Treatment delay of bone tumours, compilation of a sociodemographic risk profile: A retrospective study

<p>Abstract</p> <p>Background</p> <p>Bone tumours are comparatively rare tumours and delays in diagnosis and treatment are common. The purpose of this study was to analyse sociodemographic risk factors for bone tumour patients in order to identify those at risk of prolonged patients delay (time span from first symptoms to consultation), professional delay (from consultation to treatment) or symptom interval (from first symptoms to treatment). Understanding these relationships might enable us to shorten time to diagnosis and therapy.</p> <p>Methods</p> <p>We carried out a retrospective analysis of 265 patients with bone tumours documenting sociodemographic factors, patient delay, professional delay and symptom interval. A multivariate explorative Cox model was performed for each delay.</p> <p>Results</p> <p>Female gender was associated with a prolonged patient delay. Age under 30 years and rural living predisposes to a prolonged professional delay and symptom interval.</p> <p>Conclusion</p> <p>Early diagnosis and prompt treatment are required for successful management of most bone tumour patients. We succeeded in identifying the histology independent risk factors of age under 30 years and rural habitation for treatment delay in bone tumour patients. Knowing about the existence of these risk groups age under 30 years and female gender could help the physician to diagnose bone tumours earlier. The causes for the treatment delays of patients living in a rural area have to be investigated further. If the delay initiates in the lower education of rural general physicians, further training about bone tumours might advance early detection. Hence the outcome of patients with bone tumours could be improved.</p

A Longitudinal Comparison of Arm Morbidity in Stage I–II Breast Cancer Patients Treated with Sentinel Lymph Node Biopsy, Sentinel Lymph Node Biopsy Followed by Completion Lymph Node Dissection, or Axillary Lymph Node Dissection

Background:\ud Long-term shoulder and arm function following sentinel lymph node biopsy (SLNB) may surpass that following complete axillary lymph node dissection (CLND) or axillary lymph node dissection (ALND). We objectively examined the morbidity and compared outcomes after SLNB, SLNB + CLND, and ALND in stage I/II breast cancer patients.\ud \ud Materials and Methods:\ud Breast cancer patients who had SLNB (n = 51), SLNB + CLND (n = 55), and ALND (n = 65) were physically examined 1 day before surgery (T0), and after 6 (T1), 26 (T2), 52 (T3), and 104 (T4) weeks. Differences in 8 parameters between the affected and unaffected arms were calculated. General linear models were computed to examine time, group, and interaction effects.\ud \ud Results:\ud All outcomes changed significantly, mostly nonlinearly, over time (T0–T4). Between T1 and T4, limitations decreased in abduction (all groups); anteflexion, abduction-exorotation, abduction strength (SLNB + CLND, ALND); flexion strength (SLNB + CLND); and arm volume (SLNB, SLNB + CLND). At T4, limitations in anteflexion (SLNB, ALND), abduction (SLNB + CLND, ALND), exorotation (ALND), abduction-exorotation (all groups), and volume (SLNB + CLND, ALND) increased significantly compared with T0. The SLNB group showed an advantage in anteflexion, abduction, abduction-exorotation, and volume. Groups changed significantly but differently over time in anteflexion, abduction, abduction/exorotation, abduction strength, flexion strength, and volume. Effect sizes varied from 0.19 to 0.00.\ud \ud Conclusion:\ud Initial declines in range of motion and strength were followed by recovery, although not always to presurgery levels. Range of motion and volume outcomes were better for SLNB than ALND, but not strength. SLNB surpassed SLNB + CLND in 2 of the range of motion variables. The clinical relevance of these results is negligible

Assessing the effects of Ang-(1-7) therapy following transient middle cerebral artery occlusion

The counter-regulatory axis, Angiotensin Converting Enzyme 2, Angiotensin-(1-7), Mas receptor (ACE2/Ang-1-7/MasR), of the renin angiotensin system (RAS) is a potential therapeutic target in stroke, with Ang-(1-7) reported to have neuroprotective effects in pre-clinical stroke models. Here, an extensive investigation of the functional and mechanistic effects of Ang-(1-7) was performed in a rodent model of stroke. Using longitudinal magnetic resonance imaging (MRI) it was observed that central administration of Ang-(1-7) following transient middle cerebral artery occlusion (MCAO) increased the amount of tissue salvage compared to reperfusion alone. This protective effect was not due to early changes in blood brain barrier (BBB) permeability, microglia activation or inflammatory gene expression. However, increases in NADPH oxidase 1 (Nox1) mRNA expression were observed in the treatment group compared to control. In order to determine whether Ang-(1-7) has direct cerebrovascular effects, laser speckle contrast imaging (LSCI) was performed to measure dynamic changes in cortical perfusion following reperfusion. Delivery of Ang-(1-7) did not have any effect on cortical perfusion following reperfusion however; it showed an indication to prevent the ‘steal phenomenon’ within the contralateral hemisphere. The comprehensive series of studies have demonstrated a moderate protective effect of Ang-(1-7) when given alongside reperfusion to increase tissue salvage

Retrotransposon-Induced Heterochromatin Spreading in the Mouse Revealed by Insertional Polymorphisms

The “arms race” relationship between transposable elements (TEs) and their host has promoted a series of epigenetic silencing mechanisms directed against TEs. Retrotransposons, a class of TEs, are often located in repressed regions and are thought to induce heterochromatin formation and spreading. However, direct evidence for TE–induced local heterochromatin in mammals is surprisingly scarce. To examine this phenomenon, we chose two mouse embryonic stem (ES) cell lines that possess insertionally polymorphic retrotransposons (IAP, ETn/MusD, and LINE elements) at specific loci in one cell line but not the other. Employing ChIP-seq data for these cell lines, we show that IAP elements robustly induce H3K9me3 and H4K20me3 marks in flanking genomic DNA. In contrast, such heterochromatin is not induced by LINE copies and only by a minority of polymorphic ETn/MusD copies. DNA methylation is independent of the presence of IAP copies, since it is present in flanking regions of both full and empty sites. Finally, such spreading into genes appears to be rare, since the transcriptional start sites of very few genes are less than one Kb from an IAP. However, the B3galtl gene is subject to transcriptional silencing via IAP-induced heterochromatin. Hence, although rare, IAP-induced local heterochromatin spreading into nearby genes may influence expression and, in turn, host fitness

Brain energy rescue:an emerging therapeutic concept for neurodegenerative disorders of ageing

The brain requires a continuous supply of energy in the form of ATP, most of which is produced from glucose by oxidative phosphorylation in mitochondria, complemented by aerobic glycolysis in the cytoplasm. When glucose levels are limited, ketone bodies generated in the liver and lactate derived from exercising skeletal muscle can also become important energy substrates for the brain. In neurodegenerative disorders of ageing, brain glucose metabolism deteriorates in a progressive, region-specific and disease-specific manner — a problem that is best characterized in Alzheimer disease, where it begins presymptomatically. This Review discusses the status and prospects of therapeutic strategies for countering neurodegenerative disorders of ageing by improving, preserving or rescuing brain energetics. The approaches described include restoring oxidative phosphorylation and glycolysis, increasing insulin sensitivity, correcting mitochondrial dysfunction, ketone-based interventions, acting via hormones that modulate cerebral energetics, RNA therapeutics and complementary multimodal lifestyle changes

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency–Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research

Early Release Science of the exoplanetWASP-39b with JWST NIRISS

This is the author accepted manuscript. The final version is available from Nature Research via the DOI in this recordData Availability: The raw data from this study are publicly available via the Space Science Telescope Institute's Mikulski Archive for Space Telescopes (https://archive.stsci.edu/). The data which was used to create all of the figures in this manuscript are freely available on Zenodo and GitHub (Zenodo Link;https://github.com/afeinstein20/wasp39b_niriss_paper). All additional data is available upon request.Code Availability: The following are open-source pipelines written in Python that are available either through the Python Package Index (PyPI) or GitHub that were used throughout this work: Eureka! (https://github.com/kevin218/Eureka); nirHiss (https://github.com/afeinstein20/nirhiss); supreme-SPOON (https://github.com/radicamc/supreme-spoon); transitspectroscopy (https://github.com/nespinoza/transitspectroscopy/tree/dev); iraclis (https://github.com/uclexoplanets/Iraclis); juliet (https://github.com/nespinoza/juliet); chromatic (https://github.com/zkbt/chromatic); chromatic_fitting (https://github.com/catrionamurray/chromatic_fitting); ExoTiC-LD54, 121 (https://github.com/Exo-TiC/ExoTiC-LD); ExoTETHyS122 (https://github.com/uclexoplanets/ExoTETHyS); PICASO88,89 (https://github.com/natashabatalha/picaso); Virga94, 95 (https://github.com/natashabatalha/virga); CHIMERA (https://github.com/mrline/CHIMERA); PyMultiNest (https://github.com/JohannesBuchner/PyMultiNest); MultiNest (https://github.com/JohannesBuchner/MultiNest)The Saturn-mass exoplanet WASP-39b has been the subject of extensive efforts to determine its atmospheric properties using transmission spectroscopy. However, these efforts have been hampered by modelling degeneracies between composition and cloud properties that are caused by limited data quality. Here, we present the transmission spectrum of WASP-39 b obtained using the SOSS mode of the NIRISS instrument on JWST. This spectrum spans 0.6–2.8m in wavelength and reveals multiple water absorption bands, the potassium resonance doublet, and signatures of clouds. The precision and broad wavelength coverage of NIRISS-SOSS allows us to break model degeneracies between cloud properties and the atmospheric composition of WASP-39b, favouring a heavy element enhancement (“metallicity”) of ~10–30x the solar value, a sub-solar carbon-to-oxygen (C/O) ratio, and a solar-to-super-solar potassium-to-oxygen (K/O) ratio. The observations are also best explained by wavelength-dependent, non-gray clouds with inhomogeneous coverage of the planet’s terminator.Leverhulme TrustUK Research and Innovatio

Early Release Science of the exoplanet WASP-39b with JWST NIRSpec G395H

This is the author accepted manuscript. The final version is available from Nature Research via the DOI in this recordData Availability: The data used in this paper are associated with JWST program ERS 1366 (observation #4) and are available from the Mikulski Archive for Space Telescopes (https://mast.stsci.edu). Science data processing version (SDP_VER) 2022_2a generated the uncalibrated data that we downloaded from MAST. We used JWST Calibration Pipeline software version (CAL_VER) 1.5.3 with modifications described in the text. We used calibration reference data from context (CRDS_CTX) 0916, except as noted in the text. All the data and models presented in this publication can be found at 10.5281/zenodo.7185300.Code Availability: The codes used in this publication to extract, reduce and analyze the data are as follows; STScI JWST Calibration pipeline45 (https://github.com/spacetelescope/jwst), Eureka!53 (https://eurekadocs.readthedocs.io/en/latest/), ExoTiC-JEDI47 (https://github.com/ExoTiC/ExoTiC-JEDI), juliet71 (https://juliet.readthedocs.io/en/latest/), Tiberius15,49,50, transitspectroscopy51 (https://github.com/nespinoza/transitspectroscopy). In addition, these made use of batman65 (http://lkreidberg.github.io/batman/docs/html/index.html), celerite86 (https://celerite.readthedocs.io/en/stable/), chromatic (https://zkbt.github.io/chromatic/), Dynesty72 (https://dynesty.readthedocs.io/en/stable/index.html), emcee69 (https://emcee.readthedocs.io/en/stable/), exoplanet83 (https://docs.exoplanet.codes/en/latest/), ExoTEP75–77, ExoTHETyS79 (https://github.com/ucl-exoplanets/ExoTETHyS), ExoTiCISM57 (https://github.com/Exo-TiC/ExoTiC-ISM), ExoTiC-LD58 (https://exoticld.readthedocs.io/en/latest/), george68 (https://george.readthedocs.io/en/latest/) JAX82 (https://jax.readthedocs.io/en/latest/), LMFIT70 (https://lmfit.github.io/lmfit-py/), Pylightcurve78 (https://github.com/ucl-exoplanets/pylightcurve), Pymc3138 (https://docs.pymc.io/en/v3/index.html) and Starry84 (https://starry.readthedocs.io/en/latest/), each of which use the standard python libraries astropy139,140, matplotlib141, numpy142, pandas143, scipy64 and xarray144. The atmospheric models used to fit the data can be found at ATMO[Tremblin2015,Drummond2016,Goyal2018,Goyal2020]88–91, PHOENIX92–94, PICASO98,99 (https://natashabatalha.github.io/picaso/), Virga98,107 (https://natashabatalha.github.io/virga/), and gCMCRT115 (https://github.com/ELeeAstro/gCMCRT).Measuring the abundances of carbon and oxygen in exoplanet atmospheres is considered a crucial avenue for unlocking the formation and evolution of exoplanetary systems. Access to an exoplanet’s chemical inventory requires high precision observations, often inferred from individual molecular detections with low-resolution space-based and high-resolution ground-based facilities. Here we report the medium-resolution (R≈600) transmission spectrum of an exoplanet atmosphere between 3–5 μm covering multiple absorption features for the Saturn-mass exoplanet WASP-39b, obtained with JWST NIRSpec G395H. Our observations achieve 1.46× photon precision, providing an average transit depth uncertainty of 221 ppm per spectroscopic bin, and present minimal impacts from systematic effects. We detect significant absorption from CO2 (28.5σ ) and H2O (21.5σ ), and identify SO2 as the source of absorption at 4.1 μ m (4.8σ ). Best-fit atmospheric models range between 3× and 10× solar metallicity, with sub-solar to solar C/O ratios. These results, including the detection of SO2, underscore the importance of characterising the chemistry in exoplanet atmospheres, and showcase NIRSpec G395H as an excellent mode for time series observations over this critical wavelength range.Science and Technology Facilities Council (STFC)UKR