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Article ; Online: Cerebral microbleeds in acute respiratory distress syndrome.

Gedansky, Aron / Huang, Merry / Hassett, Catherine E / Shoskes, Aaron / Cho, Sung-Min / Buletko, Andrew Blake / Duggal, Abhijit / George, Pravin / Uchino, Ken

Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association

2023 Volume 32, Issue 10, Page(s) 107332

Abstract: Background: Cerebral microbleeds (CMB) have been observed in patients with critical illness. We sought to examine the frequency of CMB in patients with acute respiratory distress syndrome (ARDS) and association with neurologic complications including ... ...

Abstract	Background: Cerebral microbleeds (CMB) have been observed in patients with critical illness. We sought to examine the frequency of CMB in patients with acute respiratory distress syndrome (ARDS) and association with neurologic complications including acute cerebral ischemia and seizures. Methods: A retrospective review of patients with ARDS from January 2010 to October 2018 was performed. Patients with brain MRIs with susceptibility weighted imaging or gradient echo sequences were included. We compared neurologic complications and intensive care unit outcomes between patients with and without CMB. Cerebral small vessel disease (CSVD) was defined as the presence of CMB, lacunar infarcts, enlarged perivascular spaces, and white matter hyperintensities. Results: Of 678 patients with ARDS, 61 met inclusion criteria. Median age was 54 years (IQR 42-63) and 28 were males. Of 12 (20%) with CMB, 10 had lobar CMB. Four patients had CMB in the corpus callosum, all involving the splenium. Neurologic complications were more common in those with CMB including acute cerebral ischemia (41.7% versus 10.2%, p=0.008) and seizures (33.3% versus 8.2%, p=0.021). ARDS rescue therapies were more commonly used in patients with CMB (p=0.005). There was no difference in hospital mortality (41.7% versus 34.7%, p=0.652). Patients with CMB did not have a higher CSVD score than those without CMB when accounting for the presence of CMB (median=1 versus 0, p=0.891). Conclusion: CMB were present in twenty percent of patients with ARDS who had MRI and were more commonly seen in patients requiring ARDS rescue therapies.
MeSH term(s)	Male ; Humans ; Middle Aged ; Female ; Respiratory Distress Syndrome/diagnostic imaging ; Respiratory Distress Syndrome/etiology ; Respiratory Distress Syndrome/therapy ; Brain Ischemia/complications ; Brain Ischemia/diagnostic imaging ; Brain Ischemia/therapy ; Cerebral Small Vessel Diseases/complications ; Cerebral Small Vessel Diseases/diagnostic imaging ; Seizures/diagnostic imaging ; Seizures/etiology ; Cerebral Hemorrhage/complications ; Cerebral Hemorrhage/diagnostic imaging
Language	English
Publishing date	2023-08-31
Publishing country	United States
Document type	Journal Article
ZDB-ID	1131675-5
ISSN	1532-8511 ; 1052-3057
ISSN (online)	1532-8511
ISSN	1052-3057
DOI	10.1016/j.jstrokecerebrovasdis.2023.107332
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Article ; Online: Hypernatremia-induced vasopressin secretion is not altered in TRPV1-/- rats.

Tucker, Andrew Blake / Stocker, Sean D

American journal of physiology. Regulatory, integrative and comparative physiology

2016 Volume 311, Issue 3, Page(s) R451–6

Abstract: Changes in osmolality or extracellular NaCl concentrations are detected by specialized neurons in the hypothalamus to increase vasopressin (VP) and stimulate thirst. Recent in vitro evidence suggests this process is mediated by an NH2-terminal variant of ...

Abstract	Changes in osmolality or extracellular NaCl concentrations are detected by specialized neurons in the hypothalamus to increase vasopressin (VP) and stimulate thirst. Recent in vitro evidence suggests this process is mediated by an NH2-terminal variant of the transient receptor potential vanilloid type 1 (TRPV1) channel expressed by osmosensitive neurons of the lamina terminalis and vasopressinergic neurons of the supraoptic nucleus. The present study tested this hypothesis in vivo by analysis of plasma VP levels during acute hypernatremia in awake control and TRPV1(-/-) rats. TRPV1(-/-) rats were produced by a Zinc-finger-nuclease 2-bp deletion in exon 13. Intravenous injection of the TRPV1 agonist capsaicin produced hypotension and bradycardia in control rats, but this response was absent in TRPV1(-/-) rats. Infusion of 2 M NaCl (1 ml/h iv) increased plasma osmolality, electrolytes, and VP levels in both control and TRPV1(-/-) rats. However, plasma VP levels did not differ between strains at any time. Furthermore, a linear regression between plasma VP versus osmolality revealed a significant correlation in both control and TRPV1(-/-) rats, but the slope of the regression lines was not attenuated in TRPV1(-/-) versus control rats. Hypotension produced by intravenous injection of minoxidil decreased blood pressure and increased plasma VP levels similarly in both groups. Finally, both treatments stimulated thirst; however, cumulative water intakes in response to hypernatremia or hypotension were not different between control and TRPV1(-/-) rats. These findings suggest that TRPV1 channels are not necessary for VP secretion and thirst stimulated by hypernatremia.
MeSH term(s)	Animals ; Drinking ; Hypernatremia/metabolism ; Male ; Mice, Knockout ; Osmolar Concentration ; Rats ; Rats, Sprague-Dawley ; TRPV Cation Channels/genetics ; TRPV Cation Channels/metabolism ; Thirst ; Vasopressins/blood ; Vasopressins/metabolism ; Water-Electrolyte Balance
Chemical Substances	TRPV Cation Channels ; Trpv1 protein, rat ; Vasopressins (11000-17-2)
Language	English
Publishing date	2016-06-22
Publishing country	United States
Document type	Journal Article
ZDB-ID	603839-6
ISSN	1522-1490 ; 0363-6119
ISSN (online)	1522-1490
ISSN	0363-6119
DOI	10.1152/ajpregu.00483.2015
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Article ; Online: Cannabis Use and Stroke: Does a Risk Exist?

Swetlik, Carol / Migdady, Ibrahim / Hasan, Leen Z / Buletko, Andrew Blake / Price, Carrie / Cho, Sung-Min

Journal of addiction medicine

2021 Volume 16, Issue 2, Page(s) 208–215

Abstract: Aims: Cannabis use has been reported as a risk factor for stroke. We systematically review the prevalence and outcomes of stroke in people with cannabis use.: Methods: We searched MEDLINE and 6 other databases from inception to January 2020 for ... ...

Abstract	Aims: Cannabis use has been reported as a risk factor for stroke. We systematically review the prevalence and outcomes of stroke in people with cannabis use. Methods: We searched MEDLINE and 6 other databases from inception to January 2020 for studies on the relationship between cannabis use and stroke. We followed the preferred reporting items for systematic reviews and meta-analyses (PRISMA) recommendations. Two independent reviewers extracted the data. Study quality was assessed by the Newcastle-Ottawa Scale for cohort and case-control studies. Results: Seventeen studies involving 3,185,560 people with cannabis use were included. Descriptive statistics demonstrated 18,676 (median 1.1%, interquartile range [IQR] 0.3%-1.3%) experienced stroke compared with 0.8% of those without use (Odds Ratio 1.17, 95% CI 1.10-1.25). Among people with cannabis use, median age was 26.2 years (IQR 25.2-34.3 years) and mostly male (median 57.8%). Of stroke subtypes, ischemic stroke was most prevalent (median 1.2%, IQR 0.4%-1.9%), followed by undefined stroke subtype (median 1.2%, IQR 1.1%-1.2%) and hemorrhagic stroke (median 0.3%, IQR 0.1%-0.6%). The majority of people with cannabis use who experienced stroke survived (median: 85.1%, IQR 83%-87.5%) and 64.0% of people experienced a good neurologic outcome, defined as modified Rankin Scale of 0 to 3. Few studies included outcomes of vasospasm or seizure. Conclusions: In people with cannabis use, the prevalence of ischemic stroke and hemorrhagic stroke was 1.2% and 0.3%, respectively, higher than the prevalence of people without use (0.8% and 0.2%). There is insufficient information on timing, exposure, duration, and dose-responsive relationship.
MeSH term(s)	Adult ; Cannabis ; Case-Control Studies ; Cohort Studies ; Female ; Humans ; Male ; Risk Factors ; Stroke/epidemiology
Language	English
Publishing date	2021-05-17
Publishing country	Netherlands
Document type	Journal Article ; Systematic Review
ISSN	1935-3227
ISSN (online)	1935-3227
DOI	10.1097/ADM.0000000000000870
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Article ; Online: The efficacy of Euler diagrams and linear diagrams for visualizing set cardinality using proportions and numbers.

Gem Stapleton / Peter Chapman / Peter Rodgers / Anestis Touloumis / Andrew Blake / Aidan Delaney

PLoS ONE, Vol 14, Iss 3, p e

2019 Volume 0211234

Abstract: This paper presents the first empirical investigation that compares Euler and linear diagrams when they are used to represent set cardinality. A common approach is to use area-proportional Euler diagrams but linear diagrams can exploit length- ... ...

Abstract	This paper presents the first empirical investigation that compares Euler and linear diagrams when they are used to represent set cardinality. A common approach is to use area-proportional Euler diagrams but linear diagrams can exploit length-proportional straight-lines for the same purpose. Another common approach is to use numerical annotations. We first conducted two empirical studies, one on Euler diagrams and the other on linear diagrams. These suggest that area-proportional Euler diagrams with numerical annotations and length-proportional linear diagrams without numerical annotations support significantly better task performance. We then conducted a third study to investigate which of these two notations should be used in practice. This suggests that area-proportional Euler diagrams with numerical annotations most effectively supports task performance and so should be used to visualize set cardinalities. However, these studies focused on data that can be visualized reasonably accurately using circles and the results should be taken as valid within that context. Future work needs to determine whether the results generalize both to when circles cannot be used and for other ways of encoding cardinality information.
Keywords	Medicine ; R ; Science ; Q
Subject code	514
Language	English
Publishing date	2019-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
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Article ; Online: Neurologic Injuries in Noncontact Sports.

Marquardt, Robert J / Buletko, Andrew Blake / Russman, Andrew Neil

Neurologic clinics

2017 Volume 35, Issue 3, Page(s) 573–587

Abstract: Noncontact sports are associated with a variety of neurologic injuries. Concussion, vascular injury (arterial dissection), and spinal cord trauma may be less common in noncontact sports, but require special attention from the sports neurologist. Complex ... ...

Abstract	Noncontact sports are associated with a variety of neurologic injuries. Concussion, vascular injury (arterial dissection), and spinal cord trauma may be less common in noncontact sports, but require special attention from the sports neurologist. Complex regional pain disorders, muscle injury from repetitive use, dystonia, heat exposure, and vascular disorders (patent foramen ovale), occur with similar frequency in noncontact and contact sports. Management of athletes with these conditions requires an understanding of the neurologic consequences of these disorders, the risk of injury with return to play, and consideration for the benefits of exercise in health restoration and disease prevention.
MeSH term(s)	Athletes ; Athletic Injuries/epidemiology ; Athletic Injuries/etiology ; Brain Concussion/epidemiology ; Brain Concussion/etiology ; Humans ; Sports
Language	English
Publishing date	2017-08
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	1013148-6
ISSN	1557-9875 ; 0733-8619
ISSN (online)	1557-9875
ISSN	0733-8619
DOI	10.1016/j.ncl.2017.03.004
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Article ; Online: Ultra-Low DNA Input into Whole Genome Methylation Assays and Detection of Oncogenic Methylation and Copy Number Variants in Circulating Tumour DNA

Celina Whalley / Karl Payne / Enric Domingo / Andrew Blake / Susan Richman / Jill Brooks / Nikolaos Batis / Rachel Spruce / S-CORT Consortium / Hisham Mehanna / Paul Nankivell / Andrew D. Beggs

Epigenomes, Vol 5, Iss 6, p

2021 Volume 6

Abstract: Background: Abnormal CpG methylation in cancer is ubiquitous and generally detected in tumour specimens using a variety of techniques at a resolution encompassing single CpG loci to genome wide coverage. Analysis of samples with very low DNA inputs, such ...

Abstract	Background: Abnormal CpG methylation in cancer is ubiquitous and generally detected in tumour specimens using a variety of techniques at a resolution encompassing single CpG loci to genome wide coverage. Analysis of samples with very low DNA inputs, such as formalin fixed (FFPE) biopsy specimens from clinical trials or circulating tumour DNA is challenging at the genome-wide level because of lack of available input. We present the results of low input experiments into the Illumina Infinium HD methylation assay on FFPE specimens and ctDNA samples. Methods: For all experiments, the Infinium HD assay for methylation was used. In total, forty-eight FFPE specimens were used at varying concentrations (lowest input 50 ng); eighteen blood derived specimens (lowest input 10 ng) and six matched ctDNA input (lowest input 10 ng)/fresh tumour specimens (lowest input 250 ng) were processed. Downstream analysis was performed in R/Bioconductor for quality control metrics and differential methylation analysis as well as copy number calls. Results: Correlation coefficients for CpG methylation were high at the probe level averaged R2 = 0.99 for blood derived samples and R2 > 0.96 for the FFPE samples. When matched ctDNA/fresh tumour samples were compared, R2 > 0.91 between the two. Results of differential methylation analysis did not vary significantly by DNA input in either the blood or FFPE groups. There were differences seen in the ctDNA group as compared to their paired tumour sample, possibly because of enrichment for tumour material without contaminating normal. Copy number variants observed in the tumour were generally also seen in the paired ctDNA sample with good concordance via DQ plot. Conclusions: The Illumina Infinium HD methylation assay can robustly detect methylation across a range of sample types, including ctDNA, down to an input of 10 ng. It can also reliably detect oncogenic methylation changes and copy number variants in ctDNA. These findings demonstrate that these samples can now be accessed by ...
Keywords	circulating tumour DNA ; formalin fixed paraffin embedded ; epigenome ; Medicine ; R ; Biology (General) ; QH301-705.5
Subject code	310
Language	English
Publishing date	2021-02-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
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Article ; Online: IV tPA given in the golden hour for emergent large vessel occlusion stroke improves recanalization rates and clinical outcomes.

Di Lorenzo, Rodica / Saqqur, Maher / Buletko, Andrew Blake / Handshoe, Lacy Sam / Mulpur, Bhageeradh / Hardman, Julian / Donohue, Megan / Wisco, Dolora / Uchino, Ken / Hussain, M Shazam

Journal of the neurological sciences

2021 Volume 428, Page(s) 117580

Abstract: Background: Early thrombolysis for acute ischemic stroke (AIS) due to emergent large vessel occlusion (ELVO) is associated with better clinical outcome. This is thought to be due to greater tissue salvage with earlier recanalization. We explored whether ...

Abstract	Background: Early thrombolysis for acute ischemic stroke (AIS) due to emergent large vessel occlusion (ELVO) is associated with better clinical outcome. This is thought to be due to greater tissue salvage with earlier recanalization. We explored whether ultra-early administration of intravenous tissue plasminogen activator (IV tPA) within 60 min (Golden Hour) of symptom onset for AIS due to ELVO is associated with a higher rate of recanalization. Methods: We performed a retrospective analysis of recanalization rates and clinical outcomes in patients with AIS due to ELVO treated with IV tPA, comparing patients who received IV tPA within 60 min of stroke symptom onset with those treated beyond 60 min. Results: Between January 2013 and December 2016, 158 patients with AIS due to ELVO were treated with IV tPA. Of these, 25 (15.8%) patients received IV tPA within 60 min of stroke symptom onset, while the remaining 133 (84.2%) patients received IV tPA beyond 60 min. The ultra-early treatment group was found to have a higher rate of complete recanalization (28.0% vs 6.8%, 95% CI 1.78-16.63), better chance of early neurological improvement (76.0% vs 50.4%, 95% CI 1.16-8.65), favorable clinical outcomes (mRS ≤ 2 or return to premorbid mRS) (65.0% vs 36.8%, 95% CI 1.42-9.34), and lower mortality (5% vs 31.1%, 95% CI 0.01-0.74) at 90-day follow-up compared to the later treatment group. Conclusion: Our data suggest that ultra-early administration of IV tPA significantly improves recanalization rates and clinical outcomes in patients with AIS due to ELVO.
MeSH term(s)	Administration, Intravenous ; Brain Ischemia/complications ; Brain Ischemia/drug therapy ; Fibrinolytic Agents/therapeutic use ; Humans ; Retrospective Studies ; Stroke/drug therapy ; Tissue Plasminogen Activator/therapeutic use ; Treatment Outcome
Chemical Substances	Fibrinolytic Agents ; Tissue Plasminogen Activator (EC 3.4.21.68)
Language	English
Publishing date	2021-07-15
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	80160-4
ISSN	1878-5883 ; 0022-510X ; 0374-8642
ISSN (online)	1878-5883
ISSN	0022-510X ; 0374-8642
DOI	10.1016/j.jns.2021.117580
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Article ; Online: Ferroptosis as a novel form of regulated cell death

Feifei Pu / Fengxia Chen / Zhicai Zhang / Deyao Shi / Binlong Zhong / Xiao Lv / Andrew Blake Tucker / Jiaming Fan / Alexander J. Li / Kevin Qin / Daniel Hu / Connie Chen / Hao Wang / Fang He / Na Ni / Linjuan Huang / Qing Liu / William Wagstaff / Hue H. Luu /

Rex C. Haydon / Le Shen / Tong-Chuan He / Jianxiang Liu / Zengwu Shao

Genes and Diseases, Vol 9, Iss 2, Pp 347-

Implications in the pathogenesis, oncometabolism and treatment of human cancer

2022 Volume 357

Abstract: The treatment of cancer mainly involves surgical excision supplemented by radiotherapy and chemotherapy. Chemotherapy drugs act by interfering with tumor growth and inducing the death of cancer cells. Anti-tumor drugs were developed to induce apoptosis, ... ...

Abstract	The treatment of cancer mainly involves surgical excision supplemented by radiotherapy and chemotherapy. Chemotherapy drugs act by interfering with tumor growth and inducing the death of cancer cells. Anti-tumor drugs were developed to induce apoptosis, but some patient’s show apoptosis escape and chemotherapy resistance. Therefore, other forms of cell death that can overcome the resistance of tumor cells are important in the context of cancer treatment. Ferroptosis is a newly discovered iron-dependent, non-apoptotic type of cell death that is highly negatively correlated with cancer development. Ferroptosis is mainly caused by the abnormal increase in iron-dependent lipid reactive oxygen species and the imbalance of redox homeostasis. This review summarizes the progression and regulatory mechanism of ferroptosis in cancer and discusses its possible clinical applications in cancer diagnosis and treatment.
Keywords	Cancer ; Cancer therapy ; Clinical application ; Ferroptosis ; Lipid peroxidation ; Pathogenesis ; Medicine (General) ; R5-920 ; Genetics ; QH426-470
Subject code	610
Language	English
Publishing date	2022-03-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
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Article: Identification of a prognostic signature based on copy number variations (CNVs) and CNV-modulated gene expression in acute myeloid leukemia.

Niu, Changchun / Wu, Di / Li, Alexander J / Qin, Kevin H / Hu, Daniel A / Wang, Eric J / Tucker, Andrew Blake / He, Fang / Huang, Linjuan / Wang, Hao / Liu, Qing / Ni, Na / Shi, Deyao / Zhao, Xia / Wan, Yafang / Li, Tian / He, Tongchuan / Liao, Pu

American journal of translational research

2021 Volume 13, Issue 12, Page(s) 13683–13696

Abstract: Objectives: Acute myeloid leukemia (AML) is caused by multiple genetic alterations in hematopoietic progenitors, and molecular genetic analyses have provided useful information for AML diagnosis and prognostication. This study aimed to integratively ... ...

Abstract	Objectives: Acute myeloid leukemia (AML) is caused by multiple genetic alterations in hematopoietic progenitors, and molecular genetic analyses have provided useful information for AML diagnosis and prognostication. This study aimed to integratively understand the prognostic value of specific copy number variation (CNV) patterns and CNV-modulated gene expression in AML. Methods: We conducted integrative CNV profiling and gene expression analysis using data from the Therapeutically Applicable Research To Generate Effective Treatments (TARGET) and The Cancer Genome Atlas (TCGA) AML cohorts. CNV-related genes associated with survival were identified using the TARGET AML cohort and validated using the TCGA AML cohort. Genes whose CNV-modulated expression was associated with survival were also identified using the TARGET AML cohort and validated using the TCGA AML cohort, and patient bone marrow samples were then used to further validate the effects of CNV-modulated gene expression on survival. CNV and mRNA survival analyses were conducted using proportional hazards regression models (Cox regression) and the "survminer" and "survival" packages of the R Project for Statistical Computing. Genes belonging to the Kyoto Encyclopedia of Genes and Genomes (KEGG) cancer panel were extracted from KEGG cancer-related pathways. Results: One hundred two CNV-related genes (located at 7q31-34, 16q24) associated with patient survival were identified using the TARGET cohort and validated with the TCGA AML cohort. Among these 102 validated genes, three miRNA genes ( Conclusions: Overall, this study identified 102 CNV-related genes associated with patient survival and identified five genes whose expression was modulated by CNVs and associated with patient survival. Our findings are crucial for the development of new modes of prognosis evaluation and targeted therapy for AML.
Language	English
Publishing date	2021-12-15
Publishing country	United States
Document type	Journal Article
ZDB-ID	2471058-1
ISSN	1943-8141
ISSN	1943-8141
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Article ; Online: Argonaute (AGO) proteins play an essential role in mediating BMP9-induced osteogenic signaling in mesenchymal stem cells (MSCs)

Yukun Mao / Na Ni / Linjuan Huang / Jiaming Fan / Hao Wang / Fang He / Qing Liu / Deyao Shi / Kai Fu / Mikhail Pakvasa / William Wagstaff / Andrew Blake Tucker / Connie Chen / Russell R. Reid / Rex C. Haydon / Sherwin H. Ho / Michael J. Lee / Tong-Chuan He / Jian Yang /

Le Shen / Lin Cai / Hue H. Luu

Genes and Diseases, Vol 8, Iss 6, Pp 918-

2021 Volume 930

Abstract: As multipotent progenitor cells, mesenchymal stem cells (MSCs) can renew themselves and give rise to multiple lineages including osteoblastic, chondrogenic and adipogenic lineages. It's previously shown that BMP9 is the most potent BMP and induces ... ...

Abstract	As multipotent progenitor cells, mesenchymal stem cells (MSCs) can renew themselves and give rise to multiple lineages including osteoblastic, chondrogenic and adipogenic lineages. It's previously shown that BMP9 is the most potent BMP and induces osteogenic and adipogenic differentiation of MSCs. However, the molecular mechanism through which BMP9 regulates MSC differentiation remains poorly understood. Emerging evidence indicates that noncoding RNAs, especially microRNAs, may play important roles in regulating MSC differentiation and bone formation. As highly conserved RNA binding proteins, Argonaute (AGO) proteins are essential components of the multi-protein RNA-induced silencing complexes (RISCs), which are critical for small RNA biogenesis. Here, we investigate possible roles of AGO proteins in BMP9-induced lineage-specific differentiation of MSCs. We first found that BMP9 up-regulated the expression of Ago1, Ago2 and Ago3 in MSCs. By engineering multiplex siRNA vectors that express multiple siRNAs targeting individual Ago genes or all four Ago genes, we found that silencing individual Ago expression led to a decrease in BMP9-induced early osteogenic marker alkaline phosphatase (ALP) activity in MSCs. Furthermore, we demonstrated that simultaneously silencing all four Ago genes significantly diminished BMP9-induced osteogenic and adipogenic differentiation of MSCs and matrix mineralization, and ectopic bone formation. Collectively, our findings strongly indicate that AGO proteins and associated small RNA biogenesis pathway play an essential role in mediating BMP9-induced osteogenic differentiation of MSCs.
Keywords	Argonaute (AGO) proteins ; BMP9 ; Bone formation ; Lineage-specific differentiation ; Mesenchymal stem cells ; miRNA biogenesis ; Medicine (General) ; R5-920 ; Genetics ; QH426-470
Subject code	571
Language	English
Publishing date	2021-11-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
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