Tumor molecular profiling is a fundamental component of precision oncology, enabling the identification of genomic alterations in genes and pathways that can be targeted therapeutically. The ...existence of recurrent targetable alterations across distinct histologically defined tumor types, coupled with an expanding portfolio of molecularly targeted therapies, demands flexible and comprehensive approaches to profile clinically relevant genes across the full spectrum of cancers. We established a large-scale, prospective clinical sequencing initiative using a comprehensive assay, MSK-IMPACT, through which we have compiled tumor and matched normal sequence data from a unique cohort of more than 10,000 patients with advanced cancer and available pathological and clinical annotations. Using these data, we identified clinically relevant somatic mutations, novel noncoding alterations, and mutational signatures that were shared by common and rare tumor types. Patients were enrolled on genomically matched clinical trials at a rate of 11%. To enable discovery of novel biomarkers and deeper investigation into rare alterations and tumor types, all results are publicly accessible.
Synopsis
Not only AFLP but also HELLP and acute liver failure due to viruses in pregnancy meet the Swansea criteria, meriting a reappraisal and a reevaluation of the criteria.
Biomaterial assisted green synthesis of metal oxide nanoparticles plays a vital role as an eco-friendly alternate to chemical templated approach, in enhancing the physico-chemical properties of the ...solids. Herein, we have reported the synthesis of mesoporous titania nanoparticles by sol–gel method with the assistance of green tea extract (GTE). The synthesized catalysts were characterized using X-ray diffraction (XRD), Fourier transform infrared (FT-IR), Thermo gravimetric (TG), Brunauer-Emmett-Teller (BET), diffused reflectance spectroscopy UV–Visible (DRS-UV), scanning electron microscopy (SEM) and Transmission electron microscopy (TEM) analyses. The resulting nano titania exhibited excellent mesoporosity with increased surface area compared to control nano titania as evidenced from BET analysis. XRD results showed that highly crystalline anatase titania nanoparticles could be derived through controlled hydrolysis. Green tea extract also aided in shifting the optical absorption edge of titania towards the visible light region and enabled nano titania to function as an efficient photocatalyst for the photodegradation of Congo red, a model organic pollutant, under solar irradiation. Green tea extract was proved to be a suitable template for the synthesis of visible light active titania with good crystallite characteristics. Hence, it could be proposed as an environmentally benign alternate to the chemical templates for the sol–gel synthesis of titania nanoparticles.
Spray-freeze-drying (SFD) is a promising technique to produce inhalable dry powder formulations that able to retain the integrity of bioactive compounds. Therefore, in this study bromelain aerosols ...were developed using SFD by varying core-to-wall ratios (1:10, 1:25 and 1:50). The maltodextrin was used to protect the bromelain during freezing and drying stages had a significant effect on the developed aerosols; as the concentration increased, the emitted dosage level increased to around 97.2%. The particles were found to be spherical and highly porous, with geometric diameter ranging between 4.71 to 7.46 µm. All formulations were low in density, had excellent flowability and the theoretical mass median aerodynamic diameter (MMAD
t
) ranged between 2.97 to 3.33 µm. The total bromelain concentration ranged between 413.73 to 462 mg/g and the activity was found to be between 333.22 to 404.64 casein digestion units
−1
(CDU)
−1
for all three formulations. The XRD patterns explained the crystalline nature of these formulations. The in-vitro release profile showed that the release of bromelain was slow and sustained for 12 h and 46 to 55% of release was estimated. In-vitro aerosol performance of particles showed 84.28% fine particle fraction (FPF) and MMAD of 3.2 µm for the 1:25 formulation. Thus, this study confirmed that SFD can produce aerosols with desired properties and the approach can be used for pulmonary supplementation of food bioactives with good retention and activity.
Twitter helps us to know what is happening in the world and what people are talking right now. Every day, millions of Twitteraties tweet something personal or impersonal to express their emotions and ...valuable knowledge. In the health domain, disclosure of personal health information will have a long-term effect to common individuals either directly or indirectly, which emphasize the presence of unrealistic social boundaries and the need of sensitivity analysis in social media. The proposed Tweedle framework was built with 100K tweets extracted based on a set of 20 health-related cyber-keywords. The framework of Tweedle was bounded with Regret Theory for tweet annotation, content and contextual feature scores for feature selection and various machine learning algorithms for sensitivity classification. The tweets annotated in accordance with Regret Theory by domain experts of Amazon Mechanical Turkresulted in 61.5% of sensitive tweets with health data. The context and content-oriented features scoresare introduced in terms of Primary / Secondary tweet score, Named Entity Recognition Score of tweets, Term Frequency-Inverse Document Frequency(TF-IDF), Cyber-KeywordRatioin tweets, hashtag mentions, user mentions as features for classification.The Tweedle experimented Regret Theory in combination with various classifiers like Support Vector Machine, Naïve Bayes, Random Forest, Decision Tree, Logistic Regression and Recurrent Neural Network + Long Short-Term Memory for sensitivity classificationin health domain tweets.The training and testing results proved RNN + LSTM as the better performing model to identify tweets with sensitive health data.
Highlights ► Pancreatic cancer is a devastating disease with an extremely poor life expectancy. ► We investigated the efficacy of Notch signaling pathway targeted therapy in pancreatic cancer ...xenografts. ► Our results showed that the therapy is effective in targeting tumor-resident cancer stem cells. ► Notch signaling pathway targeted therapy has greater anti-tumor activity in combination with gemcitabine. ► Our preclinical results provide rationale for further investigation of this novel combination in pancreatic cancer.
Genetic ancestry plays a role in asthma health disparities.
Our aim was to evaluate the impact of ancestry on and identify genetic variants associated with asthma, total serum IgE level, and lung ...function.
A total of 436 Peruvian children (aged 9-19 years) with asthma and 291 without asthma were genotyped by using the Illumina Multi-Ethnic Global Array. Genome-wide proportions of indigenous ancestry populations from continental America (NAT) and European ancestry from the Iberian populations in Spain (IBS) were estimated by using ADMIXTURE. We assessed the relationship between ancestry and the phenotypes and performed a genome-wide association study.
The mean ancestry proportions were 84.7% NAT (case patients, 84.2%; controls, 85.4%) and 15.3% IBS (15.8%; 14.6%). With adjustment for asthma, NAT was associated with higher total serum IgE levels (P < .001) and IBS was associated with lower total serum IgE levels (P < .001). NAT was associated with higher FEV1 percent predicted values (P < .001), whereas IBS was associated with lower FEV1 values in the controls but not in the case patients. The HLA-DR/DQ region on chromosome 6 (Chr6) was strongly associated with total serum IgE (rs3135348; P = 3.438 × 10–10) and was independent of an association with the haplotype HLA-DQA1∼HLA-DQB1:04.01∼04.02 (P = 1.55 × 10–05). For lung function, we identified a locus (rs4410198; P = 5.536 × 10–11) mapping to Chr19, near a cluster of zinc finger interacting genes that colocalizes to the long noncoding RNA CTD-2537I9.5. This novel locus was replicated in an independent sample of pediatric case patients with asthma with similar admixture from Brazil (P = .005).
This study confirms the role of HLA in atopy, and identifies a novel locus mapping to a long noncoding RNA for lung function that may be specific to children with NAT.
We used a deeply sequenced dataset of 910 individuals, all of African descent, to construct a set of DNA sequences that is present in these individuals but missing from the reference human genome. We ...aligned 1.19 trillion reads from the 910 individuals to the reference genome (GRCh38), collected all reads that failed to align, and assembled these reads into contiguous sequences (contigs). We then compared all contigs to one another to identify a set of unique sequences representing regions of the African pan-genome missing from the reference genome. Our analysis revealed 296,485,284 bp in 125,715 distinct contigs present in the populations of African descent, demonstrating that the African pan-genome contains ~10% more DNA than the current human reference genome. Although the functional significance of nearly all of this sequence is unknown, 387 of the novel contigs fall within 315 distinct protein-coding genes, and the rest appear to be intergenic.
Due to their similarities in anatomy, physiology, and pharmacology to humans, mice are a valuable model system to study the generation and mechanisms modulating conventional outflow resistance and ...thus intraocular pressure. In addition, mouse models are critical for understanding the complex nature of conventional outflow homeostasis and dysfunction that results in ocular hypertension. In this review, we describe a set of minimum acceptable standards for developing, characterizing, and utilizing mouse models of open-angle ocular hypertension. We expect that this set of standard practices will increase scientific rigor when using mouse models and will better enable researchers to replicate and build upon previous findings.
The Construction and Demolition Waste Management is one of most ignored sectors in India even though the construction industry in boom within the developing economy contributing up to 25.92% of GDP. ...The rapid growth does not necessarily reveal the development unless the sustainable practices are adopted in Construction and Demolition Waste Management. Out of 150Million Tonnes being generated annually, a meager 6500Tonnes is being managed accounting to 1.3%. The present study elaborates the possibility of using the Construction and Demolition Waste in pavements/roads without any compromise in the quality of roads. Using such wastes can benefit the nation at large scales not alone economically but also environmentally thereby reducing the air pollution associated with the dusts liberated in the activities of construction and demolition. The average road construction in India is around 33km/day and usage of wastes in road indicates a saving of about Rs.904.50 Lakhs at Rs.28.50Lakhs per km. The savings are computed by considering the blending of Recycled Aggregates to an extent of 25% in concrete as per clause 4.2.1 of IS383:2016. These wastes can benefit the country at large by harnessing with latest technologies available.
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