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Article ; Online: Profiling the molecular and clinical landscape of glioblastoma utilizing the Oncology Research Information Exchange Network brain cancer database.

Demetriou, Alexandra N / Chow, Frances / Craig, David W / Webb, Michelle G / Ormond, D Ryan / Battiste, James / Chakravarti, Arnab / Colman, Howard / Villano, John L / Schneider, Bryan P / Liu, James K C / Churchman, Michelle L / Zada, Gabriel

Neuro-oncology advances

2024 Volume 6, Issue 1, Page(s) vdae046

Abstract: Background: Glioblastoma exhibits aggressive growth and poor outcomes despite treatment, and its marked variability renders therapeutic design and prognostication challenging. The Oncology Research Information Exchange Network (ORIEN) database contains ... ...

Abstract	Background: Glioblastoma exhibits aggressive growth and poor outcomes despite treatment, and its marked variability renders therapeutic design and prognostication challenging. The Oncology Research Information Exchange Network (ORIEN) database contains complementary clinical, genomic, and transcriptomic profiling of 206 glioblastoma patients, providing opportunities to identify novel associations between molecular features and clinical outcomes. Methods: Survival analyses were performed using the Logrank test, and clinical features were evaluated using Wilcoxon and chi-squared tests with Results: Key findings include an association of Conclusions: Herein, we report the first clinical, genomic, and transcriptomic analysis of ORIEN glioblastoma cases, incorporating sample reclassification under updated 2021 diagnostic criteria. These findings create multiple avenues for further investigation and reinforce the value of multi-institutional consortia such as ORIEN in deepening our knowledge of intractable diseases such as glioblastoma.
Language	English
Publishing date	2024-03-27
Publishing country	England
Document type	Journal Article
ZDB-ID	3009682-0
ISSN	2632-2498 ; 2632-2498
ISSN (online)	2632-2498
ISSN	2632-2498
DOI	10.1093/noajnl/vdae046
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Article ; Online: X-ray tomographic microscopy of Eocene coprolites from Pipestone Springs Main Pocket, southwest Montana

Sarah M. Jacquet / Jeremy-Louis Webb / John Warren Huntley / Tara Selly / James D. Schiffbauer

Frontiers in Earth Science, Vol

2023 Volume 11

Abstract: The Eocene Pipestone Springs Main Pocket (Renova Formation, Jefferson County, Montana, United States of America) is a locality renowned for its diverse Chadronian (late Eocene; ∼38–33.9 million years ago) mammalian fauna and abundant coprolites. Two ... ...

Abstract	The Eocene Pipestone Springs Main Pocket (Renova Formation, Jefferson County, Montana, United States of America) is a locality renowned for its diverse Chadronian (late Eocene; ∼38–33.9 million years ago) mammalian fauna and abundant coprolites. Two distinct coprolite size classes were previously identified in the trace fossil assemblage from which we selected representatives to investigate feeding behaviors and dietary selection of the producers. A subset of the selected coprolites was analyzed based on their compositional and taphonomic attributes using non-destructive x-ray tomographic microscopy in combination with more traditional methods including thin-section petrography, scanning electron microscopy, and energy dispersive spectroscopy. Among the features extracted in the tomographic data were skeletal fragments, including those showing evidence of bone-crushing; delicate hair molds; encrusted lithic fragments; and several irregular pores and cracks throughout the coprolites. Segmentation and volumetric renders permit quantitative assessment of the relative proportions of inclusions, revealing porosity as a primary volumetric element aside from the matrix and bone inclusions. There was no significant difference in the total volume of bone extracted between coprolite size class, though the smaller coprolites preserved a relatively higher volumetric proportion of undigested skeletal material. This multi-visualization approach provides a means to observe and evaluate differences in the coprolite gross morphology and inclusions across the two size classes, thereby offering valuable insights into the broader paleoecology of the Pipestone Springs Main Pocket coprolite producers and holding promise for comparable paleo-dietary studies of other coprolite-rich deposits.
Keywords	coprolite ; taphonomy ; μCT ; diet ; hair ; Science ; Q
Language	English
Publishing date	2023-04-01T00:00:00Z
Publisher	Frontiers Media S.A.
Document type	Article ; Online
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Article ; Online: Testing for the appropriate level of clustering in linear regression models

MacKinnon, James G. / Nielsen, Morten Ørregaard / Webb, Matthew D.

Journal of Econometrics. 2023 Aug., v. 235, no. 2 p.2027-2056

2023

Abstract: The overwhelming majority of empirical research that uses cluster-robust inference assumes that the clustering structure is known, even though there are often several possible ways in which a dataset could be clustered. We propose two tests for the ... ...

Abstract	The overwhelming majority of empirical research that uses cluster-robust inference assumes that the clustering structure is known, even though there are often several possible ways in which a dataset could be clustered. We propose two tests for the correct level of clustering in regression models. One test focuses on inference about a single coefficient, and the other on inference about two or more coefficients. We provide both asymptotic and wild bootstrap implementations. The proposed tests work for a null hypothesis of either no clustering or “fine” clustering against alternatives of “coarser” clustering. We also propose a sequential testing procedure to determine the appropriate level of clustering. Simulations suggest that the bootstrap tests perform very well under the null hypothesis and can have excellent power. An empirical example suggests that using the tests leads to sensible inferences.
Keywords	data collection ; econometrics ; empirical research ; regression analysis ; C12 ; C15 ; C21 ; C23 ; CRVE ; Grouped data ; Clustered data ; Cluster-robust variance estimator ; Robust inference ; Wild bootstrap ; Wild cluster bootstrap
Language	English
Dates of publication	2023-08
Size	p. 2027-2056.
Publishing place	Elsevier B.V.
Document type	Article ; Online
Note	Pre-press version ; Use and reproduction
ZDB-ID	1460617-3
ISSN	0304-4076
ISSN	0304-4076
DOI	10.1016/j.jeconom.2023.03.005
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Article ; Online: Common Mutation in the

Helmuth, Timothy B / Kumari, Rashmi / Palsa, Kondaiah / Neely, Elizabeth B / Slagle-Webb, Becky / Simon, Scott D / Connor, James R

Stroke

2023 Volume 54, Issue 11, Page(s) 2886–2894

Abstract: Background: Intracerebral hemorrhage (ICH) is characterized by bleeding into the brain parenchyma. During an ICH, iron released from the breakdown of hemoglobin creates a cytotoxic environment in the brain through increased oxidative stress. ... ...

Abstract	Background: Intracerebral hemorrhage (ICH) is characterized by bleeding into the brain parenchyma. During an ICH, iron released from the breakdown of hemoglobin creates a cytotoxic environment in the brain through increased oxidative stress. Interestingly, the loss of iron homeostasis is associated with the pathological process of other neurological diseases. However, we have previously shown that the H63D mutation in the homeostatic iron regulatory ( Methods: An autologous blood infusion model was utilized to create an ICH in the right striatum of H67D and wild-type mice. The motor recovery of each animal was assessed by rotarod. Neurodegeneration was measured using fluorojade-B and mitochondrial damage was assessed by immunofluorescent numbers of CytC+ (cytochrome C) neurons and CytC+ astrocytes. Finally, the molecular antioxidant response to ICH was quantified by measuring Nrf2 (nuclear factor-erythroid 2 related factor), GPX4 (glutathione peroxidase 4), and FTH1 (H-ferritin) levels in the ICH-affected and nonaffected hemispheres via immunoblotting. Results: At 3 days post-ICH, H67D mice demonstrated enhanced performance on rotarod compared with wild-type animals despite no differences in lesion size. Additionally, H67D mice displayed higher levels of Nrf2, GPX4, and FTH1 in the ICH-affected hemisphere; however, these levels were not different in the contralateral, non-ICH-affected hemisphere. Furthermore, H67D mice showed decreased degenerated neurons, CytC+ Neurons, and CytC+ astrocytes in the perihematomal area. Conclusions: Our data suggest that the H67D mutation induces a robust antioxidant response 3 days following ICH through Nrf2, GPX4, and FTH1 activation. This activation could explain the decrease in degenerated neurons, CytC+ neurons, and CytC+ astrocytes in the perihematomal region, leading to the improved motor recovery. Based on this study, further investigation into the mechanisms of this neuroprotective response and the effects of the H63D HFE mutation in a population of patients with ICH is warranted.
MeSH term(s)	Animals ; Mice ; Antioxidants ; Cerebral Hemorrhage/genetics ; Hemochromatosis Protein/genetics ; Iron/metabolism ; Mutation ; NF-E2-Related Factor 2/genetics ; NF-E2-Related Factor 2/metabolism
Chemical Substances	Antioxidants ; Hemochromatosis Protein ; HFE protein, human ; Iron (E1UOL152H7) ; NF-E2-Related Factor 2
Language	English
Publishing date	2023-09-26
Publishing country	United States
Document type	Journal Article
ZDB-ID	80381-9
ISSN	1524-4628 ; 0039-2499 ; 0749-7954
ISSN (online)	1524-4628
ISSN	0039-2499 ; 0749-7954
DOI	10.1161/STROKEAHA.123.043799
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Article ; Online: Electrochemical fluorescence switching of enhanced green fluorescent protein.

Yang, Ying / Fan, Sanjun / Webb, James A / Ma, Yuanqing / Goyette, Jesse / Chen, Xueqian / Gaus, Katharina / Tilley, Richard D / Gooding, J Justin

Biosensors & bioelectronics

2023 Volume 237, Page(s) 115467

Abstract: Switchable fluorescent proteins, for which fluorescence can be switched ON and OFF, are widely used for molecule tracking and super resolution imaging. However, the robust use of the switchable fluorescent proteins is still limited as either the ... ...

Abstract	Switchable fluorescent proteins, for which fluorescence can be switched ON and OFF, are widely used for molecule tracking and super resolution imaging. However, the robust use of the switchable fluorescent proteins is still limited as either the switching is not repeatable, or such switching requires irradiation with coupled lasers of different wavelengths. Herein, we report an electrochemical approach to reversible fluorescence switching for enhanced green fluorescent proteins (EGFP) on indium tin oxide coated glass. Our results demonstrate that negative and positive electrochemical potentials can efficiently switch the fluorescent proteins between the dim (OFF) and bright (ON) states at the single molecule level. The electrochemical fluorescence switching is fast, reversible, and may be performed up to hundreds of cycles before photobleaching occurs. These findings highlight that this method of electrochemical fluorescence switching can be incorporated into advanced fluorescence microscopy.
Language	English
Publishing date	2023-06-25
Publishing country	England
Document type	Journal Article
ZDB-ID	1011023-9
ISSN	1873-4235 ; 0956-5663
ISSN (online)	1873-4235
ISSN	0956-5663
DOI	10.1016/j.bios.2023.115467
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Article: Foraging Under Uncertainty Follows the Marginal Value Theorem with Bayesian Updating of Environment Representations.

Webb, James / Steffan, Paul / Hayden, Benjamin Y / Lee, Daeyeol / Kemere, Caleb / McGinley, Matthew

bioRxiv : the preprint server for biology

2024

Abstract: Foraging theory has been a remarkably successful approach to understanding the behavior of animals in many contexts. In patch-based foraging contexts, the marginal value theorem (MVT) shows that the optimal strategy is to leave a patch when the marginal ... ...

Abstract	Foraging theory has been a remarkably successful approach to understanding the behavior of animals in many contexts. In patch-based foraging contexts, the marginal value theorem (MVT) shows that the optimal strategy is to leave a patch when the marginal rate of return declines to the average for the environment. However, the MVT is only valid in deterministic environments whose statistics are known to the forager; naturalistic environments seldom meet these strict requirements. As a result, the strategies used by foragers in naturalistic environments must be empirically investigated. We developed a novel behavioral task and a corresponding computational framework for studying patch-leaving decisions in head-fixed and freely moving mice. We varied between-patch travel time, as well as within-patch reward depletion rate, both deterministically and stochastically. We found that mice adopt patch residence times in a manner consistent with the MVT and not explainable by simple ethologically motivated heuristic strategies. Critically, behavior was best accounted for by a modified form of the MVT wherein environment representations were updated based on local variations in reward timing, captured by a Bayesian estimator and dynamic prior. Thus, we show that mice can strategically attend to, learn from, and exploit task structure on multiple timescales simultaneously, thereby efficiently foraging in volatile environments. The results provide a foundation for applying the systems neuroscience toolkit in freely moving and head-fixed mice to understand the neural basis of foraging under uncertainty.
Language	English
Publishing date	2024-03-31
Publishing country	United States
Document type	Preprint
DOI	10.1101/2024.03.30.587253
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Article ; Online: Analysis of anemia and iron supplementation among glioblastoma patients reveals sex-biased association between anemia and survival.

Shenoy, Ganesh / Slagle-Webb, Becky / Khunsriraksakul, Chachrit / Pandya Shesh, Bhavyata / Luo, Jingqin / Khristov, Vladimir / Smith, Nataliya / Mansouri, Alireza / Zacharia, Brad E / Holder, Sheldon / Lathia, Justin D / Barnholtz-Sloan, Jill S / Connor, James R

Scientific reports

2024 Volume 14, Issue 1, Page(s) 2389

Abstract: The association between anemia and outcomes in glioblastoma patients is unclear. We analyzed data from 1346 histologically confirmed adult glioblastoma patients in the TriNetX Research Network. Median hemoglobin and hematocrit levels were quantified for ... ...

Abstract	The association between anemia and outcomes in glioblastoma patients is unclear. We analyzed data from 1346 histologically confirmed adult glioblastoma patients in the TriNetX Research Network. Median hemoglobin and hematocrit levels were quantified for 6 months following diagnosis and used to classify patients as anemic or non-anemic. Associations of anemia and iron supplementation of anemic patients with median overall survival (median-OS) were then studied. Among 1346 glioblastoma patients, 35.9% of male and 40.5% of female patients were classified as anemic using hemoglobin-based WHO guidelines. Among males, anemia was associated with reduced median-OS compared to matched non-anemic males using hemoglobin (HR 1.24; 95% CI 1.00-1.53) or hematocrit-based cutoffs (HR 1.28; 95% CI 1.03-1.59). Among females, anemia was not associated with median-OS using hemoglobin (HR 1.00; 95% CI 0.78-1.27) or hematocrit-based cutoffs (HR: 1.10; 95% CI 0.85-1.41). Iron supplementation of anemic females trended toward increased median-OS (HR 0.61; 95% CI 0.32-1.19) although failing to reach statistical significance whereas no significant association was found in anemic males (HR 0.85; 95% CI 0.41-1.75). Functional transferrin-binding assays confirmed sexually dimorphic binding in resected patient samples indicating underlying differences in iron biology. Anemia among glioblastoma patients exhibits a sex-specific association with survival.
MeSH term(s)	Adult ; Humans ; Male ; Female ; Iron ; Glioblastoma/complications ; Anemia/complications ; Hemoglobins/metabolism ; Dietary Supplements
Chemical Substances	Iron (E1UOL152H7) ; Hemoglobins
Language	English
Publishing date	2024-01-29
Publishing country	England
Document type	Journal Article
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-024-52492-8
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Article ; Online: Coronary Artery Calcification and Risk of Cardiac Complication in Geriatric Trauma Population.

King, Sarah A / Jenkins, Jacob D / Livesay, James / Yune, Ji-Ming / Mannino, Elizabeth / Webb, Jason M / Hill, Haddon C / Baljepally, Raj / Daley, Brian J / Smith, Lou M

Journal of the American College of Surgeons

2024 Volume 238, Issue 4, Page(s) 762–767

Abstract: Background: Better means of identifying patients with increased cardiac complication (CC) risk is needed. Coronary artery calcification (CAC) is reported on routine chest CT scans. We assessed the correlation of CAC and CCs in the geriatric trauma ... ...

Abstract	Background: Better means of identifying patients with increased cardiac complication (CC) risk is needed. Coronary artery calcification (CAC) is reported on routine chest CT scans. We assessed the correlation of CAC and CCs in the geriatric trauma population. Study design: A prospective, observational study of patients 55 years and older who had chest CT scan from May to September 2022 at a level 1 trauma center. Radiologists scored CAC as none, mild, moderate, or severe. None-to-mild CAC (NM-CAC) and moderate-to-severe CAC (MS-CAC) were grouped and in-hospital CCs assessed (arrhythmia, ST elevation myocardial infarction [STEMI], non-STEMI, congestive heart failure, pulmonary edema, cardiac arrest, cardiogenic shock, and cardiac mortality). Univariate and bivariate analyses were performed. Results: Five hundred sixty-nine patients had a chest CT, of them 12 were excluded due to missing CAC severity. Of 557 patients, 442 (79.3%) had none-to-mild CAC and 115 (20.7%) has MS-CAC; the MS-CAC group was older (73.3 vs 67.4 years) with fewer male patients (48.7% vs 54.5%), had higher cardiac-related comorbidities, and had higher abbreviated injury scale chest injury scores. The MS-CAC group had an increased rate of CC (odds ratio [OR] 1.81, p = 0.016). Cardiac complications statistically more common in MS-CAC were congestive heart failure (OR 3.41, p = 0.003); cardiogenic shock (OR 3.3, p = 0.006); non-STEMI I or II (OR 2.8, p = 0.017); STEMI (OR 5.9, p = 0.029); and cardiac-caused mortality (OR 5.27, p = 0.036). No statistical significance between pulmonary edema (p = 0.6), new-onset arrhythmia (p = 0.74), or cardiac arrest (p = 0.193). Conclusions: CAC as reported on chest CT scans demonstrates a significant correlation with CC and should warrant additional cardiac monitoring.
MeSH term(s)	Aged ; Humans ; Male ; Arrhythmias, Cardiac/complications ; Coronary Angiography/adverse effects ; Coronary Artery Disease/complications ; Coronary Artery Disease/diagnostic imaging ; Heart Arrest ; Heart Failure ; Prospective Studies ; Pulmonary Edema/complications ; Risk Factors ; Shock, Cardiogenic/complications ; ST Elevation Myocardial Infarction/complications ; Vascular Calcification/complications ; Vascular Calcification/diagnostic imaging ; Vascular Calcification/epidemiology ; Middle Aged ; Female
Language	English
Publishing date	2024-03-15
Publishing country	United States
Document type	Observational Study ; Journal Article
ZDB-ID	1181115-8
ISSN	1879-1190 ; 1072-7515
ISSN (online)	1879-1190
ISSN	1072-7515
DOI	10.1097/XCS.0000000000000945
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Article ; Online: Lower Extremity Splinting: A Head-to-Head Comparison of A Novel One-Step Spray-on Splint Versus Standard Splinting.

Webb, Tyler / Lynch, Daniel / Lin, James / Groth, Adam / Ly, Thuan / Martin, Kevin D

Military medicine

2021

Abstract: Introduction: Splinting is an essential component of treating many lower extremity musculoskeletal injuries; however, little development has been made in splinting technology. The purpose of this study is to evaluate the efficacy of current ... ...

Abstract	Introduction: Splinting is an essential component of treating many lower extremity musculoskeletal injuries; however, little development has been made in splinting technology. The purpose of this study is to evaluate the efficacy of current immobilization equipment for lower extremity fractures by testing a novel one-step spray-on foam splint (Fast Cast) against structural aluminum malleable (SAM) lower extremity musculoskeletal injuries and 6-inch ACE (3M Corp., Minneapolis, MN, USA) bandage splints. Materials and methods: Six orthopedic surgical residents and two medical students participated in a prospective analysis of austere splinting techniques and equipment that utilized a cadaveric model with a distal third tibia-fibula shaft fracture. Each participant was observed and scored by three fellowship trained attending orthopedic surgeons. All scoring was independent using a 5-point Likert scale based on 10 splinting criteria (50 total points possible), including quality of radiographic reduction, time to completion, safety, and sustain longitudinal traction. The Likert scale is a set of questions that reflects the respondent's degree of agreement or disagreement with a statement. Each of the 10 questions has a range of 1-5. A score of 50 means the splint performed perfectly. The lowest possible score is a 10. The participants utilized standard equipment that included SAM splints and 6-inch ACE wraps (3M Corp., Minneapolis, MN, USA) in their first attempt. A second immobilization attempt was done with a one-step spray-on foam splint (Fast Cast). After each splinting attempt, the reduction was verified with radiographic imaging. Data analysis was performed using standard descriptive statistics, Student's t-tests, and inter-rater reliability was calculated using Cronbach's alpha scores. This project is Institutional Review Board (IRB) exempt. Results: The one-step spray-on foam splinting technique was superior (P < .05) in all parameters of the Likert scale, yielding a mean overall score of 45.1 points (±3.8), safety 4.7 points, longitudinal traction 4.5 points, and time 136 seconds (±23). The SAM resulted in a mean overall score of 33.8 points (±7.3), safety 2.8 points, longitudinal traction 4.1 points, and time 170 seconds (±52). Radiographic rating was 4.1 points (±0.7) for the SAM splint and 4.5 (±0.6) for Fast Cast. The differences in time to completion and radiograph rating did not reach statistical significance (P = .12 and P = .07, respectively). Conclusion: A one-step spray-on foam splinting technique demonstrated consistent superiority in reducing fracture motion, potential soft-tissue damage, and sustained longitudinal traction as compared to the standard technique.
Language	English
Publishing date	2021-12-04
Publishing country	England
Document type	Journal Article
ZDB-ID	391061-1
ISSN	1930-613X ; 0026-4075
ISSN (online)	1930-613X
ISSN	0026-4075
DOI	10.1093/milmed/usab505
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Article: Cluster-robust inference: A guide to empirical practice

MacKinnon, James G. / Nielsen, Morten Ørregaard / Webb, Matthew D.

Journal of econometrics. 2022 Apr. 16,

2022

Abstract: Methods for cluster-robust inference are routinely used in economics and many other disciplines. However, it is only recently that theoretical foundations for the use of these methods in many empirically relevant situations have been developed. In this ... ...

Abstract	Methods for cluster-robust inference are routinely used in economics and many other disciplines. However, it is only recently that theoretical foundations for the use of these methods in many empirically relevant situations have been developed. In this paper, we use these theoretical results to provide a guide to empirical practice. We do not attempt to present a comprehensive survey of the (very large) literature. Instead, we bridge theory and practice by providing a thorough guide on what to do and why, based on recently available econometric theory and simulation evidence. To practice what we preach, we include an empirical analysis of the effects of the minimum wage on labor supply of teenagers using individual data.
Keywords	empirical research ; labor ; surveys
Language	English
Dates of publication	2022-0416
Publishing place	Elsevier B.V.
Document type	Article
Note	Pre-press version
ZDB-ID	1460617-3
ISSN	0304-4076
ISSN	0304-4076
DOI	10.1016/j.jeconom.2022.04.001
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