The compact 3T MRI system has been in continuous operation at the Mayo Clinic since March 2016. To date, over 200 patient studies have been completed, including 96 comparison studies with a clinical 3T whole-body MRI. The increased gradient performance has reliably resulted in consistently improved image quality.

How prostate cancer is initiated remains a topic of debate. In an effort to establish a human model of prostate carcinogenesis, we adapted premalignant human prostate EPT2-D5 cells to protein-free medium to generate numerous tight prostate spheres (D5HS) in monolayer culture. In contrast to EPT2-D5 cells, the newly generated D5HS efficiently formed large subcutaneous tumors and subsequent metastases in vivo, showing the tumorigenicity of D5HS spheres. A striking production of interleukin (IL)-6 mRNA and protein was found in D5HS cells. The essential roles of IL-6 and the downstream STAT3 signaling in D5HS tumor sphere formation were confirmed by neutralizing antibody, chemical inhibitors, and fluorescent pathway reporter. In addition, elevated reactive oxygen species (ROS) produced upon protein depletion was required for the activation of IL-6/STAT3 in D5HS. Importantly, a positive feedback loop was found between ROS and IL-6 during tumor sphere formation. The association of ROS/IL-6/STAT3 to the carcinogenesis of human prostate cells was further examined in xenograft tumors and verified by limiting dilution implantations. Collectively, we have for the first time established human prostate tumor-initiating cells based on physiologic adaption. The intrinsic association of ROS and IL-6/STAT3 signaling in human prostate carcinogenesis shed new light on this relationship and define therapeutic targets in this setting. Cancer Res; 73(23); 7090-100. Ó2013 AACR.

Purpose To develop a highly efficient magnetic field gradient coil for head imaging that achieves 200 mT/m and 500 T/m/s on each axis using a standard 1 MVA gradient driver in clinical whole‐body 3.0T MR magnet. Methods A 42‐cm inner diameter head‐gradient used the available 89‐ to 91‐cm warm bore space in a whole‐body 3.0T magnet by increasing the radial separation between the primary and the shield coil windings to 18.6 cm. This required the removal of the standard whole‐body gradient and radiofrequency coils. To achieve a coil efficiency ~4× that of whole‐body gradients, a double‐layer primary coil design with asymmetric x‐y axes, and symmetric z‐axis was used. The use of all‐hollow conductor with direct fluid cooling of the gradient coil enabled ≥50 kW of total heat dissipation. Results This design achieved a coil efficiency of 0.32 mT/m/A, allowing 200 mT/m and 500 T/m/s for a 620 A/1500 V driver. The gradient coil yielded substantially reduced echo spacing, and minimum repetition time and echo time. In high b = 10,000 s/mm2 diffusion, echo time (TE) < 50 ms was achieved (>50% reduction compared with whole‐body gradients). The gradient coil passed the American College of Radiology tests for gradient linearity and distortion, and met acoustic requirements for nonsignificant risk operation. Conclusions Ultra‐high gradient coil performance was achieved for head imaging without substantial increases in gradient driver power in a whole‐body 3.0T magnet after removing the standard gradient coil. As such, any clinical whole‐body 3.0T MR system could be upgraded with 3‐4× improvement in gradient performance for brain imaging.

BackgroundMedical staff fighting the COVID-19 pandemic are experiencing stress from high occupational risk, panic in the community and the extreme workload. Maintaining the psychological health of a medical team is essential for efficient functioning, but psychological intervention models for emergency medical teams are rare.AimsTo design a systematic, full-coverage psychological health support scheme for medical teams serving large-scale emergent situations, and demonstrate its effectiveness in a real-world study in Leishenshan Hospital during the COVID-19 epidemic in Wuhan, China.MethodsThe scheme integrates onsite and online mental health resources and features team-based psychosocial support and evidence-based interventions. It contained five modules, including a daily measurement of mood, a daily mood broadcast that promotes positive affirmation, a daily online peer-group activity with themes based on the challenges reported by the team, Balint groups and an after-work support team. The daily mood measurement provides information to the other modules. The scheme also respects the special psychological characteristics of medical staff by promoting their strengths.ResultsThe scheme economically supported a special medical team of 156 members with only one onsite psychiatrist. Our data reflected that the entire medical team maintained an overall positive outlook (7–9 out of 10 in a Daily Mood Index, DMI) for nearly 6 weeks of continuous working. Since the scheme promoted self-strengths and positive self-affirmation, the number of self-reports of life-related gains were high and played a significant effect on the DMI. Our follow-up investigations also revealed that multiple modules of the scheme received high attention and evaluation levels.ConclusionOur quantitative data from Leishenshan hospital, Wuhan, China, show that the programme is adequate to support the continuous high workload of medical teams. This scheme could be applied to medical teams dealing with emergent situations.

Purpose To establish peripheral nerve stimulation (PNS) thresholds for an ultra‐high performance magnetic field gradient subsystem (simultaneous 200‐mT/m gradient amplitude and 500‐T/m/s gradient slew rate; 1 MVA per axis [MAGNUS]) designed for neuroimaging with asymmetric transverse gradients and 42‐cm inner diameter, and to determine PNS threshold dependencies on gender, age, patient positioning within the gradient subsystem, and anatomical landmarks. Methods The MAGNUS head gradient was installed in a whole‐body 3T scanner with a custom 16‐rung bird‐cage transmit/receive RF coil compatible with phased‐array receiver brain coils. Twenty adult subjects (10 male, mean ± SD age = 40.4 ± 11.1 years) underwent the imaging and PNS study. The tests were repeated by displacing subject positions by 2‐4 cm in the superior–inferior and anterior–posterior directions. Results The x‐axis (left–right) yielded mostly facial stimulation, with mean ΔGmin = 111 ± 6 mT/m, chronaxie = 766 ± 76 µsec. The z‐axis (superior–inferior) yielded mostly chest/shoulder stimulation (123 ± 7 mT/m, 620 ± 62 µsec). Y‐axis (anterior–posterior) stimulation was negligible. X‐axis and z‐axis thresholds tended to increase with age, and there was negligible dependency with gender. Translation in the inferior and posterior directions tended to increase the x‐axis and z‐axis thresholds, respectively. Electric field simulations showed good agreement with the PNS results. Imaging at MAGNUS gradient performance with increased PNS threshold provided a 35% reduction in noise‐to‐diffusion contrast as compared with whole‐body performance (80 mT/m gradient amplitude, 200 T/m/sec gradient slew rate). Conclusion The PNS threshold of MAGNUS is significantly higher than that for whole‐body gradients, which allows for diffusion gradients with short rise times (under 1 msec), important for interrogating brain microstructure length scales.

Purpose:We investigate the importance of high gradient-amplitude and high slew-rate on oscillating gradient spin echo (OGSE) diffusion imaging for human brain imaging and evaluate human brain imaging with OGSE on the MAGNUS head-gradient insert (200 mT/m amplitude and 500 T/m/s slew rate). Methods: Simulations with cosine-modulated and trapezoidal-cosine OGSE at various gradient amplitudes and slew rates were performed. Six healthy subjects were imaged with the MAGNUS gradient at 3T with OGSE at frequencies up to 100 Hz and b = 450 s/mm 2 . Comparisons were made against standard pulsed gradient spin echo (PGSE) diffusion in vivo and in an isotropic diffusion phantom. Results: Simulations show that to achieve high frequency and b-value simultaneously for OGSE, high gradient amplitude, high slew rates, and high peripheral nerve stimulation limits are required. A strong linear trend for increased diffusivity (mean: 8-19%, radial: 9-27%, parallel: 8-15%) was observed in normal white matter with OGSE (20 Hz to 100 Hz) as compared to PGSE. Linear fitting to frequency provided excellent correlation, and using a short-range disorder model provided radial longterm diffusivities of D ∞,MD = 911 ± 72 µm 2 /s, D ∞,PD = 1519 ± 164 µm 2 /s, and D ∞,RD = 640 ± 111 µm 2 /s and correlation lengths of l c,MD = 0.802 ± 0.156 µm, l c,PD = 0.837 ± 0.172 µm, and l c,RD = 0.780 ± 0.174 µm. Diffusivity changes with OGSE frequency were negligible in the phantom, as expected. Conclusion: The high gradient amplitude, high slew rate, and high peripheral nerve stimulation thresholds of the MAGNUS head-gradient enables OGSE acquisition for in vivo human brain imaging. K E Y W O R D S diffusion imaging, head-gradient, microstructure | 951 TAN eT Al.

UbcH5 is the key ubiquitin-conjugating enzyme catalyzing ubiquitination during TNF-α-triggered NF-κB activation. Here, we identified an herb-derived sesquiterpene lactone compound IJ-5 as a preferential inhibitor of UbcH5 and explored its therapeutic value in inflammatory and autoimmune disease models. IJ-5 suppresses TNF-α-induced NF-κB activation and inflammatory gene transcription by inhibiting the ubiquitination of receptor-interacting protein 1 and NF-κB essential modifier, which is essential to IκB kinase activation. Mechanistic investigations revealed that IJ-5 preferentially binds to and inactivates UbcH5 by forming a covalent adduct with its active site cysteine and thereby preventing ubiquitin conjugation to UbcH5. In preclinical models, pretreatment of IJ-5 exhibited potent anti-inflammatory activity against TNF-α- and D-galactosamine-induced hepatitis and collagen-induced arthritis. These findings highlight the potential of UbcH5 as a therapeutic target for anti-TNF-α interventions and provide an interesting lead compound for the development of new anti-inflammation agents.

Osteosarcoma is a primary malignant tumor that tends to threaten children and adolescents, and the 5-year event-free survival rate has not improved significantly in the past three decades, bringing grief and economic burden to patients and society. To date, the genetic background and oncogenesis mechanisms of osteosarcoma remain unclear, impeding further research. The tumor immune microenvironment has become a recent research hot spot, providing novel but valuable insight into tumor heterogeneity and multifaceted mechanisms of tumor progression and metastasis. However, the immune microenvironment in osteosarcoma has been vigorously discussed, and the landscape of immune and non-immune component infiltration has been intensively investigated. Here, we summarize the current knowledge of the classification, features, and functions of the main infiltrating cells, complement system, and exosomes in the osteosarcoma immune microenvironment. In each section, we also highlight the complex crosstalk network among them and the corresponding potential therapeutic strategies and clinical applications to deepen our understanding of osteosarcoma and provide a reference for imminent effective therapies with reduced adverse effects.