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Article ; Online: A Millimeter-Scale Soft Robot for Tissue Biopsy Procedures.

Van Lewen, Daniel / Janke, Taylor / Austin, Ryan / Lee, Harin / Billatos, Ehab / Russo, Sheila

Advanced intelligent systems (Weinheim an der Bergstrasse, Germany)

2023 Volume 5, Issue 5

Abstract: While interest in soft robotics as surgical tools has grown due to their inherently safe interactions with the body, their feasibility is limited in the amount of force that can be transmitted during procedures. This is especially apparent in minimally ... ...

Abstract	While interest in soft robotics as surgical tools has grown due to their inherently safe interactions with the body, their feasibility is limited in the amount of force that can be transmitted during procedures. This is especially apparent in minimally invasive procedures where millimeter-scale devices are necessary for reaching the desired surgical site, such as in interventional bronchoscopy. To leverage the benefits of soft robotics in minimally invasive surgery, a soft robot with integrated tip steering, stabilization, and needle deployment capabilities is proposed for lung tissue biopsy procedures. Design, fabrication, and modeling of the force transmission of this soft robotic platform allows for integration into a system with a diameter of 3.5 mm. Characterizations of the soft robot are performed to analyze bending angle, force transmission, and expansion during needle deployment. In-vitro experiments of both the needle deployment mechanism and fully integrated soft robot validate the proposed workflow and capabilities in a simulated surgical setting.
Language	English
Publishing date	2023-01-27
Publishing country	Germany
Document type	Journal Article
ISSN	2640-4567
ISSN (online)	2640-4567
DOI	10.1002/aisy.202200326
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Article ; Online: A taxonomy of key performance errors for emergency intubation.

Weingart, Scott D / Barnicle, Ryan N / Janke, Alexander / Bhagwan, Sabrina D / Tanzi, Matthew / McKenna, Peter J / Bracey, Alexander

The American journal of emergency medicine

2023 Volume 73, Page(s) 137–144

Abstract: Study objective: Currently the videographic review of emergency intubations is an unstructured, qualitative process. We created a taxonomy of errors that impede the optimal procedural performance of emergency intubation.: Methods: This was a ... ...

Abstract	Study objective: Currently the videographic review of emergency intubations is an unstructured, qualitative process. We created a taxonomy of errors that impede the optimal procedural performance of emergency intubation. Methods: This was a prospective, observational, study reviewing a convenience sample of deidentified laryngoscopy recordings of emergency department intubations that were qualitatively flagged before the study as demonstrating suboptimal technique. These videos were coded for the presence of 13 predetermined performance errors. Our primary outcome was the incidence of each of these specified errors during emergency intubation. Errors fell into 3 categories: errors of structure recognition during laryngoscope insertion, errors of vallecula manipulation, and errors of device delivery. Results: A total of 100 intubation attempts were reviewed. The most common error was inadequate lifting force with the blade tip in the vallecula which lowered the percent of glottic opening, occurring in 45% of the attempts. The least common performance error was the premature removal of the laryngoscope during bougie placement, occurring in only 9% of the videos. Conclusion: We developed a taxonomy of 13 performance errors of laryngoscopy. Further study is warranted to determine how to best incorporate these into emergency airway training and the airway review process.
Language	English
Publishing date	2023-08-23
Publishing country	United States
Document type	Journal Article
ZDB-ID	605890-5
ISSN	1532-8171 ; 0735-6757
ISSN (online)	1532-8171
ISSN	0735-6757
DOI	10.1016/j.ajem.2023.08.035
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Article ; Online: Trends In Treat-And-Release Emergency Care Visits With High-Intensity Billing In The US, 2006-19.

Janke, Alexander T / Gettel, Cameron / Koski-Vacirca, Ryan / Lin, Michelle P / Kocher, Keith E / Venkatesh, Arjun K

Health affairs (Project Hope)

2022 Volume 41, Issue 12, Page(s) 1772–1780

Abstract: Clinicians' billing practices for professional services in the emergency department (ED) have come under scrutiny as the proportion of expensive high-intensity visits has grown in recent decades. Clinicians respond to payers' criticism by citing the ... ...

Abstract	Clinicians' billing practices for professional services in the emergency department (ED) have come under scrutiny as the proportion of expensive high-intensity visits has grown in recent decades. Clinicians respond to payers' criticism by citing the worsening health status of undifferentiated patients alongside increasing expectations of ED care, with few data available to disentangle these phenomena from coding practices. We performed an observational study of US treat-and-release ED visits using data from the Nationwide Emergency Department Sample. In 2006, 4.8 percent of treat-and-release ED visits exhibited high-intensity billing, and this figure rose to 19.2 percent by 2019. The proportion of visits for older patients, those with more comorbidities, and those with nonspecific but potentially serious diagnoses grew. Of the observed growth in high-intensity billing, 47 percent was expected, based on changes in administrative measures for patient case-mix and care services. Any emergency care reimbursement reform must account for growing patient complexity and an evolving role for EDs in the health care system.
Language	English
Publishing date	2022-12-05
Publishing country	United States
Document type	Journal Article
ZDB-ID	632712-6
ISSN	1544-5208 ; 0278-2715
ISSN (online)	1544-5208
ISSN	0278-2715
DOI	10.1377/hlthaff.2022.00484
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Article ; Online: Estimated reimbursement impact of COVID-19 on emergency physicians.

Venkatesh, Arjun K / Janke, Alexander T / Koski-Vacirca, Ryan / Rothenberg, Craig / Parwani, Vivek / Granovsky, Mike A / Burke, Laura G / Li, Shu-Xia / Pines, Jesse M

Academic emergency medicine : official journal of the Society for Academic Emergency Medicine

2023 Volume 30, Issue 6, Page(s) 636–643

Abstract: Background: The delivery and financing of health care services were altered in unprecedented ways by COVID-19 and subsequent policy responses. We estimated reimbursement losses to emergency physicians in 2020 compared to 2019 related to shifting acute ... ...

Abstract	Background: The delivery and financing of health care services were altered in unprecedented ways by COVID-19 and subsequent policy responses. We estimated reimbursement losses to emergency physicians in 2020 compared to 2019 related to shifting acute care utilization during COVID-19. Methods: This was an observational analysis of the Clinical Emergency Department Registry (CEDR) and the Nationwide Emergency Department Sample (NEDS). Study sample included all ED visits from a sample of 214 emergency department (ED) sites in the CEDR in 2019 and 2020 as well as all ED visits in the NEDS in 2019. We identified level of service billing code for evaluation and management (E&M) services, insurance payer, and geographic location of ED visits across sites in the CEDR and linked these to fee schedules to estimate total professional reimbursement across sites. Our primary analysis was to estimate reimbursement in 2020 compared to 2019 across the CEDR sites. In our secondary analysis, we linked sites in the CEDR to those in NEDS to estimate nationwide reimbursement. Results: Total E&M reimbursement for emergency physicians in the CEDR was $1.6 billion in 2019 and $1.3 billion in 2020, reflecting a 19.7% decline year over year ($308 million loss). In our secondary analysis, we estimate nationwide losses of $6.6 billion, a -19.4% decline year over year. If emergency physicians had received maximum allowable federal relief funds via CARES Act Phases 1 to 3 (2% of 2019 revenue) this would sum to $680 million (2% of the $34 billion) or 10.3% of the estimated $6.6 billion pandemic-related losses. Conclusions: Our analyses provide an estimate of the scale of economic impacts of the COVID-19 pandemic. These findings warrant consideration for policymaker relief and future redesign of emergency care financing. Ultimately, the COVID-19 pandemic likely expanded known cracks in the financing of health care into steep fault lines.
MeSH term(s)	Humans ; United States/epidemiology ; Pandemics ; COVID-19/epidemiology ; COVID-19/therapy ; Emergency Service, Hospital ; Emergency Medical Services ; Physicians
Language	English
Publishing date	2023-03-21
Publishing country	United States
Document type	Observational Study ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1329813-6
ISSN	1553-2712 ; 1069-6563
ISSN (online)	1553-2712
ISSN	1069-6563
DOI	10.1111/acem.14700
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Article ; Online: Oncometabolite D-2-Hydroxyglutarate enhances gene silencing through inhibition of specific H3K36 histone demethylases.

Janke, Ryan / Iavarone, Anthony T / Rine, Jasper

eLife

2017 Volume 6

Abstract: Certain mutations affecting central metabolism cause accumulation of the oncometabolite D-2-hydroxyglutarate which promotes progression of certain tumors. High levels of D-2-hydroxyglutarate inhibit the TET family of DNA demethylases and Jumonji family ... ...

Abstract	Certain mutations affecting central metabolism cause accumulation of the oncometabolite D-2-hydroxyglutarate which promotes progression of certain tumors. High levels of D-2-hydroxyglutarate inhibit the TET family of DNA demethylases and Jumonji family of histone demethylases and cause epigenetic changes that lead to altered gene expression. The link between inhibition of DNA demethylation and changes in expression is strong in some cancers, but not in others. To determine whether D-2-hydroxyglutarate can affect gene expression through inhibiting histone demethylases, orthologous mutations to those known to cause accumulation of D-2-hydroxyglutarate in tumors were generated in
MeSH term(s)	Gene Silencing ; Glutarates/metabolism ; Histone Demethylases/antagonists & inhibitors ; Histones/metabolism ; Protein Processing, Post-Translational ; Saccharomyces cerevisiae/enzymology ; Saccharomyces cerevisiae/genetics ; Saccharomyces cerevisiae Proteins/genetics ; Saccharomyces cerevisiae Proteins/metabolism
Chemical Substances	Glutarates ; Histones ; Saccharomyces cerevisiae Proteins ; alpha-hydroxyglutarate (2889-31-8) ; Histone Demethylases (EC 1.14.11.-)
Language	English
Publishing date	2017-03-27
Publishing country	England
Document type	Journal Article
ZDB-ID	2687154-3
ISSN	2050-084X ; 2050-084X
ISSN (online)	2050-084X
ISSN	2050-084X
DOI	10.7554/eLife.22451
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Article ; Online: Pivotal roles of PCNA loading and unloading in heterochromatin function.

Janke, Ryan / King, Grant A / Kupiec, Martin / Rine, Jasper

Proceedings of the National Academy of Sciences of the United States of America

2018 Volume 115, Issue 9, Page(s) E2030–E2039

Abstract: ... ...

Abstract	In
MeSH term(s)	Carrier Proteins/metabolism ; DNA Replication ; Gene Deletion ; Gene Expression Regulation, Fungal ; Gene Silencing ; Genome, Fungal ; Heterochromatin/metabolism ; Histones/metabolism ; Open Reading Frames ; Plasmids/metabolism ; Proliferating Cell Nuclear Antigen/metabolism ; Ribonucleases/metabolism ; S Phase ; Saccharomyces cerevisiae/metabolism ; Saccharomyces cerevisiae Proteins/metabolism ; Transcription, Genetic
Chemical Substances	Carrier Proteins ; Elg1 protein, S cerevisiae ; Heterochromatin ; Histones ; POL30 protein, S cerevisiae ; Proliferating Cell Nuclear Antigen ; Saccharomyces cerevisiae Proteins ; Ribonucleases (EC 3.1.-) ; POP2 protein, S cerevisiae (EC 3.1.13.4)
Language	English
Publishing date	2018-02-13
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.1721573115
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Article ; Online: Oncometabolite D-2-Hydroxyglutarate enhances gene silencing through inhibition of specific H3K36 histone demethylases

Ryan Janke / Anthony T Iavarone / Jasper Rine

eLife, Vol

2017 Volume 6

Abstract	Certain mutations affecting central metabolism cause accumulation of the oncometabolite D-2-hydroxyglutarate which promotes progression of certain tumors. High levels of D-2-hydroxyglutarate inhibit the TET family of DNA demethylases and Jumonji family of histone demethylases and cause epigenetic changes that lead to altered gene expression. The link between inhibition of DNA demethylation and changes in expression is strong in some cancers, but not in others. To determine whether D-2-hydroxyglutarate can affect gene expression through inhibiting histone demethylases, orthologous mutations to those known to cause accumulation of D-2-hydroxyglutarate in tumors were generated in Saccharomyces cerevisiae, which has histone demethylases but not DNA methylases or demethylases. Accumulation of D-2-hydroxyglutarate caused inhibition of several histone demethylases. Inhibition of two of the demethylases that act specifically on histone H3K36me2,3 led to enhanced gene silencing. These observations pinpointed a new mechanism by which this oncometabolite can alter gene expression, perhaps repressing critical inhibitors of proliferation.
Keywords	Heterochromatin ; D-2-Hydroxyglutarate ; Isocitrate Dehydrogenase ; Oncometabolite ; Medicine ; R ; Science ; Q ; Biology (General) ; QH301-705.5
Subject code	570
Language	English
Publishing date	2017-03-01T00:00:00Z
Publisher	eLife Sciences Publications Ltd
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Metabolism and epigenetics.

Janke, Ryan / Dodson, Anne E / Rine, Jasper

Annual review of cell and developmental biology

2015 Volume 31, Page(s) 473–496

Abstract: Epigenetic mechanisms by which cells inherit information are, to a large extent, enabled by DNA methylation and posttranslational modifications of histone proteins. These modifications operate both to influence the structure of chromatin per se and to ... ...

Abstract	Epigenetic mechanisms by which cells inherit information are, to a large extent, enabled by DNA methylation and posttranslational modifications of histone proteins. These modifications operate both to influence the structure of chromatin per se and to serve as recognition elements for proteins with motifs dedicated to binding particular modifications. Each of these modifications results from an enzyme that consumes one of several important metabolites during catalysis. Likewise, the removal of these marks often results in the consumption of a different metabolite. Therefore, these so-called epigenetic marks have the capacity to integrate the expression state of chromatin with the metabolic state of the cell. This review focuses on the central roles played by acetyl-CoA, S-adenosyl methionine, NAD(+), and a growing list of other acyl-CoA derivatives in epigenetic processes. We also review how metabolites that accumulate as a result of oncogenic mutations are thought to subvert the epigenetic program.
MeSH term(s)	Acetyl Coenzyme A/genetics ; Animals ; Chromatin/physiology ; DNA Methylation/genetics ; DNA Methylation/physiology ; Epigenesis, Genetic/genetics ; Epigenesis, Genetic/physiology ; Humans ; NAD/genetics ; Protein Processing, Post-Translational/genetics ; Protein Processing, Post-Translational/physiology ; S-Adenosylmethionine/genetics
Chemical Substances	Chromatin ; NAD (0U46U6E8UK) ; Acetyl Coenzyme A (72-89-9) ; S-Adenosylmethionine (7LP2MPO46S)
Language	English
Publishing date	2015
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S. ; Review
ZDB-ID	1293750-2
ISSN	1530-8995 ; 1081-0706
ISSN (online)	1530-8995
ISSN	1081-0706
DOI	10.1146/annurev-cellbio-100814-125544
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Article ; Online: Transitions in Atrial Fibrillation Care: A Systematic Review.

Rush, Kathy L / Burton, Lindsay / Ollivier, Rachel / Wilson, Ryan / Loewen, Peter / Janke, Robert / Schaab, Kira / Lukey, Alexandra / Galloway, Camille

Heart, lung & circulation

2019 Volume 29, Issue 7, Page(s) 1000–1014

Abstract: Background: Patients with atrial fibrillation (AF) commonly transition between care settings and providers. These transitions are often points in the health care system where errors and clinical deterioration can occur. Anticoagulation interruption or ... ...

Abstract	Background: Patients with atrial fibrillation (AF) commonly transition between care settings and providers. These transitions are often points in the health care system where errors and clinical deterioration can occur. Anticoagulation interruption or discontinuation and sub-optimal follow-up post-emergency department (ED) discharge are considered major transitional issues. Objective: The purpose of this study was to synthesise the evidence examining the impact of transitional care interventions on patient, provider, and health care utilisation outcomes. Methods: This systematic mixed studies review examined citations from four databases Medline, CINAHL, EMBASE, and Cochrane Central Controlled Register of Trials (CENTRAL) using relevant search terms. Fourteen (14) moderate to high quality articles were selected. Results: The available evidence reporting impacts of transitional interventions on health care utilisation, provider, and patient outcomes in AF patients is mixed and of variable quality. The stronger evidence revealed improvements in patient outcomes including knowledge, quality of life, and medication adherence and increased provider anticoagulant prescriptions resulting from transitional interventions. Hospital admissions and ED visits were not significantly affected by any interventions. Conclusions: Apps and educational toolkits improved patient knowledge. Pathways increased patient quality of life and provider prescription rates. There is a need for more research to determine the AF transition interventions which maximise patient, provider and health care outcomes.
MeSH term(s)	Atrial Fibrillation/physiopathology ; Atrial Fibrillation/therapy ; Emergency Service, Hospital/statistics & numerical data ; Hospitalization/trends ; Humans ; Medication Adherence ; Quality of Life ; Self Care/methods
Language	English
Publishing date	2019-12-24
Publishing country	Australia
Document type	Journal Article ; Systematic Review
ZDB-ID	2020980-0
ISSN	1444-2892 ; 1443-9506
ISSN (online)	1444-2892
ISSN	1443-9506
DOI	10.1016/j.hlc.2019.11.022
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Article ; Online: Acute myeloid leukemias with UBTF tandem duplications are sensitive to menin inhibitors.

Barajas, Juan M / Rasouli, Milad / Umeda, Masayuki / Hiltenbrand, Ryan / Abdelhamed, Sherif / Mohnani, Rebecca / Arthur, Bright / Westover, Tamara / Thomas, Melvin E / Ashtiani, Minoo / Janke, Laura J / Xu, Beisi / Chang, Ti-Cheng / Rosikiewicz, Wojciech / Xiong, Emily / Rolle, Chandra / Low, Jonathan / Krishan, Reethu / Song, Guangchun /

Walsh, Michael P / Ma, Jing / Rubnitz, Jeffrey E / Iacobucci, Ilaria / Chen, Taosheng / Krippner-Heidenreich, Anja / Zwaan, Christian M / Heidenreich, Olaf / Klco, Jeffery M

Blood

2023 Volume 143, Issue 7, Page(s) 619–630

Abstract: Abstract: UBTF tandem duplications (UBTF-TDs) have recently emerged as a recurrent alteration in pediatric and adult acute myeloid leukemia (AML). UBTF-TD leukemias are characterized by a poor response to conventional chemotherapy and a transcriptional ... ...

Abstract	Abstract: UBTF tandem duplications (UBTF-TDs) have recently emerged as a recurrent alteration in pediatric and adult acute myeloid leukemia (AML). UBTF-TD leukemias are characterized by a poor response to conventional chemotherapy and a transcriptional signature that mirrors NUP98-rearranged and NPM1-mutant AMLs, including HOX-gene dysregulation. However, the mechanism by which UBTF-TD drives leukemogenesis remains unknown. In this study, we investigated the genomic occupancy of UBTF-TD in transformed cord blood CD34+ cells and patient-derived xenograft models. We found that UBTF-TD protein maintained genomic occupancy at ribosomal DNA loci while also occupying genomic targets commonly dysregulated in UBTF-TD myeloid malignancies, such as the HOXA/HOXB gene clusters and MEIS1. These data suggest that UBTF-TD is a gain-of-function alteration that results in mislocalization to genomic loci dysregulated in UBTF-TD leukemias. UBTF-TD also co-occupies key genomic loci with KMT2A and menin, which are known to be key partners involved in HOX-dysregulated leukemias. Using a protein degradation system, we showed that stemness, proliferation, and transcriptional signatures are dependent on sustained UBTF-TD localization to chromatin. Finally, we demonstrate that primary cells from UBTF-TD leukemias are sensitive to the menin inhibitor SNDX-5613, resulting in markedly reduced in vitro and in vivo tumor growth, myeloid differentiation, and abrogation of the UBTF-TD leukemic expression signature. These findings provide a viable therapeutic strategy for patients with this high-risk AML subtype.
MeSH term(s)	Humans ; Child ; Homeodomain Proteins/genetics ; Homeodomain Proteins/metabolism ; Leukemia, Myeloid, Acute/drug therapy ; Leukemia, Myeloid, Acute/genetics ; Leukemia, Myeloid, Acute/pathology ; Transcription Factors ; Myeloid Ecotropic Viral Integration Site 1 Protein/genetics
Chemical Substances	Homeodomain Proteins ; Transcription Factors ; Myeloid Ecotropic Viral Integration Site 1 Protein
Language	English
Publishing date	2023-10-26
Publishing country	United States
Document type	Journal Article
ZDB-ID	80069-7
ISSN	1528-0020 ; 0006-4971
ISSN (online)	1528-0020
ISSN	0006-4971
DOI	10.1182/blood.2023021359
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