Identifying genetic mutations in cancer patients have been increasingly important because distinctive mutational patterns can be very informative to determine the optimal therapeutic strategy. Recent ...studies have shown that deep learning-based molecular cancer subtyping can be performed directly from the standard hematoxylin and eosin (H&E) sections in diverse tumors including colorectal cancers (CRCs). Since H&E-stained tissue slides are ubiquitously available, mutation prediction with the pathology images from cancers can be a time- and cost-effective complementary method for personalized treatment.
To predict the frequently occurring actionable mutations from the H&E-stained CRC whole-slide images (WSIs) with deep learning-based classifiers.
A total of 629 CRC patients from The Cancer Genome Atlas (TCGA-COAD and TCGA-READ) and 142 CRC patients from Seoul St. Mary Hospital (SMH) were included. Based on the mutation frequency in TCGA and SMH datasets, we chose
,
,
,
, and
genes for the study. The classifiers were trained with 360 × 360 pixel patches of tissue images. The receiver operating characteristic (ROC) curves and area under the curves (AUCs) for all the classifiers were presented.
The AUCs for ROC curves ranged from 0.693 to 0.809 for the TCGA frozen WSIs and from 0.645 to 0.783 for the TCGA formalin-fixed paraffin-embedded WSIs. The prediction performance can be enhanced with the expansion of datasets. When the classifiers were trained with both TCGA and SMH data, the prediction performance was improved.
,
,
,
, and
mutations can be predicted from H&E pathology images using deep learning-based classifiers, demonstrating the potential for deep learning-based mutation prediction in the CRC tissue slides.
Parkinson's disease (PD) is a common neurodegenerative disease whose pathological hallmark is the accumulation of intracellular α-synuclein aggregates in Lewy bodies. Lipid metabolism dysregulation ...may play a significant role in PD pathogenesis; however, large plasma lipidomic studies in PD are lacking. In the current study, we analyzed the lipidomic profile of plasma obtained from 150 idiopathic PD patients and 100 controls, taken from the 'Spot' study at Columbia University Medical Center in New York. Our mass spectrometry based analytical panel consisted of 520 lipid species from 39 lipid subclasses including all major classes of glycerophospholipids, sphingolipids, glycerolipids and sterols. Each lipid species was analyzed using a logistic regression model. The plasma concentrations of two lipid subclasses, triglycerides and monosialodihexosylganglioside (GM3), were different between PD and control participants. GM3 ganglioside concentration had the most significant difference between PD and controls (1.531±0.037 pmol/μl versus 1.337±0.040 pmol/μl respectively; p-value = 5.96E-04; q-value = 0.048; when normalized to total lipid: p-value = 2.890E-05; q-value = 2.933E-03). Next, we used a collection of 20 GM3 and glucosylceramide (GlcCer) species concentrations normalized to total lipid to perform a ROC curve analysis, and found that these lipids compare favorably with biomarkers reported in previous studies (AUC = 0.742 for males, AUC = 0.644 for females). Our results suggest that higher plasma GM3 levels are associated with PD. GM3 lies in the same glycosphingolipid metabolic pathway as GlcCer, a substrate of the enzyme glucocerebrosidase, which has been associated with PD. These findings are consistent with previous reports implicating lower glucocerebrosidase activity with PD risk.
Background
Microbial colonization of the airway plays a role in the pathogenesis of asthma; however, the effect of the upper airway microbiome on childhood asthma is not fully understood. We analyzed ...the metagenome of airway microbiome to understand the associated role of upper airway microbiome with the natural course of childhood asthma.
Methods
Nasopharyngeal swabs were collected from children with asthma, those in asthma remission, and control groups. High‐throughput sequencing was used to examine the structure and functional dynamics of the airway microbiome with respect to asthma phenotypes.
Results
The composition of microbiota differed among healthy control, asthma, and remission groups. The relative abundance of Streptococcus was negatively associated with FEV1% predicted (P = .023) and that of Staphylococcus was negatively associated with methacholine PC20 (P = .013). Genes related to arachidonic acid metabolites, lysine residues, and glycosaminoglycans in the microbiome could be associated with airway inflammation. In particular, genes related to synthesis of anti‐inflammatory prostaglandin E2 (PGE2) were not detected from the airway microbiome in the asthma group.
Conclusions
These data suggest that alterations in the composition and function of the upper airway microbiome could be related with the natural course of asthma in children.
Abstract Objective To examine current vaccine sentiment on social media by constructing and analyzing semantic networks of vaccine information from highly shared websites of Twitter users in the ...United States; and to assist public health communication of vaccines. Background Vaccine hesitancy continues to contribute to suboptimal vaccination coverage in the United States, posing significant risk of disease outbreaks, yet remains poorly understood. Methods We constructed semantic networks of vaccine information from internet articles shared by Twitter users in the United States. We analyzed resulting network topology, compared semantic differences, and identified the most salient concepts within networks expressing positive, negative, and neutral vaccine sentiment. Results The semantic network of positive vaccine sentiment demonstrated greater cohesiveness in discourse compared to the larger, less-connected network of negative vaccine sentiment. The positive sentiment network centered around parents and focused on communicating health risks and benefits, highlighting medical concepts such as measles , autism , HPV vaccine , vaccine-autism link , meningococcal disease , and MMR vaccine . In contrast, the negative network centered around children and focused on organizational bodies such as CDC, vaccine industry , doctors , mainstream media , pharmaceutical companies , and United States . The prevalence of negative vaccine sentiment was demonstrated through diverse messaging, framed around skepticism and distrust of government organizations that communicate scientific evidence supporting positive vaccine benefits. Conclusion Semantic network analysis of vaccine sentiment in online social media can enhance understanding of the scope and variability of current attitudes and beliefs toward vaccines. Our study synthesizes quantitative and qualitative evidence from an interdisciplinary approach to better understand complex drivers of vaccine hesitancy for public health communication, to improve vaccine confidence and vaccination coverage in the United States.
Probiotics may help to prevent symptoms of anxiety and depression through several putative mechanisms.
The aim of this study was to evaluate the effect of Lactobacillus rhamnosus HN001 (HN001) given ...in pregnancy and postpartum on symptoms of maternal depression and anxiety in the postpartum period. This was a secondary outcome, the primary outcome being eczema in the offspring at 12months of age.
A randomised, double-blind, placebo-controlled trial of the effect of HN001 on postnatal mood was conducted in 423 women in Auckland and Wellington, New Zealand. Women were recruited at 14–16weeks gestation.
Women were randomised to receive either placebo or HN001 daily from enrolment until 6months postpartum if breastfeeding.
Modified versions of the Edinburgh Postnatal Depression Scale and State Trait Anxiety Inventory were used to assess symptoms of depression and anxiety postpartum.
Australia NZ Clinical Trials Registry: ACTRN12612000196842.
423 women were recruited between December 2012 and November 2014. 212 women were randomised to HN001 and 211 to placebo. 380 women (89.8%) completed the questionnaire on psychological outcomes, 193 (91.0%) in the treatment group and 187 (88.6%) in the placebo group. Mothers in the probiotic treatment group reported significantly lower depression scores (HN001 mean=7·7 (SD=5·4), placebo 9·0 (6·0); effect size -1·2, (95% CI -2·3, -0·1), p=0·037) and anxiety scores (HN001 12·0 (4·0), placebo 13·0 (4·0); effect size -1·0 (-1·9, -0·2), p=0·014) than those in the placebo group. Rates of clinically relevant anxiety on screening (score>15) were significantly lower in the HN001 treated mothers (OR=0·44 (0·26, 0·73), p=0·002).
Women who received HN001 had significantly lower depression and anxiety scores in the postpartum period. This probiotic may be useful for the prevention or treatment of symptoms of depression and anxiety postpartum.
Health Research Council of New Zealand (11/318) and Fonterra Co-operative Group Ltd.
•The microbiome-gut-brain axis may be important for mental health.•We conducted a study of probiotic supplementation in pregnancy and 6months after delivery if breastfeeding.•The probiotic treatment group reported significantly lower depression and anxiety scores than those in the placebo group.
There is mounting evidence from animal studies that the microbiome-gut-brain axis may be important for mental health. Depression and anxiety in pregnancy and after birth affects 10–15% of women, although many are not recognised or treated. We conducted a double-blind placebo-controlled study of probiotic (Lactobacillus rhamnosus HN001) supplementation (from early pregnancy through to 6months after delivery if breastfeeding) on postnatal symptoms of depression and anxiety in a group (n=380) of healthy women. Mothers in the probiotic treatment group reported significantly lower depression and anxiety scores than those in the placebo group.
'Sudden' quantum quench and prethermalization have become a cross-cutting theme for discovering emergent states of matter
. Yet this remains challenging in electron matter
, especially ...superconductors
. The grand question of what is hidden underneath superconductivity (SC)
appears universal, but poorly understood. Here we reveal a long-lived gapless quantum phase of prethermalized quasiparticles (QPs) after a single-cycle terahertz (THz) quench of a Nb
Sn SC gap. Its conductivity spectra is characterized by a sharp coherent peak and a vanishing scattering rate that decreases almost linearly towards zero frequency, which is most pronounced around the full depletion of the condensate and absent for a high-frequency pump. Above a critical pump threshold, such a QP phase with coherent transport and memory persists as an unusual prethermalization plateau, without relaxation to normal and SC thermal states for an order of magnitude longer than the QP recombination and thermalization times. Switching to this metastable 'quantum QP fluid' signals non-thermal quench of coupled SC and charge-density-wave (CDW)-like orders and hints quantum control beneath the SC.
To develop a reliable and valid clinical scale measuring the severity of ataxia.
The authors devised the Scale for the Assessment and Rating of Ataxia (SARA) and tested it in two trials of 167 and ...119 patients with spinocerebellar ataxia.
The mean time to administer SARA in patients was 14.2 +/- 7.5 minutes (range 5 to 40). Interrater reliability was high, with an intraclass coefficient (ICC) of 0.98. Test-retest reliability was high with an ICC of 0.90. Internal consistency was high as indicated by Cronbach's alpha of 0.94. Factorial analysis revealed that the rating results were determined by a single factor. SARA ratings showed a linear relation to global assessments using a visual analogue scale, suggesting linearity of the scale (p < 0.0001, r(2) = 0.98). SARA score increased with the disease stage (p < 0.001) and was closely correlated with the Barthel Index (r = -0.80, p < 0.001) and part IV (functional assessment) of the Unified Huntington's Disease Rating Scale (UHDRS-IV) (r = -0.89, p < 0.0001), whereas it had only a weak correlation with disease duration (r = 0.34, p < 0.0002).
The Scale for the Assessment and Rating of Ataxia is a reliable and valid measure of ataxia, making it an appropriate primary outcome measure for clinical trials.
Treatment options are limited for patients with recurrent or metastatic squamous cell carcinoma of the head and neck (HNSCC) following progression after first-line platinum-based therapy, ...particularly in Asian countries.
In this randomised, open-label, phase III trial, we enrolled Asian patients aged ≥18-years, with histologically or cytologically confirmed recurrent/metastatic HNSCC following first-line platinum-based therapy who were not amenable for salvage surgery or radiotherapy, and had an Eastern Cooperative Oncology Group (ECOG) performance status of 0/1. Patients were randomised (2 : 1) to receive oral afatinib (40-mg/day) or intravenous methotrexate (40-mg/m2/week), stratified by ECOG performance status and prior EGFR-targeted antibody therapy. The primary end point was progression-free survival (PFS) assessed by an independent central review committee blinded to treatment allocation.
A total of 340 patients were randomised (228 afatinib; 112 methotrexate). After a median follow-up of 6.4-months, afatinib significantly decreased the risk of progression/death by 37% versus methotrexate (hazard ratio 0.63; 95% confidence interval 0.48–0.82; P-=-0.0005; median 2.9 versus 2.6-months; landmark analysis at 12 and 24-weeks, 58% versus 41%, 21% versus 9%). Improved PFS was complemented by quality of life benefits. Objective response rate was 28% with afatinib and 13% with methotrexate. There was no significant difference in overall survival. The most common grade ≥3 drug-related adverse events were rash/acne (4% with afatinib versus 0% with methotrexate), diarrhoea (4% versus 0%), fatigue (1% versus 5%), anaemia (<1% versus 5%) and leukopenia (0% versus 5%).
Consistent with the phase III LUX-Head & Neck 1 trial, afatinib significantly improved PFS versus methotrexate, with a manageable safety profile. These results demonstrate the efficacy and feasibility of afatinib as a second-line treatment option for certain patients with recurrent or metastatic HNSCC.
ClinicalTrials.gov identifier: NCT01856478.
We report the state-of-the-art performance of deep-submicrometer gate length dual-gate GaN HEMTs and cascode GaN HEMTs with 10× reduced gate-to-drain feedback capacitance compared with single-gate ...GaN HEMTs. With 150-nm gate length field-plated gate structures, these GaN HEMTs demonstrated improvement of small-signal gain by 10 dB, compared with single-gate GaN HEMTs. Large-signal load-pull measurements showed peak power-added-efficiency (PAE) of 71%-74% without harmonic tuning at 10 GHz, up to a measured continuous-wave output power level of 2.3-2.5 W. The 74% PAE is very close to a theoretical maximum PAE of 78.5% without harmonic tuning. Compared with single-gate GaN HEMTs, both the dual-gate and cascode GaN HEMTs offer~10% improvement in peak PAE at the output power of 2.3-2.5 W.
A novel transform method providing a regionally structured sparse model of residue for a video coding is proposed. Conventional learning-based video coding methods consider only the number of ...transformed coefficients in a dictionary construction but disregard any structural form of residue. A structural form of coefficients is used for another factor, specified by a set of local block patterns, in a transform design so as to yield the regionally compact distribution of the coefficients. A transform coefficient coding method is also developed because the distribution of the coefficients is different with that of conventional transforms. It is demonstrated with experiments that the proposed method outperforms the coding efficiency and visual quality over high efficiency video coding/screen content coding reference software.
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