4D printing has attracted tremendous interest since its first conceptualization in 2013. 4D printing derived from the fast growth and interdisciplinary research of smart materials, 3D printer, and ...design. Compared with the static objects created by 3D printing, 4D printing allows a 3D printed structure to change its configuration or function with time in response to external stimuli such as temperature, light, water, etc., which makes 3D printing alive. Herein, the material systems used in 4D printing are reviewed, with emphasis on mechanisms and potential applications. After a brief overview of the definition, history, and basic elements of 4D printing, the state‐of‐the‐art advances in 4D printing for shape‐shifting materials are reviewed in detail. Both single material and multiple materials using different mechanisms for shape changing are summarized. In addition, 4D printing of multifunctional materials, such as 4D bioprinting, is briefly introduced. Finally, the trend of 4D printing and the perspectives for this exciting new field are highlighted.
4D printing allows 3D printed structures to change their configurations or functions with time in response to external stimuli. Herein, the material system is reviewed based on the mechanism and potential applications for advances in 4D printing. The trends of 4D printing are discussed and the perspectives for this exciting new field are provided.
During B lymphopoiesis, recombination of the locus encoding the immunoglobulin κ-chain complex (Igk) requires expression of the precursor to the B cell antigen receptor (pre-BCR) and escape from ...signaling via the interleukin 7 receptor (IL-7R). By activating the transcription factor STAT5, IL-7R signaling maintains proliferation and represses Igk germline transcription by unknown mechanisms. We demonstrate that a STAT5 tetramer bound the Igk intronic enhancer (E(κi)), which led to recruitment of the histone methyltransferase Ezh2. Ezh2 marked trimethylation of histone H3 at Lys27 (H3K27me3) throughout the κ-chain joining region (J(κ)) to the κ-chain constant region (C(κ)). In the absence of Ezh2, IL-7 failed to repress Igk germline transcription. H3K27me3 modifications were lost after termination of IL-7R-STAT5 signaling, and the transcription factor E2A bound E(κi), which resulted in acquisition of H3K4me1 and acetylated histone H4 (H4Ac). Genome-wide analyses showed a STAT5 tetrameric binding motif associated with transcriptional repression. Our data demonstrate how IL-7R signaling represses Igk germline transcription and provide a general model for STAT5-mediated epigenetic transcriptional repression.
ABSTRACT
We present spatially resolved Echelle spectroscopy of an intervening Mg ii–Fe ii–Mg i absorption-line system detected at zabs = 0.73379 towards the giant gravitational arc PSZ1 ...G311.65–18.48. The absorbing gas is associated with an inclined disc-like star-forming galaxy, whose major axis is aligned with the two arc-segments reported here. We probe in absorption the galaxy’s extended disc continuously, at ≈3 kpc sampling, from its inner region out to 15× the optical radius. We detect strong ($W_0^{2796}\gt 0.3$Å) coherent absorption along 13 independent positions at impact parameters D = 0–29 kpc on one side of the galaxy, and no absorption at D = 28–57 kpc on the opposite side (all de-lensed distances at zabs). We show that (1) the gas distribution is anisotropic; (2) $W_0^{2796}$, $W_0^{2600}$, $W_0^{2852}$, and the ratio $W_0^{2600}\!/W_0^{2796}$, all anticorrelate with D; (3) the $W_0^{2796}$–D relation is not cuspy and exhibits significantly less scatter than the quasar-absorber statistics; (4) the absorbing gas is co-rotating with the galaxy out to D ≲ 20 kpc, resembling a ‘flat’ rotation curve, but at D ≳ 20 kpc velocities decline below the expectations from a 3D disc-model extrapolated from the nebular O ii emission. These signatures constitute unambiguous evidence for rotating extra-planar diffuse gas, possibly also undergoing enriched accretion at its edge. Arguably, we are witnessing some of the long-sought processes of the baryon cycle in a single distant galaxy expected to be representative of such phenomena.
Female breast cancer accounts for 15.2% of all new cancer cases in the United States, with a continuing increase in incidence despite efforts to discover new targeted therapies. With an approximate ...failure rate of 85% for therapies in the early phases of clinical trials, there is a need for more translatable, new preclinical in vitro models that include cellular heterogeneity, extracellular matrix, and human-derived biomaterials. Specifically, adipose tissue and its resident cell populations have been identified as necessary attributes for current preclinical models. Adipose-derived stromal/stem cells (ASCs) and mature adipocytes are a normal part of the breast tissue composition and not only contribute to normal breast physiology but also play a significant role in breast cancer pathophysiology. Given the recognized pro-tumorigenic role of adipocytes in tumor progression, there remains a need to enhance the complexity of current models and account for the contribution of the components that exist within the adipose stromal environment to breast tumorigenesis. This review article captures the current landscape of preclinical breast cancer models with a focus on breast cancer microphysiological system (MPS) models and their counterpart patient-derived xenograft (PDX) models to capture patient diversity as they relate to adipose tissue.
The current study assessed the impact of the COVID-19 pandemic on children with PANS/PANDAS, a condition characterized by sudden-onset obsessive-compulsive, tic, or restrictive eating symptoms ...following infection. We conducted an anonymous survey between February and June 2021 of 254 self-reported caregivers of minors with PANS/PANDAS. Caregivers answered questions regarding PANS/PANDAS symptoms, telehealth care, and intention to vaccinate their child against COVID-19. PANS/PANDAS symptoms during COVID-19 infections were assessed when applicable. Children’s OCD symptoms and coercive behaviors towards caregivers, along with the caregivers’ mental health, relationship satisfaction, and burden, were assessed using standardized questionnaires. A majority of respondents endorsed a negative impact on their child’s friendships, relationships with extended family, hobbies, and academic skills due to the pandemic. Children with suspected or diagnosed COVID-19 experienced new or worsened psychiatric symptoms, particularly mood lability, OCD, and anxiety. Telehealth care was the preferred treatment modality if the child had mild symptoms of PANS/PANDAS. A majority of caregivers reported high levels of relationship dissatisfaction and caregiver burden. As expected, these data suggest an overall negative impact of the COVID-19 pandemic on children with PANS/PANDAS and their caregivers.
ABSTRACT
We present gravitational-arc tomography of the cool-warm enriched circumgalactic medium (CGM) of an isolated galaxy (‘G1’) at z ≈ 0.77. Combining VLT/MUSE adaptive-optics and Magellan/MagE ...echelle spectroscopy, we obtain partially resolved kinematics of Mg ii in absorption and O ii in emission. The unique arc configuration allows us to probe 42 spatially independent arc positions transverse to G1, plus four positions in front of it. The transverse positions cover G1’s minor and major axes at impact parameters of ≈10–30 and ≈60 kpc, respectively. We observe a direct kinematic connection between the cool-warm enriched CGM (traced by Mg ii) and the interstellar medium (traced by O ii). This provides strong evidence for the existence of an extended disc that co-rotates with the galaxy out to tens of kiloparsecs. The Mg ii velocity dispersion (σ ≈ 30–100 km s−1, depending on position) is of the same order as the modelled galaxy rotational velocity (vrot ≈ 80 km s−1), providing evidence for the presence of a turbulent and pressure-supported CGM component. We regard the absorption to be modulated by a galactic-scale outflow, as it offers a natural scenario for the observed line-of-sight dispersion and asymmetric profiles observed against both the arcs and the galaxy. An extended enriched co-rotating disc together with the signatures of a galactic outflow, are telltale signs of metal recycling in the z ∼ 1 CGM.
A total of 271 patients were prospectively followed up to determine whether patients whose hospital stay is complicated by diarrhea due to Clostridium difficile experience differences in cost and ...length of stay and survival rates when compared with patients whose stay is not complicated by C. difficile-associated diarrhea. Forty patients (15%) developed nosocomial C. difficile-associated diarrhea. These patients incurred adjusted hospital costs of $3669-that is, 54% (95% confidence interval CI, 17%-103%)-higher than patients whose course was not complicated by C. difficile-associated diarrhea. The extra length of stay attributable to C. difficile-associated diarrhea was 3.6 days (95% CI, 1.5-6.2). C. difficile-associated diarrhea was not associated with excess 3-month or 1-year mortality after adjustment for age, comorbidity, and disease severity. On the basis of the findings of this study, a conservative estimate of the cost of this disease in the United States exceeds $1.1 billion per year.
Objectives
The aim of this cross-sectional study was to apply a novel software to measure and compare levels of nonverbal synchrony, as a potential indicator of communication quality, in video ...recordings of racially-concordant and racially-discordant oncology interactions. Predictions include that the levels of nonverbal synchrony will be greater during racially-concordant interactions than racially-discordant interactions, and that levels of nonverbal synchrony will be associated with traditional measures of communication quality in both racially-concordant and racially-discordant interactions.
Design
This is a secondary observational analysis of video-recorded oncology treatment discussions collected from 2 previous studies.
Setting
Two National Cancer Institute-designated Comprehensive Cancer Centers and another large urban cancer center.
Participants
Participants from Study 1 include 161 White patients with cancer and 11 White medical oncologists. Participants from Study 2 include 66 Black/African-American patients with cancer and 17 non-Black medical oncologists. In both studies inclusion criteria for patients was a recent cancer diagnosis; in Study 2 inclusion criteria was identifying as Black/African American.
Main outcome measures
Nonverbal synchrony and communication quality.
Results
Greater levels of nonverbal synchrony were observed in racially-discordant interactions than in racially-concordant interactions. Levels of nonverbal synchrony were associated with indicators of communication quality, and these associations were more consistently found in racially-discordant interactions.
Conclusion
This study advances clinical communication and disparities research by successfully applying a novel approach capturing the unconscious nature of communication, and revealing differences in communication in racially-discordant and racially-concordant oncology interactions. This study highlights the need for further exploration of nonverbal aspects relevant to patient-physician interactions.
PfSPZ Vaccine, composed of radiation-attenuated, aseptic, purified, cryopreserved Plasmodium falciparum sporozoites, is administered by direct venous inoculation (DVI) for maximal efficacy against ...malaria. A critical issue for advancing vaccines that are administered intravenously is the ability to efficiently administer them across multiple age groups. As part of a pediatric safety, immunogenicity, and efficacy trial in western Kenya, we evaluated the feasibility and tolerability of DVI, including ease of venous access, injection time, and crying during the procedure across age groups. Part 1 was an age de-escalation, dose escalation trial in children aged 13 months-5 years and infants aged 5–12 months; part 2 was a vaccine efficacy trial including only infants, using the most skilled injectors from part 1. Injectors could use a vein viewer, if needed. A total of 1222 injections (target 0.5 mL) were initiated by DVI in 511 participants (36 were 5–9-year-olds, 65 were 13–59-month-olds, and 410 infants). The complete volume was injected in 1185/1222 (97.0%) vaccinations, 1083/1185 (91.4%) achieved with the first DVI. 474/511 (92.8%) participants received only complete injections, 27/511 (5.3%) received at least one partial injection (<0.5 mL), and in 10/511 (2.0%) venous access was not obtained. The rate of complete injections by single DVI for infants improved from 77.1% in part 1 to 92.8% in part 2. No crying occurred in 51/59 (86.4%) vaccinations in 5–9-year-olds, 25/86 (29.1%) vaccinations in 13–59-month-olds and 172/1067 (16.1%) vaccinations in infants. Mean administration time ranged from 2.6 to 4.6 minutes and was longer for younger age groups.
These data show that vaccination by DVI was feasible and well tolerated in infants and children in this rural hospital in western Kenya, when performed by skilled injectors. We also report that shipping and storage in liquid nitrogen vapor phase was simple and efficient. (Clinicaltrials.gov NCT02687373).
ABSTRACT
We use spatially resolved spectroscopy of a distant giant gravitational arc to test orientation effects on Mg ii absorption equivalent width (EW) and covering fraction (〈κ〉) in the ...circumgalactic medium of a foreground star-forming galaxy (G1) at z ∼ 0.77. Forty-two spatially-binned arc positions uniformly sample impact parameters (D) to G1 between 10 and 30 kpc and azimuthal angles α between 30° and 90° (minor axis). We find an EW-D anticorrelation, akin to that observed statistically in quasar absorber studies, and an apparent correlation of both EW and 〈κ〉 with α, revealing a non-isotropic gas distribution. In line with our previous results on Mg ii kinematics suggesting the presence of outflows in G1, at minimum a simple 3D static double-cone model (to represent the trace of bipolar outflows) is required to recreate the EW spatial distribution. The D and α values probed by the arc cannot confirm the presence of a disc, but the data highly disfavour a disc alone. Our results support the interpretation that the EW-α correlation observed statistically using other extant probes is partly shaped by bipolar metal-rich winds.
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