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Article ; Online: Urinary exosomal expression of activator of G protein signaling 3 in polycystic kidney disease.

Keri, Krishna C / Regner, Kevin R / Dall, Aaron T / Park, Frank

2018 Volume 11, Issue 1, Page(s) 359

Abstract: Objective: PKD is a genetic disease that is characterized by abnormally proliferative epithelial cells in the kidney and liver. Urinary exosomes have been previously examined as a source of unique proteins that may be used to diagnose and monitor the ... ...

Abstract	Objective: PKD is a genetic disease that is characterized by abnormally proliferative epithelial cells in the kidney and liver. Urinary exosomes have been previously examined as a source of unique proteins that may be used to diagnose and monitor the progression of PKD. Previous studies by our group have shown that AGS3, which is a receptor-independent regulator G-proteins, was markedly upregulated in RTECs during kidney injury including PKD. In this study, our goal was to determine whether AGS3 could be measured in exosomes using animals and humans with PKD. Results: In our study, urinary exosomes were isolated from PCK rats and the control Sprague-Dawley (SD) rats. AGS3 expression was significantly increased (P < 0.05) in PKD versus SD rats at 16 weeks of age. This increase was detectable in a time-dependent manner from 8 weeks of age and peaked at ~ 16-20 weeks (length of study). Similarly, in exosomes from human urine samples with PKD, AGS3 expression was significantly increased (P < 0.05) compared to healthy human controls where AGS3 was largely undetectable. In conclusion, the detection of AGS3 in urinary exosomes may be a novel biomarker for PKD, and provide new insight into the biology of tubular epithelial cell function during cystic disease progression.
MeSH term(s)	Adult ; Aged ; Animals ; Biomarkers/urine ; Carrier Proteins/urine ; Disease Models, Animal ; Exosomes/metabolism ; Female ; Guanine Nucleotide Dissociation Inhibitors/urine ; Humans ; Male ; Middle Aged ; Polycystic Kidney Diseases/diagnosis ; Polycystic Kidney Diseases/urine ; Rats ; Rats, Sprague-Dawley ; Young Adult
Chemical Substances	Biomarkers ; Carrier Proteins ; GPSM1 protein, human ; Gpsm1 protein, rat ; Guanine Nucleotide Dissociation Inhibitors
Language	English
Publishing date	2018-06-07
Publishing country	England
Document type	Journal Article
ZDB-ID	2413336-X
ISSN	1756-0500 ; 1756-0500
ISSN (online)	1756-0500
ISSN	1756-0500
DOI	10.1186/s13104-018-3467-6
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Article ; Online: The significance of margins in pediatric Non-Rhabdomyosarcoma soft tissue sarcomas: Consensus on surgical margin definition harmonization from the INternational Soft Tissue SaRcoma ConsorTium (INSTRuCT).

Sparber-Sauer, Monika / Ferrari, Andrea / Spunt, Sheri L / Vokuhl, Christian / Casey, Dana / Lautz, Timothy B / Meyer, William H / Walterhouse, David O / Pajtler, Kristian W / Alaggio, Rita / Schmidt, Andreas / Safwat, Akmal / Timmermann, Beate / Dall'Igna, Patrizia / Chen, Sonja / Weiss, Aaron R / Orbach, Daniel

Cancer medicine

2023 Volume 12, Issue 10, Page(s) 11719–11730

Abstract: Background: Margin status following surgery in children, adolescents, and young adults with soft tissue sarcomas is controversial and has been defined differently by various specialties, with definitions changing over time and by cooperative group. The ... ...

Abstract	Background: Margin status following surgery in children, adolescents, and young adults with soft tissue sarcomas is controversial and has been defined differently by various specialties, with definitions changing over time and by cooperative group. The International Soft Tissue Sarcoma Consortium (INSTRuCT) is a collaboration of the Children's Oncology Group (COG) Soft Tissue Sarcoma Committee, European pediatric Soft Tissue sarcoma Study Group (EpSSG), and the European Cooperative Weichteilsarkom Studiengruppe (CWS) devoted to improving patient outcomes by pooling and mining cooperative group clinical trial data. Methods: The INSTRuCT non-rhabdomyosarcoma soft tissue sarcoma (NRSTS) working group aimed to develop international harmonized recommendations regarding surgical margin assessment and definitions in children and adolescents with soft tissue tumors. Results and conclusion: This review addresses accepted principles and areas of controversy, including the perspectives of surgeons, pathologists, radiation oncologists, and pediatric oncologists, to develop a framework for building common guidelines for future research.
MeSH term(s)	Child ; Adolescent ; Young Adult ; Humans ; Margins of Excision ; Consensus ; Sarcoma/surgery ; Sarcoma/pathology ; Soft Tissue Neoplasms/surgery
Language	English
Publishing date	2023-02-06
Publishing country	United States
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	2659751-2
ISSN	2045-7634 ; 2045-7634
ISSN (online)	2045-7634
ISSN	2045-7634
DOI	10.1002/cam4.5671
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Article: Hypergraph coloring complexes.

Breuer, Felix / Dall, Aaron / Kubitzke, Martina

Discrete mathematics

2013 Volume 312, Issue 16, Page(s) 2407–2420

Abstract: The aim of this paper is to generalize the notion of the coloring complex of a graph to hypergraphs. We present three different interpretations of those complexes-a purely combinatorial one and two geometric ones. It is shown, that most of the properties, ...

Abstract	The aim of this paper is to generalize the notion of the coloring complex of a graph to hypergraphs. We present three different interpretations of those complexes-a purely combinatorial one and two geometric ones. It is shown, that most of the properties, which are known to be true for coloring complexes of graphs, break down in this more general setting, e.g., Cohen-Macaulayness and partitionability. Nevertheless, we are able to provide bounds for the [Formula: see text]- and [Formula: see text]-vectors of those complexes which yield new bounds on chromatic polynomials of hypergraphs. Moreover, though it is proven that the coloring complex of a hypergraph has a wedge decomposition, we provide an example showing that in general this decomposition is not homotopy equivalent to a wedge of spheres. In addition, we can completely characterize those hypergraphs whose coloring complex is connected.
Language	English
Publishing date	2013-04-23
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	1468087-7
ISSN	0012-365X
ISSN	0012-365X
DOI	10.1016/j.disc.2012.04.027
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Article ; Online: Urinary exosomal expression of activator of G protein signaling 3 in polycystic kidney disease

Krishna C. Keri / Kevin R. Regner / Aaron T. Dall / Frank Park

BMC Research Notes, Vol 11, Iss 1, Pp 1-

2018 Volume 6

Abstract: Abstract Objective PKD is a genetic disease that is characterized by abnormally proliferative epithelial cells in the kidney and liver. Urinary exosomes have been previously examined as a source of unique proteins that may be used to diagnose and monitor ...

Abstract	Abstract Objective PKD is a genetic disease that is characterized by abnormally proliferative epithelial cells in the kidney and liver. Urinary exosomes have been previously examined as a source of unique proteins that may be used to diagnose and monitor the progression of PKD. Previous studies by our group have shown that AGS3, which is a receptor-independent regulator G-proteins, was markedly upregulated in RTECs during kidney injury including PKD. In this study, our goal was to determine whether AGS3 could be measured in exosomes using animals and humans with PKD. Results In our study, urinary exosomes were isolated from PCK rats and the control Sprague–Dawley (SD) rats. AGS3 expression was significantly increased (P < 0.05) in PKD versus SD rats at 16 weeks of age. This increase was detectable in a time-dependent manner from 8 weeks of age and peaked at ~ 16–20 weeks (length of study). Similarly, in exosomes from human urine samples with PKD, AGS3 expression was significantly increased (P < 0.05) compared to healthy human controls where AGS3 was largely undetectable. In conclusion, the detection of AGS3 in urinary exosomes may be a novel biomarker for PKD, and provide new insight into the biology of tubular epithelial cell function during cystic disease progression.
Keywords	Polycystic kidney disease ; Urine exosomes ; Kidney ; Western blot analysis ; Biomarker ; Medicine ; R ; Biology (General) ; QH301-705.5 ; Science (General) ; Q1-390
Subject code	610
Language	English
Publishing date	2018-06-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
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Article ; Online: BK virus nephritis after renal transplantation.

Dall, Aaron / Hariharan, Sundaram

Clinical journal of the American Society of Nephrology : CJASN

2008 Volume 3 Suppl 2, Page(s) S68–75

Abstract: BK virus nephritis is an increasing problem and is posing a threat to improving renal transplant graft survival. The pathogenesis of this condition remains to be investigated. Higher prevalence of BK virus infection in recent years has been correlated ... ...

Abstract	BK virus nephritis is an increasing problem and is posing a threat to improving renal transplant graft survival. The pathogenesis of this condition remains to be investigated. Higher prevalence of BK virus infection in recent years has been correlated with declining acute rejection rates and the use of potent immunosuppressive agents. Patients with this infection usually have asymptomatic viremia and/or nephritis with or without worsening of renal function. The diagnosis of this disease is based on detecting the virus or its effects in urine, blood, and renal tissue. In the past, approximately 30 to 60% of patients with BK virus nephritis developed graft failure. In recent years, the combination of early detection, prompt diagnosis, and therapies including preventive measures have resulted in better outcomes.
MeSH term(s)	BK Virus ; Humans ; Kidney Transplantation ; Nephritis/epidemiology ; Nephritis/virology ; Polyomavirus Infections/diagnosis ; Polyomavirus Infections/epidemiology ; Polyomavirus Infections/therapy ; Postoperative Complications/diagnosis ; Postoperative Complications/epidemiology ; Postoperative Complications/virology ; Risk Factors ; Tumor Virus Infections/diagnosis ; Tumor Virus Infections/epidemiology ; Tumor Virus Infections/therapy
Language	English
Publishing date	2008-02-28
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2226665-3
ISSN	1555-905X ; 1555-9041
ISSN (online)	1555-905X
ISSN	1555-9041
DOI	10.2215/CJN.02770707
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Article ; Online: XFEL Microcrystallography of Self-Assembling Silver

Aleksich, Mariya / Paley, Daniel W / Schriber, Elyse A / Linthicum, Will / Oklejas, Vanessa / Mittan-Moreau, David W / Kelly, Ryan P / Kotei, Patience A / Ghodsi, Anita / Sierra, Raymond G / Aquila, Andrew / Poitevin, Frédéric / Blaschke, Johannes P / Vakili, Mohammad / Milne, Christopher J / Dall'Antonia, Fabio / Khakhulin, Dmitry / Ardana-Lamas, Fernando / Lima, Frederico /

Journal of the American Chemical Society

2023 Volume 145, Issue 31, Page(s) 17042–17055

Abstract: New synthetic hybrid materials and their increasing complexity have placed growing demands on crystal growth for single-crystal X-ray diffraction analysis. Unfortunately, not all chemical systems are conducive to the isolation of single crystals for ... ...

Abstract	New synthetic hybrid materials and their increasing complexity have placed growing demands on crystal growth for single-crystal X-ray diffraction analysis. Unfortunately, not all chemical systems are conducive to the isolation of single crystals for traditional characterization. Here, small-molecule serial femtosecond crystallography (smSFX) at atomic resolution (0.833 Å) is employed to characterize microcrystalline silver
Language	English
Publishing date	2023-07-31
Publishing country	United States
Document type	Journal Article
ZDB-ID	3155-0
ISSN	1520-5126 ; 0002-7863
ISSN (online)	1520-5126
ISSN	0002-7863
DOI	10.1021/jacs.3c02183
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Article ; Online: Detrimental Immediate- and Medium-Term Clinical Effects of Right Ventricular Pacing in Patients With Myocardial Fibrosis.

Saunderson, Christopher E D / Paton, Maria F / Brown, Louise A E / Gierula, John / Chew, Pei G / Das, Arka / Sengupta, Anshuman / Craven, Thomas P / Chowdhary, Amrit / Koshy, Aaron / White, Hazel / Levelt, Eylem / Dall'Armellina, Erica / Garg, Pankaj / Witte, Klaus K / Greenwood, John P / Plein, Sven / Swoboda, Peter P

Circulation. Cardiovascular imaging

2021 Volume 14, Issue 5, Page(s) e012256

Abstract: Background: Long-term right ventricular (RV) pacing leads to heart failure or a decline in left ventricular (LV) function in up to a fifth of patients. We aimed to establish whether patients with focal fibrosis detected on late gadolinium enhancement ... ...

Abstract	Background: Long-term right ventricular (RV) pacing leads to heart failure or a decline in left ventricular (LV) function in up to a fifth of patients. We aimed to establish whether patients with focal fibrosis detected on late gadolinium enhancement cardiovascular magnetic resonance (CMR) have deterioration in LV function after RV pacing. Methods: We recruited 84 patients with LV ejection fraction ≥40% into 2 observational CMR studies. Patients (n=34) with a dual-chamber device and preserved atrioventricular conduction underwent CMR in 2 asynchronous pacing modes (atrial asynchronous and dual-chamber asynchronous) to compare intrinsic atrioventricular conduction with forced RV pacing. Patients (n=50) with high-grade atrioventricular block underwent CMR before and 6 months after pacemaker implantation to investigate the medium-term effects of RV pacing. Results: The key findings were (1) initiation of RV pacing in patients with fibrosis, compared with those without, was associated with greater immediate changes in both LV end-systolic volume index (5.3±3.5 versus 2.1±2.4 mL/m Conclusions: Fibrosis detected on CMR is associated with immediate- and medium-term deterioration in LV function following RV pacing and could be used to identify those at risk of heart failure before pacemaker implantation.
MeSH term(s)	Aged ; Cardiac Pacing, Artificial/methods ; Cardiomyopathies/diagnosis ; Cardiomyopathies/physiopathology ; Cardiomyopathies/therapy ; Electrocardiography ; Fibrosis/diagnosis ; Fibrosis/drug therapy ; Fibrosis/physiopathology ; Follow-Up Studies ; Humans ; Magnetic Resonance Imaging, Cine/methods ; Male ; Middle Aged ; Myocardium/pathology ; Retrospective Studies ; Time Factors ; Treatment Outcome ; Ventricular Function, Right/physiology
Language	English
Publishing date	2021-05-18
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2435045-X
ISSN	1942-0080 ; 1941-9651
ISSN (online)	1942-0080
ISSN	1941-9651
DOI	10.1161/CIRCIMAGING.120.012256
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Article ; Online: Outcomes of patients receiving maintenance dialysis admitted over weekends.

Sakhuja, Ankit / Schold, Jesse D / Kumar, Gagan / Dall, Aaron / Sood, Puneet / Navaneethan, Sankar D

American journal of kidney diseases : the official journal of the National Kidney Foundation

2013 Volume 62, Issue 4, Page(s) 763–770

Abstract: Background: Hospital admissions over weekends have been associated with worse outcomes in different patient populations. The cause of this difference in outcomes remains unclear; however, different staffing patterns over weekends have been speculated to ...

Abstract	Background: Hospital admissions over weekends have been associated with worse outcomes in different patient populations. The cause of this difference in outcomes remains unclear; however, different staffing patterns over weekends have been speculated to contribute. We evaluated outcomes in patients on maintenance dialysis therapy admitted over weekends using a national database. Study design: Retrospective cohort study. Setting & participants: We included nonelective admissions of adult patients (≥18 years) on maintenance dialysis therapy (n = 3,278,572) identified using appropriate International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes for 2005-2009 using the Nationwide Inpatient Sample database. Predictor: Weekend versus weekday admission. Outcomes: The primary outcome measure was all-cause in-hospital mortality. Secondary outcomes included mortality by day 3 of admission, length of hospital stay, time to death, and discharge disposition. Measurements: We adjusted for patient and hospital characteristics, payer, year, comorbid conditions, and primary discharge diagnosis common to maintenance dialysis patients. Results: There were an estimated 704,491 admissions over weekends versus 2,574,081 over weekdays. Unadjusted all-cause in-hospital mortality was 40,666 (5.8%) for weekend admissions in comparison to 138,517 (5.4%) for weekday admissions (P < 0.001). In a multivariable model, patients admitted over weekends had higher all-cause in-hospital mortality (OR, 1.06; 95% CI, 1.01-1.10) in comparison to those admitted over weekdays and higher mortality during the first 3 days of admission (OR, 1.18; 95% CI, 1.10-1.26). Patients admitted over weekends were less likely to be discharged to home, had longer hospital stays, and had shorter times to death compared with those admitted over weekdays on adjusted analysis. Limitations: Use of ICD-9-CM codes to identify patients, defining weekend as midnight Friday to midnight Sunday. Conclusions: Maintenance dialysis patients admitted over weekends have increased mortality rates and longer lengths of stay compared with those admitted over weekdays. Further studies are needed to identify the reasons for worse outcomes for weekend admissions in this patient population.
MeSH term(s)	Adolescent ; Adult ; Aged ; Aged, 80 and over ; Cohort Studies ; Female ; Hospital Mortality ; Hospitalization/statistics & numerical data ; Humans ; Male ; Middle Aged ; Renal Dialysis/mortality ; Retrospective Studies ; Treatment Outcome ; Young Adult
Language	English
Publishing date	2013-05-11
Publishing country	United States
Document type	Comparative Study ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	604539-x
ISSN	1523-6838 ; 0272-6386
ISSN (online)	1523-6838
ISSN	0272-6386
DOI	10.1053/j.ajkd.2013.03.014
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Article ; Online: PIK3C2B inhibition improves function and prolongs survival in myotubular myopathy animal models.

Sabha, Nesrin / Volpatti, Jonathan R / Gonorazky, Hernan / Reifler, Aaron / Davidson, Ann E / Li, Xingli / Eltayeb, Nadine M / Dall'Armi, Claudia / Di Paolo, Gilbert / Brooks, Susan V / Buj-Bello, Ana / Feldman, Eva L / Dowling, James J

The Journal of clinical investigation

2016 Volume 126, Issue 9, Page(s) 3613–3625

Abstract: Myotubular myopathy (MTM) is a devastating pediatric neuromuscular disorder of phosphoinositide (PIP) metabolism resulting from mutations of the PIP phosphatase MTM1 for which there are no treatments. We have previously shown phosphatidylinositol-3- ... ...

Abstract	Myotubular myopathy (MTM) is a devastating pediatric neuromuscular disorder of phosphoinositide (PIP) metabolism resulting from mutations of the PIP phosphatase MTM1 for which there are no treatments. We have previously shown phosphatidylinositol-3-phosphate (PI3P) accumulation in animal models of MTM. Here, we tested the hypothesis that lowering PI3P levels may prevent or reverse the MTM disease process. To test this, we targeted class II and III PI3 kinases (PI3Ks) in an MTM1-deficient mouse model. Muscle-specific ablation of Pik3c2b, but not Pik3c3, resulted in complete prevention of the MTM phenotype, and postsymptomatic targeting promoted a striking rescue of disease. We confirmed this genetic interaction in zebrafish, and additionally showed that certain PI3K inhibitors prevented development of the zebrafish mtm phenotype. Finally, the PI3K inhibitor wortmannin improved motor function and prolonged lifespan of the Mtm1-deficient mice. In all, we have identified Pik3c2b as a genetic modifier of Mtm1 mutation and demonstrated that PIK3C2B inhibition is a potential treatment strategy for MTM. In addition, we set the groundwork for similar reciprocal inhibition approaches for treating other PIP metabolic disorders and highlight the importance of modifier gene pathways as therapeutic targets.
MeSH term(s)	Androstadienes/chemistry ; Animals ; Animals, Genetically Modified ; Class II Phosphatidylinositol 3-Kinases/genetics ; Class II Phosphatidylinositol 3-Kinases/physiology ; Disease Models, Animal ; Female ; Male ; Mice ; Mice, Knockout ; Motor Skills/drug effects ; Muscle, Skeletal/metabolism ; Myopathies, Structural, Congenital/genetics ; Myopathies, Structural, Congenital/therapy ; Phenotype ; Phosphatidylinositol 3-Kinases/genetics ; Phosphatidylinositol 3-Kinases/physiology ; Protein Tyrosine Phosphatases, Non-Receptor/metabolism ; Zebrafish
Chemical Substances	Androstadienes ; Phosphatidylinositol 3-Kinases (EC 2.7.1.-) ; Class II Phosphatidylinositol 3-Kinases (EC 2.7.1.137) ; PIK3C3 protein, mouse (EC 2.7.1.137) ; Pik3c2b protein, mouse (EC 2.7.1.137) ; Protein Tyrosine Phosphatases, Non-Receptor (EC 3.1.3.48) ; myotubularin (EC 3.1.3.48) ; wortmannin (XVA4O219QW)
Language	English
Publishing date	2016-08-22
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	3067-3
ISSN	1558-8238 ; 0021-9738
ISSN (online)	1558-8238
ISSN	0021-9738
DOI	10.1172/JCI86841
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Article ; Online: Interdisciplinary pharmacometrics linking oseltamivir pharmacology, influenza epidemiology and health economics to inform antiviral use in pandemics.

Kamal, Mohamed A / Smith, Patrick F / Chaiyakunapruk, Nathorn / Wu, David B C / Pratoomsoot, Chayanin / Lee, Kenneth K C / Chong, Huey Yi / Nelson, Richard E / Nieforth, Keith / Dall, Georgina / Toovey, Stephen / Kong, David C M / Kamauu, Aaron / Kirkpatrick, Carl M / Rayner, Craig R

British journal of clinical pharmacology

2017 Volume 83, Issue 7, Page(s) 1580–1594

Abstract: Aims: A modular interdisciplinary platform was developed to investigate the economic impact of oseltamivir treatment by dosage regimen under simulated influenza pandemic scenarios.: Methods: The pharmacology module consisted of a pharmacokinetic ... ...

Abstract	Aims: A modular interdisciplinary platform was developed to investigate the economic impact of oseltamivir treatment by dosage regimen under simulated influenza pandemic scenarios. Methods: The pharmacology module consisted of a pharmacokinetic distribution of oseltamivir carboxylate daily area under the concentration-time curve at steady state (simulated for 75 mg and 150 mg twice daily regimens for 5 days) and a pharmacodynamic distribution of viral shedding duration obtained from phase II influenza inoculation data. The epidemiological module comprised a susceptible, exposed, infected, recovered (SEIR) model to which drug effect on the basic reproductive number (R Results: Oseltamivir 75 mg relative to no treatment reduced the median number of infected patients, increased change in quality-adjusted life years by deaths averted, and was cost-saving under all scenarios; 150 mg relative to 75 mg was not cost effective in low transmissibility scenarios but was cost saving in high transmissibility scenarios. Conclusion: This methodological study demonstrates proof of concept that the disciplines of pharmacology, disease epidemiology and health economics can be linked in a single quantitative framework.
MeSH term(s)	Antiviral Agents/economics ; Antiviral Agents/pharmacology ; Antiviral Agents/therapeutic use ; Cost-Benefit Analysis/methods ; Humans ; Influenza, Human/drug therapy ; Influenza, Human/economics ; Influenza, Human/epidemiology ; Influenza, Human/mortality ; Interdisciplinary Communication ; Methods ; Models, Theoretical ; Oseltamivir/economics ; Oseltamivir/pharmacology ; Oseltamivir/therapeutic use ; Pandemics/economics
Chemical Substances	Antiviral Agents ; Oseltamivir (20O93L6F9H)
Language	English
Publishing date	2017-02-20
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	188974-6
ISSN	1365-2125 ; 0306-5251 ; 0264-3774
ISSN (online)	1365-2125
ISSN	0306-5251 ; 0264-3774
DOI	10.1111/bcp.13229
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