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Paige M Anderson, Allison A Vanderbilt College of Medicine and Life Sciences, University of Toledo, Toledo, OH, USA Abstract: Cultural competence (CC) training has become a required part of medical education to create future physicians dedicated to decreasing health disparities. However, current training seems to be inadequate as research has demonstrated gaps between CC training and clinical behaviors of students. One aspect that is potentially contributing to this gap is the lack of physician education of CC. Without it being something not only taught in the classroom, but also modeled and taught in the clinical setting, CC will continue to be a theoretical concept instead of a skill set that changes the way that future physicians interact with patients and make decisions about patient care. To change this, we propose the implementation of a Train the Trainer model in which the preclinical professor in charge of CC education trains Clerkship and Residency Directors who then can train and supervise the physicians and residents in their departments on CC to better implement it into the formal and informal curriculum of clerkships. Keywords: cultural competence, Train the Trainer, physician education, undergraduate medical education, health disparities, clerkship curriculum

Heterostructured materials are an emerging class of materials with superior performances that are unattainable by their conventional homogeneous counterparts. They consist of heterogeneous zones with dramatic (>100%) variations in mechanical and/or physical properties. The interaction in these hetero-zones produces a synergistic effect where the integrated property exceeds the prediction by the rule-of-mixtures. The heterostructured materials field explores heterostructures to control defect distributions, long-range internal stresses, and nonlinear inter-zone interactions for unprecedented performances. This paper is aimed to provide perspectives on this novel field, describe the state-of-the-art of heterostructured materials, and identify and discuss key issues that deserve additional studies.

We examine characteristics and correlates of households in the United States that are most likely to have children at risk of inadequate nutrition - those that report very low food security (VLFS) among their children. Using 11 years of the Current Population Survey, plus data from the National Health and Nutrition Examination Survey (NHANES), we describe these households in great detail with the goal of trying to understand how these households differ from households without such severe food insecurity. While household income certainly plays an important role in determining VLFS among children, we find that even after flexibly controlling for income-to-poverty rates some household characteristics and patterns of program participation have important additional explanatory power. Finally, our examination of the NHANES data suggests an important role for both mental and physical health of adults in the household in determining the food security status of children.

DIII-D has four neutral beamlines (NB). Each of these beamlines has two ion sources, each of which injects up to 2.5 MW for 3 s. These beamlines intersect the vacuum vessel at an angle of 19.5 deg off from radial, enabling current drive in the same direction as the plasma current (co-injection). In 2004, one of these beamlines (210 deg) was rotated to provide counter-injection (opposite of plasma current). A different beamline (150 deg) has been modified to have the capability to provide off-axis neutral beam current drive. The goal of the off-axis injection is to have the center of the ion sources aimed at a position 40 cm below the geometric center of the plasma. To achieve this off-axis injection, the beamline requires a mechanical lifting system that can elevate the beamline up to 16.5 deg from horizontal. The beamline also requires more strongly vertically focused ion sources (in order to pass the beam through a reduced effective aperture) as well as modified internal components. Additionally, the design of the new internal components incorporated modifications to allow for the doubling of ion source pulse lengths without the need for active cooling. This paper discusses the various beamline system design requirements for off-axis injection, as well as the results from the actual commissioning of the beamline. Overviews of the design and performance of mechanical lifting system (hydraulics and controls), focused ion sources, flexible beamline support systems (vacuum, cryogenic, power and water cooling), and internal beamline collimators are included. Additionally, the in-vessel monitoring and shine-through protection requirements are discussed. The actual data obtained during beamline commissioning and during normal physics operations is also presented. © 2011 IEEE.

DIII-D has four neutral beamlines (NB). Each of these beamlines has two ion sources, each of which injects up to 2.5 MW for 3 s. These beamlines intersect the vacuum vessel at an angle of 19.5 deg off from radial, enabling current drive in the same direction as the plasma current (co-injection). In 2004, one of these beamlines (210 deg) was rotated to provide counter-injection (opposite of plasma current). A different beamline (150 deg) has been modified to have the capability to provide off-axis neutral beam current drive. The goal of the off-axis injection is to have the center of the ion sources aimed at a position 40 cm below the geometric center of the plasma. To achieve this off-axis injection, the beamline requires a mechanical lifting system that can elevate the beamline up to 16.5 deg from horizontal. The beamline also requires more strongly vertically focused ion sources (in order to pass the beam through a reduced effective aperture) as well as modified internal components. Additionally, the design of the new internal components incorporated modifications to allow for the doubling of ion source pulse lengths without the need for active cooling. This paper discusses the various beamline system design requirements for off-axis injection, as well as the results from the actual commissioning of the beamline. Overviews of the design and performance of mechanical lifting system (hydraulics and controls), focused ion sources, flexible beamline support systems (vacuum, cryogenic, power and water cooling), and internal beamline collimators are included. Additionally, the in-vessel monitoring and shine-through protection requirements are discussed. The actual data obtained during beamline commissioning and during normal physics operations is also presented. © 2011 IEEE.

Modification of the two existing DIII-D neutral beamlines is planned to allow vertical steering to provide off-axis neutral beam current drive (NBCD) peaked as far off-axis as half the plasma minor radius. New calculations for a downward-steered beam indicate strong current drive with good localization off-axis so long as the toroidal magnetic field, BT, and the plasma current, Ip, point in the same direction. This is due to good alignment of neutral beam injection (NBI) with the local pitch of the magnetic field lines. This model has been tested experimentally on DIII-D by injecting equatorially mounted NBs into reduced size plasmas that are vertically displaced with respect to the vessel midplane. The existence of off-axis NBCD is evident in the changes seen in sawtooth behaviour in the internal inductance. By shifting the plasma upwards or downwards, or by changing the sign of the toroidal field, off-axis NBCD profiles measured with motional Stark effect data and internal loop voltage show a difference in amplitude (40-45%) consistent with differences predicted by the changed NBI alignment with respect to the helicity of the magnetic field lines. The effects of NBI direction relative to field line helicity can be large even in ITER: off-axis NBCD can be increased by more than 30% if the BT direction is reversed. Modification of the DIII-D NB system will strongly support scenario development for ITER and future tokamaks as well as provide flexible scientific tools for understanding transport, energetic particles and heating and current drive. © 2009 IAEA, Vienna.

The goals of DIII-D advanced tokamak (AT) experiments are investigation and optimization of the upper limits of energy confinement and MHD stability in a tokamak plasma, and simultaneous maximization of the fraction of non-inductive current drive. Significant overall progress has been made in the past two years, as the performance figure of merit βNH89P of 9 has been achieved in ELMing H mode for over 16τE without sawteeth. The tokamak was also operated at βNH ≈ 7 for over 35τE or 3τR, with the duration limited by the hardware. Real time feedback control of β (at 95% of the stability boundary), optimizing the plasma shape (e.g., δ, divertor strike and X points, double/single null balance) and particle control (ne/nGW ≈ 0.3, Zeff < 2.0) were necessary for the long pulse results. A new quiescent double barrier (QDB) regime with simultaneous inner and edge transport barriers and no ELMs has been discovered with a βNH89P of 7. The QDB regime has been obtained to date only with counter NBI. Further modification and control of internal transport barriers (ITBs) has also been demonstrated with impurity injection (broader barrier), pellets and ECH (strong electron barrier). The new Divertor-2000, a key ingredient in all these discharges, provides effective density, impurity and heat flux control in the high triangularity plasma shapes. Discharges at ne/nGW ≈ 1.4 have been obtained with gas puffing by maintaining the edge pedestal pressure; this operation is easier with Divertor-2000. We are developing several other tools required for AT operation, including real time feedback control of resistive wall modes with external coils and control of neoclassical tearing modes with ECCD.

Objective: The direct anterior approach (DAA) is a recognized technique for total hip arthroplasty (THA) that spares soft tissue. Functional and clinical outcomes following THA via the DAA in patients with complex acetabular deformities, specifically coxa profunda (CP) and protrusio acetabuli (PA), have yet to be determined. Methods : A retrospective analysis was conducted on 188 primary THA cases, including 100 CP hips and 88 PA hips, performed via the DAA. Functional and clinical outcomes were evaluated by means of the Western Ontario and McMaster Universities Arthritis Index (WOMAC) and Harris Hip Score (HHS) preoperatively and at a mean follow-up of 46 ± 14 months. Furthermore, potential complications were assessed. Results : From the preoperative to the latest postoperative visit, a significant improvement in the WOMAC total score was observed (CP: -34.89 ± 20.66; PA: -40.38 ± 21.11). The length of stay (LOS) was the only parameter predictive of the postoperative WOMAC total score, with each day of LOS increasing the postoperative WOMAC by a mean of 1.77 points ( p < 0.01). The HHS improved by 38.37 ± 14.23 (PA-group) and 32.79 ± 14.89 points (CP-group). No significant difference in the patient-reported outcome measures (PROMs) between the CP- and PA-group was found. The survival rate for any revision was 97.70% (PA-group) and 92.80% (CP-group). Conclusion : The results of this study indicate that the minimally invasive DAA was not predictive of the functional and clinical outcome following DAA-THA in patients with CP and PA. Improvements in the mean WOMAC and HHS scores were above or within the reported MCID. Additionally, revision rates were well below those reported in the literature for short and intermediate follow-up periods.

Purpose: Ewing Sarcoma (ES), a rare cancer with a pathognomonic translocation resulting in the Ewing sarcoma gene (EWS)::FLI1 oncoprotein, has a poor prognosis in the relapsed/refractory (R/R) setting. Tokalas (TK)216 was designed to bind EWS::FLI1 proteins directly, disrupt protein-protein interactions, and inhibit transcription factor function. TK216 plus vincristine showed synergistic activity in preclinical tumor models. To our knowledge, we report the results of a first-in-class, first-in-human phase I/II trial of TK216 in R/R ES., Patients and Methods: TK216 was administered intravenously as a continuous infusion to patients with R/R ES in 11 cohorts. The dosing duration of 7 days was later extended to 10, 14, and 28 days. Vincristine could be added on day 1 after cycle 2, per investigators' choice. The trial used a 3 + 3 design with an expansion cohort at the recommended phase II dose (RP2D)., Results: A total of 85 patients with a median age of 27 years (range, 11-77) were enrolled. The maximum tolerated dose for the 14-day infusion of TK216, 200 mg/m 2 once daily, was determined in cohort 9 and selected as the RP2D. The median previous number of systemic therapies regimens was three (range, 1-10). The most frequent-related adverse events in patients treated at the RP2D included neutropenia (44.7%), anemia (29.4%), leukopenia (29.4%), febrile neutropenia (15.3%), thrombocytopenia (11.8%), and infections (17.6%). In cohorts 9 and 10, two patients had a complete response, one had a partial response, and 14 had stable disease; the 6-month progression-free survival was 11.9%. There were no responses among the eight patients in cohort 11., Conclusion: TK216 administered as 14-day continuous infusion with or without vincristine was well tolerated and showed limited activity at the RP2D in R/R ES.

Background: Aseptic loosening is the most common mode of failure after total knee arthroplasty. Despite this, the diagnosis often remains challenging and mainly relies on imaging modalities. Until today, no biomarker exists to aid in diagnosing loosening of the implants. As zirconium (Zr) is often found in bone cement, where it serves as radiopacifier, this study aimed to establish Zr as a synovial biomarker for loosened cemented knee prostheses., Methods: A total of 31 patients scheduled for revision of a cemented knee prostheses were included. In all patients, the initial used cement contained Zr. After arthrotomy, specimens of synovial fluid were taken and levels of Zr were measured by inductively coupled plasma mass spectrometry. Depending on the necessary amount of force for explantation, the implants were graded "loose" or "well-fixed". Preoperative radiographs were evaluated by 2 independent physicians., Results: The concentration of Zr in the synovial fluid differed significantly (P < .001) between the "loose" (mean 170.9 μg/L, range 0 to 1941 μg/L) and the "well-fixed" (mean 0.6 μg/L, range 0 to 6 μg/L) implants. The receiver operating characteristic analysis revealed 0.25 μg/l as an optimal cutoff value leading to a sensitivity of 0.84, a specificity of 0.92, a positive predictive value of 0.94, and a negative predictive value of 0.79. There was no significant difference in the diagnostic performance compared to radiographs (P = .66)., Conclusions: Zirconium proved to be a reliable novel synovial biomarker for diagnosing aseptic loosening of knee prothesis fixed with cement containing Zr. This biomarker should not be interpreted in isolation, but in combination with existing diagnostic tools., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

AbstractThe assumption in current U.S. mainstream medicine is that birthing requires hospitalization. In fact, while the American College of Obstetricians and Gynecologists supports the right of every birthing person to make a medically informed decision about their delivery, they do not recommend home birth owing to data indicating greater neonatal morbidity and mortality. In this article, we examine the evidence surrounding home birth in the United States and its current limitations, as well as the ethical considerations around birth setting.

Background: Rapidly destructive osteoarthritis (RDO) of the hip joint is characterised by the rapid destruction of the femoral head with or without acetabular involvement. There has been increasing interest in this disease over the past years; however, the entity is still poorly understood, and its pathophysiology remains unknown. Yet, there is ample evidence today that increased bone metabolism might play a role in the onset and progression of the disease. Vitamin D is of utmost importance to maintain a balanced bone metabolism. However, whether vitamin D deficiency is involved in disease development remains to be elucidated. Further, the vitamin D status of patients with RDO has not yet been analysed. For this reason, the objective of this study was to assess the vitamin D status of patients with RDO. Moreover, the aim was to clarify whether there is a difference in the vitamin D status of patients with RDO compared with patients with primary osteoarthritis (OA)., Methods: In this single-centre analysis, the 25(OH)D, PTH, and calcium levels of 29 patients who presented with RDO between 2020 and 2022 were assessed., Results: Altogether, 97% of patients (28/29) were vitamin D deficient, a further 3% (1/29) were vitamin D insufficient, and not a single patient presented with a sufficient vitamin D status. Notably, the vitamin D levels of RDO patients (mean = 11.04 ng/mL) were significantly lower than the vitamin D levels of patients with OA (mean = 22.16 ng/mL, p = 0.001)., Conclusion: In conclusion, we found a widespread and high rate of vitamin D deficiency in patients with RDO. Hence, we believe that 25(OH)D status should routinely be analysed in these patients.

Objective: Direct anterior approach total hip replacement (DAA-THR) is gaining increased interest due to its tissue-sparing nature and rapid recovery. Obesity has been shown to be a significant parameter influencing cup positioning in DAA-THR. It was the intention of this retrospective study to examine how obesity would influence the restoration of native hip biomechanical parameters during DAA-THR., Materials and Methods: A total of 74 patients from a high-volume university orthopedic center after unilateral DAA-THA were included. Patients were retrospectively allocated to a study group (BMI > 30 kg/m 2 ) and a control group (BMI < 30 kg/m 2 ). Furthermore, propensity-score matching for baseline parameters was performed, leaving 30 patients in each group. Biomechanical parameters of the hip (i.e., femoral offset (FO), abductor lever arm (ABL), acetabular offset (AO), center of rotation (COR), stem alignment (SA), body weight lever arm (BWL), cup inclination (CI), and leg length discrepancy (LLD) were evaluated on standardized plain radiographs, and parameters were compared to the native contralateral hip., Results: Mean BMI in the study group was 35.07 ± 5.13 kg/m 2 and 25.43 ± 2.64 kg/m 2 in the control group. There was a significant decrease of the ABL only in the study cohort ( p = 0.01). CI and SA did not differ between both cohorts. FO was slightly increased compared to the native hip in both groups. There was a marginally higher but non-significant proportion of improper FO restoration in the study group (19 vs. 16 patients, p = 0.60)., Conclusions: Obesity, as quantified by BMI, only has a limited impact on the adequate reconstruction of native biomechanical parameters of the hip during DAA-THR. ABL was the only parameter to be significantly decreased in the overweight patients after DAA-THR. Therefore, special care should be taken on proper acetabular reaming and consequent seating of the cup in the obese patient to avoid excessive lateral positioning.

Introduction: The AMADEUS (Area Measurement And DEpth and Underlying Structures) score has advanced to a commonly used tool for MRI-based chondral defect severity grading prior to cartilage knee surgery. It was the intention of this study to assess the AMADEUS for a potential correlation with clinical data by patient-reported outcome measures (PROMs)., Methods: A total of 51 patients undergoing ACI (autologous chondrocyte implantation) between 2016 and 2022 were found eligible and retrospectively analyzed. All patients were registered in the German Cartilage Registry prior to surgery and follow-up data were collected using the Knee Osteoarthritis Outcome score (KOOS), the International Knee Documentation Committee (IKDC) Form and the numeric rating scale (NRS). Pre-operative MRI images were scored by three raters using the AMADEUS classification system, and an overall AMADEUS score was calculated which was subsequently correlated with pre- and post-operative PROMs., Results: Mean patient age was 32.67 ± 8.37 years and mean defect size area 343.04 mm 2  ± 139.45 mm 2 . No correlative capacity of the pre- and postoperative IKDC, KOOS or NRS scores was found with the AMADEUS final score or any of its subscores. From the pre- to postoperative visit, a significant improvement of the PROMs (IKDC: 45.53 ± 21.00 vs. 59.83 ± 17.93, p = 0.04; KOOS Pain: 58.00 ± 16.70 vs. 76.06 ± 19.20, p = 0.03; KOOS ADL: 64.17 ± 18.76 vs. 82.11 ± 16.68, p < 0.01; KOOS Sports: 26.11 ± 18.52 vs. 50.56 ± 23.94, p = 0.01; KOOS QOL: 25.50 ± 14.26 ± 45.28 ± 19.03, p = 0.00) was found. Intraclass correlation coefficients showed an overall good interrater agreement for the AMADEUS total score (ICC = 0.75)., Conclusions: Study results suggest no correlative capacity of the AMADEUS with routinely used PROMs in patients undergoing ACI. Therefore, radiographically assessed cartilage defect characteristics poorly translate to pre- and postoperative patient-reported outcome data., (© 2023. The Author(s).)

The neutrophil to lymphocyte ratio (NTLR) and absolute lymphocyte count (ALC) recovery are prognostic across many cancers. We investigated whether NLTR predicts SBRT success or survival in a metastatic sarcoma cohort treated with SBRT from 2014 and 2020 (N = 42). Wilcox Signed Rank Test and Friedman Test compare NTLR changes with local failure vs. local control (N = 138 lesions). Cox analyses identified factors associated with overall survival. If local control was successful, NLTR change was not significant (p = 0.30). However, NLTR significantly changed in patients with local failure (p = 0.027). The multivariable Cox model demonstrated higher NLTR before SBRT was associated with worse overall survival (p = 0.002). The optimal NTLR cut point was 5 (Youden index: 0.418). One-year overall survival in SBRT metastatic sarcoma cohort was 47.6% (CI 34.3%-66.1%). Patients with an NTLR above 5 had a one-year overall survival of 37.7% (21.4%-66.3%); patients with an NTLR below 5 had a significantly improved overall survival of 63% (43.3%-91.6%, p = 0.014). Since NTLR at the time of SBRT was significantly associated with local control success and overall survival in metastatic sarcoma treated with SBRT, future efforts to reduce tumor inhibitory microenvironment factors and improve lymphocyte recovery should be investigated., (© 2023. The Author(s).)

Purpose: There is little evidence proving the concept of partial weight-bearing to be efficient and feasible. Using insole pressure measurement systems, this study aimed to explore the compliance to prescribed weight-bearing restrictions after total knee arthroplasty (TKA)., Methods: 50 patients after TKA were recruited in a prospective manner. They were advised to limit weight-bearing of the affected limb to 200 N. True load was measured via insole force-sensors on day one after surgery (M1) and before discharge (M2). Compliance to the rehabilitation protocol was the primary outcome parameter., Results: At M1 and M2 compliance to the rehabilitation protocol was 0% und 2%, respectively. 84% (M1) and 90% (M2) of patients overloaded the affected limb during every step. The affected limb was loaded with 50% ± 14% (M1) and 57% ± 17% (M2) of body weight. Patients older than 65 loaded the affected limb on average 17% (M1) and 34% (M2) more than their younger counterparts did. This difference was even more pronounced when walking stairs up (49% increase on average) and down (53% increase on average)., Conclusion: Surgeons must take into consideration that the ability to maintain partial weight-bearing after TKA is highly dependent on the age of the patient and the achievable load reduction is determined by the patient's body weight., (© 2023. The Author(s).)

Total hip arthroplasty (THA) is commonly performed using off-the-shelf implants. In the case of a severe mismatch between the anatomy of the proximal femur and the geometry of the stem, the use of custom-made stems might become necessary. The goal of this study was to investigate the precision of the implantation of custom-made stems of one manufacturer (CTX stem, AQ Implants) and to determine risk factors for malpositioning. All patients receiving a custom-made CTX stem between 2014 and 2020 at six high-volume academic centers were retrospectively recruited. The achieved position of the stem, as determined by stem version, stem coronal angle, and implantation depth on radiographs, was compared to the plan. The influence of radiographic and demographic parameters on the position was investigated. The results revealed a high variability of the achieved implant position in relation to the preoperative plan. While the stem coronal angle only differed slightly from the intended position, the stem version and the implantation depth showed a high frequency and amount of deviation. Right stems showed significantly higher positions than planned. Surgeons must be aware of this potential problem when implanting custom-made stems.

The current Response Evaluation Criteria in Solid Tumors for measuring tumor response in osteosarcoma may be sub-optimal, as even responsive bone tumors may show limited change in tumor diameters. This limits the use of traditional imaging assessment tools. Therefore, discerning osteosarcoma response to therapy on magnetic resonance imaging before surgery is often difficult, and it is typically evaluated after surgery by assessing the amount of necrosis in resected surgical specimens. To address these challenges, sodium fluoride (Na 18 F) positron emission tomography/computed tomography (PET/CT) scans can be utilized to better image bone response to therapy, as, fluoride is avidly taken up by bone. Na 18 F Response Criteria in Solid Tumors (NAFCIST) has been developed as a novel method to evaluate treatment response using Na 18 F PET/CT. Current evidence supporting NAFCIST comes from a pilot study that evaluated alpha particle radium-223 in patients with osteosarcoma. In this review, practical guidance for utilizing NAFCIST in the context of bone tumors is illustrated to aid future studies., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: The direct anterior approach (DAA) represents a well-recognized soft tissue sparing technique for primary total hip arthroplasty (THA). The feasibility and suitability of the DAA in cases of complex acetabular deformities, namely coxa profunda (CP) and protrusio acetabuli (PA), remain to be determined., Methods: A total of 188 cases of CP (100 cases) and PA (88 cases) hips undergoing primary THA via the DAA were retrospectively analyzed. Surgical and radiographic parameters were evaluated and potential complications were assessed. Finally, successful implantation was defined if surgical and radiographic parameters were well within established values of non-complex primary THA., Results: In 159 hips, the medial border of the acetabular component was transferred laterally to the ilioischial line, corresponding to a fully treated acetabular protrusion. In 23 (12.23%) cases, mild, and in 5 (2.66%) cases, moderate residual acetabular protrusion remained after THA. Postoperatively, 11.40% (PA group) and 9.00% (CP group) had a leg length discrepancy (LLD) greater than 10 mm. The mean operative time was significantly less than 60 min. A linear relationship between the BMI and operative time was observed, with an additional 0.9 min of operative time per BMI unit. Overall, complications were rare and did not differ between the two groups., Conclusion: The results of this study suggest that the DAA is a suitable approach for primary THA in patients with coxa profunda and acetabular protrusion if performed by experienced surgeons familiar with the DAA. Obese patients with acetabular protrusion may pose a significant limitation to the DAA and caution should be advised in cases of obesity.

(1) Background: EWS fusion genes are associated with Ewing sarcoma and other Ewing family tumors including desmoplastic small round tumor, DSRCT. We utilize a clinical genomics workflow to reveal real-world frequencies of EWS fusion events, cataloging events that are similar, or divergent at the EWS breakpoint. (2) Methods: EWS fusion events from our next-generation sequencing panel (NGS) samples were first sorted by breakpoint or fusion junctions to map out the frequency of breakpoints. Fusion results were illustrated as in-frame fusion peptides involving EWS and a partner gene. (3) Results: From 2471 patient pool samples for fusion analysis at the Cleveland Clinic Molecular Pathology Laboratory, we identified 182 fusion samples evolved with the EWS gene. They are clustered in several breakpoints: chr22:29683123 (65.9%), and chr22:29688595 (2.7%). About 3/4 of Ewing sarcoma and DSRCT tumors have an identical EWS breakpoint motif at Exon 7 (SQQSSSYGQQ-) fused to a specific part of FLI1 (NPSYDSVRRG or-SSLLAYNTSS), ERG (NLPYEPPRRS), FEV (NPVGDGLFKD) or WT1 (SEKPYQCDFK). Our method also worked with Caris transcriptome data, too. Our primary clinical utility is to use this information to identify neoantigens for therapeutic purposes. (4) Conclusions and future perspectives: our method allows interpretation of what peptides result from the in-frame translation of EWS fusion junctions. These sequences, coupled with HLA-peptide binding data, are used to identify potential sequences of cancer-specific immunogenic peptides for Ewing sarcoma or DSRCT patients. This information may also be useful for immune monitoring (e.g., circulating T-cells with fusion-peptide specificity) to detect vaccine candidates, responses, or residual disease.

In prodromal and early schizophrenia, disorders of attention and perception are associated with structural and chemical brain abnormalities and with dysfunctional corticothalamic networks exhibiting disturbed brain rhythms. The underlying mechanisms are elusive. The non-competitive NMDA receptor antagonist ketamine simulates the symptoms of prodromal and early schizophrenia, including disturbances in ongoing and task & sensory-related broadband beta-/gamma-frequency (17-29 Hz/30-80 Hz) oscillations in corticothalamic networks. In normal healthy subjects and rodents, complex integration processes, like sensory perception, induce transient, large-scale synchronised beta/gamma oscillations in a time window of a few hundred ms (200-700 ms) after the presentation of the object of attention (e.g., sensory stimulation). Our goal was to use an electrophysiological multisite network approach to investigate, in lightly anesthetised rats, the effects of a single psychotomimetic dose (2.5 mg/kg, subcutaneous) of ketamine on sensory stimulus-induced oscillations. Ketamine transiently increased the power of baseline beta/gamma oscillations and decreased sensory-induced beta/gamma oscillations. In addition, it disrupted information transferability in both the somatosensory thalamus and the related cortex and decreased the sensory-induced thalamocortical connectivity in the broadband gamma range. The present findings support the hypothesis that NMDA receptor antagonism disrupts the transfer of perceptual information in the somatosensory cortico-thalamo-cortical system., (© 2022 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Purpose: The Area Measurement And Depth Underlying Structures (AMADEUS) classification system has been proposed as a valuable tool for magnetic resonance (MR)-based grading of preoperatively encountered chondral defects of the knee joint. However, the potential relationship of this novel score with clinical data was yet to determine. It was the primary intention of this study to assess the correlative relationship of the AMADEUS with patient reported outcome scores in patients undergoing medial open-wedge high tibial valgus osteotomy (HTO). Furthermore, the arthroscopic ICRS (International Cartilage Repair Society) grade evaluation was tested for correlation with the AMADEUS classification system., Methods: This retrospective, monocentric study found a total of 70 individuals that were indicated for HTO due to degenerative chondral defects of the medial compartment between 2008 and 2019. A preoperative MR image as well as a pre-osteotomy diagnostic arthroscopy for ICRS grade evaluation was mandatory for all patients. The Knee Osteoarthritis Outcome Score (KOOS) including its five subscale scores (KOOS-ADL, KOOS-QOL, KOOS-Sports, KOOS-Pain, KOOS-Symptoms) was obtained preoperatively and at a mean follow-up of 41.2 ± 26.3 months. Preoperative chondral defects were evaluated using the AMADEUS classification system and the final AMADEUS scores were correlated with the pre- and postoperative KOOS subscale sores. Furthermore, arthroscopic ICRS defect severity was correlated with the AMADEUS classification system., Results: There was a statistically significant correlation between the AMADEUS BME (bone marrow edema) subscore and the KOOS Symptoms subscore at the preoperative visit (r = 0.25, p = 0.04). No statistically significant monotonic association between the AMADEUS total score and the AMADEUS grade with pre- and postoperative KOOS subscale scores were found. Intraoperatively obtained ICRS grade did reveal a moderate correlative relation with the AMADEUS total score and the AMADEUS grade (r = 0.28, p = 0.02)., Conclusions: The novel AMADEUS classification system largely lacks correlative capacity with patient reported outcome measures in patients undergoing HTO. The MR tomographic appearance of bone marrow edema is the only parameter predictive of the clinical outcome at the preoperative visit., (© 2023. The Author(s).)

Background: The incidence of conversion total hip arthroplasty (cTHA) following reduction and fixation for proximal femur fractures will increase in parallel to the aging population worldwide., Objective: The goal of this study is to report the frequency of bacterial detection and the outcome of cTHA at the authors' institution and to analyze preoperative factors that correlate with higher rates of bacterial growth and septic revision., Methods: 48 patients who had been converted to THA after osteosynthesis of a proximal femur fracture either by a one- or two-stage procedure were included. Septic failure rate and the frequency of bacterial detection at the time of fixation device removal were calculated. The influence of different preoperative factors was examined by the odds ratio. A receiver operating characteristic curve of c-reactive protein (CRP) for detection of bacterial growth at the time of fixation device removal was calculated., Results: 18.8% patients showed positive bacterial cultures, with Staph. epidermidis being the most frequent pathogen (33.3%). Septic failure after cTHA occurred in 4.2%. Fixation with cephalomedullary nails and complications with the internal fixation showed higher odds for bacterial growth at time of cTHA. CRP for predicting bacterial growth had an area under the curve of 0.661. Implant survival was worse when temporary spacers were used., Conclusion: Bacterial detection rate at the time of cTHA is high, whereas septic failure rates are low. Isolated evaluation of inflammatory blood markers without other diagnostic modalities for infection is not decisive and does not justify a two-stage approach with implantation of a temporary spacer.

Osteosarcoma is a high-grade sarcoma characterized by osteoid formation, nearly universal expression of IGF1R and with a subset expressing HER-2. These qualities provide opportunities for the use of the alpha particle-emitting isotopes to provide targeted radiation therapy via alpha particles precisely to bone-forming tumors in addition to IFG1R or Her-2 expressing metastases. This review will detail experience using the alpha emitter radium-223 ( 223 Ra, tradename Xofigo), that targets bone formation, in osteosarcoma, specifically related to patient selection, use of gemcitabine for radio-sensitization, and using denosumab to increasing the osteoblastic phenotype of these cancers. A case of an inoperable left upper lobe vertebral-paraspinal-mediastinal osteoblastic lesion treated successfully with 223 Ra combined with gemcitabine is described. Because not all areas of osteosarcoma lesions are osteoblastic, but nearly all osteosarcoma cells overexpress IGF1R, and some subsets expressing Her-2, the anti-IGF1R antibody FPI-1434 linked to actinium-225 ( 225 Ac) or the Her-2 antibody linked to thorium-227 ( 227 Th) may become other means to provide targeted alpha particle therapy against osteosarcoma (NCT03746431 and NCT04147819)., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Anderson, Subbiah and Trucco.)

Ifosfamide is an antitumor agent with activity against various malignancies in pediatric patients. As a prodrug, ifosfamide requires metabolic activation, which occurs via a saturable, multistep equilibrium-based process. Due to these metabolic characteristics, the method of administration can affect its therapeutic and toxic effects. This single-center, retrospective review describes the tolerability of continuous infusion and bolus administration of ifosfamide in 10 pediatric patients with Ewing sarcoma. The primary objective was to report the hematologic toxicities of patients with differing administration methods. Secondary objectives included collecting information on nonhematologic toxicities and incidence of treatment delays and dose reductions. Ultimately, 48 cycles of ifosfamide were administered as bolus administration and 24 as continuous infusion. Patients receiving bolus administration had lower hemoglobin and platelet nadirs resulting in more transfusions and treatment delays when compared proportionally to continuous infusion. With the results of this case series, continuous infusion ifosfamide appears to be safe and feasible for outpatient administration and may offer an advantage from a hematologic adverse event profile but would need to be confirmed in a larger cohort., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

It is increasingly recognized that networks of brain areas work together to accomplish computational goals. However, functional connectivity networks are not often compared between different behavioral states and across different frequencies of electrical oscillatory signals. In addition, connectivity is always defined as the strength of signal relatedness between two atlas-based anatomical locations. Here, we performed an exploratory analysis using data collected from high-density arrays in the prefrontal cortex (PFC), striatum (STR), and ventral tegmental area (VTA) of male rats. These areas have all been implicated in a wide range of different tasks and computations including various types of memory as well as reward valuation, habit formation and execution, and skill learning. Novel intraregional clustering analyses identified patterns of spatially restricted, temporally coherent, and frequency-specific signals that were reproducible across days and were modulated by behavioral states. Multiple clusters were identified within each anatomical region, indicating a mesoscopic scale of organization. Generalized eigendecomposition (GED) was used to dimension-reduce each cluster to a single component time series. Dense intercluster connectivity was modulated by behavioral state, with connectivity becoming reduced when the animals were exposed to a novel object, compared with a baseline condition. Behavior-modulated connectivity changes were seen across the spectrum, with δ, θ, and γ all being modulated. These results demonstrate the brain's ability to reorganize functionally at both the intra- and inter-regional levels during different behavioral states. NEW & NOTEWORTHY We applied novel clustering techniques to discover functional subregional anatomical patches that changed with behavioral conditions but were frequency specific and stable across days. By taking into account these changes in intraregional signal generator location and extent, we were able to reveal a richer picture of inter-regional functional connectivity than would otherwise have been possible. These findings reveal that the brain's functional organization changes with state at multiple levels of scale.