Summary
Introduction
Women with polycystic ovary syndrome (PCOS) have increased risk of metabolic syndrome. The relative contribution of clinical, demographic or biochemical factors to metabolic ...syndrome in PCOS is not known. A literature search was conducted in MEDLINE, CINAHL, EMBASE and clinical trial registries. Of 4530 studies reviewed, 59 were included in the systematic review and 27 in the meta‐analysis and meta‐regression. In good and fair quality studies, women with PCOS had an overall increased prevalence of metabolic syndrome (odds ratio, OR 3.35, 95% confidence interval, CI 2.44, 4.59). Increased prevalence of metabolic syndrome occurred in overweight or obese women with PCOS (OR 1.88, 95% 1.16, 3.04) but not in lean women (OR 1.45, 95% CI 0.35, 6.12). In meta‐regression analyses, the markers of metabolic syndrome diagnostic criteria (waist circumference, high‐density lipoprotein cholesterol, triglyceride, blood pressure), BMI, glucose tolerance (2‐hr oral glucose tolerance test) and surrogate markers of insulin resistance (HOMA‐IR) but not markers of reproductive dysfunction (sex hormone binding globulin, testosterone, PCOS phenotypes) contributed significantly to the heterogeneity in the prevalence of metabolic syndrome. Women with PCOS have increased risk of metabolic syndrome which was associated with obesity and metabolic features but not with indices of hyperandrogenism.
Abstract
We report results from continued timing observations of PSR J0740+6620, a high-mass, 2.8 ms radio pulsar in orbit with a likely ultracool white dwarf companion. Our data set consists of ...combined pulse arrival-time measurements made with the 100 m Green Bank Telescope and the Canadian Hydrogen Intensity Mapping Experiment telescope. We explore the significance of timing-based phenomena arising from general relativistic dynamics and variations in pulse dispersion. When using various statistical methods, we find that combining ∼1.5 yr of additional, high-cadence timing data with previous measurements confirms and improves on previous estimates of relativistic effects within the PSR J0740+6620 system, with the pulsar mass
m
p
=
2.08
−
0.07
+
0.07
M
⊙
(68.3% credibility) determined by the relativistic Shapiro time delay. For the first time, we measure secular variation in the orbital period and argue that this effect arises from apparent acceleration due to significant transverse motion. After incorporating contributions from Galactic differential rotation and off-plane acceleration in the Galactic potential, we obtain a model-dependent distance of
d
=
1.14
−
0.15
+
0.17
kpc (68.3% credibility). This improved distance confirms the ultracool nature of the white dwarf companion determined from recent optical observations. We discuss the prospects for future observations with next-generation facilities, which will likely improve the precision on
m
p
for J0740+6620 by an order of magnitude within the next few years.
Multiparametric Magnetic Resonance Imaging (MRI) can provide detailed information of the physical characteristics of rectum tumours. Several investigations suggest that volumetric analyses on ...anatomical and functional MRI contain clinically valuable information. However, manual delineation of tumours is a time consuming procedure, as it requires a high level of expertise. Here, we evaluate deep learning methods for automatic localization and segmentation of rectal cancers on multiparametric MR imaging. MRI scans (1.5T, T2-weighted, and DWI) of 140 patients with locally advanced rectal cancer were included in our analysis, equally divided between discovery and validation datasets. Two expert radiologists segmented each tumor. A convolutional neural network (CNN) was trained on the multiparametric MRIs of the discovery set to classify each voxel into tumour or non-tumour. On the independent validation dataset, the CNN showed high segmentation accuracy for reader1 (Dice Similarity Coefficient (DSC = 0.68) and reader2 (DSC = 0.70). The area under the curve (AUC) of the resulting probability maps was very high for both readers, AUC = 0.99 (SD = 0.05). Our results demonstrate that deep learning can perform accurate localization and segmentation of rectal cancer in MR imaging in the majority of patients. Deep learning technologies have the potential to improve the speed and accuracy of MRI-based rectum segmentations.
The most recent version of the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of metastatic non-small-cell lung cancer (NSCLC) ...was published in 2016. At the ESMO Asia Meeting in November 2017 it was decided by both ESMO and the Chinese Society of Clinical Oncology (CSCO) to convene a special guidelines meeting immediately after the Chinese Thoracic Oncology Group Annual Meeting 2018, in Guangzhou, China. The aim was to adapt the ESMO 2016 guidelines to take into account the ethnic differences associated with the treatment of metastatic NSCLC cancer in Asian patients. These guidelines represent the consensus opinions reached by experts in the treatment of patients with metastatic NSCLC representing the oncological societies of China (CSCO), Japan (JSMO), Korea (KSMO), Malaysia (MOS), Singapore (SSO) and Taiwan (TOS). The voting was based on scientific evidence, and was independent of both the current treatment practices and the drug availability and reimbursement situations in the six participating Asian countries. During the review process, the updated ESMO 2018 Clinical Practice Guidelines for metastatic NSCLC were released and were also considered, during the final stages of the development of the Pan-Asian adapted Clinical Practice Guidelines.
Immunotherapy is regarded as one of the major breakthroughs in cancer treatment. Despite its success, only a subset of patients responds—urging the quest for predictive biomarkers. We hypothesize ...that artificial intelligence (AI) algorithms can automatically quantify radiographic characteristics that are related to and may therefore act as noninvasive radiomic biomarkers for immunotherapy response.
In this study, we analyzed 1055 primary and metastatic lesions from 203 patients with advanced melanoma and non-small-cell lung cancer (NSCLC) undergoing anti-PD1 therapy. We carried out an AI-based characterization of each lesion on the pretreatment contrast-enhanced CT imaging data to develop and validate a noninvasive machine learning biomarker capable of distinguishing between immunotherapy responding and nonresponding. To define the biological basis of the radiographic biomarker, we carried out gene set enrichment analysis in an independent dataset of 262 NSCLC patients.
The biomarker reached significant performance on NSCLC lesions (up to 0.83 AUC, P<0.001) and borderline significant for melanoma lymph nodes (0.64 AUC, P=0.05). Combining these lesion-wide predictions on a patient level, immunotherapy response could be predicted with an AUC of up to 0.76 for both cancer types (P<0.001), resulting in a 1-year survival difference of 24% (P=0.02). We found highly significant associations with pathways involved in mitosis, indicating a relationship between increased proliferative potential and preferential response to immunotherapy.
These results indicate that radiographic characteristics of lesions on standard-of-care imaging may function as noninvasive biomarkers for response to immunotherapy, and may show utility for improved patient stratification in both neoadjuvant and palliative settings.
Injectable biomimetic hydrogels have great potential for use in regenerative medicine as cellular delivery vectors. However, they can suffer from issues relating to hypoxia, including poor cell ...survival, differentiation, and functional integration owing to the lack of an established vascular network. Here we engineer a hybrid myoglobin:peptide hydrogel that can concomitantly deliver stem cells and oxygen to the brain to support engraftment until vascularisation can occur naturally. We show that this hybrid hydrogel can modulate cell fate specification within progenitor cell grafts, resulting in a significant increase in neuronal differentiation. We find that the addition of myoglobin to the hydrogel results in more extensive innervation within the host tissue from the grafted cells, which is essential for neuronal replacement strategies to ensure functional synaptic connectivity. This approach could result in greater functional integration of stem cell-derived grafts for the treatment of neural injuries and diseases affecting the central and peripheral nervous systems.
ABSTRACT
We determined Faraday rotation measures (RMs) towards 137 pulsars in the northern sky, using Low-Frequency Array (LOFAR) observations at 110–190 MHz. This low-frequency RM catalogue, the ...largest to date, improves the precision of existing RM measurements on average by a factor of 20 – due to the low frequency and wide bandwidth of the data, aided by the RM-synthesis method. We report RMs towards 25 pulsars for the first time. The RMs were corrected for ionospheric Faraday rotation to increase the accuracy of our catalogue to ≈0.1 rad m−2. The ionospheric RM correction is currently the largest contributor to the measurement uncertainty. In addition, we find that the Faraday dispersion functions towards pulsars are extremely Faraday thin – mostly less than 0.001 rad m−2. We use these new precise RM measurements (in combination with existing RMs, dispersion measures, and distance estimates) to estimate the scale height of the Galactic halo magnetic field: 2.0 ± 0.3 kpc for Galactic quadrants i and ii above and below the Galactic plane (we also evaluate the scale height for these regions individually). Overall, our initial low-frequency catalogue provides valuable information about the 3D structure of the Galactic magnetic field.
Epitheliotropic intestinal T-cell lymphoma (EITL, also known as type II enteropathy-associated T-cell lymphoma) is an aggressive intestinal disease with poor prognosis and its molecular alterations ...have not been comprehensively characterized. We aimed to identify actionable easy-to-screen alterations that would allow better diagnostics and/or treatment of this deadly disease. By performing whole-exome sequencing of four EITL tumor-normal pairs, followed by amplicon deep sequencing of 42 tumor samples, frequent alterations of the JAK-STAT and G-protein-coupled receptor (GPCR) signaling pathways were discovered in a large portion of samples. Specifically, STAT5B was mutated in a remarkable 63% of cases, JAK3 in 35% and GNAI2 in 24%, with the majority occurring at known activating hotspots in key functional domains. Moreover, STAT5B locus carried copy-neutral loss of heterozygosity resulting in the duplication of the mutant copy, suggesting the importance of mutant STAT5B dosage for the development of EITL. Dysregulation of the JAK-STAT and GPCR pathways was also supported by gene expression profiling and further verified in patient tumor samples. In vitro overexpression of GNAI2 mutants led to the upregulation of pERK1/2, a member of MEK-ERK pathway. Notably, inhibitors of both JAK-STAT and MEK-ERK pathways effectively reduced viability of patient-derived primary EITL cells, indicating potential therapeutic strategies for this neoplasm with no effective treatment currently available.
Background
Human papillomavirus (HPV)‐positive oropharyngeal squamous cell carcinoma (OPSCC) have better prognosis and treatment response compared to HPV‐negative OPSCC. This study aims to ...noninvasively predict HPV status of OPSCC using clinical and/or radiological variables.
Methods
Seventy‐seven magnetic resonance radiomic features were extracted from T1‐weighted postcontrast images of the primary tumor of 153 patients. Logistic regression models were created to predict HPV status, determined with immunohistochemistry, based on clinical variables, radiomic features, and its combination. Model performance was evaluated using area under the curve (AUC).
Results
Model performance showed AUCs of 0.794, 0.764, and 0.871 for the clinical, radiomic, and combined models, respectively. Smoking, higher T‐classification (T3 and T4), larger, less round, and heterogeneous tumors were associated with HPV‐negative tumors.
Conclusion
Models based on clinical variables and/or radiomic tumor features can predict HPV status in OPSCC patients with good performance and can be considered when HPV testing is not available.
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