Systematic Literature Review of the Presentation and Management of Pediatric Relapsing Polychondritis.

INTRODUCTION: Pediatric Relapsing Polychondritis (RP) is a rare autoimmune disorder that causes inflammation and damage to cartilage in children. Common symptoms include pain, swelling and deformities in the ears, nose, trachea, joints, and eyes. The lack of research on the pediatric population necessitates further evaluation of the literature on pediatric RP to summarize existing patterns in presentation, management, and treatment. METHODS: A systematic review was conducted on PubMed and Embase from 1947 to April 2023 on RP in patients under 21 years old abiding by the 2020 PRISMA checklist. Only patient presentations meeting McAdam criteria for RP and including information on management were included. RESULTS: From the 304 initial studies, 54 studies were included for final analysis with a total of 68 patients, who were predominantly female (65%). With a median diagnostic delay of 1 year, the mean age of onset was 12 years old. The most common symptoms on presentation included bilateral auricular chondritis (69%), nasal cartilage inflammation (62%), and respiratory tract chondritis (63%). The most commonly reported information in the literature for the initial workup usually included CT/MRI (72%), bronchoscopy (57%), biopsy (51%), and labs (88%), which most commonly displayed elevated ESR (59%). The most common medications were corticosteroids (91%) and methotrexate (35%) and the most common procedural treatment was tracheostomy (38%). The most efficacious treatment options were monoclonal antibodies (87%, n = 15) and corticosteroids (66%, n = 62) used in 22% and 91% of patients, respectively. The most commonly used monoclonal antibody therapy was infliximab (13%, n = 9). CONCLUSION: The most common presentation for pediatric RP includes chondritis of the ear, nose, and respiratory tract. The most effective treatment options include corticosteroids and monoclonal antibody therapy, such as infliximab. Our findings highlight increasing remission achieved with anti-rheumatic drugs and monoclonal antibody treatment, especially alongside corticosteroids.

Additive Manufacturing of SmartEx QD 100 Designed Oral Three-Dimensional Printlets Containing Isoniazid for Immediate Gastric Release by Selective Laser Sintering.

The selection of appropriate materials and compatibility of selected materials with drugs and formulations are limiting steps in three-dimensional printing technology. In this study, SmartEx QD 100 (SM QD 100) was introduced as a novel, coprocessed, unexplored excipient that can be used in SLS-mediated 3D printing. The current study aimed to evaluate the feasibility of fabricating SM QD 100 containing INH-embedded SLS-mediated immediate gastric release tablets. The prepared physical mixtures were subjected to the fabrication of 3D printlets by using SLS-mediated 3D printing. The fabricated 3D printlets were subjected to physicochemical characterization by using various analytical techniques. After oral administration of sintered 3D printlets to rabbits, samples were collected and pharmacokinetic parameters were analyzed using the developed LC-APCI-MS/MS method. The optimized batch was able to release 100% INH within 15 min, which confirmed the immediate gastric release. Similarly, sintered 3D printlets were stable under accelerated stability conditions for three months. Finally, the pharmacokinetic parameters revealed the rate and extent of absorption of INH from sintered 3D printlets. As evidenced by in vitro and in vivo analyses, SM QD 100 was able to sinter SLS-mediated INH-embedded stable immediate gastric release tablets. SM QD 100 is a novel material for SLS-mediated 3D printing in pharmaceutical applications.

Management of Vertebral Defects, Anal Atresia, Cardiac Defects, Tracheoesophageal Fistula or Atresia, Renal Anomalies, and Limb Abnormalities (VACTERL) in a Child With Complex Medical Needs in the Foster Care System: A Pediatric Case Study.

Vertebral defects, anal atresia, cardiac defects, tracheoesophageal fistula or atresia, renal anomalies, and limb abnormalities (VACTERL) association is a complex congenital condition characterized by the presence of malformations that affect various organ systems. Most children born with VACTERL association require surgery shortly after birth, often undergoing multiple procedures during infancy, which can lead to a wide range of physical challenges. The unique combination of malformations in these children in addition to having complex care needs that need to be met can result in physical and social difficulties in their daily lives, affecting both their own and their caregivers' quality of life. In some cases, children with complex medical needs are placed in foster care. When children with complex health needs enter the foster care system, there is a risk of overwhelming the caretaker, leading to their needs continuing to be unmet. Pediatricians have a role not only in helping support families but also in knowing what resources are available to meet these needs, which can be dependent on what their communities offer. Pediatricians require current training to navigate their state's foster care system. This training allows pediatricians to effectively collaborate with foster families while also assisting and coordinating complex care to support these families. We present a case of a child with complex health needs placed in the foster care system, facing multiple healthcare challenges, with care delayed due to difficulty attending appointments. Highlighted is the importance of delivering supportive, personalized, and multidisciplinary care to families with children who have complex health needs, including when caretakers are within the foster care system.

A comparison of machine learning methods for recovering noisy and missing 4D flow MRI data.

Experimental blood flow measurement techniques are invaluable for a better understanding of cardiovascular disease formation, progression, and treatment. One of the emerging methods is time-resolved three-dimensional phase-contrast magnetic resonance imaging (4D flow MRI), which enables noninvasive time-dependent velocity measurements within large vessels. However, several limitations hinder the usability of 4D flow MRI and other experimental methods for quantitative hemodynamics analysis. These mainly include measurement noise, corrupt or missing data, low spatiotemporal resolution, and other artifacts. Traditional filtering is routinely applied for denoising experimental blood flow data without any detailed discussion on why it is preferred over other methods. In this study, filtering is compared to different singular value decomposition (SVD)-based machine learning and autoencoder-type deep learning methods for denoising and filling in missing data (imputation). An artificially corrupted and voxelized computational fluid dynamics (CFD) simulation as well as in vitro 4D flow MRI data are used to test the methods. SVD-based algorithms achieve excellent results for the idealized case but severely struggle when applied to in vitro data. The autoencoders are shown to be versatile and applicable to all investigated cases. For denoising, the in vitro 4D flow MRI data, the denoising autoencoder (DAE), and the Noise2Noise (N2N) autoencoder produced better reconstructions than filtering both qualitatively and quantitatively. Deep learning methods such as N2N can result in noise-free velocity fields even though they did not use clean data during training. This work presents one of the first comprehensive assessments and comparisons of various classical and modern machine-learning methods for enhancing corrupt cardiovascular flow data in diseased arteries for both synthetic and experimental test cases.

Comprehensive assessment of Zingiber sianginensis: Phytometabolomic analysis and its impact on oxidative stress biomarkers.

In India, ginger is highly valued for cultural and medicinal purposes. Besides traditional uses, ginger has been proven for its efficacy in cancer, chemotherapy-induced nausea, bacterial infections, neuroinflammation, and oxidative stress. This study focuses on Zingiber sianginensis, a rare ginger species in the Siang region of Arunachal Pradesh, India. This study studied pharmacognostical evaluation, phytometabolomics analysis, and its effect on oxidative stress biomarkers. Microscopic and chemical tests were employed for pharmacognostical evaluation, revealing distinctive characteristics of Zingiber sianginensis, such as non-close collateral vascular bundles and unique cork layers. Chemical tests, including the phloroglucinol and hydrochloric acid test, differentiated Zingiber sianginensis from Zingiber officinale Roscoe. Phytometabolomics analysis, using Gas Chromatography-Mass Spectrometry (GC/MS) and Liquid Chromatography-Electrospray Ionisation-Quadrupole Time of Flight-Mass Spectrometry (LC-ESI-QTOF-MS/MS) techniques, identified a diverse range of metabolites in Zingiber sianginensis, including polyphenols, monoterpenoids, diterpenoids, sesquiterpenoids, and organic compounds. The LC-ESI-QTOF-MS/MS analysis revealed 158 compounds, verified through cross-referencing with established databases. Heavy metal analysis by Inductively Coupled Plasma-Mass Spectrometry (ICP-MS) confirmed that Zingiber sianginensis complies with safety standards, showing concentrations of heavy metals within acceptable limits. The isolation and characterization of compounds from Zingiber sianginensis identified natural products such as (R)-(-)- alpha-Curcumene (1), 1-Dehydro-[10]-gingerdione (2), 6-Shogaol (3), and 6-Gingerol (4). Quantification of 6-gingerol revealed that Zingiber sianginensis contains approximately twice the amount compared to Zingiber officinale Roscoe's, suggesting its potential as a source for higher 6-gingerol content. The hydroalcoholic extract of Zingiber sianginensis exhibited antioxidant properties, reducing oxidative stress biomarkers in human dermal fibroblast cells treated with rotenone. Allantoin and 3-bromotyrosine levels significantly decreased, indicating the extract's potential in combating oxidative stress-related disorders. Overall, this comprehensive study provides valuable insights into the pharmacognostical, phytometabolomic, and safety aspects of Zingiber sianginensis, highlighting its potential as a source of bioactive compounds with health benefits.

Comprehensive assessment of per and polyfluoroalkyl substances (PFAS) contamination in groundwater of Kamrup, Assam, India: occurrence, health risks, and metabolomic insights.

Per-and polyfluoroalkyl substances (PFAS) are synthetic chemicals that are known for their environmental persistence and adverse health effects. This study comprehensively assessed PFAS contamination in the Kamrup region of Assam, India, focusing on its presence in groundwater and associated health risks. The analysis detected 12 PFAS in groundwater samples from both the Kamrup Metro and Rural regions. In Kamrup Rural, Perfluorohexanoic acid (PFHxA), perfluorononanoic acid (PFNA), and perfluorooctanesulfonic acid (PFOS) were prevalent, whereas in Kamrup Metro, PFNA and PFOS were dominant, based on detection frequencies. These findings are noteworthy, as they demonstrate the widespread presence of PFAS in groundwater, a vital source of drinking water in the region. The assessment of PFAS health risks in India involved hazard quotient calculations for different age groups. Perfluorobutanesulfonic acid (PFBS) posed the highest risk, ranking children > boys > men > girls > women. Overall, ∑PFAS had low hazard (HQ: 0.27-0.41). Further, this study assessed PFBS and PFOS toxicity in human kidney epithelial cell lines (HEK293T) cells, revealing that PFBS was more cytotoxic than PFOS. The study examined the metabolomics of HEK293T cells after PFBS exposure, revealing significant alterations in lipid metabolism, particularly glycerophospholipids, potentially affecting cellular function and health. These findings underscore the importance of monitoring PFAS contamination in drinking water sources, especially in regions such as Kamrup, where groundwater is a primary source. Our metabolomics results show significant health effects at the cellular level, raising concerns about the impact of PFAS exposure on human health. This study highlights PFAS contamination in Kamrup, Assam's groundwater and its health risks, providing valuable insights for policymakers and public health management.

Initial Clinical Experience With a Novel Robotically Assisted Platform for Combined Mini-Percutaneous Nephrolithotomy and Flexible Ureteroscopic Lithotripsy.

PURPOSE: We sought to evaluate the technical feasibility of performing a combined robotically assisted mini-percutaneous nephrolithotomy (PCNL) and flexible ureteroscopy (URS) procedure by a single urologist using the MONARCH Platform, Urology (Johnson & Johnson MedTech, Redwood City, California). MATERIAL AND METHODS: In this prospective, first-in-human clinical trial, 13 patients underwent robotically-assisted PCNL for renal calculi at the University of California-Irvine, Department of Urology. Successful completion of the procedure was assessed as the primary endpoint. Postoperative adverse events were monitored for 30 days following the completion of the procedure. Stone ablation efficiency was evaluated on postoperative day 30 with low-dose 2-3 mm slice CT scans. Patients were classified according to the maximum length of their residual stone fragments as either absolute stone-free (Grade A), < 2 mm remnants (Grade B), or 2.1-4.0 mm remnants (Grade C). RESULTS: The combined robotic mini-PCNL and URS procedure was successfully completed in 12 of 13 procedures. No robotic device-related adverse events occurred. Preoperative stone burden was quantified by both maximum linear measurement (median 32.8 mm) as well as by CT-based volume (median 1645.9 mm3). Using the unique robotically assisted targeting system, percutaneous access was gained directly through the center of the renal papilla in a single pass in all cases. Median operative time was 187 minutes (range: 83-383 minutes). On postoperative day 30, a 98.7% (range: 72.9%-100.0%) volume reduction was achieved, with 5 Grade A (38.5%), 1 Grade B (7.7%), and 2 Grade C (15.4%). Three patients experienced complications (2 grade 1 and one grade 2 Clavien-Dindo). CONCLUSIONS: Our preliminary investigation demonstrates the safety, efficacy, and feasibility of a unique robotic-assisted combined mini-PCNL and URS platform.

Development and Initial Evaluation of a Cost-Effective Force Sensor for Ureteroscopic Application.

Purpose: Retrograde intrarenal surgery is the gold-standard treatment for most kidney stones. During ureteroscopy, ureteral access sheath insertion at forces greater than 8.0 Newtons (N) risks high-grade ureteral injury. To monitor force, our institution utilizes a unique, Bluetooth-equipped device (i.e., the University of California-Irvine Force Sensor). Given the unique nature of the force sensor, we sought to develop an inexpensive and accessible force sensor based on Boyle's law and the specific amount of force required to compress an occluded 1.0 mL syringe. Materials and Methods: We evaluated three brands of 1.0 mL syringes. After setting the plunger at 1.0 mL, the syringe was occluded, and the syringe plunger was compressed. The syringe volume was recorded when the applied force on the plunger reached 4.0 N, 6.0 N, and 8.0 N. Multiple trials were performed to assess reliability and reproducibility. A method for applying this clinically was also developed. Results: The precise force thresholds identified for a 1.0 mL Luer-Lok™ Syringe (Becton Dickinson, Franklin Lakes, NJ) were 0.30 mL for 4.00 N, 0.20 mL for 6.00 N, and 0.15 mL for 8.00 N. The 1.0 mL Tuberculin Syringe and 1.0 mL Luer Slip Syringe were less precise, but compression from 1.0 to 0.40 mL, 0.25 mL, and 0.20 mL corresponded to force sensor readings that did not exceed 4.00 N, 6.00 N, and 8.00 N, respectively. Conclusions: Based on volume changes, 4.00 N, 6.00 N, and 8.00 N of force can be reliably and reproducibly achieved using an occluded 1.0 mL syringe.

Studies on cationic ocular emulsions containing bipartitioned oil droplets to codeliver cyclosporin A and etodolac.

Background: To prepare ocular emulsions containing bipartitioned oil droplets to entrap cyclosporin A (0.05% w/w) and etodolac (0.2% w/w) by using castor, olive and silicon oils. Methods: The physicochemical characterizations of prepared emulsions were performed. The drug's biodistribution profiles and pharmacokinetic parameters from emulsions were checked using the ultraperformance liquid chromatography-tandem mass spectrometry method in the ocular tissues of the healthy rabbit eye model. Results: The emulsions displayed 365.13 ± 7.21 nm size and 26.45 ± 2.09 mV zeta potential. The ferrying of two drugs after releasing from emulsions occurred across corneal/conjunctival tissues to enter the vitreous and sclera following a single drop administration into the rabbit's eyes. Conclusion: The dual drug-loaded emulsions were more likely to produce synergistic anti-inflammatory activity for managing moderate-to-severe dry eye disease.

[Box: see text].

Avoiding "Needless" nephrectomy: What is the role of small renal mass biopsy in 2024?

Current guidelines do not mandate routine preoperative renal mass biopsy (RMB) for small renal masses (SRMs), which results in a considerable rate (18%-26%) of needless nephrectomy/partial nephrectomy for benign renal tumors. In light of this ongoing practice, a narrative review was conducted to examine the role of routine RMB for SRM. First, arguments justifying the current non-biopsy approach to SRM are critically reviewed and contested. Second, as a standalone procedure, RMB is critically assessed; RMB was found to have higher sensitivity, specificity, and an equal or lower complication rate when compared with other commonly preoperatively biopsied solid organ tumors (e.g., breast, prostate, lung, pancreas, thyroid, and liver). Based on the foregoing information, we propose a paradigm shift in SRM management, advocating for an updated policy in which partial nephrectomy or nephrectomy for SRM invariably occurs only after a preoperative biopsy confirms that a SRM is indeed malignant.

An Unusual Case of Apixaban-Induced Small Vessel Vasculitis: Leukocytoclastic Vasculitis.

Apixaban is a rare cause of drug-induced leukocytoclastic vasculitis (LCV). We report a case of apixaban-induced LCV in a 55-year-old male with deep vein thrombosis who developed systemic symptoms and pruritic rash in the bilateral lower extremity after 17 days of apixaban therapy. A skin biopsy confirmed the LCV, and he was diagnosed with apixaban-induced LCV after ruling out all other possible causes. His condition improved after apixaban discontinuation, supportive management, and oral prednisone. Our case highlights the early diagnosis and management of drug-induced LCV and also describes the existing literature to highlight existing knowledge and potential mechanisms underlying anticoagulant-induced vasculitis.

Determinants that enable disordered protein assembly into discrete condensed phases.

Cells harbour numerous mesoscale membraneless compartments that house specific biochemical processes and perform distinct cellular functions. These protein- and RNA-rich bodies are thought to form through multivalent interactions among proteins and nucleic acids, resulting in demixing via liquid-liquid phase separation. Proteins harbouring intrinsically disordered regions (IDRs) predominate in membraneless organelles. However, it is not known whether IDR sequence alone can dictate the formation of distinct condensed phases. We identified a pair of IDRs capable of forming spatially distinct condensates when expressed in cells. When reconstituted in vitro, these model proteins do not co-partition, suggesting condensation specificity is encoded directly in the polypeptide sequences. Through computational modelling and mutagenesis, we identified the amino acids and chain properties governing homotypic and heterotypic interactions that direct selective condensation. These results form the basis of physicochemical principles that may direct subcellular organization of IDRs into specific condensates and reveal an IDR code that can guide construction of orthogonal membraneless compartments.

Surgical Force: Initial Study and Clinical Implications in the Assessment of Ureteral Access Sheath Induced Injury.

Purpose: Ureteral access sheaths (UAS) pose the risk of severe ureteral injury. Our prior studies revealed forces ≤6 Newtons (N) prevent ureteral injury. Accordingly, we sought to define the force urologists and residents in training typically use when placing a UAS. Materials and Methods: Among urologists and urology residents attending two annual urological conferences in 2022, 121 individuals were recruited for the study. Participants inserted 12F, 14F, and 16F UAS into a male genitourinary model containing a concealed force sensor; they also provided demographic information. Analysis was completed using t-tests and Chi-square tests to identify group differences when passing a 16F sheath UAS. Participant traits associated with surpassing or remaining below a minimal force threshold were also explored through polychotomous logistic regression. Results: Participant force distributions were as follows: ≤4N (29%), >6N (45%), and >8N (32%). More years of practice were significantly associated with exerting >6N relative to forces between 4N and 6N; results for >8N relative to 4N and 8N were similar. Compared to high-volume ureteroscopists (those performing >20 ureteroscopies/month), physicians performing ≤20 ureteroscopies/month were significantly less likely to exert forces ≤4N (p = 0.017 and p = 0.041). Of those surpassing 6N and 8N, 15% and 18%, respectively, were high-volume ureteroscopists. Conclusions: Despite years of practice or volume of monthly ureteroscopic cases performed, most urologists failed to pass 16F access sheaths within the ideal range of 4N to 6N (74% of participants) or within a predefined safe range of 4N to 8N (61% of participants).

AKR1B1 drives hyperglycemia-induced metabolic reprogramming in MASLD-associated hepatocellular carcinoma.

Background & Aims: The mechanism behind the progressive pathological alteration in metabolic dysfunction-associated steatotic liver disease/steatohepatitis (MASLD/MASH)-associated hepatocellular carcinoma (HCC) is poorly understood. In the present study, we investigated the role of the polyol pathway enzyme AKR1B1 in metabolic switching associated with MASLD/MASH and in the progression of HCC. Methods: AKR1B1 expression was estimated in the tissue and plasma of patients with MASLD/MASH, HCC, and HCC with diabetes mellitus. The role of AKR1B1 in metabolic switching in vitro was assessed through media conditioning, lentiviral transfection, and pharmacological probes. A proteomic and metabolomic approach was applied for the in-depth investigation of metabolic pathways. Preclinically, mice were subjected to a high-fructose diet and diethylnitrosamine to investigate the role of AKR1B1 in the hyperglycemia-mediated metabolic switching characteristic of MASLD-HCC. Results: A significant increase in the expression of AKR1B1 was observed in tissue and plasma samples from patients with MASLD/MASH, HCC, and HCC with diabetes mellitus compared to normal samples. Mechanistically, in vitro assays revealed that AKR1B1 modulates the Warburg effect, mitochondrial dynamics, the tricarboxylic acid cycle, and lipogenesis to promote hyperglycemia-mediated MASLD and cancer progression. A pathological increase in the expression of AKR1B1 was observed in experimental MASLD-HCC, and expression was positively correlated with high blood glucose levels. High-fructose diet + diethylnitrosamine-treated animals also exhibited statistically significant elevation of metabolic markers and carcinogenesis markers. AKR1B1 inhibition with epalrestat or NARI-29 inhibited cellular metabolism in in vitro and in vivo models. Conclusions: Pathological AKR1B1 modulates hepatic metabolism to promote MASLD-associated hepatocarcinogenesis. Aldose reductase inhibition modulates the glycolytic pathway to prevent precancerous hepatocyte formation. Impact and implications: This research work highlights AKR1B1 as a druggable target in metabolic dysfunction-associated steatotic liver disease (MASLD) and hepatocellular carcinoma (HCC), which could provide the basis for the development of new chemotherapeutic agents. Moreover, our results indicate the potential of plasma AKR1B1 levels as a prognostic marker and diagnostic test for MASLD and associated HCC. Additionally, a major observation in this study was that AKR1B1 is associated with the promotion of the Warburg effect in HCC.

Alkaline Water: Help or Hype for Uric Acid and Cystine Urolithiasis?

PURPOSE: The consumption of alkaline water, water with an average pH of 8 to 10, has been steadily increasing globally as proponents claim it to be a healthier alternative to regular water. Urinary alkalinization therapy is frequently prescribed in patients with uric acid and cystine urolithiasis, and as such we analyzed commercially available alkaline waters to assess their potential to increase urinary pH. MATERIALS AND METHODS: Five commercially available alkaline water brands (Essentia, Smart Water Alkaline, Great Value Hydrate Alkaline Water, Body Armor SportWater, and Perfect Hydration) underwent anion chromatography and direct chemical measurements to determine the mineral contents of each product. The alkaline content of each bottle of water was then compared to that of potassium citrate (the gold standard for urinary alkalinization) as well as to other beverages and supplements used to augment urinary citrate and/or the urine pH. RESULTS: The pH levels of the bottled alkaline water ranged from 9.69 to 10.15. Electrolyte content was minimal, and the physiologic alkali content was below 1 mEq/L for all brands of alkaline water. The alkali content of alkaline water is minimal when compared to common stone treatment alternatives such as potassium citrate. In addition, several organic beverages, synthetic beverages, and other supplements contain more alkali content than alkaline water, and can achieve the AUA and European Association of Urology alkali recommendation of 30 to 60 mEq per day with ≤ 3 servings/d. CONCLUSIONS: Commercially available alkaline water has negligible alkali content and thus provides no added benefit over tap water for patients with uric acid and cystine urolithiasis.

Electromotive Drug Administration in the Porcine Renal Pelvis: First Report.

Introduction: Electromotive Drug Administration (EMDA) amplifies drug delivery deep into targeted tissues. We tested, for the first time, the ability of EMDA to deliver methylene blue into the urothelium of the renal pelvis. Materials and Methods: In an anesthetized female pig, both proximal ureters were transected two inches distal to the ureteropelvic junction. An 8F dual lumen catheter and a 5F fenestrated catheter with an indwelling silver wire were inserted into both renal pelvises following which methylene blue (0.1%) was infused at a rate of 5 mL/min for 20 minutes. In one pelvis, a 4 mA positive pulsed electrical current was applied to the silver wire. Results: In contrast to the control pelvis, the EMDA side macroscopically exhibited dense homogeneous staining; microscopy revealed penetration of methylene blue into the urothelium/lamina propria. Conclusion: In the porcine renal pelvis, application of EMDA increased the penetration of a charged molecule into the urothelium/lamina propria.

Efficient and Accurate Computed Tomography-Based Stone Volume Determination: Development of an Automated Artificial Intelligence Algorithm.

PURPOSE: Given the shortcomings of current stone burden characterization (maximum diameter or ellipsoid formulas), we sought to investigate the diagnostic accuracy and precision of a University of California, Irvine-developed artificial intelligence (AI) algorithm for determining stone volume determination. MATERIALS AND METHODS: A total of 322 noncontrast CT scans were retrospectively obtained from patients with a diagnosis of urolithiasis. The largest stone in each noncontrast CT scan was designated the "index stone." The 3D volume of the index stone using 3D Slicer technology was determined by a validated reviewer; this was considered the "ground truth" volume. The AI-calculated index stone volume was subsequently compared with ground truth volume as well with the scalene, prolate, and oblate ellipsoid formulas estimated volumes. RESULTS: There was a nearly perfect correlation between the AI-determined volume and the ground truth (R=0.98). While the AI algorithm was efficient for determining the stone volume for all sizes, its accuracy improved with larger stone size. Moreover, the AI stone volume produced an excellent 3D pixel overlap with the ground truth (Dice score=0.90). In comparison, the ellipsoid formula-based volumes performed less well (R range: 0.79-0.82) than the AI algorithm; for the ellipsoid formulas, the accuracy decreased as the stone size increased (mean overestimation: 27%-89%). Lastly, for all stone sizes, the maximum linear stone measurement had the poorest correlation with the ground truth (R range: 0.41-0.82). CONCLUSIONS: The University of California, Irvine AI algorithm is an accurate, precise, and time-efficient tool for determining stone volume. Expanding the clinical availability of this program could enable urologists to establish better guidelines for both the metabolic and surgical management of their urolithiasis patients.

Integrative Placental Multi-Omics Analysis Reveals Perturbed Pathways and Potential Prognostic Biomarkers in Gestational Hypertension.

BACKGROUND: Gestational hypertension (GH) is a severe complication that occurs after 20 weeks of pregnancy; however, its molecular mechanisms are not yet fully understood. OBJECTIVE: Through this case-control discovery phase study, we aimed to find disease-specific candidate placental microRNAs (miRNAs) and metabolite markers for differentiating GH by integrating next-generation sequencing and metabolomics multi-omics analysis of placenta. Using small RNA sequencing and metabolomics of placental tissues of healthy pregnant (HP, n = 24) and GH subjects (n = 20), the transcriptome and metabolome were characterized in both groups. RESULTS: The study identified a total of 44 downregulated placental miRNAs which includes three novel, three mature and 38 precursor miRNAs. Six miRNAs including three mature (hsa-miR-181a-5p, hsa-miR-498-5p, and hsa-miR-26b-5p) and three novel (NC_000016.10_1061, NC_000005.10_475, and NC_000001.11_53) were considered for final target prediction and functional annotation. Integrative analysis of differentially expressed miRNAs and metabolites yielded five pathways such as purine, glutathione, glycerophospholipid, inositol phosphate and ß-alanine to be significantly perturbed in GH. We present fourteen genes (LPCAT1, LPCAT2, DGKH, PISD, GPAT2, PTEN, SACM1L, PGM2, AMPD3, AK7, AK3, CNDP1, IDH2, and ODC1) and eight metabolites (xanthosine, xanthine, spermine, glycine, CDP-Choline, glyceraldehyde 3-phosphate, ß-alanine, and histidine) with potential to distinguish GH and HP. CONCLUSION: The differential expression of miRNAs, their target genes, altered metabolites and metabolic pathways in GH patients were identified for the first time in our study. Further, the altered miRNAs and metabolites were integrated to build their inter-connectivity network. The findings obtained from our study may be used as a valuable source to further unravel the molecular pathways associated with GH and also for the evaluation of prognostic markers.