Some coordination occurs via cortical hubs-brain regions that coactivate with functional networks other than their own. Adult cortical hubs map into three distinct profiles, but less is known about hub categories during development, when critical improvement in cognition occurs. We identify four distinct hub categories in a large youth sample (n = 567, ages 8.5-17.2), each exhibiting more diverse connectivity profiles than adults. Youth hubs integrating control-sensory processing split into two distinct categories (visual …

Reliability Of Mri Interpretation Of Discoid Lateral Meniscus: A Multicenter Study, Emily L. Niu, Matthew D. Milewski, Craig J. Finlayson, Zachary S. Stinson, Elaine Joughin, Jeffrey J. Nepple, Gregory A. Schmale, Prism Meniscus Research Interest Group, Jennifer Beck

2020-Current year OA Pubs

BACKGROUND: Discoid lateral meniscus (DLM) has a varied and complex morphology that can be challenging to assess and treat. Preoperative magnetic resonance imaging (MRI) is frequently used for diagnosis and surgical planning; however, it is not known whether surgeons are reliable and accurate in their interpretation of MRI findings when defining the pathomorphology of DLM.

HYPOTHESIS: Surgeons experienced in treating DLM are able to reliably interpret DLM pathology using MRI.

STUDY DESIGN: Cohort study (diagnosis); Level of evidence, 3.

METHODS: Knee MRI scans from 44 patients (45 knees) were selected from a pool of surgically treated patients with DLM. Five …

Scanning Electron Microscopy Of Human Islet Cilia, Alexander J Polino, Sanja Sviben, Isabella Melena, David W Piston, Jing W Hughes

2020-Current year OA Pubs

Human islet primary cilia are vital glucose-regulating organelles whose structure remains uncharacterized. Scanning electron microscopy (SEM) is a useful technique for studying the surface morphology of membrane projections like cilia, but conventional sample preparation does not reveal the submembrane axonemal structure, which holds key implications for ciliary function. To overcome this challenge, we combined SEM with membrane-extraction techniques to examine primary cilia in native human islets. Our data show well-preserved cilia subdomains which demonstrate both expected and unexpected ultrastructural motifs. Morphometric features were quantified when possible, including axonemal length and diameter, microtubule conformations, and chirality. We further describe a ciliary …

Peptide-Based Nanoparticles For Systemic Extrahepatic Delivery Of Therapeutic Nucleotides, Samuel A Wickline, Kirk K Hou, Hua Pan

2020-Current year OA Pubs

Peptide-based nanoparticles (PBN) for nucleotide complexation and targeting of extrahepatic diseases are gaining recognition as potent pharmaceutical vehicles for fine-tuned control of protein production (up- and/or down-regulation) and for gene delivery. Herein, we review the principles and mechanisms underpinning self-assembled formation of PBN, cellular uptake, endosomal release, and delivery to extrahepatic disease sites after systemic administration. Selected examples of PBN that have demonstrated recent proof of concept in disease models in vivo are summarized to offer the reader a comparative view of the field and the possibilities for clinical application.

Hyperhydration To Improve Kidney Outcomes In Children With Shiga Toxin-Producing E. Coli Infection: A Multinational Embedded Cluster Crossover Randomized Trial (The Hiko Stec Trial), Stephen B Freedman, David Schnadower, Myka Estes, T Charles Casper, Stuart L Goldstein, Silviu Grisaru, Andrew T Pavia, Benjamin S Wilfond, Melissa Metheney, Kadyn Kimball, Phillip I Tarr, Hyperhydration To Improve Kidney Outcomes In Children With Shiga Toxin-Producing E. Coli Infection (Hiko-Stec) Study Team

2020-Current year OA Pubs

BACKGROUND: Shiga toxin-producing E. coli (STEC) infections affect children and adults worldwide, and treatment remain solely supportive. Up to 15-20% of children infected by high-risk STEC (i.e., E. coli that produce Shiga toxin 2) develop hemolytic anemia, thrombocytopenia, and kidney failure (i.e., hemolytic uremic syndrome (HUS)), over half of whom require acute dialysis and 3% die. Although no therapy is widely accepted as being able to prevent the development of HUS and its complications, several observational studies suggest that intravascular volume expansion (hyperhydration) may prevent end organ damage. A randomized trial is needed to confirm or refute this hypothesis.

METHODS: …

Team-Focused Implementation Strategies To Improve Implementation Of Mental Health Screening And Referral In Rural Children's Advocacy Centers: Study Protocol For A Pilot Cluster Randomized Hybrid Type 2 Trial, Elizabeth A Mcguier, Gregory A Aarons, Jaely D Wright, John C Fortney, Byron J Powell, Scott D Rothenberger, Laurie R Weingart, Elizabeth Miller, David J Kolko

2020-Current year OA Pubs

BACKGROUND: Children's Advocacy Centers (CACs) use multidisciplinary teams to investigate and respond to maltreatment allegations. CACs play a critical role in connecting children with mental health needs to evidence-based mental health treatment, especially in low-resourced rural areas. Standardized mental health screening and referral protocols can improve CACs' capacity to identify children with mental health needs and encourage treatment engagement. In the team-based context of CACs, teamwork quality is likely to influence implementation processes and outcomes. Implementation strategies that target teams and apply the science of team effectiveness may enhance implementation outcomes in team-based settings.

METHODS: We will use Implementation Mapping …

Evaluation Of Pitting Corrosion By Dynamic Speckle Pattern Analysis, Omid Pedram, Ramin Jamali, Vahid Abbasian, Vahideh Farzam Rad, Arash Darafsheh, Ramin Khamedi, Esmaeil Poursaeidi, Ali-Reza Moradi

2020-Current year OA Pubs

There is an increasing interest in non-destructive and real-time high-resolution approaches for corrosion studies in metals. In this paper, we propose the dynamic speckle pattern method as a low-cost, easy-to-implement, and quasi in-situ optical technique for the quantitative evaluation of pitting corrosion. This type of corrosion occurs in a specific area of a metallic structure and causes holes formation leading to structural failure. A Custom 450 stainless steel sample, placed in 3.5 wt% NaCl solution and applied to a [Formula: see text] potential to initiate the corrosion, is used as the sample. The speckle patterns formed by the scattering of …

Tau Accumulation In Autosomal Dominant Alzheimer's Disease: A Longitudinal [18f]Flortaucipir Study, Antoinette O'Connor, Shaney Flores, Russ Hornbeck, Eric Mcdade, Brian A Gordon, Randall J Bateman, Tammie L S Benzinger, Et Al.

2020-Current year OA Pubs

Cortical tau accumulation is a key pathological event that partly defines Alzheimer's disease (AD) onset and is associated with cognitive decline and future disease progression. However, an improved understanding of the timing and pattern of early tau deposition in AD and how this may be tracked in vivo is needed. Data from 59 participants involved in two longitudinal cohort studies of autosomal dominant AD (ADAD) were used to investigate whether tau PET can detect and track presymptomatic change; seven participants were symptomatic, and 52 were asymptomatic but at a 50% risk of carrying a pathogenic mutation. All had baseline flortaucipir …

Induction Of A Torpor-Like Hypothermic And Hypometabolic State In Rodents By Ultrasound, Yaoheng Yang, Jinyun Yuan, Rachael L Field, Dezhuang Ye, Zhongtao Hu, Kevin Xu, Lu Xu, Yan Gong, Yimei Yue, Alexxai V Kravitz, Michael R Bruchas, Jianmin Cui, Jonathan R Brestoff, Hong Chen

2020-Current year OA Pubs

Torpor is an energy-conserving state in which animals dramatically decrease their metabolic rate and body temperature to survive harsh environmental conditions. Here, we report the noninvasive, precise and safe induction of a torpor-like hypothermic and hypometabolic state in rodents by remote transcranial ultrasound stimulation at the hypothalamus preoptic area (POA). We achieve a long-lasting (>24 h) torpor-like state in mice via closed-loop feedback control of ultrasound stimulation with automated detection of body temperature. Ultrasound-induced hypothermia and hypometabolism (UIH) is triggered by activation of POA neurons, involves the dorsomedial hypothalamus as a downstream brain region and subsequent inhibition of thermogenic …

Upregulation Of The Oct3/4 Network In Basal Breast Cancer Is Associated With Its Metastatic Potential And Shows Tissue Dependent Variability, Robin G Rajan, Raisa I Krutilina, Tatyana N Ignatova, Zoran S Pavicevich, Galina M Dulatova, Maria A Lane, Arindam R Chatterjee, Robert J Rooney, Mymoon Antony, Vivian R Hagerty, Nickolay V Kukekov, Khalid A Hanafy, Frank D Vrionis

2020-Current year OA Pubs

Adaptive plasticity of Breast Cancer stem cells (BCSCs) is strongly correlated with cancer progression and resistance, leading to a poor prognosis. In this study, we report the expression profile of several pioneer transcription factors of the