Well-differentiated liposarcomas (WDLS) are low-grade lipomatous tumors with low malignant potential. Previous review identified controversy on whether upfront wide resection is necessary when they ...occur on the trunk or the extremities. MDM2 amplification is a genetic mutation typically present in WDLS and absent in benign lipomas (BL). We aimed to study the influence of MDM2 status on the management/recurrences of lipomatous tumors in the trunk or the extremities.
All patients with lipomatous tumors with MDM2 testing in the Province of Alberta between 2015 and 2020 were identified from the Cancer Cytogenetics Laboratory dataset. High grade sarcomas, retroperitoneal, head/neck, or groin tumors were excluded. Primary outcome measures including MDM2 status, surgical margin, local recurrence, reoperation rate, dedifferentiation, and metastasis were abstracted from chart review. Descriptive statistics were used to analyse treatment patterns and recurrence rates according to MDM2 status.
Total of 764 charts were retrieved, and 282 were included for analysis. 33 showed MDM2 amplification (11.7%), and 2 of them had local recurrence (6.1%). Two patients with recurrent tumors underwent limb-salvaging reoperation (6.1%), but no dedifferentiation or metastasis was seen.
Findings in this study confirmed the benign behaviour of truncal/extremities lipomas with no MDM2 amplification. Given we found a 6.1% recurrence rate in MDM2 amplified tumors, a prolong follow up of this subset of patients is warranted. Overall, regardless of the MDM2 status, we believe an initial marginal excision is a reasonable surgical approach as recurrences are rare, and they can be managed with re-excision when they occur.
•With upfront marginal resection of truncal or extremities atypical lipomatous tumors/well-differentiated liposarcomas, overall local recurrence rate of 1.4% and reoperation rate of 1.1% were achieved.•When tumors showed MDM2 amplification, local recurrence rate of 6.1% was found as opposed to 0.8% in tumors with no MDM2 amplification.•There was no dedifferentiation or metastasis found with local recurrence.
T cells represent a critical effector of cell-mediated immunity. Activated T cells engage in metabolic reprogramming during effector differentiation to accommodate dynamic changes in energy demands. ...Here, we show that the hormone, insulin, and downstream signaling through its insulin receptor shape adaptive immune function through modulating T cell metabolism. T cells lacking insulin receptor expression (LckCre+ Insrfl/fl) show reduced antigen-specific proliferation and compromised production of pro-inflammatory cytokines. In vivo, T cell-specific insulin receptor deficiency reduces T cell-driven colonic inflammation. In a model of severe influenza infection with A/PR8 (H1N1), lack of insulin receptor on T cells curtails antigen-specific immunity to influenza viral antigens. Mechanistically, insulin receptor signaling reinforces a metabolic program that supports T cell nutrient uptake and associated glycolytic and respiratory capacities. These data highlight insulin receptor signaling as an important node integrating immunometabolic pathways to drive optimal T cell effector function in health and disease.
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•Insulin receptor signaling controls T cell proliferation and cytokine production•T cell-intrinsic insulin resistance dampens T cell pro-inflammatory function•T cell insulin receptor stimulation drives protective immunity against influenza•Insulin receptor modulates T cell function through controlling cell metabolism
Tsai et al. report that insulin signaling plays an important role in tuning the immune response. Specifically, insulin receptor signaling has an impact on T cell glucose metabolism and amino acid handling. In mouse models, insulin receptor-deficient T cells exhibit reduced inflammatory potential and poor protective immunity against H1N1 influenza infection.
The psychological wellbeing of healthcare workers has been impacted by the high levels of stress many have experienced during the Coronavirus Disease 2019 (COVID-19) pandemic. This study aimed to ...examine the feasibility and acceptability of a brief online course focused on introducing evidence-based skills that could increase resilience and decreases emotional distress in healthcare workers during the pandemic.
Employees of a large healthcare system completed a mental health survey at baseline, and then one month and two months after some employees participated in an online resilience-enhancement course consisting of three 12–19 min videos focused on mindfulness, mentalization, and self-compassion.
A total of 554 participants completed the baseline survey, endorsing moderate to high levels of emotional distress. Of those who completed all three assessments and participated in the course (n = 38), significant improvements in resilience and reductions in emotional distress were found one and two months later, in comparison to those who did not participate in the course (n = 110). Discussion: These findings suggest that a brief, online intervention can improve the mental health of healthcare workers during a crisis such as the COVID-19 pandemic.
The
-directed differentiation of pluripotent stem cells (PSCs) through stimulation of developmental signaling pathways can generate mature somatic cell types for basic laboratory studies or ...regenerative therapies. However, there has been significant uncertainty regarding a method to separately derive lung versus thyroid epithelial lineages, as these two cell types each originate from Nkx2-1
foregut progenitors and the minimal pathways claimed to regulate their distinct lineage specification
or
have varied in previous reports. Here, we employ PSCs to identify the key minimal signaling pathways (Wnt+BMP versus BMP+FGF) that regulate distinct lung- versus thyroid-lineage specification, respectively, from foregut endoderm. In contrast to most previous reports, these minimal pathways appear to be evolutionarily conserved between mice and humans, and FGF signaling, although required for thyroid specification, unexpectedly appears to be dispensable for lung specification. Once specified, distinct Nkx2-1
lung or thyroid progenitor pools can now be independently derived for functional 3D culture maturation, basic developmental studies or future regenerative therapies.
We present new arcminute-resolution maps of the Cosmic Microwave Background temperature and polarization anisotropy from the Atacama Cosmology Telescope, using data taken from 2013{2016 at 98 and 150 ...GHz. The maps cover more than 17,000 deg(^2), the deepest 600 deg(^2) with noise levels below 10µK-arcmin. We use the power spectrum derived from almost 6,000 deg(^2) of these maps to constrain cosmology. The ACT data enable a measurement of the angular scale of features in both the divergence-like polarization and the temperature anisotropy, tracing both the velocity and density at last-scattering. From these one can derive the distance to the last-scattering surface and thus infer the local expansion
rate, H0. By combining ACT data with large-scale information from WMAP we measure H0 = 67:6±1:1 km/s/Mpc, at 68% confidence, in excellent agreement with the independently measured Planck satellite estimate (from ACT alone we find H0 = 67:9± 1:5 km/s/Mpc). The ΛCDM model provides a good fit to the ACT data, and we find no evidence for deviations: both the spatial curvature, and the departure from the standard lensing signal in the
spectrum, are zero to within 1σ; the number of relativistic species, the primordial Helium fraction, and the running of the spectral index are consistent with ΛCDM predictions to within 1.5{2.2σ. We compare ACT, WMAP, and Planck at the parameter level and find good consistency; we investigate how the constraints on the correlated spectral index and baryon density parameters readjust when adding CMB large-scale information that ACT does not measure. The DR4 products presented here will be publicly released on the NASA Legacy Archive for Microwave Background Data Analysis.
We present the temperature and polarization angular power spectra of the CMB measured by the Atacama Cosmology Telescope (ACT) from 5400 deg
2
of the 2013–2016 survey, which covers >15000 deg
2
at 98 ...and 150 GHz. For this analysis we adopt a blinding strategy to help avoid confirmation bias and, related to this, show numerous checks for systematic error done before unblinding. Using the likelihood for the cosmological analysis we constrain secondary sources of anisotropy and foreground emission, and derive a “CMB-only” spectrum that extends to ℓ=4000. At large angular scales, foreground emission at 150 GHz is ∼1% of TT and EE within our selected regions and consistent with that found by
Planck
. Using the same likelihood, we obtain the cosmological parameters for ΛCDM for the ACT data alone with a prior on the optical depth of τ=0.065±0.015. ΛCDM is a good fit. The best-fit model has a reduced χ
2
of 1.07 (PTE=0.07) with
H
0
=67.9±1.5 km/s/Mpc. We show that the lensing BB signal is consistent with ΛCDM and limit the celestial EB polarization angle to ψ
P
=−0.07
̂
±0.09
̂
. We directly cross correlate ACT with
Planck
and observe generally good agreement but with some discrepancies in TE. All data on which this analysis is based will be publicly released.
The concentration of chloride in sweat remains the most robust biomarker for confirmatory diagnosis of cystic fibrosis (CF), a common life-shortening genetic disorder. Early diagnosis via ...quantitative assessment of sweat chloride allows prompt initiation of care and is critically important to extend life expectancy and improve quality of life. The collection and analysis of sweat using conventional wrist-strapped devices and iontophoresis can be cumbersome, particularly for infants with fragile skin, who often have insufficient sweat production. Here, we introduce a soft, epidermal microfluidic device ("sweat sticker") designed for the simple and rapid collection and analysis of sweat. Intimate, conformal coupling with the skin supports nearly perfect efficiency in sweat collection without leakage. Real-time image analysis of chloride reagents allows for quantitative assessment of chloride concentrations using a smartphone camera, without requiring extraction of sweat or external analysis. Clinical validation studies involving patients with CF and healthy subjects, across a spectrum of age groups, support clinical equivalence compared to existing device platforms in terms of accuracy and demonstrate meaningful reductions in rates of leakage. The wearable microfluidic technologies and smartphone-based analytics reported here establish the foundation for diagnosis of CF outside of clinical settings.
Transplantation approaches using cellular bridges, fetal central nervous system cells, fibroblasts expressing neurotrophin-3 (ref. 6), hybridoma cells expressing inhibitory protein-blocking ...antibodies, or olfactory nerves ensheathing glial cells transplanted into the acutely injured spinal cord have produced axonal regrowth or functional benefits. Transplants of rat or cat fetal spinal cord tissue into the chronically injured cord survive and integrate with the host cord, and may be associated with some functional improvements. In addition, rats transplanted with fetal spinal cord cells have shown improvements in some gait parameters, and the delayed transplantation of fetal raphe cells can enhance reflexes. We transplanted neural differentiated mouse embryonic stem cells into a rat spinal cord 9 days after traumatic injury. Histological analysis 2-5 weeks later showed that transplant-derived cells survived and differentiated into astrocytes, oligodendrocytes and neurons, and migrated as far as 8 mm away from the lesion edge. Furthermore, gait analysis demonstrated that transplanted rats showed hindlimb weight support and partial hindlimb coordination not found in 'sham-operated' controls or control rats transplanted with adult mouse neocortical cells.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Radiation therapy plays an important role in the multidisciplinary management of breast cancer. Recent years have seen improvements in breast cancer survival and a greater appreciation of potential ...long-term morbidity associated with the dose and volume of irradiated organs. Proton therapy reduces the dose to nontarget structures while optimizing target coverage. However, there remain additional financial costs associated with proton therapy, despite reductions over time, and studies have yet to demonstrate that protons improve upon the treatment outcomes achieved with photon radiation therapy. There remains considerable heterogeneity in proton patient selection and techniques, and the rapid technological advances in the field have the potential to affect evidence evaluation, given the long latency period for breast cancer radiation therapy recurrence and late effects. In this consensus statement, we assess the data available to the radiation oncology community of proton therapy for breast cancer, provide expert consensus recommendations on indications and technique, and highlight ongoing trials' cost-effectiveness analyses and key areas for future research.
This article describes 22 cases of breakthrough SARS‐CoV‐2 infection among over 14,000 fully vaccinated skilled nursing facility residents and staff. The majority of such infections were asymptomatic ...or were associated with mild symptoms, and there was no intra‐ facility spread related to these cases. This report suggests that postvaccination breakthrough infections are rare, but also confirms that vaccines do not offer 100% protection even in nonimmunosuppressed hosts, thus underscoring the need for studies of vaccine efficacy in immunosuppressed transplant recipients.
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