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Article ; Online: Response to Dr. DiCarlo-Cohen.

Williams, Jacqueline P

Journal of applied clinical medical physics

2023 Volume 24, Issue 6, Page(s) e14046

Language	English
Publishing date	2023-05-22
Publishing country	United States
Document type	Letter ; Comment
ZDB-ID	2010347-5
ISSN	1526-9914 ; 1526-9914
ISSN (online)	1526-9914
ISSN	1526-9914
DOI	10.1002/acm2.14046
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Article ; Online: Living in a Crab Bucket.

Williams, Jacqueline P

Radiation research

2020 Volume 194, Issue 5, Page(s) 449–451

MeSH term(s)	Attitude of Health Personnel ; Financing, Government ; Humans ; National Institutes of Health (U.S.) ; Peer Review, Research/ethics ; Peer Review, Research/standards ; Peer Review, Research/trends ; Prejudice/ethics ; Prejudice/psychology ; Publication Bias ; Publishing/standards ; Radiobiology ; United States
Language	English
Publishing date	2020-11-12
Publishing country	United States
Document type	Journal Article
ZDB-ID	80322-4
ISSN	1938-5404 ; 0033-7587
ISSN (online)	1938-5404
ISSN	0033-7587
DOI	10.1667/RADE-20-00162
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Article: Animal Models for Radiotherapy Research: All (Animal) Models Are Wrong but Some Are Useful.

Butterworth, Karl T / Williams, Jacqueline P

Cancers

2021 Volume 13, Issue 6

Abstract: The distinguished statistician, George E [ ... ]. ...

Abstract	The distinguished statistician, George E [...].
Language	English
Publishing date	2021-03-16
Publishing country	Switzerland
Document type	Editorial
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers13061319
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Article ; Online: Modeling normal bladder injury after radiation therapy.

Kerns, Sarah L / Williams, Jacqueline P / Marples, Brian

International journal of radiation biology

2023 Volume 99, Issue 7, Page(s) 1046–1054

Abstract: Purpose: For decades, Dr. John Moulder has been a leading radiation biologist and one of the few who consistently supported the study of normal tissue responses to radiation. His meticulous modeling and collaborations across the field have offered a ... ...

Abstract	Purpose: For decades, Dr. John Moulder has been a leading radiation biologist and one of the few who consistently supported the study of normal tissue responses to radiation. His meticulous modeling and collaborations across the field have offered a prime example of how research can be taken from the bench to the bedside and back, with the ultimate goal of providing benefit to patients. Much of the focus of John's work was on mitigating damage to the kidney, whether as the result of accidental or deliberate clinical exposures. Following in his footsteps, we offer here a brief overview of work conducted in the field of radiation-induced bladder injury. We then describe our own preclinical experimental studies which originated as a response to reports from a clinical genome-wide association study (GWAS) investigating genomic biomarkers of normal tissue toxicity in prostate cancer patients treated with radiotherapy. In particular, we discuss the use of Renin-Angiotensin System (RAS) inhibitors as modulators of injury, agents championed by the Moulder group, and how RAS inhibitors are associated with a reduction in some measures of toxicity. Using a murine model, along with precise CT-image guided irradiation of the bladder using single and fractionated dosing regimens, we have been able to demonstrate radiation-induced functional injury to the bladder and mitigation of this functional damage by an inhibitor of angiotensin-converting enzyme targeting the RAS, an experimental approach akin to that used by the Moulder group. We consider our scientific trajectory as a bedside-to-bench approach because the observation was made clinically and investigated in a preclinical model; this experimental approach aligns with the exemplary career of Dr. John Moulder. Conclusions: Despite the differences in functional endpoints, recent findings indicate a commonality between bladder late effects and the work in kidney pioneered by Dr. John Moulder. We offer evidence that targeting the RAS pathway may provide a targetable pathway to reducing late bladder toxicity.
MeSH term(s)	Male ; Humans ; Animals ; Mice ; Urinary Bladder ; Genome-Wide Association Study ; Kidney/radiation effects ; Prostatic Neoplasms/radiotherapy ; Radiation Injuries/etiology ; Radiation Injuries/drug therapy
Language	English
Publishing date	2023-03-07
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	3065-x
ISSN	1362-3095 ; 0020-7616 ; 0955-3002
ISSN (online)	1362-3095
ISSN	0020-7616 ; 0955-3002
DOI	10.1080/09553002.2023.2182000
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Article ; Online: In support of ICRP's call to action to strengthen expertise in radiological protection worldwide.

Newhauser, Wayne D / Williams, Jacqueline P / Noska, Michael A / Bluth, Edward I / Townsend, Lawrence W / Tolmachev, Sergey Y / Dewji, Shaheen A

Radiation and environmental biophysics

2023 Volume 62, Issue 3, Page(s) 287–288

MeSH term(s)	Radiation Dosage ; Radiation Protection
Language	English
Publishing date	2023-07-12
Publishing country	Germany
Document type	Letter ; Comment
ZDB-ID	124987-3
ISSN	1432-2099 ; 0301-634X
ISSN (online)	1432-2099
ISSN	0301-634X
DOI	10.1007/s00411-023-01038-z
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Article ; Online: Pharmacologic Manipulation of Complement Receptor 3 Prevents Dendritic Spine Loss and Cognitive Impairment After Acute Cranial Radiation.

Hinkle, Joshua J / Olschowka, John A / Williams, Jacqueline P / O'Banion, M Kerry

International journal of radiation oncology, biology, physics

2023

Abstract: Purpose: Cranial irradiation induces healthy tissue damage that can lead to neurocognitive complications, negatively affecting patient quality of life. One damage indicator associated with cognitive impairment is loss of neuronal spine density. We ... ...

Abstract	Purpose: Cranial irradiation induces healthy tissue damage that can lead to neurocognitive complications, negatively affecting patient quality of life. One damage indicator associated with cognitive impairment is loss of neuronal spine density. We previously demonstrated that irradiation-mediated spine loss is microglial complement receptor 3 (CR3) and sex dependent. We hypothesized that these changes are associated with late-delayed cognitive deficits and amenable to pharmacologic intervention. Methods and materials: Our model of cranial irradiation (acute, 10 Gy gamma) used male and female CR3-wild type and CR3-deficient Thy-1 YFP mice of C57BL/6 background. Forty-five days after irradiation and behavioral testing, we quantified spine density and markers of microglial reactivity in the hippocampal dentate gyrus. In a separate experiment, male Thy-1 YFP C57BL/6 mice were treated with leukadherin-1, a modulator of CR3 function. Results: We found that male mice demonstrate irradiation-mediated spine loss and cognitive deficits but that female and CR3 knockout mice do not. These changes were associated with greater reactivity of microglia in male mice. Pharmacologic manipulation of CR3 with LA1 prevented spine loss and cognitive deficits in irradiated male mice. Conclusions: This work improves our understanding of irradiation-mediated mechanisms and sex dependent responses and may help identify novel therapeutics to reduce irradiation-induced cognitive decline and improve patient quality of life.
Language	English
Publishing date	2023-12-23
Publishing country	United States
Document type	Journal Article
ZDB-ID	197614-x
ISSN	1879-355X ; 0360-3016
ISSN (online)	1879-355X
ISSN	0360-3016
DOI	10.1016/j.ijrobp.2023.12.017
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Article ; Online: Saving normal tissues - a goal for the ages.

Groves, Angela M / Williams, Jacqueline P

International journal of radiation biology

2019 Volume 95, Issue 7, Page(s) 920–935

Abstract: Almost since the earliest utilization of ionizing radiation, many within the radiation community have worked toward either preventing (i.e. protecting) normal tissues from unwanted radiation injury or rescuing them from the downstream consequences of ... ...

Abstract	Almost since the earliest utilization of ionizing radiation, many within the radiation community have worked toward either preventing (i.e. protecting) normal tissues from unwanted radiation injury or rescuing them from the downstream consequences of exposure. However, despite over a century of such investigations, only incremental gains have been made toward this goal and, with certainty, no outright panacea having been found. In celebration of the 60th anniversary of the
MeSH term(s)	Animals ; History, 20th Century ; History, 21st Century ; Humans ; Neoplasms/radiotherapy ; Radiation Dosage ; Radiation Injuries/history ; Radiation Injuries/prevention & control ; Radiation Protection/methods ; Radiation-Protective Agents ; Radiobiology/methods ; Radiotherapy/adverse effects
Chemical Substances	Radiation-Protective Agents
Language	English
Publishing date	2019-03-29
Publishing country	England
Document type	Historical Article ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, N.I.H., Intramural ; Review
ZDB-ID	3065-x
ISSN	1362-3095 ; 0020-7616 ; 0955-3002
ISSN (online)	1362-3095
ISSN	0020-7616 ; 0955-3002
DOI	10.1080/09553002.2019.1589654
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Article ; Online: Digital Spatial Profiling Identifies Distinct Molecular Signatures of Vascular Lesions in Pulmonary Arterial Hypertension.

Tuder, Rubin M / Gandjeva, Aneta / Williams, Sarah / Kumar, Sushil / Kheyfets, Vitaly O / Hatton-Jones, Kyle Matthew / Starr, Jacqueline R / Yun, Jeong / Hong, Jason / West, Nicholas P / Stenmark, Kurt R

American journal of respiratory and critical care medicine

2024

Abstract: Rationale: Idiopathic Pulmonary Arterial Hypertension (IPAH) is characterized by extensive pulmonary vascular remodeling due to plexiform and obliterative lesions, media hypertrophy, inflammatory cell infiltration, and alterations of the adventitia.: ... ...

Abstract	Rationale: Idiopathic Pulmonary Arterial Hypertension (IPAH) is characterized by extensive pulmonary vascular remodeling due to plexiform and obliterative lesions, media hypertrophy, inflammatory cell infiltration, and alterations of the adventitia. Objective: Test the hypothesis that microscopic IPAH vascular lesions express unique molecular profiles, which collectively are different from control pulmonary arteries. Methods: We used digital spatial transcriptomics to profile the genome-wide differential transcriptomic signature of key pathological lesions (plexiform, obliterative, intima+media hypertrophy, and adventitia) in IPAH lungs (n= 11) and compared these data to the intima+media and adventitia of control pulmonary artery (n=5). Results: We detected 8273 transcripts in the IPAH lesions and control lung pulmonary arteries. Plexiform lesions and IPAH adventitia exhibited the greatest number of differentially expressed genes when compared with intima-media hypertrophy and obliterative lesions. Plexiform lesions in IPAH showed enrichment for (i) genes associated with TGFβ-signaling and (ii) mutated genes affecting the extracellular matrix and endothelial-mesenchymal transformation. Plexiform lesions and IPAH adventitia showed upregulation of genes involved in immune and interferon signaling, coagulation, and complement pathways. Cellular deconvolution indicated variability in the number of vascular and inflammatory cells between IPAH lesions, which underlies the differential transcript profiling. Conclusions: IPAH lesions express unique molecular transcript profiles enriched for pathways involving pathogenetic pathways, including genetic disease drivers, innate and acquired immunity, hypoxia sensing, and angiogenesis signaling. These data provide a rich molecular-structural framework in IPAH vascular lesions that inform novel biomarkers and therapeutic targets in this highly morbid disease.
Language	English
Publishing date	2024-04-03
Publishing country	United States
Document type	Journal Article
ZDB-ID	1180953-x
ISSN	1535-4970 ; 0003-0805 ; 1073-449X
ISSN (online)	1535-4970
ISSN	0003-0805 ; 1073-449X
DOI	10.1164/rccm.202307-1310OC
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Article ; Online: Normal tissue damage: its importance, history and challenges for the future.

Williams, Jacqueline P / Newhauser, Wayne

The British journal of radiology

2018 Volume 92, Issue 1093, Page(s) 20180048

Abstract: Sir Oliver Scott, a philanthropist and radiation biologist and, therefore, the epitome of a gentleman and a scholar, was an early Director of the BECC Radiobiology Research Unit at Mount Vernon. His tenure preceded that of Jack Fowler, with both ... ...

Abstract	Sir Oliver Scott, a philanthropist and radiation biologist and, therefore, the epitome of a gentleman and a scholar, was an early Director of the BECC Radiobiology Research Unit at Mount Vernon. His tenure preceded that of Jack Fowler, with both contributing to basic, translational and clinical thought and application in radiation across the globe. With respect to this review, Fowler's name in particular has remained synonymous with the use of models, both animal and mathematical, that assess and quantify the biological mechanisms that underlie radiation-associated normal tissue toxicities. An understanding of these effects is critical to the optimal use of radiation therapy in the clinic; however, the role that basic sciences play in clinical practice has been undergoing considerable change in recent years, particularly in the USA, where there has been a growing emphasis on engineering and imaging to improve radiation delivery, with empirical observations of clinical outcome taking the place of models underpinned by evidence from basic science experiments. In honour of Scott and Fowler's work, we have taken this opportunity to review how our respective fields of radiation biology and radiation physics have intertwined over the years, affecting the clinical use of radiation with respect to normal tissue outcomes. We discuss the past and current achievements, with the hope of encouraging a revived interest in physics and biology as they relate to radiation oncology practice, since, like Scott and Fowler, we share the goal of improving the future outlook for cancer patients.
MeSH term(s)	Animals ; Female ; Forecasting ; Humans ; Male ; Neoplasms/pathology ; Neoplasms/radiotherapy ; Radiation Injuries/prevention & control ; Radiation Oncology/standards ; Radiation Oncology/trends ; Radiobiology/trends ; Radiotherapy/adverse effects ; Radiotherapy/methods ; Radiotherapy Dosage ; Reference Values
Language	English
Publishing date	2018-04-09
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2982-8
ISSN	1748-880X ; 0007-1285
ISSN (online)	1748-880X
ISSN	0007-1285
DOI	10.1259/bjr.20180048
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Article ; Online: Virtual Surgical Planning in Craniosynostosis Reduces Operative Time and Length of Stay for Cranial Vault Remodeling.

Almeida, Mariana N / Alper, David P / Williams, Mica C G / Ihnat, Jacqueline M H / Parikh, Neil / Diluna, Michael / Alperovich, Michael

The Journal of craniofacial surgery

2023 Volume 34, Issue 7, Page(s) 1931–1933

Abstract: ... utilized VSP. There was no difference in average age at surgery (9.3±5.7 mo versus 13.2±31.1 mo, P =0.39 ... P <0.001) and a shorter length of stay (3.9±1.3 versus 4.6±1.7 d, P =0.01). There were no ...

Abstract	Cranial vault remodeling (CVR) with and without frontal orbital advancement remodels the skull in craniosynostosis. Virtual surgical planning (VSP) for preoperative planning has been previously shown to be effective in CVR. In this study, the authors aimed to evaluate the impact of VSP on operative and perioperative efficiency for craniosynostosis surgery. A retrospective chart review was conducted of patients with craniosynostosis who underwent CVR. Patient demographics, perioperative variables, use of VSP, and complications were obtained. Perioperative variables collected include operative time and length of stay. An independent t test was used to compare variables from patients who had surgery with VSP and patients who did not. Records were available for 126 patients with craniosynostosis who underwent CVR of whom 79 (62.7%) utilized VSP. There was no difference in average age at surgery (9.3±5.7 mo versus 13.2±31.1 mo, P =0.39). Surgeries planned using VSP demonstrated a decreased operative time of 1.3 hours (3.7±1.1 versus 5.0±1.1 h, P <0.001) and a shorter length of stay (3.9±1.3 versus 4.6±1.7 d, P =0.01). There were no differences in complication rates of dehiscence, infection, returns to the operating room, or 30-day readmission. These trends were similar among patients who underwent fronto-orbital advancement in addition to CVR. Virtual surgical planning was associated with decreased operative time and length of stay for patients with craniosynostosis and comparable complication rates. Virtual surgical planning is an effective tool for reducing anesthetic exposure time.
Language	English
Publishing date	2023-08-29
Publishing country	United States
Document type	Journal Article
ZDB-ID	1159501-2
ISSN	1536-3732 ; 1049-2275
ISSN (online)	1536-3732
ISSN	1049-2275
DOI	10.1097/SCS.0000000000009697
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