Gas-Phase Fractionation Data-Independent Acquisition Analysis of 3D Cocultured Spheroid Tumor Model Reveals Altered Translational Processes and Signaling Using Proteomics.

Colorectal cancer (CRC) contains considerable heterogeneity; therefore, models of the disease must also reflect the multifarious components. Compared to traditional 2D models, 3D cellular models, such as tumor spheroids, have the utility to determine the drug efficacy of potential therapeutics. Monoculture spheroids are well-known to recapitulate gene expression, cell signaling, and pathophysiological gradients of avascularized tumors. However, they fail to mimic the stromal cell influence present in CRC, which is known to perturb drug efficacy and is associated with metastatic, late-stage colorectal cancer. This study seeks to develop a cocultured spheroid model using carcinoma and noncancerous fibroblast cells. We characterized the proteomic profile of cocultured spheroids in comparison to monocultured spheroids using data-independent acquisition with gas-phase fractionation. Specifically, we determined that proteomic differences related to translation and mTOR signaling are significantly increased in cocultured spheroids compared to monocultured spheroids. Proteins related to fibroblast function, such as exocytosis of coated vesicles and secretion of growth factors, were significantly differentially expressed in the cocultured spheroids. Finally, we compared the proteomic profiles of both the monocultured and cocultured spheroids against a publicly available data set derived from solid CRC tumors. We found that the proteome of the cocultured spheroids more closely resembles that of the patient samples, indicating their potential as tumor mimics.

Fluorochrome-dependent specific changes in spectral profiles using different compensation beads or primary cells in full spectrum cytometry.

Full spectrum flow cytometry is a powerful tool for immune monitoring on a single-cell level and with currently available machines, panels of 40 or more markers per sample are possible. However, with an increased panel size, spectral unmixing issues arise, and appropriate single stain reference controls are required for accurate experimental results and to avoid unmixing errors. In contrast to conventional flow cytometry, full spectrum flow cytometry takes into account even minor differences in spectral signatures and requires the full spectrum of each fluorochrome to be identical in the reference control and the fully stained sample to ensure accurate and reliable results. In general, using the cells of interest is considered optimal, but certain markers may not be expressed at sufficient levels to generate a reliable positive control. In this case, compensation beads show some significant advantages as they bind a consistent amount of antibody independent of its specificity. In this study, we evaluated two types of manufactured compensation beads for use as reference controls for 30 of the most commonly used and commercially available fluorochromes in full spectrum cytometry and compared them to human and murine primary leukocytes. While most fluorochromes show the same spectral profile on beads and cells, we demonstrate that specific fluorochromes show a significantly different spectral profile depending on which type of compensation beads is used, and some fluorochromes should be used on cells exclusively. Here, we provide a list of important considerations when selecting optimal reference controls for full spectrum flow cytometry.

Feasibility of Autofluorescence Using Overlay Imaging for the Detection of Parathyroid Glands: Defining Standards.

BACKGROUND: The aim of this study is to define standards for the use of near-infrared autofluorescence (NIRAF)-based overlay imaging via EleVision IR (Medtronic, Dublin, Ireland) and to evaluate its clinical applicability. PATIENTS AND METHODS: This prospective study included 189 patients who had undergone open thyroid and/or parathyroid surgery and in whom EleVision IR was applied to visualize at least one parathyroid gland (PG) between January 2021 and May 2022 in a tertiary referral care center. Whether the PGs were first localized by the surgeon or by overlay imaging was noted. Handling of the device, application time and duration, distance, infrared intensity (IR%), and the angle of each measurement were analyzed. In thyroidectomies, the specimens were subsequently scanned for further PGs. NIRAF patterns and intensities were described. RESULTS: Overall, 543 PGs were analyzed in 158 (83.6%) surgeries of thyroid glands (TGs) and in 49 (25.9%) surgeries for hyperparathyroidism. In 111 (58.7%) patients, identical numbers of PGs were detected by the surgeon and by overlay imaging. While a larger number of PGs was identified by the surgeon in 48 (25.4%) patients, overlay imaging served to detect more PGs in 30 (15.9%) cases. In four (2.1%) patients, PGs were visualized post-thyroidectomy due to their autofluorescence on the specimen. NIRAF-based overlay imaging was applied to depict the PGs early on after exposure by the surgeon. The ideal distance for the measurement ranged between 8 and 12 cm with an angle of 90° and a mean IR% of 34.5% (± 17.6). CONCLUSIONS: Considering the standard operating procedures, NIRAF-based overlay imaging can be used as an adjunct tool for intraoperative localization.

Dynamic (live) 3D roadmap as navigational tool in multiplug brain arteriovenous malformation embolization: technical note.

PURPOSE: Treatment of brain arteriovenous malformation (bAVM) includes microsurgical excision, stereotactic radiosurgery, endovascular embolization, or combination. With bAVM embolization, complete angiographic obliteration ranges from 12.5 to 51%, and higher total occlusion rate is seen in SM grades I to III, ranging from 96 to 100%. METHODS: In this paper, we illustrate the use of 3D rotational angiography and dynamic (live) 3D roadmap functions in endovascular treatment of bAVM. A single dynamic 3D roadmap or two dynamic 3D roadmaps obtained help tremendously in navigation of microcatheters and wires along the parent artery and bAVM feeders. RESULTS: This method eliminates the need for repeated 2D angiograms and roadmaps for new working projections every time the C-arm position is changed for cannulation of different feeders, thereby reducing radiation dose. No instances of misalignment error, vascular perforation, or thromboembolic phenomena were observed in the 21 embolization cases performed within the previous 2 years while utilizing this feature. CONCLUSION: The dynamic 3D roadmap is an extremely useful tool for multiple-feeder cannulation, by reducing the use of multiple 2D angiograms, providing intraprocedural live and adjustable 3D roadmap for better mental orientation to angioarchitecture of the bAVM, which further aids in the overall complete angiographic obliteration rate of bAVM in a single session especially in multiplug embolization technique.

Optimizing conduction system pacing lead placement utilizing the image overlay technique.

The His-bundle has several locations from which conduction system pacing can be achieved. Some locations offer better sensing, thresholds and paced QRS durations. Existing techniques to aid repositioning of an already deployed, but sub-optimally placed lead, include either simple memory of the initial lead position combined with its observation on an x-ray review screen or utilizing an additional vascular access and pacing lead with the first lead serving as a real-time marker (Two-lead technique). We describe a novel, readily available, cost-efficient, imaging-based approach to assist in the re-positioning of a pacing lead for His-bundle pacing (the Image Overlay Technique).

Suitable habitat shifts and ecological niche overlay assessments among benthic Oplegnathus species in response to climate change.

Climate change has had a significant impact on many marine organisms. To investigate the effects of environmental changes on deep-water benthic fishes, we selected the genus Oplegnathus and applied species distribution modeling and ecological niche modeling. From the last glacial maximum to the present, the three Oplegnathus species (O. conwayi, O. robinsoni, and O. peaolopesi) distributed in the Cape of Good Hope region of southern Africa experienced fitness zone fluctuations of 39.9%, 13%, and 5.7%, respectively. In contrast, O. fasciatus and O. punctatus, which were primarily distributed in the western Pacific Ocean, had fitness zone fluctuations of -6.5% and 11.7%, respectively. Neither the O. insignis nor the O. woodward varied by more than 5% over the period. Under future environmental conditions, the range of variation in fitness zones for the three southern African Oplegnathus species was expected to be between -30.8% and -26.5%, while the range of variation in fitness zones for the two western Pacific stonefish species was expected to remain below 13%. In addition, the range of variation in the fitness zones of the O. insignis was projected to be between -2.3% and 7.1%, and the range of variation in the fitness zones of the O. woodward is projected to be between -5.7% and -2%. The results indicated that O. fasciatus and O. punctatus had a wide distribution and high expansion potential, while Oplegnathus species might have originated in western Pacific waters. Our results showed that benthic fishes were highly adaptable to extreme environments, such as the last glacial maximum. The high ecological niche overlap between Oplegnathus species in the same region suggested that they competed with each other. Future research could explore the impacts of environmental change on marine organisms and make conservation and management recommendations.

Delineation of groundwater potential zones and its extent of contamination from the hard rock aquifers in west-Bengal, India.

This study evaluates the groundwater potential and quality in the parts of Chhotanagpur Gneissic Complex situated in the East Indian Shield. The region has faced groundwater development challenges for several decades. Therefore, in the study area, it is crucial to address the depletion of both groundwater quality and quantity, as this facilitates the identification of potential uncontaminated groundwater zones. The present study interprets the groundwater potential zones (GWPZ) utilizing an analytical hierarchical process (AHP) integrated with hydrogeochemical analysis. Several thematic maps were prepared to delineate the GPWZ. It has been found that ∼0.6% of the study area has a very good potential zone, 14.4% has good, 52% has moderate, and approximately 32% and 0.9% have low to very low prospective groundwater resources, respectively. The authentication of results was found to be excellent (91.4%) with the Area Under Curve (AUC). Analysis of hydrogeochemical data suggests that Mixed Ca-Na-HCO3, Mixed Ca-Mg-Cl, Ca-HCO3, and Na-Cl are the dominant water types in the study area. The principal component analysis suggests that Na+, Mg2+, Cl-, NO3-, and SO42- significantly contribute to groundwater chemistry. The K-means clustering and hierarchical cluster analysis classified groundwater samples into three clusters based on the hydrogeochemical characteristics. It is inferred that silicate weathering and reverse ion reactions through rock-water interaction control geogenic processes for groundwater chemistry. It is also inferred that regions with poor to unsuitable water quality indexes also have low GWPZ. Further, groundwater for irrigation is also accessed and found unsuitable at some locations. This research contributes to comprehending groundwater characteristics in analogous geological regions globally. Additionally, it assists in implementing preventive actions to mitigate groundwater contamination, consequently lowering health risks and formulating sustainable plans for the future.

Optical coherence tomography homography for detection of retinal displacement: a validation study.

PURPOSE: Retinal displacement following rhegmatogenous retinal detachment (RRD) has been associated with inferior functional outcomes. Recent evidence using an overlay technique suggests that fundus-autofluorescence underestimates post-RRD repair retinal displacement. This study aims to validate the overlay technique in normal eyes and to determine its sensitivity and specificity at detecting retinal displacement. METHODS: We conducted a retrospective case series involving 66 normal eyes, each with at least two separate infrared (IR) images at different time points. Overlay of the two images was based on manual marking of choroidal and optic nerve head (ONH) landmarks. For each set of two IR images, computer code for homography generated two outputs, flipping view video and an overlay picture. First, validation of choroidal/ONH alignment was performed using the flipping view video to ensure accurate manual markings. Then, two different masked graders (AB + IM) evaluated the overlays for presence of retinal displacement. 16 control eyes following RRD repair with detected retinal displacement on FAF imaging assessed sensitivity and specificity of the technique. RESULTS: 94% of overlays were found to be well aligned (62/66). 11 cases exhibited errors on flipping view analysis (choroidal/ONH misalignment). Those 11 cases had a significantly higher rate of retinal displacement (false positives) compared to cases without errors (8/11,72% Vs 54/55,98%,P = 0.001). Sensitivity and specificity of the overlay technique for detecting retinal displacement considering only adequate flipping view cases (n = 55) were calculated as 100% and 98%, respectively. CONCLUSIONS: IR overlay emerges as a reliable and valid method for detecting retinal displacement, exhibiting excellent sensitivity and specificity.

The Overlay, a New Solution for Volume Variations in the Residual Limb for Individuals with a Transtibial Amputation.

BACKGROUND: The company Ethnocare has developed the Overlay, a new pneumatic solution for managing volumetric variations (VVs) of the residual limb (RL) in transtibial amputees (TTAs), which improves socket fitting. However, the impact of the Overlay during functional tasks and on the comfort and pain felt in the RL is unknown. METHODS: 8 TTAs participated in two evaluations, separated by two weeks. We measured compensatory strategies (CS) using spatio-temporal parameters and three-dimensional lower limb kinematics and kinetics during gait and sit-to-stand (STS) tasks. During each visit, the participant carried out our protocol while wearing the Overlay and prosthetic folds (PFs), the most common solution to VV. Between each task, comfort and pain felt were assessed using visual analog scales. RESULTS: While walking, the cadence with the Overlay was 105 steps/min, while it was 101 steps/min with PFs (p = 0.021). During 35% and 55% of the STS cycle, less hip flexion was observed while wearing the Overlay compared to PFs (p = 0.004). We found asymmetry coefficients of 13.9% with the Overlay and 17% with PFs during the STS (p = 0.016) task. Pain (p = 0.031), comfort (p = 0.017), and satisfaction (p = 0.041) were better with the Overlay during the second visit. CONCLUSION: The Overlay's impact is similar to PFs' but provides less pain and better comfort.

Modelling Asphalt Overlay As-Built Roughness Based on Profile Transformation-Case for Paver Using Automatic Levelling System.

The as-built roughness, or smoothness obtained during pavement construction, plays an important role in road engineering since it serves as an indicator for both the level of service provided to users and the overall standard of construction quality. Being able to predict as-built roughness is therefore important for supporting pavement design and management decision making. An as-built IRI prediction model for asphalt overlays based on profile transformation was proposed in a previous study. The model, used as basis for this work, was developed for the case of wheeled pavers without automatic screed levelling. This study presents further development of the base prediction model, including the use of an automatic screed control system through a long-distance averaging mobile reference. Formulation of linear systems that constitute the model are presented for the case of a wheeled paver using contactless acoustic sensors set-up over a floating levelling beam attached to the paver. To calibrate the model, longitudinal profile data from the Long-Term Pavement Performance SPS-5 experiment was used, obtaining a mean error of 0.17 m/km for the predicted IRI. The results obtained demonstrate the potential of the proposed approach as a modelling alternative.

New adhesive rehabilitation technique with indexed occlusal tabletops made by 3D printing technology.

OBJECTIVE: In oral rehabilitation, a full mouth minimal invasive treatment can represent a major challenge for the patient and the dentist. The purpose of this article is to present a new technique to restore eroded teeth and recover the vertical dimension with a simple and predictable technique. CLINICAL CONSIDERATIONS: Occlusal tabletop restorations are a suitable conservative option to restore anatomy and vertical dimension augmentation but highly sensitive. The cementation of those restorations without stable landmarks, the cement excess removal, the insertion path, or the time needed are some of the difficulties can be faced. Now a days with the new CAD-CAM techniques is possible to develop a new occlusal tabletop manufacturing alternative utilizing 3D-printed technology by unifying the restorations with a customized connector that allows us to print several onlays at same time, as a single object, also being cemented at once. CONCLUSIONS: This protocol reduces the technique sensitivity of a vertical dimension oral rehabilitation process, reduce the chair time, enhancing the patient-comfort and delivers a unique way to restore dental lost anatomy as a definitive or temporary way with printing materials. CLINICAL SIGNIFICANCE: With the advent of new CAD-CAM 3D printing materials, which are increasingly versatile and gaining favor among clinicians, it is now possible to address complex clinical situations with greater predictability. This technology enables the development of treatment solutions that are both effective and efficient, consequently reducing clinical time for the patient.

The fracture strength and the failure mode of lithium disilicate or resin nano ceramics as a crown, overlay, or endocrown restoration on endodontically treated teeth.

INTRODUCTION: Different materials and restorative concepts have been proposed over the years to restore endodontically treated teeth (ETT). Monolithic ceramic and composite restoration can be lute to the tooh, without the use of a post. However, little is known how the material stiffness and presence of a composite core will affect the survival and failure mode. The objective of this in-vitro study was to evaluate the fracture strength and failure mode of endodontically treated molars, restored with ceramic or hybrid composite monolithic restoration, in the presence of absence of a composite core. MATERIALS AND METHODS: Sixty depulped molars were restored with a lithium-disilicate (e.max CAD) or hybrid composite (Cerasmart) restoration. Both materials were used in a monolithic approach, but with 3 different designs: (a) monolithic endocrown, (b) crown with a separate composite core, and (c) overlay without core buildup or pulpal extension. Ten sound teeth were used as control group. All groups were thermocycled (10,000 cycles), subsequently loaded in a chewing simulator (100,000 cycles) and finally loaded until fracture. RESULTS: Peak fracture loads and failure modes were registered. No significant differences were seen between the groups in terms of fracture load. Failure modes were statistically significantly different among groups with significant correlation between restoration type and material. (p < 0.001 and p = 0.033, respectively). No group presented significantly higher fracture resistance. Although ceramic crowns and overlays presented the highest repairability, all restored ETT were within the range of the intact tooth' fracture strength. CONCLUSION: No restoration presented significant different fracture loads. However, the type of restoration and material choice were correlated to the fracture mode.

Comparative evaluation of marginal adaptation and fatigue resistance of endodontically treated premolars restored with direct and indirect coronal restorations: an in vitro study.

BACKGROUND: An optimum restoration for reconstructing endodontically treated teeth should provide excellent marginal adaptation, high fracture resistance as well as maximum tooth structure conservation. The purpose of this study was to evaluate the marginal adaptation and fatigue resistance of different coronal restorations in endodontically treated premolars. METHODS: Thirty sound maxillary first premolars were endodontically treated and received MOD cavities. Teeth were randomly allocated into three groups (n = 10) according to the type of coronal restoration: Group R: polyethylene fibers (ribbond), fibers-reinforced composite (everX posterior) and final layer of nano-hybrid composite. Group O: indirect lithium disilicate overlay and Group C: fiber-post, resin composite restoration, and lithium disilicate crown. Marginal gap assessment was performed before and after thermocycling (5000 cycles) using stereomicroscope. Samples were subjected to stepwise-stress loading starting at 200 N, and increased by 100 N in each step until failure occurred. Statistical analysis was done by One-way ANOVA followed Tukey`s Post Hoc test for multiple comparison. Paired t test was used to compare the marginal adaptation before and after thermocycling. Survival probability was evaluated by Life table survival analysis. Failure mode analysis was performed with Chi-square test. RESULTS: Marginal gap was significantly the lowest in group R (37.49 ± 5.05) and (42.68 ± 2.38), while being the highest in group C (59.78 ± 5.67) and (71.52 ± 5.18) in before and after thermocycling respectively (P < 0.0001). Fatigue resistance was the highest for group O (1310.8 ± 196.7), and the lowest for group R (905.4 ± 170.51) with a significant difference between groups (P < 0.0001). Crown group had the highest percentage (80%) of catastrophic failure, while, overlay group exhibited the lowest (20%). CONCLUSIONS: Direct restoration without cuspal coverage using ribbon fibers with short FRC provided better marginal adaptation than indirect overlays and crowns, but fatigue resistance wasn't significantly improved. Adhesive ceramic overlays showed the best fatigue performance and the least catastrophic failure rate compared to both direct fiber-reinforced composite and indirect ceramic full coverage restorations. CLINICAL SIGNIFICANCE: Indirect adhesive overlays are a suitable, more conservative restorative option for endodontically treated teeth than full coverage restorations, especially when tooth structure is severely compromised.

Fracture strength of ceramic overlays with immediate dentin sealing and same-day delivery.

Limited research is available evaluating whether the reported in vitro benefit of immediate dentin sealing (IDS)-namely, increased bond strength to tooth structure-can be acquired in the era of same-day (SD) dentistry. The purpose of this study was to compare the fracture strengths of ceramic overlays fabricated with a delayed dentin sealing (DDS) technique or an IDS technique under 1-hour SD or 2-week multiple-day (MD) delivery conditions. Forty extracted, healthy maxillary third molars were prepared for a lithium disilicate overlay restoration and divided into 4 groups of 10 teeth each. In the SD-DDS group, the teeth were prepared and then stored for 1 hour in artificial saliva, and the adhesion protocol (bonding agent and resin cement) was applied at the time of delivery of the ceramic overlay. In the SD-IDS group, the teeth were prepared, the adhesive protocol was applied immediately, and the teeth were stored for 1 hour before delivery of the overlay. The protocols for the MD-DDS and MD-IDS groups were identical to SD-DDS and SD-IDS, respectively, except that the teeth were provisionalized and stored for 2 weeks prior to delivery of the overlay. Specimens were thermocycled and subjected to cyclic functional loading before they were loaded to failure in a universal testing machine using a rod resting on the buccal incline of the palatal cusp. Two-way analysis of variance tests revealed no statistically significant differences in fracture strength between the groups based on dentin sealing (P = 0.331) or delivery time (P = 0.314). The specimens demonstrated 2 fracture types; either a portion of the ceramic cohesively fractured, leaving the tooth intact, or the ceramic and part of the tooth fractured. There were no instances in which the restoration itself delaminated during fracture testing. A Kruskal-Wallis test indicated there were no statistically significant differences in fracture modes between the groups. In this in vitro study, IDS did not provide a significant increase in the fracture strength of overlay restorations compared with DDS, regardless of whether the restorations were delivered the same day or after 2 weeks of storage.

Cloud-based fusion imaging improves operative metrics during fenestrated endovascular aneurysm repair.

OBJECTIVE: Endovascular treatment of complex aortic pathology has been associated with increases in procedural-related metrics, including the operative time and radiation exposure. Three-dimensional fusion imaging technology has decreased the radiation dose and iodinated contrast use during endovascular aneurysm repair. The aim of the present study was to report our institutional experience with the use of a cloud-based fusion imaging platform during fenestrated endovascular aneurysm repair (FEVAR). METHODS: A retrospective review of a prospectively maintained aortic database was performed to identify all patients who had undergone FEVAR with commercially available devices (Zenith Fenestrated; Cook Medical Inc, Bloomington, IN) between 2013 and 2020 and all endovascular aneurysm repairs performed using Cydar EV Intelligent Maps (Cydar Medical, Cambridge, UK). The Cydar EV cohort was reviewed further to select all FEVARs performed with overlay map guidance. The patient demographic, clinical, and procedure metrics were analyzed, with a comparative analysis of FEVAR performed without and with the Cydar EV imaging platform. Patients were excluded from comparative analysis if the data were incomplete in the dataset or they had a documented history of prior open or endovascular abdominal aortic aneurysm repair. RESULTS: During the 7-year study period, 191 FEVARs had been performed. The Cydar EV imaging platform was implemented in 2018 and used in 124 complex endovascular aneurysm repairs, including 69 consecutive FEVARs. A complete dataset was available for 137 FEVARs. With exclusion to select for de novo FEVAR, a comparative analysis was performed of 53 FEVAR without and 63 with Cydar EV imaging guidance. The cohorts were similar in patient demographics, medical comorbidities, and aortic aneurysm characteristics. No significant difference was noted between the two groups for major adverse postoperative events, length of stay, or length of intensive care unit stay. The use of Cydar EV resulted in nonsignificant decreases in the mean fluoroscopy time (69.3 ± 28 minutes vs 66.2 ± 33 minutes; P = .598) and operative time (204.4 ± 64 minutes vs 186 ± 105 minutes; P = .278). A statistically significant decrease was found in the iodinated contrast volume (105 ± 44 mL vs 83 ± 32 mL; P = .005), patient radiation exposure using the dose area product (1,049,841 mGy/cm2 vs 630,990 mGy/cm2; P < .001) and cumulative air kerma levels (4518 mGy vs 3084 mGy; P = .02) for patients undergoing FEVAR with Cydar EV guidance. CONCLUSIONS: At our aortic center, we have observed a trend toward shorter operative times and significant reductions in both iodinated contrast use and radiation exposure during FEVAR using the Cydar EV intelligent maps. Intelligent map guidance improved the efficiency of complex endovascular aneurysm repair, providing a safer intervention for both patient and practitioner.

A phantom for targeted endomyocardial biopsy training.

Endomyocardial biopsy (EMB) of the right ventricular (RV) septal surface during cardiac catheterization is the standard method to assess cardiac allograft rejection, heart failure, or inflammatory cardiomyopathies. We developed methodology using a three-dimensional (3D) printed phantom to provide proof of concept for using biplane overlay technology for targeted EMB. A standard bioptome and steerable sheath were used to discern feasibility of biopsy for seven regions of the RV septum guided by 3D overlay. This novel biopsy phantom can help train operators in biopsy techniques, and biplane overlay technology has the potential to advance targeted EMB in transplant and cardiomyopathy populations.

The borderland of multiple sclerosis and functional neurological disorder: A call for clinical research and vigilance.

BACKGROUND AND PURPOSE: Functional neurological disorders (FNDs) have attracted much attention from the neurological medical community over the last decades as new developments in neurosciences have reduced stigma around these by showing brain network dysfunctions. An overlap with other neurological conditions such as multiple sclerosis (MS) is well known by clinicians but there is a lack of clinical and fundamental research in this field to better define diagnosis and therapeutic decisions, as well as a lack of deep understanding of the underlying pathophysiology. AIM: We aimed to provide a critical commentary on the state of knowledge about the borderland between FNDs and MS. METHODS: We based our commentary on a joint point of view between an FND specialist and an MS expert. RESULTS: A brief review of the previous literature and relevant new studies covering the overlap between FNDs and MS is presented, along with suggestions for future research directions. CONCLUSION: There are clear diagnostic criteria for both FNDs and MS and a strict application of these will help better diagnosis and prevent unnecessary treatment escalation in MS or absence of referral to multimodal therapy in FND. Better teaching of younger neurologists is needed as well as prospective research focusing on pathophysiology.

Molecular overlay-guided design of new CDK2 inhibitor thiazepinopurines: Synthesis, anticancer, and mechanistic investigations.

Adopting the molecular overlay approach, three novel sets of thiazepinopurines with expected cytotoxicity and CDK2 inhibition potential were designed and synthesized. This was accomplished through the heteroannelation of purines, for the first time, with thiazepine. The obtained thiazepinopurines derivatives were assessed for their cytotoxicity toward tumor cells of three different types, HepG2, MCF-7, and PC-3 as well as one normal cell (WI38). Among the studied compounds, 3b and 3c exhibited significant antiproliferative activity against tumor cells presenting IC50 range of 5.52-17.09 µM in comparison with Roscovitine (9.32-13.82 µM). Additionally, both compounds displayed superior selectivity indices (SI = 3.00-7.15) toward tested cancer cells. The 4-chlorophenyl analog 3b has shown the best selectivity index, and hence it has been subjected to additional investigations to determine its proper mechanistic effect. Accordingly, the CDK2 inhibition potential, apoptosis induction, and cell cycle analysis of MCF-7 were evaluated. Results revealed that this analog displayed a potent CDK2 inhibition potential with an IC50 value of 0.219 µM. Findings also showed that 3b was thought to arrest MCF-7 cell cycle at S phase together with apoptosis induction by the increased expression of Bax, Caspase-8, and -9 markers with a concomitant decrease in Bcl-2 expression. Besides, the probable interaction of 3b with CDK2 binding pocket was investigated by molecular docking.

A new alternative technique for the guidance of transjugular intrahepatic portosystemic shunt creation using DSA overlay reference.

BACKGROUND: Portal vein puncture (PVP) is a critical step during transjugular intrahepatic portosystemic shunt (TIPS) and correlates to several complications. Techniques guiding PVP are needed. PURPOSE: To evaluate the safety, feasibility, and efficiency of digital subtraction angiography (DSA) overlay reference during TIPS creation and compare it with transhepatic portal vein (THPV) guiding. MATERIAL AND METHODS: The clinical records of 185 patients at three medical centers who underwent TIPS placement were reviewed. Portal vein access was guided by THPV guiding in 120 cases and DSA overlay reference in 60 cases. The number of punctures, portal vein entry time, procedural adverse events, technical and hemodynamic success rate were analyzed to compare the safety, feasibility, and efficiency of the two methods. RESULTS: The median numbers of punctures in group 1 and group 2 were 2 (1-4) and 2 (1-5), respectively (P = 0.094). There was no statistical difference between two groups in needle passes. The median portal vein entry time of group 1 was 12 min (8-16 min) and 13 min (8-16 min) in group 2. No significant difference was found in the PVP time (P = 0.802). Arterioportal fistula formation occurred in 15 patients in group 1; two patients in group 2 had hepatic artery injury. The patients in group 2 had lower rates of procedural adverse events (P = 0.047). Median dose area product of G1 was lower than G2 statistically (P<0.001). There was no significant difference in total fluoroscopy time (P = 0.856). CONCLUSION: DSA overlay reference has lower procedural adverse events rates compared with THPV guiding TIPS. It seems to be a safe and effective method for guiding PVP.

Global development and future trends of artificial sweetener research based on bibliometrics.

Artificial sweeteners have sparked a heated debate worldwide due to their ambiguous impacts on public and environmental health and food safety and quality. Many studies on artificial sweeteners have been conducted; however, none scientometric studies exist in the field. This study aimed to elaborate on the knowledge creation and development of the field of artificial sweeteners and predict the frontiers of knowledge based on bibliometrics. In particular, this study combined VOSviewer, CiteSpace, and Bibliometrix to visualize the mapping of knowledge production, covered 2389 relevant scientific publications (1945-2022), and systematically analyzed articles and reviews (n = 2101). Scientific publications on artificial sweeteners have been growing at an annual rate of 6.28% and globally attracting 7979 contributors. Susan J. Brown with total publications (TP) of 17, average citation per article (AC) of 36.59, and Hirsch (h)-index of 12 and Robert F. Margolskee (TP = 12; AC = 2046; h-index = 11) were the most influential scholars. This field was clustered into four groups: eco-environment and toxicology, physicochemical mechanisms, public health and risks, and nutrition metabolism. The publications about environmental issues, in particular, "surface water," were most intensive during the last five years (2018-2022). Artificial sweeteners are gaining importance in the monitoring and assessment of environmental and public health. Results of the dual-map overlay showed that the future research frontiers tilt toward molecular biology, immunology, veterinary and animal sciences, and medicine. Findings of this study are conducive to identifying knowledge gaps and future research directions for scholars.