We introduce the antibody landscape, a method for the quantitative analysis of antibodymediated immunity to antigenically variable pathogens, achieved by accounting for antigenic variation among ...pathogen strains. We generated antibody landscapes to study immune profiles covering 43 years of influenza A/H3N2 virus evolution for 69 individuals monitored for infection over 6 years and for 225 individuals pre- and postvaccination. Upon infection and vaccination, titers increased broadly, including previously encountered viruses far beyond the extent of cross-reactivity observed after a primary infection. We explored implications for vaccination and found that the use of an antigenically advanced virus had the dual benefit of inducing antibodies against both advanced and previous antigenic clusters. These results indicate that preemptive vaccine updates may improve influenza vaccine efficacy in previously exposed individuals.
The hybrid algorithm for chronic total occlusion (CTO) percutaneous coronary intervention (PCI) was developed to improve procedural outcomes. Large, prospective studies validating the algorithm in a ...broad multicenter setting with operators of different experience levels are lacking.
The RECHARGE (REgistry of Crossboss and Hybrid procedures in FrAnce, the NetheRlands, BelGium and UnitEd Kingdom) registry aims to report achievable results using the hybrid algorithm.
Between January 2014 and October 2015, consecutive patients undergoing hybrid CTO-PCI were prospectively enrolled in 17 centers. Procedural techniques, outcomes, and in-hospital complications were analyzed.
A total of 1,253 CTO-PCIs were performed in 1,177 patients, of which 86% were men. Mean age was 66 ± 11 years. The average Japanese CTO score was 2.0 ± 1.0, and was higher in the failure group (2.6 ± 0.6 vs. 1.9 ± 1.0; p < 0.001). Overall procedure success was 86% and major in-hospital complications occurred in 2.6%. Antegrade wire escalation was the preferred primary strategy in 77%, followed by retrograde (17%) and antegrade dissection re-entry strategies (7%). Primary strategies were successful in 60%. Consecutive strategies were applied in 34% and were successful in 74%. Antegrade dissection re-entry and retrograde strategies were the most common bailout strategies and were successful in 67% and 62%, respectively. Median procedure and fluoroscopy time were 90 (interquartile range IQR: 60 to 120) min and 35 (IQR: 21 to 55) min, contrast volume was 250 (IQR: 180 to 340) ml, and radiation doses (air kerma and dose area product) were 1.6 (IQR: 1.0 to 2.7) Gy and 98 (IQR: 57 to 168) Gy·cm
, respectively.
High procedure and patient success rates, combined with a low event rate and improved procedural characteristics, support further use of the hybrid algorithm for a broad community of appropriately trained CTO operators.
A highly pathogenic avian influenza virus, H5N1, caused disease outbreaks in poultry in China and seven other east Asian countries between late 2003 and early 2004; the same virus was fatal to humans ...in Thailand and Vietnam. Here we demonstrate a series of genetic reassortment events traceable to the precursor of the H5N1 viruses that caused the initial human outbreak in Hong Kong in 1997 and subsequent avian outbreaks in 2001 and 2002. These events gave rise to a dominant H5N1 genotype (Z) in chickens and ducks that was responsible for the regional outbreak in 2003-04. Our findings indicate that domestic ducks in southern China had a central role in the generation and maintenance of this virus, and that wild birds may have contributed to the increasingly wide spread of the virus in Asia. Our results suggest that H5N1 viruses with pandemic potential have become endemic in the region and are not easily eradicable. These developments pose a threat to public and veterinary health in the region and potentially the world, and suggest that long-term control measures are required.
The American Cancer Society (ACS) recommends that individuals with a cervix initiate cervical cancer screening at age 25 years and undergo primary human papillomavirus (HPV) testing every 5 years ...through age 65 years (preferred); if primary HPV testing is not available, then individuals aged 25 to 65 years should be screened with cotesting (HPV testing in combination with cytology) every 5 years or cytology alone every 3 years (acceptable) (strong recommendation). The ACS recommends that individuals aged >65 years who have no history of cervical intraepithelial neoplasia grade 2 or more severe disease within the past 25 years, and who have documented adequate negative prior screening in the prior 10 years, discontinue all cervical cancer screening (qualified recommendation). These new screening recommendations differ in 4 important respects compared with the 2012 recommendations: 1) The preferred screening strategy is primary HPV testing every 5 years, with cotesting and cytology alone acceptable where access to US Food and Drug Administration‐approved primary HPV testing is not yet available; 2) the recommended age to start screening is 25 years rather than 21 years; 3) primary HPV testing, as well as cotesting or cytology alone when primary testing is not available, is recommended starting at age 25 years rather than age 30 years; and 4) the guideline is transitional, ie, options for screening with cotesting or cytology alone are provided but should be phased out once full access to primary HPV testing for cervical cancer screening is available without barriers. Evidence related to other relevant issues was reviewed, and no changes were made to recommendations for screening intervals, age or criteria for screening cessation, screening based on vaccination status, or screening after hysterectomy. Follow‐up for individuals who screen positive for HPV and/or cytology should be in accordance with the 2019 American Society for Colposcopy and Cervical Pathology risk‐based management consensus guidelines for abnormal cervical cancer screening tests and cancer precursors.
MicroRNAs (miRNAs) regulate mRNA stability and protein expression, and certain miRNAs have been demonstrated to act either as oncogenes or tumor suppressors. Differential miRNA expression signatures ...have been documented in many human cancers but the role of miRNAs in endometrioid endometrial cancer (EEC) remains poorly understood. This study identifies significantly dysregulated miRNAs of EEC cells, and characterizes their impact on the malignant phenotype. We studied the expression of 365 human miRNAs using Taqman low density arrays in EECs and normal endometriums. Candidate differentially expressed miRNAs were validated by quantitative real‐time PCR. Expression of highly dysregulated miRNAs was examined in vitro through the effect of anti‐/pre‐miRNA transfection on the malignant phenotype. We identified 16 significantly dysregulated miRNAs in EEC and 7 of these are novel findings with respect to EEC. Antagonizing the function of miR‐7, miR‐194 and miR‐449b, or overexpressing miR‐204, repressed migration, invasion and extracellular matrix‐adhesion in HEC1A endometrial cancer cells. FOXC1 was determined as a target gene of miR‐204, and two binding sites in the 3′‐untranslated region were validated by dual luciferase reporter assay. FOXC1 expression was inversely related to miR‐204 expression in EEC. Functional analysis revealed the involvement of FOXC1 in migration and invasion of HEC1A cells. Our results present dysfunctional miRNAs in endometrial cancer and identify a crucial role for miR‐204‐FOXC1 interaction in endometrial cancer progression. This miRNA signature offers a potential biomarker for predicting EEC outcomes, and targeting of these cancer progression‐ and metastasis‐related miRNAs offers a novel potential therapeutic strategy for the disease.
The development of deep neural networks is facilitating more advanced digital analysis of histopathologic images. We trained a convolutional neural network for multiclass segmentation of digitized ...kidney tissue sections stained with periodic acid-Schiff (PAS).
We trained the network using multiclass annotations from 40 whole-slide images of stained kidney transplant biopsies and applied it to four independent data sets. We assessed multiclass segmentation performance by calculating Dice coefficients for ten tissue classes on ten transplant biopsies from the Radboud University Medical Center in Nijmegen, The Netherlands, and on ten transplant biopsies from an external center for validation. We also fully segmented 15 nephrectomy samples and calculated the network's glomerular detection rates and compared network-based measures with visually scored histologic components (Banff classification) in 82 kidney transplant biopsies.
The weighted mean Dice coefficients of all classes were 0.80 and 0.84 in ten kidney transplant biopsies from the Radboud center and the external center, respectively. The best segmented class was "glomeruli" in both data sets (Dice coefficients, 0.95 and 0.94, respectively), followed by "tubuli combined" and "interstitium." The network detected 92.7% of all glomeruli in nephrectomy samples, with 10.4% false positives. In whole transplant biopsies, the mean intraclass correlation coefficient for glomerular counting performed by pathologists versus the network was 0.94. We found significant correlations between visually scored histologic components and network-based measures.
This study presents the first convolutional neural network for multiclass segmentation of PAS-stained nephrectomy samples and transplant biopsies. Our network may have utility for quantitative studies involving kidney histopathology across centers and provide opportunities for deep learning applications in routine diagnostics.
This paper is the second in a pair of papers presenting data release 1 (DR1) of the Herschel Astrophysical Terahertz Large Area Survey (H-ATLAS), the largest single open-time key project carried out ...with the Herschel
Space Observatory. The H-ATLAS is a wide-area imaging survey carried out in five photometric bands at 100, 160, 250, 350 and 500 μm covering a total area of 600 deg2. In this paper, we describe the identification of optical counterparts to submillimetre sources in DR1, comprising an area of 161 deg2 over three equatorial fields of roughly 12 × 4.5 deg centred at 9h, 12h and 14
${^{\rm h}_{.}}$
5, respectively. Of all the H-ATLAS fields, the equatorial regions benefit from the greatest overlap with current multi-wavelength surveys spanning ultraviolet (UV) to mid-infrared regimes, as well as extensive spectroscopic coverage. We use a likelihood ratio technique to identify Sloan Digital Sky Survey counterparts at r < 22.4 for 250-μm-selected sources detected at ≥4σ (≈28 mJy). We find ‘reliable’ counterparts (reliability R ≥ 0.8) for 44 835 sources (39 per cent), with an estimated completeness of 73.0 per cent and contamination rate of 4.7 per cent. Using redshifts and multi-wavelength photometry from GAMA and other public catalogues, we show that H-ATLAS-selected galaxies at z < 0.5 span a wide range of optical colours, total infrared (IR) luminosities and IR/UV ratios, with no strong disposition towards mid-IR-classified active galactic nuclei in comparison with optical selection. The data described herein, together with all maps and catalogues described in the companion paper, are available from the H-ATLAS website at www.h-atlas.org.
IMPORTANCE: Breast cancer is a leading cause of premature mortality among US women. Early detection has been shown to be associated with reduced breast cancer morbidity and mortality. OBJECTIVE: To ...update the American Cancer Society (ACS) 2003 breast cancer screening guideline for women at average risk for breast cancer. PROCESS: The ACS commissioned a systematic evidence review of the breast cancer screening literature to inform the update and a supplemental analysis of mammography registry data to address questions related to the screening interval. Formulation of recommendations was based on the quality of the evidence and judgment (incorporating values and preferences) about the balance of benefits and harms. EVIDENCE SYNTHESIS: Screening mammography in women aged 40 to 69 years is associated with a reduction in breast cancer deaths across a range of study designs, and inferential evidence supports breast cancer screening for women 70 years and older who are in good health. Estimates of the cumulative lifetime risk of false-positive examination results are greater if screening begins at younger ages because of the greater number of mammograms, as well as the higher recall rate in younger women. The quality of the evidence for overdiagnosis is not sufficient to estimate a lifetime risk with confidence. Analysis examining the screening interval demonstrates more favorable tumor characteristics when premenopausal women are screened annually vs biennially. Evidence does not support routine clinical breast examination as a screening method for women at average risk. RECOMMENDATIONS: The ACS recommends that women with an average risk of breast cancer should undergo regular screening mammography starting at age 45 years (strong recommendation). Women aged 45 to 54 years should be screened annually (qualified recommendation). Women 55 years and older should transition to biennial screening or have the opportunity to continue screening annually (qualified recommendation). Women should have the opportunity to begin annual screening between the ages of 40 and 44 years (qualified recommendation). Women should continue screening mammography as long as their overall health is good and they have a life expectancy of 10 years or longer (qualified recommendation). The ACS does not recommend clinical breast examination for breast cancer screening among average-risk women at any age (qualified recommendation). CONCLUSIONS AND RELEVANCE: These updated ACS guidelines provide evidence-based recommendations for breast cancer screening for women at average risk of breast cancer. These recommendations should be considered by physicians and women in discussions about breast cancer screening.
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