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Article ; Online: Population-based analysis of radiation-induced gliomas after cranial radiotherapy for childhood cancers.

Leary, Jacob B / Anderson-Mellies, Amy / Green, Adam L

2022 Volume 4, Issue 1, Page(s) vdac159

Abstract: Background: Cranial radiotherapy (RT) used for pediatric CNS cancers and leukemias carries a risk of secondary CNS malignancies, including radiation-induced gliomas (RIG). Our aim was to characterize the epidemiology of RIG.: Methods: This ... ...

Abstract	Background: Cranial radiotherapy (RT) used for pediatric CNS cancers and leukemias carries a risk of secondary CNS malignancies, including radiation-induced gliomas (RIG). Our aim was to characterize the epidemiology of RIG. Methods: This retrospective study used SEER data (1975-2016). Cohort 1 included patients diagnosed with glioma as a second malignancy ≥2 years after receiving treatment for a first malignancy diagnosed at 0-19 years, either a primary CNS tumor (1a, Results: For Cohort 1, 0.77% of patients receiving cranial RT developed RIG. 3.39% of patients receiving cranial RT for primary CNS tumors fell in cohort 2. Median latency to RIG diagnosis was 11.1 years and was significantly shorter for cohort 1b than 1a. Median OS for cohort 1 was 9.0 months. Receiving surgery, radiation, or chemotherapy were all associated with a nonstatistically significant improvement in OS ( Conclusion: A total of 1%-4% of patients undergoing cranial RT for pediatric cancers later developed RIG, which can occur 3-35 years after RT. Given the substantial and likely underestimated impact on overall CNS tumor mortality, RIG is deserving of increased attention in preclinical and clinical studies.
Language	English
Publishing date	2022-10-03
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/vdac159
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Article: Who discovers the firearm suicide decedent: an epidemiologic characterization of survivor-victims.

Barnard, Leslie M / Leavitt, Colton / Spark, Talia L / Leary, Jacob B / Wallace, Erik A

Injury epidemiology

2022 Volume 9, Issue 1, Page(s) 45

Abstract: Background: Suicide is the tenth leading cause of death in the United States, with over half of cases involving firearms. Despite research indicating negative effects of exposure to suicide, there is little research on who typically finds the body of ... ...

Abstract	Background: Suicide is the tenth leading cause of death in the United States, with over half of cases involving firearms. Despite research indicating negative effects of exposure to suicide, there is little research on who typically finds the body of the suicide decedent. Understanding who finds the body of the suicide decedent may be important to understand trauma and mental health effects. Findings: Of the 332 people who died by suicide in El Paso County, Colorado, 182 (55%) used firearms. Those who died by firearm suicide were more likely to be male (83.5% vs. 67.3%) have military affiliation (39.0% vs. 19.3%) and were less likely to have a known mental health diagnosis (47.3% vs. 64.7%) compared to those who died from other means. Most suicide decedents were found by a family member or friend (60.2%). The remaining decedents were found by a stranger/acquaintance (21.0%) or a first responder (22.4%) One-fifth of suicides involved forced witnessing (19%) and the majority were already deceased when the body was discovered (73.2%). Conclusions: While most suicide decedents are discovered by a family member or a friend, it is unknown what the bereavement and trauma-related outcomes are among people who discover a suicide decedent who has died by violent means, especially by firearms. Further studies exploring who discovers suicide decedents and targeted postvention strategies for supporting impacted family, friends, first responders, and strangers are needed.
Language	English
Publishing date	2022-12-12
Publishing country	England
Document type	Journal Article
ZDB-ID	2764253-7
ISSN	2197-1714
ISSN	2197-1714
DOI	10.1186/s40621-022-00408-3
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Article ; Online: Associations between white matter integrity and postural control in adults with traumatic brain injury.

Zampieri, Cris / Leary, Jacob B / Shahim, Pashtun / Damiano, Diane / Ho, Pei-Shu / Pham, Dzung L / Chan, Leighton

PloS one

2023 Volume 18, Issue 11, Page(s) e0288727

Abstract: Abnormalities of postural sway have been extensively reported in traumatic brain injury (TBI). However, the underlying neural correlates of balance disturbances in TBI remain to be elucidated. Studies in children with TBI have reported associations ... ...

Abstract	Abnormalities of postural sway have been extensively reported in traumatic brain injury (TBI). However, the underlying neural correlates of balance disturbances in TBI remain to be elucidated. Studies in children with TBI have reported associations between the Sensory Organization Test (SOT) and measures of white matter (WM) integrity with diffusion tensor imaging (DTI) in brain areas responsible for multisensory integration. This study seeks to replicate those associations in adults as well as explore relationships between DTI and the Limits of Stability (LOS) Test. Fifty-six participants (43±17 years old) with a history of TBI were tested 30 days to 5 years post-TBI. This study confirmed results in children for associations between the SOT and the medial lemniscus as well as middle cerebellar peduncle, and revealed additional associations with the posterior thalamic radiation. Additionally, this study found significant correlations between abnormal LOS scores and impaired WM integrity in the cingulum, corpus callosum, corticopontine and corticospinal tracts, fronto-occipital fasciculi, longitudinal fasciculi, medial lemniscus, optic tracts and thalamic radiations. Our findings indicate the involvement of a broad range of WM tracts in the control of posture, and demonstrate the impact of TBI on balance via disruptions to WM integrity.
MeSH term(s)	Child ; Humans ; Adult ; Middle Aged ; White Matter/diagnostic imaging ; Diffusion Tensor Imaging/methods ; Brain/diagnostic imaging ; Brain Injuries, Traumatic/diagnostic imaging ; Postural Balance
Language	English
Publishing date	2023-11-27
Publishing country	United States
Document type	Journal Article
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0288727
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Article ; Online: Frequency and Nature of Genomic Alterations in ERBB2-Altered Urothelial Bladder Cancer.

Leary, Jacob B / Enright, Thomas / Bakaloudi, Dimitra Rafailia / Basnet, Alina / Bratslavsky, Gennady / Jacob, Joseph / Spiess, Philippe E / Li, Roger / Necchi, Andrea / Kamat, Ashish M / Pavlick, Dean C / Danziger, Natalie / Huang, Richard S P / Lin, Douglas I / Cheng, Liang / Ross, Jeffrey / Talukder, Rafee / Grivas, Petros

Targeted oncology

2024

Abstract: Background: Human epidermal growth factor-2 (HER2) overexpression is an oncogenic driver in many solid tumors, including urothelial bladder cancer (UBC). In addition, activating mutations in the ERBB2 gene have been shown to play an oncogenic role ... ...

Abstract	Background: Human epidermal growth factor-2 (HER2) overexpression is an oncogenic driver in many solid tumors, including urothelial bladder cancer (UBC). In addition, activating mutations in the ERBB2 gene have been shown to play an oncogenic role similar to ERBB2 amplification. Objective: To describe and compare the frequency and nature of genomic alterations (GA) of ERBB2-altered (mutations, amplification) and ERBB2 wild-type UBC. Patients and methods: Using a hybrid capture-based comprehensive profiling assay, 9518 UBC cases were grouped by ERBB2 alteration and evaluated for all classes of genomic alterations (GA), tumor mutational burden (TMB), microsatellite instability (MSI), genome-wide loss of heterozygosity (gLOH), and genomic mutational signature. PD-L1 expression was measured by immunohistochemistry (Dako 22C3). Categorical statistical comparisons were performed using Fisher's exact tests. Results: A total of 602 (6.3%) UBC cases featured ERBB2 extracellular domain short variant (SV) GA (ECDmut+), 253 (2.7%) cases featured ERBB2 kinase domain SV GA (KDmut+), 866 (9.1%) cases had ERBB2 amplification (amp+), and 7797 (81.9%) cases were ERBB2 wild-type (wt). European genetic ancestry of ECDmut+ was higher than ERBB2wt. Numerous significant associations were observed when comparing GA by group. Notably among these, CDKN2A/MTAP loss were more frequent in ERBB2wt versus ECDmut+ and amp+. ERBB3 GA were more frequent in ECDmut+ and KDmut+ than ERBB2wt. TERT GA were more frequent in ECDmut+, KDmut+, and amp+ versus ERBB2wt. TOP2A amplification was significantly more common in ECDmut+ and amp+ versus ERBB2wt, and TP53 SV GA were significantly higher in ERBB2 amp+ versus ERBB2wt. Mean TMB levels were significantly higher in ECDmut+, KDmut+, and amp+ than in ERBB2wt. Apolipoprotein B mRNA-editing enzyme, catalytic polypeptides (APOBEC) signature was more frequent in ECDmut+, KDmut+, and amp+ versus ERBB2wt. No significant differences were observed in PD-L1 status between groups, while gLOH-high status was more common in amp+ versus ERBB2wt. MSI-high status was more frequent in KDmut+ versus ERBB2wt, and in ERBB2wt than in amp+. Conclusions: We noted important differences in co-occurring GA in ERBB2-altered (ECDmut+, KDmut+, amp+) versus ERBB2wt UBC, as well as higher mean TMB and higher APOBEC mutational signature in the ERBB2-altered groups. Our results can help refine future clinical trial designs and elucidate possible response and resistance mechanisms for ERBB2-altered UBC.
Language	English
Publishing date	2024-04-03
Publishing country	France
Document type	Journal Article
ZDB-ID	2222136-0
ISSN	1776-260X ; 1776-2596
ISSN (online)	1776-260X
ISSN	1776-2596
DOI	10.1007/s11523-024-01056-x
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Article ; Online: Estimating premorbid intelligence in persons with traumatic brain injury: an examination of the Test of Premorbid Functioning.

Joseph, Annie-Lori C / Lippa, Sara M / McNally, Shannon M / Garcia, Katelyn M / Leary, Jacob B / Dsurney, John / Chan, Leighton

Applied neuropsychology. Adult

2019 Volume 28, Issue 5, Page(s) 535–543

Abstract: Knowledge of intelligence is essential for interpreting cognitive performance following traumatic brain injury (TBI). The Test of Premorbid Functioning (ToPF), a word reading test co-normed with the Wechsler Adult Intelligence Scale ... ...

Abstract	Knowledge of intelligence is essential for interpreting cognitive performance following traumatic brain injury (TBI). The Test of Premorbid Functioning (ToPF), a word reading test co-normed with the Wechsler Adult Intelligence Scale 4
MeSH term(s)	Adult ; Brain Injuries, Traumatic/complications ; Humans ; Intelligence ; Intelligence Tests ; Neuropsychological Tests ; Wechsler Scales
Language	English
Publishing date	2019-09-13
Publishing country	United States
Document type	Journal Article
ZDB-ID	2673736-X
ISSN	2327-9109 ; 2327-9095
ISSN (online)	2327-9109
ISSN	2327-9095
DOI	10.1080/23279095.2019.1661247
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Zs.A 4952: Show issues

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Article ; Online: Environmental enrichment as a viable neurorehabilitation strategy for experimental traumatic brain injury.

Bondi, Corina O / Klitsch, Kyle C / Leary, Jacob B / Kline, Anthony E

Journal of neurotrauma

2014 Volume 31, Issue 10, Page(s) 873–888

Abstract: Environmental enrichment (EE) emerged as a robust independent variable capable of influencing behavioral outcome in experimental studies after the fortuitous observation by renowned neuropsychologist Donald O. Hebb that rats raised as pets in his home ... ...

Abstract	Environmental enrichment (EE) emerged as a robust independent variable capable of influencing behavioral outcome in experimental studies after the fortuitous observation by renowned neuropsychologist Donald O. Hebb that rats raised as pets in his home performed markedly better on problem-solving tasks than those kept in the laboratory. In the subsequent years, numerous studies ensued demonstrating that EE was also capable of inducing neuroplasticity in normal (i.e., noninjured) rats. These behavioral and neural alterations provided the impetus for investigating EE as a potential therapy for traumatic brain injury (TBI), which, over the past two decades, has resulted in several reports. Hence, the aim of this review is to integrate the findings and present the current state of EE as a viable neurorehabilitation strategy for TBI. Using the specific key term searches "traumatic brain injury" and "environmental enrichment" or "enriched environment," 30 and 30 experimental TBI articles were identified by PubMed and Scopus, respectively. Of these, 27 articles were common to both search engines. An additional article was found on PubMed using the key terms "enriched environment" and "fluid percussion." A review of the bibliographies in the 34 articles did not yield additional citations. The overwhelming consensus of the 34 publications is that EE benefits behavioral and histological outcome after brain injury produced by various models. Further, the enhancements are observed in male and female as well as adult and pediatric rats and mice. Taken together, these cumulative findings provide strong support for EE as a generalized and robust preclinical model of neurorehabilitation. However, to further enhance the model and to more accurately mimic the clinic, future studies should continue to evaluate EE during more rehabilitation-relevant conditions, such as delayed and shorter time periods, as well as in combination with other therapeutic approaches, as we have been doing for the past few years.
MeSH term(s)	Animals ; Brain Injuries/rehabilitation ; Disease Models, Animal ; Environment ; Mice ; Rats
Language	English
Publishing date	2014-04-17
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	645092-1
ISSN	1557-9042 ; 0897-7151
ISSN (online)	1557-9042
ISSN	0897-7151
DOI	10.1089/neu.2014.3328
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Zs.A 2016: Show issues

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Article ; Online: Brain Volume, Connectivity, and Neuropsychological Performance in Mild Traumatic Brain Injury: The Impact of Post-Traumatic Stress Disorder Symptoms.

Lopez, Katherine C / Leary, Jacob B / Pham, Dzung L / Chou, Yi-Yu / Dsurney, John / Chan, Leighton

Journal of neurotrauma

2016 Volume 34, Issue 1, Page(s) 16–22

Abstract: Post-traumatic stress disorder (PTSD) is commonly associated with mild traumatic brain injury (mTBI). To better understand their relationship, we examined neuroanatomical structures and neuropsychological performance in a sample of individuals with mTBI, ...

Abstract	Post-traumatic stress disorder (PTSD) is commonly associated with mild traumatic brain injury (mTBI). To better understand their relationship, we examined neuroanatomical structures and neuropsychological performance in a sample of individuals with mTBI, with and without PTSD symptoms. Thirty-nine subjects with mTBI were dichotomized into those with (n = 12) and without (n = 27) significant PTSD symptoms based on scores on the PTSD Checklist. Using a region-of-interest approach, fronto-temporal volumes, fiber bundles obtained by diffusion tensor imaging, and neuropsychological scores were compared between the two groups. After controlling for total intracranial volume and age, subjects with mTBI and PTSD symptoms exhibited volumetric differences in the entorhinal cortex, an area associated with memory networks, relative to mTBI-only patients (F = 4.28; p = 0.046). Additionally, subjects with PTSD symptoms showed reduced white matter integrity in the right cingulum bundle (axial diffusivity, F = 6.04; p = 0.020). Accompanying these structural alterations, mTBI and PTSD subjects also showed impaired performance in encoding (F = 5.98; p = 0.019) and retrieval (F = 7.32; p = 0.010) phases of list learning and in tests of processing speed (Wechsler Adult Intelligence Scale Processing Speed Index, F = 12.23; p = 0.001; Trail Making Test A, F = 5.56; p = 0.024). Increased volume and white matter disruptions in these areas, commonly associated with memory functions, may be related to functional disturbances during cognitively demanding tasks. Differences in brain volume and white matter integrity between mTBI subjects and those with mTBI and co-morbid PTSD symptoms point to neuroanatomical differences that may underlie poorer recovery of mTBI subjects who experience PTSD symptoms. These findings support theoretical models of PTSD and its relationship to learning deficits.
MeSH term(s)	Adult ; Aged ; Brain/diagnostic imaging ; Brain Concussion/diagnostic imaging ; Brain Concussion/psychology ; Cohort Studies ; Cross-Sectional Studies ; Female ; Humans ; Male ; Middle Aged ; Nerve Net/diagnostic imaging ; Neuropsychological Tests ; Organ Size ; Psychomotor Performance/physiology ; Stress Disorders, Post-Traumatic/diagnostic imaging ; Stress Disorders, Post-Traumatic/psychology
Language	English
Publishing date	2016-06-10
Publishing country	United States
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, N.I.H., Intramural
ZDB-ID	645092-1
ISSN	1557-9042 ; 0897-7151
ISSN (online)	1557-9042
ISSN	0897-7151
DOI	10.1089/neu.2015.4323
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Zs.A 2016: Show issues

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Article ; Online: Combination therapies for neurobehavioral and cognitive recovery after experimental traumatic brain injury: Is more better?

Kline, Anthony E / Leary, Jacob B / Radabaugh, Hannah L / Cheng, Jeffrey P / Bondi, Corina O

Progress in neurobiology

2016 Volume 142, Page(s) 45–67

Abstract: Traumatic brain injury (TBI) is a significant health care crisis that affects two million individuals in the United Sates alone and over ten million worldwide each year. While numerous monotherapies have been evaluated and shown to be beneficial at the ... ...

Abstract	Traumatic brain injury (TBI) is a significant health care crisis that affects two million individuals in the United Sates alone and over ten million worldwide each year. While numerous monotherapies have been evaluated and shown to be beneficial at the bench, similar results have not translated to the clinic. One reason for the lack of successful translation may be due to the fact that TBI is a heterogeneous disease that affects multiple mechanisms, thus requiring a therapeutic approach that can act on complementary, rather than single, targets. Hence, the use of combination therapies (i.e., polytherapy) has emerged as a viable approach. Stringent criteria, such as verification of each individual treatment plus the combination, a focus on behavioral outcome, and post-injury vs. pre-injury treatments, were employed to determine which studies were appropriate for review. The selection process resulted in 37 papers that fit the specifications. The review, which is the first to comprehensively assess the effects of combination therapies on behavioral outcomes after TBI, encompasses five broad categories (inflammation, oxidative stress, neurotransmitter dysregulation, neurotrophins, and stem cells, with and without rehabilitative therapies). Overall, the findings suggest that combination therapies can be more beneficial than monotherapies as indicated by 46% of the studies exhibiting an additive or synergistic positive effect versus on 19% reporting a negative interaction. These encouraging findings serve as an impetus for continued combination studies after TBI and ultimately for the development of successful clinically relevant therapies.
MeSH term(s)	Animals ; Brain Injuries, Traumatic/metabolism ; Brain Injuries, Traumatic/psychology ; Brain Injuries, Traumatic/therapy ; Cognitive Behavioral Therapy/methods ; Combined Modality Therapy/methods ; Humans ; Neuroprotective Agents/pharmacology ; Neuroprotective Agents/therapeutic use ; Recovery of Function ; Stem Cell Transplantation/methods
Chemical Substances	Neuroprotective Agents
Language	English
Publishing date	2016-05-07
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	185535-9
ISSN	1873-5118 ; 0301-0082
ISSN (online)	1873-5118
ISSN	0301-0082
DOI	10.1016/j.pneurobio.2016.05.002
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Se 205: Show issues

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Article ; Online: Spontaneous recovery after controlled cortical impact injury is not impeded by intermittent administration of the antipsychotic drug risperidone.

Carlson, Lauren J / Bao, Gina C / Besagar, Sonya / Leary, Jacob B / Radabaugh, Hannah L / Bondi, Corina O / Kline, Anthony E

Neuroscience letters

2018 Volume 682, Page(s) 69–73

Abstract: Several preclinical studies have reported that daily administration of the antipsychotic drug (APD) risperidone (RISP) impedes recovery after traumatic brain injury (TBI). However, it is not known whether intermittent dosing would produce similar ... ...

Abstract	Several preclinical studies have reported that daily administration of the antipsychotic drug (APD) risperidone (RISP) impedes recovery after traumatic brain injury (TBI). However, it is not known whether intermittent dosing would produce similar deleterious effects. The relevance of providing APDs intermittently is that not all patients in rehabilitation require daily treatments to manage TBI-induced agitation. Hence, the goal of the current study was to test the hypothesis that intermittent (vs. daily) administration of RISP would be less disturbing to motor and cognitive recovery after TBI. Anesthetized adult male rats were subjected to either a cortical impact of moderate severity or sham injury and then were randomly assigned to groups receiving intraperitoneal injections of vehicle (VEH; 1.0 mL/kg) or RISP (0.45 mg/kg) 1x, 3x, or 7x per week until the completion of behavioral testing, which consisted of motor and cognitive assessments on post-operative days 1-5 and 14-19, respectively. The group receiving RISP 7x week exhibited greater motor and cognitive impairment compared to those receiving RISP 1x or 3x per week, or VEH [p<0.05]. Moreover, no differences were observed between the intermittent RISP groups vs. VEH [p>0.05], which supports the hypothesis. A potential clinical ramification is that RISP may be safe to manage agitation after TBI, but only when used sparingly.
MeSH term(s)	Animals ; Antipsychotic Agents/administration & dosage ; Brain Injuries, Traumatic/drug therapy ; Brain Injuries, Traumatic/physiopathology ; Brain Injuries, Traumatic/psychology ; Cerebral Cortex/drug effects ; Cerebral Cortex/injuries ; Cognition/drug effects ; Cognition/physiology ; Drug Administration Schedule ; Male ; Maze Learning/drug effects ; Maze Learning/physiology ; Rats ; Rats, Sprague-Dawley ; Recovery of Function/drug effects ; Recovery of Function/physiology ; Risperidone/administration & dosage
Chemical Substances	Antipsychotic Agents ; Risperidone (L6UH7ZF8HC)
Language	English
Publishing date	2018-06-06
Publishing country	Ireland
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	194929-9
ISSN	1872-7972 ; 0304-3940
ISSN (online)	1872-7972
ISSN	0304-3940
DOI	10.1016/j.neulet.2018.06.007
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Zs.A 1166: Show issues

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Article ; Online: Disruption of basal forebrain cholinergic neurons after traumatic brain injury does not compromise environmental enrichment-mediated cognitive benefits.

Moschonas, Eleni H / Leary, Jacob B / Memarzadeh, Kimiya / Bou-Abboud, Carine E / Folweiler, Kaitlin A / Monaco, Christina M / Cheng, Jeffrey P / Kline, Anthony E / Bondi, Corina O

Brain research

2020 Volume 1751, Page(s) 147175

Abstract: Environmental enrichment (EE) attenuates traumatic brain injury (TBI)-induced loss of medial septal (MS) choline acetyltransferase (ChAT)-cells and enhances spatial learning and memory vs. standard (STD) housing. Whether basal forebrain cholinergic ... ...

Abstract	Environmental enrichment (EE) attenuates traumatic brain injury (TBI)-induced loss of medial septal (MS) choline acetyltransferase (ChAT)-cells and enhances spatial learning and memory vs. standard (STD) housing. Whether basal forebrain cholinergic neurons (BFCNs) are important mediators of EE-induced benefits after TBI requires further investigation. Anesthetized female rats were randomly assigned to intraseptal infusions of the immunotoxin 192-IgG-saporin (SAP; 0.22 μg in 1.0 μL) or vehicle (VEH; 1.0 μL IgG) followed immediately by a cortical impact (2.8 mm deformation depth at 4 m/s) or sham injury and divided into EE and STD housing. Spatial learning and memory retention were assessed on post-operative days 14-19. MS ChAT
MeSH term(s)	Animals ; Basal Forebrain/metabolism ; Basal Forebrain/physiology ; Brain Injuries, Traumatic/physiopathology ; Brain Injuries, Traumatic/psychology ; Brain Injuries, Traumatic/therapy ; Cholinergic Neurons/metabolism ; Cholinergic Neurons/physiology ; Cognition/physiology ; Environment ; Female ; Maze Learning/physiology ; Memory/physiology ; Psychomotor Performance/physiology ; Rats ; Rats, Sprague-Dawley ; Spatial Learning/physiology
Language	English
Publishing date	2020-10-26
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1200-2
ISSN	1872-6240 ; 0006-8993
ISSN (online)	1872-6240
ISSN	0006-8993
DOI	10.1016/j.brainres.2020.147175
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