IU Indianapolis ScholarWorks :: Browsing by Author "Williams, James C."

Browsing by Author "Williams, James C."

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An atlas of healthy and injured cell states and niches in the human kidney
(Springer Nature, 2023) Lake, Blue B.; Menon, Rajasree; Winfree, Seth; Hu, Qiwen; Ferreira, Ricardo Melo; Kalhor, Kian; Barwinska, Daria; Otto, Edgar A.; Ferkowicz, Michael; Diep, Dinh; Plongthongkum, Nongluk; Knoten, Amanda; Urata, Sarah; Mariani, Laura H.; Naik, Abhijit S.; Eddy, Sean; Zhang, Bo; Wu, Yan; Salamon, Diane; Williams, James C.; Wang, Xin; Balderrama, Karol S.; Hoover, Paul J.; Murray, Evan; Marshall, Jamie L.; Noel, Teia; Vijayan, Anitha; Hartman, Austin; Chen, Fei; Waikar, Sushrut S.; Rosas, Sylvia E.; Wilson, Francis P.; Palevsky, Paul M.; Kiryluk, Krzysztof; Sedor, John R.; Toto, Robert D.; Parikh, Chirag R.; Kim, Eric H.; Satija, Rahul; Greka, Anna; Macosko, Evan Z.; Kharchenko, Peter V.; Gaut, Joseph P.; Hodgin, Jeffrey B.; KPMP Consortium; Eadon, Michael T.; Dagher, Pierre C.; El-Achkar, Tarek M.; Zhang, Kun; Kretzler, Matthias; Jain, Sanjay; Medicine, School of Medicine
Understanding kidney disease relies on defining the complexity of cell types and states, their associated molecular profiles and interactions within tissue neighbourhoods1. Here we applied multiple single-cell and single-nucleus assays (>400,000 nuclei or cells) and spatial imaging technologies to a broad spectrum of healthy reference kidneys (45 donors) and diseased kidneys (48 patients). This has provided a high-resolution cellular atlas of 51 main cell types, which include rare and previously undescribed cell populations. The multi-omic approach provides detailed transcriptomic profiles, regulatory factors and spatial localizations spanning the entire kidney. We also define 28 cellular states across nephron segments and interstitium that were altered in kidney injury, encompassing cycling, adaptive (successful or maladaptive repair), transitioning and degenerative states. Molecular signatures permitted the localization of these states within injury neighbourhoods using spatial transcriptomics, while large-scale 3D imaging analysis (around 1.2 million neighbourhoods) provided corresponding linkages to active immune responses. These analyses defined biological pathways that are relevant to injury time-course and niches, including signatures underlying epithelial repair that predicted maladaptive states associated with a decline in kidney function. This integrated multimodal spatial cell atlas of healthy and diseased human kidneys represents a comprehensive benchmark of cellular states, neighbourhoods, outcome-associated signatures and publicly available interactive visualizations.
Anatomy Preparedness in Medical Education: Determining and Building Sufficient Preparedness in Professional Anatomy Courses
(2023-08) Balle, Megan C.; McNulty, Margaret A.; Agosto, Elizabeth R.; Byram, Jessica N.; Graunke, Steven S.; Magee, Paula A.; Williams, James C.
Widely accepted as a foundational course within health professions education, anatomy is often taken at the beginning of the health professional curriculum and students are expected to be prepared for the rigors of the course. Anatomy preparedness, evaluated in this study, has been defined as matriculating into a graduate or professional anatomy course with an adequate foundation in basic anatomy knowledge. In a mixed-methods study, pre-requisite syllabi of physician assistant students were analyzed via deductive content analysis to explore common traits within each group. The top and bottom 10% performing students were invited to participate in semi-structured interviews, n=5 participated. Additionally, correlation analyses were used to determine whether performance on a basic anatomy pre-quiz could aid in identifying allied health students with the potential to struggle in a professional anatomy course. A post-course survey was given to determine in which anatomy topics students felt underprepared upon matriculation, prior anatomy experience, feelings of preparedness, and anatomy pre-requisite recommendation. Finally, a pre-matriculation program targeting under-represented in medicine (URiM) students and those at-risk for failure in the medical program was developed. Correlation analyses were used to determine if there was a relationship between performance in the pre-matriculation program and the medical anatomy course. The same post-course survey was administered and focus groups were conducted; transcripts were analyzed via deductive content analysis. Syllabi traits critical to student success included exposure to specimens/prosections, practical exams, and supply of study resources; interviewees also perceived these traits to be important. Twenty-question pre-quiz scores significantly and positively correlated with student performance in their professional anatomy course. Students reported feeling deficient in anatomicomedical terminology and the nervous system. The pre-matriculation program was a success, with students performing at or above average within their cohort and compared to other URiM students. Both allied health and pre-matriculation students recommended taking anatomy prior to professional school. As seen in this study, students are capable of success with the proper resources and support. Furthermore, allied health and medical students recognized the importance of anatomy preparedness for success in health professional anatomy coursework and their openness to resources aimed at supporting their success.
Calcium Tartrate Tetrahydrate, Case Report of a Novel Human Kidney Stone
(Mary Ann Liebert, 2017-12-01) Kleinguetl, Colin; Williams, James C.; Ibrahim, Samar A.; Daudon, Michel; Bird, Erin T.; El Tayeb, Marawan M.; Anatomy and Cell Biology, School of Medicine
Background: Calcium tartrate tetrahydrate has been reported as the main mineral in urinary stones in rats that have significant tartrate in their diet, but in humans, there has been only one mention of calcium tartrate stones in the form of bladder stone, and that case was in Africa., Case Presentation: Patient is a 34-year-old Caucasian male who presented with typical symptoms of nephrolithiasis. CT abd/pelvis (renal stone protocol) revealed a 2 cm nonobstructing stone of the right renal pelvis. Patient underwent an uncomplicated right percutaneous nephrolithotomy and was noted to be stone free after surgery. Stone analysis was difficult with regard to determining composition, but was finally identified as calcium tartrate tetrahydrate., Conclusion: This was an unusual case, as this is the first recorded case of a calcium tartrate tetrahydrate outside of Africa. This type of stone had only been mainly described in rat models with dl-bitartrate in their diet. Our patient was an otherwise healthy, relatively muscular individual with no obvious source for this stone other than a vitamin and amino acid supplement that he takes regularly that contains l-carnitine (as tartrate) and choline (as bitartrate and citrate). The prevalence of this stone type is presently unknown, as stone analysis laboratories have not had the ability to recognize it. Although a connection between the supplement and stone formation is conjecture at this time, we believe this necessitates further investigation.
Contrasting histopathology and crystal deposits in kidneys of idiopathic stone formers who produce hydroxy apatite, brushite, or calcium oxalate stones
(Wiley, 2014-04) Evan, Andrew P.; Lingeman, James E.; Worcester, Elaine M.; Sommer, Andre J.; Phillips, Carrie L.; Williams, James C.; Coe, Fredric L.; Department of Anatomy & Cell Biology, School of Medicine
Our previous work has shown that stone formers who form calcium phosphate (CaP) stones that contain any brushite (BRSF) have a distinctive renal histopathology and surgical anatomy when compared with idiopathic calcium oxalate stone formers (ICSF). Here we report on another group of idiopathic CaP stone formers, those forming stone containing primarily hydroxyapatite, in order to clarify in what ways their pathology differs from BRSF and ICSF. Eleven hydroxyapatite stone formers (HASF) (2 males, 9 females) were studied using intra-operative digital photography and biopsy of papillary and cortical regions to measure tissue changes associated with stone formation. Our main finding is that HASF and BRSF differ significantly from each other and that both differ greatly from ICSF. Both BRSF and ICSF patients have significant levels of Randall's plaque compared with HASF. Intra-tubular deposit number is greater in HASF than BRSF and nonexistent in ICSF while deposit size is smaller in HASF than BRSF. Cortical pathology is distinctly greater in BRSF than HASF. Four attached stones were observed in HASF, three in 25 BRSF and 5-10 per ICSF patient. HASF and BRSF differ clinically in that both have higher average urine pH, supersaturation of CaP, and calcium excretion than ICSF. Our work suggests that HASF and BRSF are two distinct and separate diseases and both differ greatly from ICSF.
Detection of different kidney stone types: an ex vivo comparison of ultrashort echo time MRI to reference standard CT
(Elsevier, 2016-01) Ibrahim, El-Sayed H.; Cernigliaro, Joseph G.; Pooley, Robert A.; Bridges, Mellena D.; Giesbrandt, Jamie G.; Williams, James C.; Haley, William E.; Department of Anatomy and Cell Biology, School of Medicine
BACKGROUND AND PURPOSE: With the development of ultrashort echo time (UTE) sequences, it may now be possible to detect kidney stones by using magnetic resonance imaging (MRI). In this study, kidney stones of varying composition and sizes were imaged using both UTE MRI as well as the reference standard of computed tomography (CT), with different surrounding materials and scan setups. METHODS: One hundred and fourteen kidney stones were inserted into agarose and urine phantoms and imaged both on a dual-energy CT (DECT) scanner using a standard renal stone imaging protocol and on an MRI scanner using the UTE sequence with both head and body surface coils. A subset of the stones representing all composition types and sizes was then inserted into the collecting system of porcine kidneys and imaged in vitro with both CT and MRI. RESULTS: All of the stones were visible on both CT and MRI imaging. DECT was capable of differentiating between uric acid and nonuric acid stones. In MRI imaging, the choice of coil and large field of view (FOV) did not affect stone detection or image quality. The MRI images showed good visualization of the stones' shapes, and the stones' dimensions measured from MRI were in good agreement with the actual values (R(2)=0.886, 0.895, and 0.81 in the agarose phantom, urine phantom, and pig kidneys, respectively). The measured T2 relaxation times ranged from 4.2 to 7.5ms, but did not show significant differences among different stone composition types. CONCLUSIONS: UTE MRI compared favorably with the reference standard CT for imaging stones of different composition types and sizes using body surface coil and large FOV, which suggests potential usefulness of UTE MRI in imaging kidney stones in vivo.
Dual-Energy CT for Quantification of Urinary Stone Composition in Mixed Stones: A Phantom Study
(American Roentgen Ray Society, 2016-08) Leng, Shuai; Huang, Alice; Montoya, Juan; Duan, Xinhui; Williams, James C.; McCollough, Cynthia H.; Department of Anatomy & Cell Biology, IU School of Medicine
Purpose To demonstrate the feasibility of using dual-energy computed tomography to accurately quantify uric acid and non-uric-acid components in urinary stones having mixed composition. Materials and Methods A total of 24 urinary stones were analyzed with microCT to serve as the reference standard for uric acid and non-uric-acid composition. These stones were placed in water phantoms to simulate body attenuation of slim to obese adults and scanned on a third-generation dual-source scanner using dual-energy modes adaptively selected based on phantom size. CT number ratio, which is distinct for different materials, was calculated for each pixel of the stones. Each pixel was then classified as uric acid and non-uric-acid by comparing the CT number ratio with preset thresholds ranging from 1.1 to 1.7. Minimal, maximal and root-mean-square errors were calculated by comparing composition to the reference standard and the threshold with the minimal root-mean-square-error was determined. A paired t-test was performed to compare the stone composition determined with dual-energy CT with the reference standard obtained with microCT. Results The optimal CT number ratio threshold ranged from 1.27 to 1.55, dependent on phantom size. The root-mean-square error ranged from 9.60% to 12.87% across all phantom sizes. Minimal and maximal absolute error ranged from 0.04% to 1.24% and from 22.05% to 35.46%, respectively. Dual-energy CT and the reference microCT did not differ significantly on uric acid and non-uric-acid composition (P from 0.20 to 0.96, paired t-test). Conclusion Accurate quantification of uric acid and non-uric-acid composition in mixed stones is possible using dual-energy CT.
Impact of stone type on cavitation in burst wave lithotripsy
(Acoustical Society of America, 2018-12-26) Hunter, Christopher; Maxwell, Adam D.; Cunitz, Bryan; Dunmire, Barbrina; Sorensen, Mathew D.; Williams, James C.; Randad, Akshay; Bailey, Michael; Kreider, Wayne; Anatomy and Cell Biology, School of Medicine
Non-invasive kidney stone treatments such as shock wave lithotripsy (SWL) and burst wave lithotripsy (BWL) rely on the delivery of pressure waves through tissue to the stone. In both SWL and BWL, the potential to hinder comminution by exciting cavitation proximal to the stone has been reported. To elucidate how different stones alter prefocal cavitation in BWL, different natural and synthetic stones were treated in vitro using a therapy transducer operating at 350 kHz (peak negative pressure 7 MPa, pulse length 20 cycles, pulse repetition frequency 10 Hz). Stones were held in a confined volume of water designed to mimic the geometry of a kidney calyx, with the water filtered and degassed to maintain conditions for which the cavitation threshold (in the absence of a stone) matches that from in vivo observations. Stone targeting and cavitation monitoring were performed via ultrasound imaging using a diagnostic probe aligned coaxially with the therapy transducer. Quantitative differences in the extent and location of cavitation activity were observed for different stone types—e.g., “softer” stones (natural and synthetic) that disintegrate into “dusty” fragments produced larger prefocal cavitation clouds. Future work will focus on correlation of such cavitation metrics with stone fragmentation.
An in vivo demonstration of efficacy and acute safety of burst wave lithotripsy using a porcine model
(Acoustical Society of America, 2019-02-06) Wang, Yak-Nam; Kreider, Wayne; Hunter, Chris; Cunitz, Bryan W.; Thiel, Jeff; Starr, Frank; Dai, Jessica C.; Nazari, Yasser; Lee, Donghoon; Williams, James C.; Bailey, Micheal R.; Maxwell, Adam D.; Anatomy and Cell Biology, School of Medicine
Burst wave lithotripsy (BWL) is a new non-invasive method for stone comminution using bursts of sub-megahertz ultrasound. A porcine model of urolithiasis and techniques to implement BWL treatment has been developed to evaluate its effectiveness and acute safety. Six human calcium oxalate monohydrate stones (6–7 mm) were hydrated, weighed, and surgically implanted into the kidneys of three pigs. Transcutaneous stone treatments were performed with a BWL transducer coupled to the skin via an external water bath. Stone targeting and treatment monitoring were performed with a co-aligned ultrasound imaging probe. Treatment exposures were applied in three 10-minute intervals for each stone. If sustained cavitation in the parenchyma was observed by ultrasound imaging feedback, treatment was paused and the pressure amplitude was decreased for the remaining time. Peak negative focal pressures between 6.5 and 7 MPa were applied for all treatments. After treatment, stone fragments were removed from the kidneys. At least 50% of each stone was reduced to <2 mm fragments. 100% of four stones were reduced to <4 mm fragments. Magnetic resonance imaging showed minimal injury to the functional renal volume. This study demonstrated that BWL could be used to effectively fragment kidney stones with minimal injury.
Introduction of a Renal Papillary Grading System for Patients with Nephrolithiasis
(Mary Ann Liebert, Inc., 2015-12-03) Borofsky, Michael Seth; Paonessa, Jessica E.; Evan, Andrew P.; Williams, James C.; Coe, Fredric L.; Worcester, Elaine M.; Lingeman, James E.; Urology, School of Medicine
Introduction: An overlooked finding at the time of renal endoscopy for patients with nephrolithiasis is the appearance of the renal papillae. Recent work has demonstrated that it is possible to distinguish specific stone-forming phenotypes by endoscopic patterns of papillary appearance alone.1-4 These variable expressions are likely to have clinical significance; yet, the ability to pursue such research efforts remains limited by the lack of a standardized system to describe these findings. Herein, we describe a novel grading system designed to standardize and simplify the description of renal papillary appearance in stone formers at the time of endoscopy. Materials and Methods: Since 1999, 342 patients have been prospectively enrolled and given consent to be part of an NIH funded project studying the pathogenesis of stone formation at a single institution (Methodist Hospital, Indiana University Health). Patients have been treated and studied using both percutaneous and retrograde ureteroscopic approaches. Digital scopes are utilized when feasible along with fluoroscopy to map the affected renal unit(s), and stones are removed and analyzed individually when possible.5 Results: Four recurring abnormal papillary features were identified based upon the collective knowledge and expertise of the primary research team. Each variable was then quantitated based on the severity in appearance. Three features believed to be associated with papillary injury include ductal plugging, pitting, and loss of papillary contour. Ductal plugging is evident as either suburothelial deposits of yellow mineral or as dilated ducts of Bellini, presumably left behind after a plug has passed. These two subfeatures are considered the same for the purposes of grading. Pitting reflects crater-like erosion of the papillary surface. Loss of contour reflects global depression of the papilla relative to the surrounding tissue. Upon papillary inspection, each papilla receives a numerical grade from 0 to 2 for each of these measured domains. The three scores are then added together to create a sum total score regarding the degree of papillary injury ranging from 0 to 6. The fourth feature, the amount of Randall's plaque, is evident as white deposits along the papillary surface. It is not known to cause papillary injury6 and, as such, is designated with an alphabetical subscore (a-c) rather than a number. Each papilla then receives a final unique score incorporating both the sum numerical and alphabetical grade. Reference examples are shown in the accompanying video. Conclusions: The creation of a standardized system to describe the papillary appearance in stone formers has considerable clinical and academic utility. On a clinical level, it could be applied as a tool to document intraoperative findings and determine changes in papillary appearance over time in recurrent stone formers. It also has the potential to distinguish high-risk patients with more pressing needs of metabolic evaluations, medical therapy, and surveillance imaging. As a research tool, it would help create a common language to describe papillary appearance and improve collaboration between researchers. It also might allow surgeons to better correlate endoscopic findings to pathological findings and clinical outcomes such as stone analysis, associated metabolic diseases, risk of progressive renal injury, and stone recurrence.
Label-free proteomic methodology for the analysis of human kidney stone matrix composition.
(BMC, 2016) Witzmann, Frank A.; Evan, Andrew P.; Coe, Fredric L.; Worcester, Elaine M.; Lingeman, James E.; Williams, James C.; Department of Cellular & Integrative Physiology, IU School of Medicine
Background: Kidney stone matrix protein composition is an important yet poorly understood aspect of nephrolithiasis. We hypothesized that this proteome is considerably more complex than previous reports have indicated and that comprehensive proteomic profiling of the kidney stone matrix may demonstrate relevant constitutive differences between stones. We have analyzed the matrices of two unique human calcium oxalate stones (CaOx-Ia and CaOx-Id) using a simple but effective chaotropic reducing solution for extraction/solubilization combined with label-free quantitative mass spectrometry to generate a comprehensive profile of their proteomes, including physicochemical and bioinformatic analysis.` Results: We identified and quantified 1,059 unique protein database entries in the two human kidney stone samples, revealing a more complex proteome than previously reported. Protein composition reflects a common range of proteins related to immune response, inflammation, injury, and tissue repair, along with a more diverse set of proteins unique to each stone. Conclusion: The use of a simple chaotropic reducing solution and moderate sonication for extraction and solubilization of kidney stone powders combined with label-free quantitative mass spectrometry has yielded the most comprehensive list to date of the proteins that constitute the human kidney stone proteome. Electronic supplementary material: The online version of this article (doi:10.1186/s12953-016-0093-x) contains supplementary material, which is available to authorized users.

Browsing by Author "Williams, James C."

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