Comparative study of thulium fiber laser versus holmium:yttrium-aluminum-garnet laser for ureteric stone management with semi-rigid ureteroscopy: A prospective, single-center study.

Objective: To compare the efficacy and safety of thulium fiber laser (TFL) and holmium:yttrium-aluminum-garnet (Ho:YAG) laser for ureteric stone management with semi-rigid ureteroscopy. Methods: In a prospective study from January 2020 to December 2021, we compared 40 patients in each group who underwent semi-rigid ureteroscopic lithotripsy with TFL and that with Ho:YAG laser. Stone volume, stone density, stone fragmentation rates, total lasing time, total operative time, endoscopic vision, retropulsion and stone free rates were analyzed in both groups and compared. Results: Mean stone volume was comparable in the TFL group and the Ho:YAG laser group (282.45 [standard deviation, SD 139.79] mm3 vs. 279.49 [SD 312.52] mm3; p=0.964). Mean stone density was also comparable in the TFL group and the Ho:YAG laser group (1135.30 [SD 317.04] Hounsfield unit vs. 1131.75 [SD 283.03] Hounsfield unit; p=0.959). The mean stone fragmentation rates calculated as stone volume divided by lasing time were 25.85 (SD 10.61) mm3/min and 21.37 (SD 14.13) mm3/min in the TFL group and the Ho:YAG laser group, respectively (p=0.113). The mean total lasing time (10.15 [SD] 4.69 min vs. 11.43 [SD 4.56] min; p=0.222), mean operative time (25.13 [SD 9.51] min vs. 25.54 [SD 10.32] min; p=0.866), and mean total hospital stay (2.62 [SD 0.77] days vs. 2.61 [SD 0.84] days; p=0.893) were comparable in the TFL group and in the Ho:YAG group. The vision was better and retropulsion was less in the TFL group. The stone-free rate at 1 month postoperatively was slightly better in the TFL group (100% vs. 90%; p=0.095). Conclusion: TFL technology was associated with the comparable total surgical time, total lasing time, and stone fragmentation rate with Ho:YAG laser. However, TFL had better endoscopic vision, lesser stone retropulsion, and slightly better stone-free rates.

Long-term outcomes of urethral balloon dilation for anterior urethral stricture: A prospective cohort study.

Objective: To prospectively follow up a cohort of anterior urethral stricture disease patients managed with balloon dilation (BD) for 3 years to evaluate the long-term outcomes and to study factors that contribute to recurrence. Methods: This study included men who had urethral BD for significant anterior urethral stricture disease between January 2017 and March 2019. Data about the patient age, stricture characteristics, and recurrence date were recorded, along with information on postoperative indwelling catheter use and operative complications. Furthermore, information about the self-calibration procedure was collected and where available, free flow (FF) measurements during the follow-up period were recorded and analyzed. Success was defined as a lack of symptoms and acceptable FF rates (maximum flow rate>12 mL/s). Results: The final analysis was conducted on 187 patients. The mean follow-up period was 37 months. The long-term overall success rate at the end of our study was 66.8%. Our recurrence rate was 7.4% at 12 months, 24.7% at 24 months, and reached 33.2% at the end of our study. The time to recurrence ranged from 91 days to 1635 days, with a mean of 670 days. The stricture-free survival was significantly shorter with lengthy peno-bulbar (p=0.031) and multiple strictures (p=0.015), and in the group of patients who were not committed to self-calibration protocol (p<0.011). However, post-procedural self-calibration was the most important factor that may have decreased the incidence of recurrence (odds ratio=5.85). Adjuvant self-calibration after BD not only reduced the recurrence rate from 85.4% in the non-self-calibration group to 15.1% in the self-calibration one (p<0.001), but also improved the overall stricture-free survival and FF parameters. Conclusion: Urethral BD has a high recurrence rate in the long-term, especially with long and multiple strictures. Adjuvant self-calibration has proven to reduce the recurrence risk and the need for re-intervention.

Primary Ewing sarcoma/primitive neuroectodermal tumors of the kidney: Case series of eight cases from a single center with follow-up details.

Introduction: We aim to share the experience of a single center in the management of eight cases of renal primitive neuroectodermal tumor (PNET) which are uncommon, aggressive tumors. The objectives were to study the presentation of the disease, the treatment offered and its outcomes, and the comparison of the treatment with published literature. Methods: The single-center renal PNET data of all patients were retrospectively reviewed from 2011 to 2022. Renal PNET was seen in eight patients. Minimum follow-up period of 1 year was required. Results: Male-to-female ratio was 7:1. The mean age was 26.5 years. All were locally advanced tumors on presentation. One patient had an inferior vena cava thrombus, one patient had metastases on presentation, and two patients had tumor extending to paranephric space. The diagnosis was made by histopathology supported by immunohistochemistry showing CD99 positivity. All patients were treated with radical nephrectomy, followed by chemotherapy in all and radiotherapy in three patients. Two patients expired at 3½ and 6 years after surgery, the remaining six are alive at a median follow-up period of 34.5 months. Conclusion: Renal PNET is an uncommon renal tumor which is aggressive and requires multimodal therapy for prolonged survival.

Methane Quantification Performance of the Quantitative Optical Gas Imaging (QOGI) System Using Single-Blind Controlled Release Assessment.

Quantitative optical gas imaging (QOGI) system can rapidly quantify leaks detected by optical gas imaging (OGI) cameras across the oil and gas supply chain. A comprehensive evaluation of the QOGI system's quantification capability is needed for the successful adoption of the technology. This study conducted single-blind experiments to examine the quantification performance of the FLIR QL320 QOGI system under near-field conditions at a pseudo-realistic, outdoor, controlled testing facility that mimics upstream and midstream natural gas operations. The study completed 357 individual measurements across 26 controlled releases and 71 camera positions for release rates between 0.1 kg Ch4/h and 2.9 kg Ch4/h of compressed natural gas (which accounts for more than 90% of typical component-level leaks in several production facilities). The majority (75%) of measurements were within a quantification factor of 3 (quantification error of -67% to 200%) with individual errors between -90% and 831%, which reduced to -79% to +297% when the mean of estimates of the same controlled release from multiple camera positions was considered. Performance improved with increasing release rate, using clear sky as plume background, and at wind speeds ≤1 mph relative to other measurement conditions.

Comprehensive Evaluation and Arthroscopic Management of Circumferential Labral Tears Following Traumatic First Time Shoulder Dislocation: A Case Report and Review.

Introduction: Pan-labral tears, commonly associated with recurrent shoulder dislocations, are a well-documented pathology. However, circumferential pan-labral tears following a first-time shoulder dislocation represent a rare and scarcely reported entity in the literature. Accurate diagnosis requires a comprehensive clinical history, physical examination, and further evaluation, often involving MRI. Even with advanced imaging, the acute nature of the injury can lead to the oversight of pan-labral tears, necessitating arthroscopic assessment for definitive diagnosis. Repairing such extensive glenoid labral tears presents a challenging task, requiring skilled surgeons to utilize accessory portals and percutaneous techniques for optimal visualization and anchor placement trajectory. To the best of our knowledge, this case report represents the first documentation of a pan-labral tear associated with a 1st-time shoulder dislocation. Case Report: A 27-year-old Asian male presented with pain and limited range of motion in the left shoulder following a single episode of anterior shoulder dislocation during cricket. Initial X-rays were unremarkable, but subsequent MRI revealed an anteroinferior labral tear with intact rotator cuffs. Arthroscopic evaluation disclosed a pan-labral tear, prompting meticulous repair under general and locoregional anesthesia. The patient achieved full recovery postoperatively. Conclusion: While pan-labral tears are typically linked to recurrent dislocations, this case underscores their occurrence in a 1st-time traumatic shoulder dislocation without overt clinical signs or fractures. Arthroscopic repair demands careful intraoperative planning to achieve optimal tensioning and alignment of labral and capsular tissues. This report contributes to the limited literature on pan-labral tears associated with initial shoulder dislocations, emphasizing the importance of arthroscopic evaluation for accurate diagnosis and successful repair.

3D Imaging Reveals Changes in the Neurovascular Architecture of the Murine Calvarium with Aging.

Calvarial nerves, along with vasculature, influence skull formation during development and following injury, but it remains unclear how calvarial nerves are spatially distributed during postnatal growth and aging. Studying the spatial distribution of nerves in the skull remains challenging due to a lack of methods to image and quantify 3D structures in intact bone. To visualize calvarial 3D neurovascular architecture, we imaged nerves and endothelial cells with lightsheet microscopy. We employed machine-learning-based segmentation to facilitate high-resolution characterization from post-natal day 0 (P0) to Week 80 (80wk). We found that TUBB3+ nerve density decreased with aging with the frontal bone demonstrating earlier onset age-related nerve loss than the parietal bone. In addition, nerves in the periosteum and dura mater exhibited similar yet distinct temporal patterns of nerve growth and loss. While no difference was observed in TUBB3+ nerves during skeletal maturation (P0 → 12wk), we did observe an increase in the volume of unmyelinated nerves in the dura mater. Regarding calvarial vasculature, larger CD31hiEmcn- vessel density increased with aging, while CD31hiEmcnhi vessel density was reduced. For all nerve markers studied, calvarial nerves maintained a preferential spatial association with CD31hiEmcnhi vessels that decreased with aging. Additionally, we used a model of Apert syndrome that demonstrates early coronal suture fusion to explore the impact of suture-related disease on neurovascular architecture. We identified a mild dysregulation of dural nerves and minor shifts in vessel populations. Collectively, this 3D, spatiotemporal characterization of calvarial nerves throughout the lifespan and provides new insights into age-induced neurovascular architecture.

Large-Scale Controlled Experiment Demonstrates Effectiveness of Methane Leak Detection and Repair Programs at Oil and Gas Facilities.

Most jurisdictions around the globe use leak detection and repair (LDAR) programs to find and fix methane leaks from oil and gas operations. In this work, we empirically evaluate the efficacy of LDAR programs using a large-scale, bottom-up, randomized controlled field experiment across ∼200 oil and gas sites in Red Deer, Canada. We find that tanks are the single largest source of emissions, contributing to nearly 60% of the total emissions. The average number of leaks at treatment sites that underwent repair reduced by ∼50% compared to the control sites. Although control sites did not see a reduction in the number of leaks, emissions reduced by approximately 36%, suggesting potential impact of routine maintenance activities to find and fix large leaks. By tracking tags on leaking equipment over time, we find a high degree of persistence; leaks that are repaired remain fixed in follow-up surveys, while non-repaired leaks remain emitting at a similar rate, suggesting that any increase in observed leak emissions following LDAR surveys are likely from new leaks. Our results show that a focus on equipment and sites that are prone to high emissions, such as tanks and oil sites, is key to cost-effective mitigation.

The Role of Emission Size Distribution on the Efficacy of New Technologies to Reduce Methane Emissions from the Oil and Gas Sector.

Methane emissions from oil and gas operations exhibit skewed distributions. New technologies such as aerial-based leak detection surveys promise cost-effective detection of large emitters (greater than 10 kg/h). Recent policies such as the US Environmental Protection Agency (EPA) methane rule that allow the use of new technologies as part of leak detection and repair (LDAR) programs require a demonstration of equivalence with existing optical gas imaging (OGI) based LDAR programs. In this work, we illustrate the impact of emission size distribution on the equivalency condition between the OGI and site-wide survey technologies. Emission size distributions compiled from aerial measurements include significantly more emitters between 1 and 10 kg/h and lower average emission rates for large emitters compared to the emission distribution in the EPA rule. As a result, we find that equivalence may be achieved at lower site-wide survey frequencies when using technologies with detection thresholds below 10 kg/h, compared to the EPA rule. However, equivalence cannot be achieved with a detection threshold of 30 kg/h at any survey frequency, because most emitters across most US basins exhibit emission rates below 30 kg/h. We find that equivalence is a complex tradeoff among technology choice, design of LDAR programs, and survey frequency that can have more than one unique solution set.

Glycolate oxidase-1 gene variants influence the risk of hyperoxaluria and renal stone development.

PURPOSE: Oxalate is an excellent calcium ion attractor with great abundance in the human body, and the liver is the major source of oxalate. The Glycolate oxidase-1 (GOX1) gene is solely responsible for the glycolate and glyoxylate metabolism and produces oxalate. This study has been designed to comprehend the association of genetic variants of the GOX1 gene with the risk of hyperoxaluria and renal stone disease in the Indian population. METHOD: The present study is a candidate gene approach prospective case-control study carried out on 300 participants (150 cases and 150 controls) at Muljibhai Patel Urological Hospital, Gujarat, India. Biochemical parameters, including serum levels of calcium, creatinine, parathyroid hormone, and 24-h urine metabolites, were performed. The genotyping of GOX1 gene variants rs6086287, rs2235250, rs2255183, and rs2294303 was performed using a customized TaqMan assay probe by RT-PCR. RESULT: Parathyroid hormone, serum creatinine, and urine metabolites were significantly elevated in nephrolithiasis compared to healthy individuals. All mutated homozygous genotypes GG (rs6086287), TT (rs2235250), GG (rs2255183), and CC (rs2294303) were significantly associated with a high risk of renal stone disease. Individuals diagnosed with hyperoxaluria and carrying TG (rs6086287), AG (rs2255183), and TT (rs2294303) genotypes have a significantly high risk of renal stone disease. Moreover, haplotype analysis and correlation analysis also confirmed the strong association between genetic variants and nephrolithiasis. CONCLUSION: Genetic variants of the GOX1 genes were associated with renal stone disease. In the presence of risk genotype and hyperoxaluria, the susceptibility to develop renal stone disease risk gets modulated.

Retroperitoneal approach for robot living donor nephrectomy: A step-by-step description of technical nuances.

Open, pure or hand-assisted laparoscopic, natural orifice transluminal endoscopic surgical (NOTES) and robotic approaches (Transperitoneal or retroperitoneal) are the described approaches for living donor nephrectomy. We describe the procedural steps of a robotic living donor nephrectomy (RLDN) retroperitoneal (RRLDN) technique using a da Vinci X surgical system and three robotic arms. This is the first reported case with the retroperitoneal robotic approach. The procedure in brief is as follows. First, with the patient placed in full flank position, the camera port is placed at the level of the Petit's triangle apex. Retroperitoneal space is created by turning the index finger in a 180° movement through this port and a gloves balloon. The second 8mm port was inserted, 8 cm far from the first port, The peritoneum is reflected medially and downward off of the transversus abdominis muscle laparoscopically, respectively along the anterior and posterior axillary line; 3-5 cm caudally to the last one, a 12 mm AirSeal® assistant port is placed in the same manner. Only then, the port is placed under direct vision. The robotic ports placement will result in a caudally convex arc. This technique, due to the extensive use of the surgeon index, implies fast access to the retroperitoneum, protects the underlying anatomical structures from damage, and, due to the trocar positioning along an arc, lowers the arm conflict risk.

Multimodality imaging reveals angiogenic evolution in vivo during calvarial bone defect healing.

The healing of calvarial bone defects is a pressing clinical problem that involves the dynamic interplay between angiogenesis and osteogenesis within the osteogenic niche. Although structural and functional vascular remodeling (i.e., angiogenic evolution) in the osteogenic niche is a crucial modulator of oxygenation, inflammatory and bone precursor cells, most clinical and pre-clinical investigations have been limited to characterizing structural changes in the vasculature and bone. Therefore, we developed a new multimodality imaging approach that for the first time enabled the longitudinal (i.e., over four weeks) and dynamic characterization of multiple in vivo functional parameters in the remodeled vasculature and its effects on de novo osteogenesis, in a preclinical calvarial defect model. We employed multi-wavelength intrinsic optical signal (IOS) imaging to assess microvascular remodeling, intravascular oxygenation (SO2), and osteogenesis; laser speckle contrast (LSC) imaging to assess concomitant changes in blood flow and vascular maturity; and micro-computed tomography (µCT) to validate volumetric changes in calvarial bone. We found that angiogenic evolution was tightly coupled with calvarial bone regeneration and corresponded to distinct phases of bone healing, such as injury, hematoma formation, revascularization, and remodeling. The first three phases occurred during the initial two weeks of bone healing and were characterized by significant in vivo changes in vascular morphology, blood flow, oxygenation, and maturity. Overall, angiogenic evolution preceded osteogenesis, which only plateaued toward the end of bone healing (i.e., four weeks). Collectively, these data indicate the crucial role of angiogenic evolution in osteogenesis. We believe that such multimodality imaging approaches have the potential to inform the design of more efficacious tissue-engineering calvarial defect treatments.

Initial experience of comparison between two slimmest single-use flexible ureteroscopes: Indoscope Sleek (Bioradmedisys™) Versus Uscope PU3033A (Pusen™): A single-center prospective study.

PURPOSE: A single-use digital flexible ureteroscope (fURS) has become a cost-effective alternative option to reusable fURS. The requirement of large-diameter access sheath for passage of 9.5 Fr single-use fURS has not always achieved in the first attempt in all cases leading to stage stone clearance. Recently, two slimmest single-use digital disposable fURSs have been introduced by Bioradmedisys™ and Pusen™ to mitigate the accessibility problem, without or with small size access sheath. Primary objective was to compare in vivo performance and surgical outcomes with two single-use fURS: 7.5Fr Indoscope (Bioradmedisys™, Pune, India) and 7.5Fr Uscope PU3033A (Pusen, Zhuhai, China). METHODS: 60 patients undergoing Retrograde Intrarenal Surgery (RIRS) with < 2 cm renal stones were prospectively randomized into: Group A (30 patients) for Indoscope and Group B (30 patients) for Uscope PU3033A. Pre-operative, intra-operative, and post-operative parameters were evaluated. In vivo visibility and maneuverability were rated on 5-point Likert scale by the operating surgeon. At one-month stone clearance was assessed with ultrasound and X-ray KUB. Data were analyzed using SPSS 23.0. RESULTS: Patient demographics and stone characteristics were comparable in both groups. Indoscope had significantly higher visibility (p < 0.05) than Uscope; however, the maneuverability scores were comparable between both the groups (p > 0.05). 28 patients in group A and 26 patients in group B achieved complete stone clearance (p = 0.38). Scope failure was observed in 1 case of group B (p = 0.31). CONCLUSION: We conclude that 7.5Fr Indoscope has better vision than 7.5Fr Uscope and the rest of in vivo performances were comparable with similar outcomes and complications among both scopes.

Study of the predictive factors affecting outcomes of patients undergoing transperitoneal laparoscopic donor nephrectomy.

PURPOSE: We aim to study the preoperative and intraoperative factors and compare against specific outcomes in patients undergoing transperitoneal laparoscopic donor nephrectomy and see if we could find what were the predictive factors for these outcomes. METHODS: This is a prospective cohort study done in a single high-volume transplant center. 153 kidney donors were evaluated over a period of 1 year. The preoperative factors such as age, gender, smoking status, obesity, visceral obesity, perinephric fat thickness, number of vessels, anatomic abnormalities, comorbidities, and side of kidney and intraoperative factors such as lay of colon on the kidney, height of splenic or hepatic flexure of colon, loaded or unloaded colon, and sticky mesenteric fat were compared against specific outcomes such as duration of surgery, duration of hospital stay, postoperative paralytic ileus, and postoperative wound complications. RESULTS: Multivariate logistic regression models were used to study the variables of interest against the various outcomes. There were three positive risk factors for increased hospital stay, which were perinephric fat thickness and height of splenic or hepatic flexure of colon and smoking history. There was one positive risk factor for postoperative paralytic ileus which is lay of colon with relation to kidney and there was one positive risk factor for postoperative wound complication which was visceral fat area. CONCLUSION: The predictive factors for adverse postoperative outcomes after transperitoneal laparoscopic donor nephrectomy were perinephric fat thickness, height of splenic or hepatic flexure, smoking status, lay or redundancy of colon with relation to kidney and visceral fat area.

Toward Multiscale Measurement-Informed Methane Inventories: Reconciling Bottom-Up Site-Level Inventories with Top-Down Measurements Using Continuous Monitoring Systems.

Government policies and corporate strategies aimed at reducing methane emissions from the oil and gas sector increasingly rely on measurement-informed, site-level emission inventories, as conventional bottom-up inventories poorly capture temporal variability and the heavy-tailed nature of methane emissions. This work is based on an 11-month methane measurement campaign at oil and gas production sites. We find that operator-level top-down methane measurements are lower during the end-of-project phase than during the baseline phase. However, gaps persist between end-of-project top-down measurements and bottom-up site-level inventories, which we reconcile with high-frequency data from continuous monitoring systems (CMS). Specifically, we use CMS to (i) validate specific snapshot measurements and determine how they relate to the temporal emission profile of a given site and (ii) create a measurement-informed, site-level inventory that can be validated with top-down measurements to update conventional bottom-up inventories. This work presents a real-world demonstration of how to reconcile CMS rate estimates and top-down snapshot measurements jointly with bottom-up inventories at the site level. More broadly, it demonstrates the importance of multiscale measurements when creating measurement-informed, site-level emission inventories, which is a critical aspect of recent regulatory requirements in the Inflation Reduction Act, voluntary methane initiatives such as the Oil and Gas Methane Partnership 2.0, and corporate strategies.

Stage Migration in Renal Malignancies in COVID Era: A Single-Center Analysis.

The COVID-19 disease, caused by SARS-CoV-2 virus, attained the status of a pandemic by March 2020. There was apprehension among patients suffering from renal malignancies about balancing cancer treatment and preventing COVID-19 infection transmission. We analyzed 184 patients with renal malignancies retrospectively, who presented to our institute over 2 years: 91 patients of renal malignancies in pre-COVID era (March 2019-Feb 2020) and 93 patients in COVID era (March 2020-Feb 2021). The parameters analyzed were age, tumor size, clinical presentation, clinical stage, pathological stage, nuclear grade, and presence of metastasis. Level of significance was kept at 95%, and p value <0.05 was considered significant. The age of patients was comparable in both groups (p: 0.381). Clinical presentation was also similar in both groups whereas there were more cases diagnosed during routine evaluation in pre-COVID era (p: 0.022). Tumor size was 5.84 ± 3.03cm vs. 7.10±3.83cm (p: 0.017) in pre-COVID vs. COVID era, respectively. Patients in COVID era had significantly higher clinical stage (p = 0.041), pathological stage (p =0.027), nuclear grade (p = 0.007), and presence of metastasis (p = 0.005) as compared to pre-COVID era. Patients, who underwent Nephron-sparing surgery, also had higher pathological stage in COVID era. COVID overshadowed the management of renal malignancies. There was a clear shift and stage migration in patients of renal malignancies in COVID era as compared to pre-COVID era, probably because of less routine health check-ups and patients deferring hospital visits due to fear of contracting COVID infection.

Quantification of Cerebral Vascular Autoregulation Immediately Following Resuscitation from Cardiac Arrest.

Cerebral vascular autoregulation is impaired following resuscitation from cardiac arrest (CA), and its quantification may allow assessing CA-induced brain injury. However, hyperemia occurring immediately post-resuscitation limits the application of most metrics that quantify autoregulation. Therefore, to characterize autoregulation during this critical period, we developed three novel metrics based on how the cerebrovascular resistance (CVR) covaries with changes in cerebral perfusion pressure (CPP): (i) Î¸CVR, which quantifies the CVR vs CPP gradient, (ii) a CVR-based transfer function analysis, and (iii) CVRx, the correlation coefficient between CPP and CVR. We tested these metrics in a model of asphyxia induced CA and resuscitation using seven adult male Wistar rats. Mean arterial pressure (MAP) and cortical blood flow recorded for 30 min post-resuscitation via arterial cannulation and laser speckle contrast imaging, were used as surrogates of CPP and cerebral blood flow (CBF), while CVR was computed as the CPP/CBF ratio. Using our metrics, we found that the status of cerebral vascular autoregulation altered substantially during hyperemia, with changes spread throughout the 0-0.05 Hz frequency band. Our metrics push the boundary of how soon autoregulation can be assessed, and if validated against outcome markers, may help develop a reliable metric of brain injury post-resuscitation.

Vascular phenotyping of the invasive front in breast cancer using a 3D angiogenesis atlas.

OBJECTIVE: Vascular remodeling at the invasive tumor front (ITF) plays a critical role in progression and metastasis of triple negative breast cancer (TNBC). Therefore, there is a crucial need to characterize the vascular phenotype (i.e. changes in the structure and function of vasculature) of the ITF and tumor core (TC) in TNBC. This requires high-resolution, 3D structural and functional microvascular data that spans the ITF and TC (i.e. ∼4-5 mm from the tumor's edge). Since such data are often challenging to obtain with most conventional imaging approaches, we employed a unique "3D whole-tumor angiogenesis atlas" derived from orthotopic xenografts to characterize the vascular phenotype of the ITF and TC in TNBC. METHODS: First, high-resolution (8 µm) computed tomography (CT) images of "whole-tumor" microvasculature were acquired from eight orthotopic TNBC xenografts, of which three tumors were excised at post-inoculation day 21 (i.e. early-stage) and five tumors were excised at post-inoculation day 35 (i.e. advanced-stage). These 3D morphological CT data were combined with soft tissue contrast from MRI as well as functional data generated in silico using image-based hemodynamic modeling to generate a multi-layered "angiogenesis atlas". Employing this atlas, blood vessels were first spatially stratified within the ITF (i.e. ≤1 mm from the tumor's edge) and TC (i.e. >1 mm from the tumor's edge) of each tumor xenograft. Then, a novel method was developed to visualize and characterize microvascular remodeling and perfusion changes in terms of distance from the tumor's edge. RESULTS: The angiogenesis atlas enabled the 3D visualization of changes in tumor vessel growth patterns, morphology and perfusion within the ITF and TC. Early and advanced stage tumors demonstrated significant differences in terms of their edge-to-center distributions for vascular surface area density, vascular length density, intervessel distance and simulated perfusion density (p â‰ª 0.01). Elevated vascular length density, vascular surface area density and perfusion density along the circumference of the ITF was suggestive of a preferential spatial pattern of angiogenic growth in this tumor cohort. Finally, we demonstrated the feasibility of differentiating the vascular phenotypes of ITF and TC in these TNBC xenografts. CONCLUSIONS: The combination of a 3D angiogenesis atlas and image-based hemodynamic modeling heralds a new approach for characterizing the role of vascular remodeling in cancer and other diseases.

Cognitive-motor dual-task interference in adults with sickle cell disease.

BACKGROUND: Sickle cell disease (SCD) is a genetic disorder that causes physical and cognitive impairment due to hemolysis, painful vaso-occlusion episodes, joint avascular necrosis, and strokes. As individuals with SCD age and develop conditions impacting their physical and cognitive function, their ability to multitask successfully and safely may decline. Cognitive-motor dual-task interference occurs when there is deterioration in one or both tasks while dual-tasking relative to single-tasking. Dual-task assessment (DTA) is a valuable measure of physical and cognitive function; however, there is limited data on DTA in adults with SCD. RESEARCH QUESTION: Is DTA a feasible and safe method of measuring physical and cognitive function in adults with SCD? What patterns of cognitive-motor interference occur in adults with SCD? METHODS: We enrolled 40 adults with SCD (mean age 44 years, range 20-71) in a single-center prospective cohort study. We used usual gait speed as the measure of motor performance and verbal fluency (F, A, and S) as the measure of cognitive performance. We measured feasibility as the proportion of consented participants able to complete the DTA. We calculated the relative dual-task effect (DTE %) for each task and identified patterns of dual-task interference. RESULTS: Most consented participants completed the DTA (91%, 40/44) and there were no adverse events. There were 3 main dual-task interference patterns for the first trial using letter 'A': Motor Interference (53%, n = 21), Mutual Interference (23%, n = 9), and Cognitive-Priority Tradeoff (15%, n = 6). For the second trial using letter 'S', there were two main dual-task interference patterns: Cognitive-Priority Tradeoff (53%, n = 21) and Motor Interference (25%, n = 10). STATEMENT OF SIGNIFICANCE: DTA was feasible and safe in adults with SCD. We identified specific patterns of cognitive-motor interference. This study supports further evaluation of DTA as a potentially useful tool to measure physical and cognitive function in ambulatory adults with SCD.

Vascular-centric mapping of in vivo blood oxygen saturation in preclinical models.

Assessing intravascular blood oxygen saturation (SO2) is crucial for characterizing in vivo microenvironmental changes in preclinical models of injury and disease. However, most conventional optical imaging techniques for mapping in vivo SO2 assume or compute a single value of the optical path-length in tissue. This is especially detrimental when mapping in vivo SO2 in experimental disease or wound healing models that are characterized by vascular and tissue remodeling. Therefore, to circumvent this limitation we developed an in vivo SO2 mapping technique that utilizes hemoglobin-based intrinsic optical signal (IOS) imaging combined with a vascular-centric estimation of optical path-lengths. In vivo arterial and venous SO2 distributions derived with this approach closely matched those reported in the literature, while those derived using the single path-length (i.e. conventional) approach did not. Moreover, in vivo cerebrovascular SO2 strongly correlated (R2 > 0.7) with changes in systemic SO2 measured with a pulse oximeter during hypoxia and hyperoxia paradigms. Finally, in a calvarial bone healing model, in vivo SO2 assessed over four weeks was spatiotemporally correlated with angiogenesis and osteogenesis (R2 > 0.6). During the early stages of bone healing (i.e. day 10), angiogenic vessels surrounding the calvarial defect exhibited mean SO2 that was elevated by10 % (p < 0.05) relative to that observed at a later stage (i.e., day 26), indicative of their role in osteogenesis. These correlations were not evident with the conventional SO2 mapping approach. The feasibility of our wide field-of-view in vivo SO2 mapping approach illustrates its potential for characterizing the microvascular environment in applications ranging from tissue engineering to cancer.

SPP1 and UMOD gene variants are synergistically associated with risk of renal stone disease.

OBJECTIVE: Calcium and oxalate are the most abundant metabolites present in the stone matrix. The SPP1 and UMOD gene has specific expression in kidneys and are involved in various stages of stone formation. Therefore, genetic variants in the SPP1 and UMOD genes may enhance the development of renal stone disease. This study has been designed to understand the association of genetic variants of SPP1 and UMOD genes with renal stone disease. MATERIALS AND METHOD: A prospective study has been carried out, including 150 renal stone disease patients and 150 healthy individuals. Biochemical parameters were performed, including serum calcium levels, creatinine, parathyroid hormone, and 24-Hour urine metabolites. The genotyping of SPP1 (rs1126616) and UMOD (rs4293393) gene variants were performed using a customized TaqMan probe. T-test was used for continuous biochemical data analysis. The Chi-square test has been applied to assess the risk of a particular genotype associated with renal stone disease. In addition, correlation analysis for biochemical parameters and genetic variants with the renal stone disease has been performed using Shapley additive explanations (SHAP) values calculated with the help of the pycaret library. RESULT: Renal stone patients had significantly higher levels of parathyroid hormone (93.37 ± 52.78 pg/ml vs 64.67 ± 31.50 pg/ml, P=<0.0001), serum creatinine (0.94 ± 0.38 mg/dl vs 0.77 ± 0.17 mg/dl, P=<0.0001) and 24hr urine metabolites in comparison to the healthy controls. Heterozygous (CT) variant of SPP1 and homozygous (GG) variant of UMOD genes were significantly associated with an increased risk of developing the renal stone disease (p = 0.0100, OR = 2.06, 95 %CI = 1.13-3.75; p=<0.0001, OR = 5.773, 95 % CI = 2.03-16.38, respectively). Individuals with hyperparathyroidism and CC (SPP1) and GG (UMOD) genotypes have a high risk (P = 0.0055, OR = 2.75, 95 %CI = 1.35-5.67; P = 0.0129, OR = 10.03, 95 %CI = 1.60-110.40, respectively) of developing a renal stone. In addition, individuals with hypercalciuria and TT genotype of SPP1 (P = 0.0112, OR = 2.92, 95 % CI = 1.33-6.35), AG genotype of UMOD (P=<0.0001, OR = 5.45, 95 %CI = 2.24-13.96) and GG genotype of UMOD (P=<0.0001, OR = 10.02, 95 %CI = 3.53-24.63) have high risk of developing renal stones. Moreover, Individuals with hyperoxaluria and AG + GG (UMOD) genotype have a greater risk (P=<0.0001, OR = 7.35, 95 % CI = 3.83-13.68) of developing a renal stone. The renal stone risk was persistent (P=<0.0002, OR = 2.44, 95 % CI = 1.52-3.86) when analyzed for the synergistic effect of risk genotypes of SPP1 (CT) and UMOD (GG) gene. Further, correlation analysis also confirmed the strong association between genetic variants and renal stone development. CONCLUSION: Genetic variants of the SPP1 and UMOD genes were associated with renal stone disease. In the presence of risk genotype and hyperparathyroidism, hypercalciuria, and hyperoxaluria, the susceptibility to develop the renal stone disease risk gets modulated.