Abstract: Water splitting catalysed by earth-abundant materials is pivotal for global-scale production of non-fossil fuels, yet our understanding of the active catalyst structure and reactivity is still insufficient. Here we report on the structurally reversible evolution of crystalline Co3O4 electrocatalysts during oxygen evolution reaction identified using advanced in situ X-ray techniques. At electrode potentials facilitating oxygen evolution, a sub-nanometre shell of the Co3O4 is transformed into an X-ray amorphous CoOx(OH)y which comprises di-μ-oxo-bridged Co(3+/4+) ions. Unlike irreversible amorphizations, here, the formation of the catalytically-active layer is reversed by re-crystallization upon return to non-catalytic electrode conditions. The Co3O4 material thus combines the stability advantages of a controlled, stable crystalline material with high catalytic activity, thanks to the structural flexibility of its active amorphous oxides. We propose that crystalline oxides may be tailored for generating reactive amorphous surface layers at catalytic potentials, just to return to their stable crystalline state under rest conditions.

Abstract: In this paper, an aqueous extract of fresh leaves of Pedalium murex was used for the synthesis of silver (Ag) nanoparticles. Different biological methods are gaining recognition for the production of silver nanoparticles (AgNPs) due to their multiple applications. The use of plants in the green synthesis of nanoparticles emerges as a cost-effective and eco-friendly approach. Characterization of nanoparticles was done using different methods, which include; ultraviolet–visible spectroscopy (UV–Vis), Fourier transform infrared (FTIR), powder X-ray diffraction (XRD), field emission scanning electron microscope (FE-SEM), energy dispersive X-ray analysis (EDAX), fluorescence emission spectroscopy, transmission electron microscope (TEM), dynamic light scattering (DLS), zeta potential and antibacterial activity. UV–visible spectrum of the aqueous medium containing silver nanoparticles showed absorption peak at around 430 nm. Fourier transform infrared spectra had shown that the biomolecule compounds were responsible for the reduction and capping material of silver nanoparticles. XRD study showed the particles to be crystalline in nature, with a face-centered cubic (fcc) structure. The size and stability were detected using DLS and zeta potential analysis. The antibacterial activity of AgNPs against generally found bacteria was assessed to find their potential use in silver-containing antibacterial product.

Abstract: We point out a connection between the emergence of bulk locality in AdS/CFT and the theory of quantum error correction. Bulk notions such as Bogoliubov transformations, location in the radial direction, and the holographic entropy bound all have natural CFT interpretations in the language of quantum error correction. We also show that the question of whether bulk operator reconstruction works only in the causal wedge or all the way to the extremal surface is related to the question of whether or not the quantum error correcting code realized by AdS/CFT is also a “quantum secret sharing scheme”, and suggest a tensor network calculation that may settle the issue. Interestingly, the version of quantum error correction which is best suited to our analysis is the somewhat nonstandard “operator algebra quantum error correction” of Beny, Kempf, and Kribs. Our proposal gives a precise formulation of the idea of “subregion-subregion” duality in AdS/CFT, and clarifies the limits of its validity.

Abstract: A test of lepton universality, performed by measuring the ratio of the branching fractions of the $B^{0} \rightarrow K^{*0}\mu^{+}\mu^{-}$ and $B^{0} \rightarrow K^{*0}e^{+}e^{-}$ decays, $R_{K^{*0}}$, is presented The $K^{*0}$ meson is reconstructed in the final state $K^{+}\pi^{-}$, which is required to have an invariant mass within 100$\mathrm{\,MeV}c^2$ of the known $K^{*}(892)^{0}$ mass The analysis is performed using proton-proton collision data, corresponding to an integrated luminosity of about 3$\mathrm{\,fb}^{-1}$, collected by the LHCb experiment at centre-of-mass energies of 7 and 8$\mathrm{\,TeV}$ The ratio is measured in two regions of the dilepton invariant mass squared, $q^{2}$, to be \begin{eqnarray*} R_{K^{*0}} = \begin{cases} 066~^{+~011}_{-~007}\mathrm{\,(stat)} \pm 003\mathrm{\,(syst)} & \textrm{for } 0045 < q^{2} < 11~\mathrm{\,GeV^2}c^4 \, , \\ 069~^{+~011}_{-~007}\mathrm{\,(stat)} \pm 005\mathrm{\,(syst)} & \textrm{for } 11\phantom{00} < q^{2} < 60~\mathrm{\,GeV^2}c^4 \, \end{cases} \end{eqnarray*} The corresponding 954\% confidence level intervals are $[052, 089]$ and $[053, 094]$ The results, which represent the most precise measurements of $R_{K^{*0}}$ to date, are compatible with the Standard Model expectations at the level of 21--23 and 24--25 standard deviations in the two $q^{2}$ regions, respectively

Abstract: Cancer cells metastasize through the bloodstream either as single migratory circulating tumor cells (CTCs) or as multicellular groupings (CTC clusters). Existing technologies for CTC enrichment are designed to isolate single CTCs, and although CTC clusters are detectable in some cases, their true prevalence and significance remain to be determined. Here we developed a microchip technology (the Cluster-Chip) to capture CTC clusters independently of tumor-specific markers from unprocessed blood. CTC clusters are isolated through specialized bifurcating traps under low-shear stress conditions that preserve their integrity, and even two-cell clusters are captured efficiently. Using the Cluster-Chip, we identified CTC clusters in 30-40% of patients with metastatic breast or prostate cancer or with melanoma. RNA sequencing of CTC clusters confirmed their tumor origin and identified tissue-derived macrophages within the clusters. Efficient capture of CTC clusters will enable the detailed characterization of their biological properties and role in metastasis.

Abstract: Two-dimensional carbides and nitrides of transition metals, known as MXenes, are a fast-growing family of materials that have attracted attention as energy storage materials. MXenes are mainly prepared from Al-containing MAX phases (where A = Al) by Al dissolution in F-containing solution; most other MAX phases have not been explored. Here a redox-controlled A-site etching of MAX phases in Lewis acidic melts is proposed and validated by the synthesis of various MXenes from unconventional MAX-phase precursors with A elements Si, Zn and Ga. A negative electrode of Ti3C2 MXene material obtained through this molten salt synthesis method delivers a Li+ storage capacity of up to 738 C g−1 (205 mAh g−1) with high charge–discharge rate and a pseudocapacitive-like electrochemical signature in 1 M LiPF6 carbonate-based electrolyte. MXenes prepared via this molten salt synthesis route may prove suitable for use as high-rate negative-electrode materials for electrochemical energy storage applications. Two-dimensional transition metal carbides and nitrides, known as MXenes, are currently considered as energy storage materials. A generic Lewis acidic etching route for preparing high-rate negative-electrode MXenes with enhanced electrochemical performance in non-aqueous electrolyte is now proposed.

Abstract: Importance Estimates of familial cancer risk from population-based studies are essential components of cancer risk prediction. Objective To estimate familial risk and heritability of cancer types in a large twin cohort. Design, Setting, and Participants Prospective study of 80 309 monozygotic and 123 382 same-sex dizygotic twin individuals (N = 203 691) within the population-based registers of Denmark, Finland, Norway, and Sweden. Twins were followed up a median of 32 years between 1943 and 2010. There were 50 990 individuals who died of any cause, and 3804 who emigrated and were lost to follow-up. Exposures Shared environmental and heritable risk factors among pairs of twins. Main Outcomes and Measures The main outcome was incident cancer. Time-to-event analyses were used to estimate familial risk (risk of cancer in an individual given a twin’s development of cancer) and heritability (proportion of variance in cancer risk due to interindividual genetic differences) with follow-up via cancer registries. Statistical models adjusted for age and follow-up time, and accounted for censoring and competing risk of death. Results A total of 27 156 incident cancers were diagnosed in 23 980 individuals, translating to a cumulative incidence of 32%. Cancer was diagnosed in both twins among 1383 monozygotic (2766 individuals) and 1933 dizygotic (2866 individuals) pairs. Of these, 38% of monozygotic and 26% of dizygotic pairs were diagnosed with the same cancer type. There was an excess cancer risk in twins whose co-twin was diagnosed with cancer, with estimated cumulative risks that were an absolute 5% (95% CI, 4%-6%) higher in dizygotic (37%; 95% CI, 36%-38%) and an absolute 14% (95% CI, 12%-16%) higher in monozygotic twins (46%; 95% CI, 44%-48%) whose twin also developed cancer compared with the cumulative risk in the overall cohort (32%). For most cancer types, there were significant familial risks and the cumulative risks were higher in monozygotic than dizygotic twins. Heritability of cancer overall was 33% (95% CI, 30%-37%). Significant heritability was observed for the cancer types of skin melanoma (58%; 95% CI, 43%-73%), prostate (57%; 95% CI, 51%-63%), nonmelanoma skin (43%; 95% CI, 26%-59%), ovary (39%; 95% CI, 23%-55%), kidney (38%; 95% CI, 21%-55%), breast (31%; 95% CI, 11%-51%), and corpus uteri (27%; 95% CI, 11%-43%). Conclusions and Relevance In this long-term follow-up study among Nordic twins, there was significant excess familial risk for cancer overall and for specific types of cancer, including prostate, melanoma, breast, ovary, and uterus. This information about hereditary risks of cancers may be helpful in patient education and cancer risk counseling.

Abstract: Plant root secreted compounds alter the gene expression of associated microorganisms by acting as signal molecules that either stimulate or repel the interaction with beneficial or harmful species, respectively. However, it is still unclear whether two distinct groups of beneficial bacteria, non-plant-associated (soil) strains and plant-associated (endophytic) strains, respond uniformly or variably to the exposure with root exudates. Therefore, Bacillus mycoides, a potential biocontrol agent and plant growth-promoting bacterium, was isolated from the endosphere of potatoes and from soil of the same geographical region. Confocal fluorescence microscopy of plants inoculated with GFP-tagged B. mycoides strains showed that the endosphere isolate EC18 had a stronger plant colonization ability and competed more successfully for the colonization sites than the soil isolate SB8. To dissect these phenotypic differences, the genomes of the two strains were sequenced and the transcriptome response to potato root exudates was compared. The global transcriptome profiles evidenced that the endophytic isolate responded more pronounced than the soil-derived isolate and a higher number of significant differentially expressed genes were detected. Both isolates responded with the alteration of expression of an overlapping set of genes, which had previously been reported to be involved in plant-microbe interactions; including organic substance metabolism, oxidative reduction, and transmembrane transport. Notably, several genes were specifically upregulated in the endosphere isolate EC18, while being oppositely downregulated in the soil isolate SB8. These genes mainly encoded membrane proteins, transcriptional regulators or were involved in amino acid metabolism and biosynthesis. By contrast, several genes upregulated in the soil isolate SB8 and downregulated in the endosphere isolate EC18 were related to sugar transport, which might coincide with the different nutrient availability in the two environments. Altogether, the presented transcriptome profiles provide highly improved insights into the life strategies of plant-associated endophytes and soil isolates of B. mycoides.

Abstract: In most cities, the taxi industry is highly regulated and utilizes technology developed in the 1940s. Ride sharing services such as Uber and Lyft, which use modern internet-based mobile technology to connect passengers and drivers, have begun to compete with traditional taxis. This paper examines the efficiency of ride sharing services vis-a-vis taxis by comparing the capacity utilization rate of UberX drivers with that of traditional taxi drivers in five cities. The capacity utilization rate is measured by the fraction of time a driver has a fare-paying passenger in the car while he or she is working, and by the share of total miles that drivers log in which a passenger is in their car. The main conclusion is that, in most cities with data available, UberX drivers spend a significantly higher fraction of their time, and drive a substantially higher share of miles, with a passenger in their car than do taxi drivers. Four factors likely contribute to the higher capacity utilization rate of UberX drivers: 1) Uber’s more efficient driver-passenger matching technology; 2)the larger scale of Uber than taxi companies; 3) inefficient taxi regulations; and 4) Uber’s flexible labor supply model and surge pricing more closely match supply with demand throughout the day.

Abstract: Malignant tumors do not only contain cancer cells. Normal cells from the body also infiltrate tumors. These often include a variety of immune cells that can help detect and kill cancer cells. Many evidences suggest that the proportion of different immune cell types in a tumor can affect tumor growth and which treatments are effective. Researchers often study tumors by measuring the expression of genes, i.e., which genes are active in tumors. However, the proportion of different cell types in the tumor is often not measured for tumors studied at the gene expression level. Racle et al. have now demonstrated that a new computer-based tool can accurately detect all the main cell types in a tumor directly from the expression of genes in this tumor. The tool is called “Estimating the Proportion of Immune and Cancer cells” – or EPIC for short. It compares the level of expression of genes in a tumor with a library of the gene expression profiles from specific cell types that can be found in tumors and uses this information to predict how many of each type of cell are present. Experimental measurements of several human tumors confirmed that EPIC’s predictions are accurate. EPIC is freely available online. Since the active genes in tumors from many patients have already been documented together with clinical data, researchers could use EPIC to investigate whether the cell types in a tumor affect how harmful it is or how well a particular treatment works on it. In the future, this information could help to identify the best treatment for a particular patient and may reveal new genes that cause malignant tumors to develop and grow.

Abstract: We present a new technique for learning visual-semantic embeddings for cross-modal retrieval. Inspired by hard negative mining, the use of hard negatives in structured prediction, and ranking loss functions, we introduce a simple change to common loss functions used for multi-modal embeddings. That, combined with fine-tuning and use of augmented data, yields significant gains in retrieval performance. We showcase our approach, VSE++, on MS-COCO and Flickr30K datasets, using ablation studies and comparisons with existing methods. On MS-COCO our approach outperforms state-of-the-art methods by 8.8% in caption retrieval and 11.3% in image retrieval (at R@1).

Abstract: Even though automated functional annotation of genes represents a fundamental step in most genomic and metagenomic workflows, it remains challenging at large scales. Here, we describe a major upgrade to eggNOG-mapper, a tool for functional annotation based on precomputed orthology assignments, now optimized for vast (meta)genomic data sets. Improvements in version 2 include a full update of both the genomes and functional databases underlying eggNOG v5, as well as several efficiency enhancements and new features. Most notably, eggNOG-mapper v2 now allows: (i) de novo gene prediction from raw contigs, (ii) built-in pairwise orthology prediction, (iii) fast protein domain discovery, and (iv) automated GFF decoration. eggNOG-mapper v2 is available as a standalone tool or as an online service at http://emapperdev.compgenomics.org.

Abstract: This paper provides an overview of the main perspectives and themes emerging in research on open innovation (OI). The paper is the result of a collaborative process among several OI scholars – having a common basis in the recurrent Professional Development Workshop on ‘Researching Open Innovation’ at the Annual Meeting of the Academy of Management. In this paper, we present opportunities for future research on OI, organised at different levels of analysis. We discuss some of the contingencies at these different levels, and argue that future research needs to study OI – originally an organisational-level phenomenon – across multiple levels of analysis. While our integrative framework allows comparing, contrasting and integrating various perspectives at different levels of analysis, further theorising will be needed to advance OI research. On this basis, we propose some new research categories as well as questions for future research – particularly those that span across research domains that have so far developed in isolation.

Abstract: Amy Peacock, Janni Leung, Sarah Larney, Samantha Colledge, Matthew Hickman, Jurgen Rehm, Gary A. Giovino, Robert West, Wayne Hall, Paul Griffiths, Robert Ali, Linda Gowing, John Marsden, Alize J. Ferrari, Jason Grebely, Michael Farrell and Louisa Degenhardt

Abstract: Background Monitoring the reasons why a considerable number of people do not receive recommended vaccinations allows identification of important trends over time, and designing and evaluating strategies to address vaccine hesitancy and increase vaccine uptake. Existing validated measures assessing vaccine hesitancy focus primarily on confidence in vaccines and the system that delivers them. However, empirical and theoretical work has stated that complacency (not perceiving diseases as high risk), constraints (structural and psychological barriers), calculation (engagement in extensive information searching), and aspects pertaining to collective responsibility (willingness to protect others) also play a role in explaining vaccination behavior. The objective was therefore to develop a validated measure of these 5C psychological antecedents of vaccination. Methods and findings Three cross-sectional studies were conducted. Study 1 uses factor analysis to develop an initial scale and assesses the sub-scales' convergent, discriminant, and concurrent validity (N = 1,445, two German convenience-samples). In Study 2, a sample representative regarding age and gender for the German population (N = 1,003) completed the measure for vaccination in general and for specific vaccinations to assess the potential need for a vaccine-specific wording of items. Study 3 compared the novel scale's performance with six existing measures of vaccine hesitancy (N = 350, US convenience-sample). As an outcome, a long (15-item) and short (5-item) 5C scale were developed as reliable and valid indicators of confidence, complacency, constraints, calculation, and collective responsibility. The 5C sub-scales correlated with relevant psychological concepts, such as attitude (confidence), perceived personal health status and invulnerability (complacency), self-control (constraints), preference for deliberation (calculation), and communal orientation (collective responsibility), among others. The new scale provided similar results when formulated in a general vs. vaccine-specific way (Study 2). In a comparison of seven measures the 5C scale was constantly among the scales that explained the highest amounts of variance in analyses predicting single vaccinations (between 20% and 40%; Study 3). The present studies are limited to the concurrent validity of the scales. Conclusions The 5C scale provides a novel tool to monitor psychological antecedents of vaccination and facilitates diagnosis, intervention design and evaluation. Its short version is suitable for field settings and regular global monitoring of relevant antecedents of vaccination.

Abstract: Neural network based end-to-end text to speech (TTS) has significantly improved the quality of synthesized speech. Prominent methods (e.g., Tacotron 2) usually first generate mel-spectrogram from text, and then synthesize speech from the mel-spectrogram using vocoder such as WaveNet. Compared with traditional concatenative and statistical parametric approaches, neural network based end-to-end models suffer from slow inference speed, and the synthesized speech is usually not robust (i.e., some words are skipped or repeated) and lack of controllability (voice speed or prosody control). In this work, we propose a novel feed-forward network based on Transformer to generate mel-spectrogram in parallel for TTS. Specifically, we extract attention alignments from an encoder-decoder based teacher model for phoneme duration prediction, which is used by a length regulator to expand the source phoneme sequence to match the length of the target mel-spectrogram sequence for parallel mel-spectrogram generation. Experiments on the LJSpeech dataset show that our parallel model matches autoregressive models in terms of speech quality, nearly eliminates the problem of word skipping and repeating in particularly hard cases, and can adjust voice speed smoothly. Most importantly, compared with autoregressive Transformer TTS, our model speeds up mel-spectrogram generation by 270x and the end-to-end speech synthesis by 38x. Therefore, we call our model FastSpeech.

Abstract: The ongoing coronavirus disease 2019 (COVID-19) pandemic has prioritized the development of small-animal models for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We adapted a clinical isolate of SARS-CoV-2 by serial passaging in the respiratory tract of aged BALB/c mice. The resulting mouse-adapted strain at passage 6 (called MASCp6) showed increased infectivity in mouse lung and led to interstitial pneumonia and inflammatory responses in both young and aged mice after intranasal inoculation. Deep sequencing revealed a panel of adaptive mutations potentially associated with the increased virulence. In particular, the N501Y mutation is located at the receptor binding domain (RBD) of the spike protein. The protective efficacy of a recombinant RBD vaccine candidate was validated by using this model. Thus, this mouse-adapted strain and associated challenge model should be of value in evaluating vaccines and antivirals against SARS-CoV-2.

Abstract: Nakamoto’s famous blockchain protocol enables achieving consensus in a so-called permissionless setting—anyone can join (or leave) the protocol execution, and the protocol instructions do not depend on the identities of the players. His ingenious protocol prevents “sybil attacks” (where an adversary spawns any number of new players) by relying on computational puzzles (a.k.a. “moderately hard functions”) introduced by Dwork and Naor (Crypto’92).

Abstract: Summary Background For most older women with early breast cancer, standard treatment after breast-conserving surgery is adjuvant whole-breast radiotherapy and adjuvant endocrine treatment. We aimed to assess the effect omission of whole-breast radiotherapy would have on local control in older women at low risk of local recurrence at 5 years. Methods Between April 16, 2003, and Dec 22, 2009, 1326 women aged 65 years or older with early breast cancer judged low-risk (ie, hormone receptor-positive, axillary node-negative, T1–T2 up to 3 cm at the longest dimension, and clear margins; grade 3 tumour histology or lymphovascular invasion, but not both, were permitted), who had had breast-conserving surgery and were receiving adjuvant endocrine treatment, were recruited into a phase 3 randomised controlled trial at 76 centres in four countries. Eligible patients were randomly assigned to either whole-breast radiotherapy (40–50 Gy in 15–25 fractions) or no radiotherapy by computer-generated permuted block randomisation, stratified by centre, with a block size of four. The primary endpoint was ipsilateral breast tumour recurrence. Follow-up continues and will end at the 10-year anniversary of the last randomised patient. Analyses were done by intention to treat. The trial is registered on ISRCTN.com, number ISRCTN95889329. Findings 658 women who had undergone breast-conserving surgery and who were receiving adjuvant endocrine treatment were randomly assigned to receive whole-breast irradiation and 668 were allocated to no further treatment. After median follow-up of 5 years (IQR 3·84–6·05), ipsilateral breast tumour recurrence was 1·3% (95% CI 0·2–2·3; n=5) in women assigned to whole-breast radiotherapy and 4·1% (2·4–5·7; n=26) in those assigned no radiotherapy (p=0·0002). Compared with women allocated to whole-breast radiotherapy, the univariate hazard ratio for ipsilateral breast tumour recurrence in women assigned to no radiotherapy was 5·19 (95% CI 1·99–13·52; p=0·0007). No differences in regional recurrence, distant metastases, contralateral breast cancers, or new breast cancers were noted between groups. 5-year overall survival was 93·9% (95% CI 91·8–96·0) in both groups (p=0·34). 89 women died; eight of 49 patients allocated to no radiotherapy and four of 40 assigned to radiotherapy died from breast cancer. Interpretation Postoperative whole-breast radiotherapy after breast-conserving surgery and adjuvant endocrine treatment resulted in a significant but modest reduction in local recurrence for women aged 65 years or older with early breast cancer 5 years after randomisation. However, the 5-year rate of ipsilateral breast tumour recurrence is probably low enough for omission of radiotherapy to be considered for some patients. Funding Chief Scientist Office (Scottish Government), Breast Cancer Institute (Western General Hospital, Edinburgh).

Abstract: Background The perinatal and maternal consequences of induction of labor at 39 weeks among low-risk nulliparous women are uncertain. Methods In this multicenter trial, we randomly assigned...

Abstract: Tensor networks provide a natural framework for exploring holographic duality because they obey entanglement area laws. They have been used to construct explicit toy models realizing many of the interesting structural features of the AdS/CFT correspondence, including the non-uniqueness of bulk operator reconstruction in the boundary theory. In this article, we explore the holographic properties of networks of random tensors. We find that our models naturally incorporate many features that are analogous to those of the AdS/CFT correspondence. When the bond dimension of the tensors is large, we show that the entanglement entropy of all boundary regions, whether connected or not, obey the Ryu-Takayanagi entropy formula, a fact closely related to known properties of the multipartite entanglement of assistance. We also discuss the behavior of Renyi entropies in our models and contrast it with AdS/CFT. Moreover, we find that each boundary region faithfully encodes the physics of the entire bulk entanglement wedge, i.e., the bulk region enclosed by the boundary region and the minimal surface. Our method is to interpret the average over random tensors as the partition function of a classical ferromagnetic Ising model, so that the minimal surfaces of Ryu-Takayanagi appear as domain walls. Upon including the analog of a bulk field, we find that our model reproduces the expected corrections to the Ryu-Takayanagi formula: the bulk minimal surface is displaced and the entropy is augmented by the entanglement of the bulk field. Increasing the entanglement of the bulk field ultimately changes the minimal surface behavior topologically, in a way similar to the effect of creating a black hole. Extrapolating bulk correlation functions to the boundary permits the calculation of the scaling dimensions of boundary operators, which exhibit a large gap between a small number of low-dimension operators and the rest. While we are primarily motivated by the AdS/CFT duality, the main results of the article define a more general form of bulk-boundary correspondence which could be useful for extending holography to other spacetimes.

Abstract: The following guidelines are a summary of the evidence presented in the 2015 International Consensus on Cardiopulmo nary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations (CoSTR).1,2 Throughout the online version of this publication, live links are provided so the reader can connect directly to systematic reviews on the International Liaison Committee on Resuscitation (ILCOR) Scientific Evidence Evaluation and Review System (SEERS) website. These links are indicated by a combination of letters and numbers (eg, NRP 787). We encourage readers to use the links and review the evidence and appendices. These guidelines apply primarily to newly born infants transitioning from intrauterine to extrauterine life. The recommendations are also applicable to neonates who have completed newborn transition and require resuscitation during the first weeks after birth.3 Practitioners who resuscitate infants at birth or at any time during the initial hospitalization should consider following these guidelines. For purposes of these guidelines, the terms newborn and neonate apply to any infant during the initial hospitalization. The term newly born applies specifically to an infant at the time of birth.3 Immediately after birth, infants who are breathing and crying may undergo delayed cord clamping (see Umbilical Cord Management section). However, until more evidence is available, infants who are not breathing or crying should have the cord clamped (unless part of a delayed cord clamping research protocol), so that resuscitation measures can commence promptly. Approximately 10% of newborns require some assistance to begin breathing at birth. Less than 1% require extensive resuscitation measures,4 such as cardiac compressions and medications. Although most newly born infants successfully transition from intrauterine to extrauterine life without special help, because of the large total number of births, a significant number will require some degree of resuscitation.3 Newly born infants who do not …

Abstract: Patients with cancer are presumed to be at increased risk from COVID-19 infection-related fatality due to underlying malignancy, treatment-related immunosuppression, or increased comorbidities. A total of 218 COVID-19-positive patients from March 18, 2020, to April 8, 2020, with a malignant diagnosis were identified. A total of 61 (28%) patients with cancer died from COVID-19 with a case fatality rate (CFR) of 37% (20/54) for hematologic malignancies and 25% (41/164) for solid malignancies. Six of 11 (55%) patients with lung cancer died from COVID-19 disease. Increased mortality was significantly associated with older age, multiple comorbidities, need for ICU support, and elevated levels of D-dimer, lactate dehydrogenase, and lactate in multivariate analysis. Age-adjusted CFRs in patients with cancer compared with noncancer patients at our institution and New York City reported a significant increase in case fatality for patients with cancer. These data suggest the need for proactive strategies to reduce likelihood of infection and improve early identification in this vulnerable patient population. SIGNIFICANCE: COVID-19 in patients with cancer is associated with a significantly increased risk of case fatality, suggesting the need for proactive strategies to reduce likelihood of infection and improve early identification in this vulnerable patient population.This article is highlighted in the In This Issue feature, p. 890.

Abstract: Given semantic descriptions of object classes, zeroshot learning aims to accurately recognize objects of the unseen classes, from which no examples are available at the training stage, by associating them to the seen classes, from which labeled examples are provided. We propose to tackle this problem from the perspective of manifold learning. Our main idea is to align the semantic space that is derived from external information to the model space that concerns itself with recognizing visual features. To this end, we introduce a set of "phantom" object classes whose coordinates live in both the semantic space and the model space. Serving as bases in a dictionary, they can be optimized from labeled data such that the synthesized real object classifiers achieve optimal discriminative performance. We demonstrate superior accuracy of our approach over the state of the art on four benchmark datasets for zero-shot learning, including the full ImageNet Fall 2011 dataset with more than 20,000 unseen classes.

Abstract: T-cell genome engineering holds great promise for cell-based therapies for cancer, HIV, primary immune deficiencies, and autoimmune diseases, but genetic manipulation of human T cells has been challenging. Improved tools are needed to efficiently "knock out" genes and "knock in" targeted genome modifications to modulate T-cell function and correct disease-associated mutations. CRISPR/Cas9 technology is facilitating genome engineering in many cell types, but in human T cells its efficiency has been limited and it has not yet proven useful for targeted nucleotide replacements. Here we report efficient genome engineering in human CD4(+) T cells using Cas9:single-guide RNA ribonucleoproteins (Cas9 RNPs). Cas9 RNPs allowed ablation of CXCR4, a coreceptor for HIV entry. Cas9 RNP electroporation caused up to ∼40% of cells to lose high-level cell-surface expression of CXCR4, and edited cells could be enriched by sorting based on low CXCR4 expression. Importantly, Cas9 RNPs paired with homology-directed repair template oligonucleotides generated a high frequency of targeted genome modifications in primary T cells. Targeted nucleotide replacement was achieved in CXCR4 and PD-1 (PDCD1), a regulator of T-cell exhaustion that is a validated target for tumor immunotherapy. Deep sequencing of a target site confirmed that Cas9 RNPs generated knock-in genome modifications with up to ∼20% efficiency, which accounted for up to approximately one-third of total editing events. These results establish Cas9 RNP technology for diverse experimental and therapeutic genome engineering applications in primary human T cells.

Abstract: Pre-training and fine-tuning, e.g., BERT, have achieved great success in language understanding by transferring knowledge from rich-resource pre-training task to the low/zero-resource downstream tasks. Inspired by the success of BERT, we propose MAsked Sequence to Sequence pre-training (MASS) for the encoder-decoder based language generation tasks. MASS adopts the encoder-decoder framework to reconstruct a sentence fragment given the remaining part of the sentence: its encoder takes a sentence with randomly masked fragment (several consecutive tokens) as input, and its decoder tries to predict this masked fragment. In this way, MASS can jointly train the encoder and decoder to develop the capability of representation extraction and language modeling. By further fine-tuning on a variety of zero/low-resource language generation tasks, including neural machine translation, text summarization and conversational response generation (3 tasks and totally 8 datasets), MASS achieves significant improvements over the baselines without pre-training or with other pre-training methods. Specially, we achieve the state-of-the-art accuracy (37.5 in terms of BLEU score) on the unsupervised English-French translation, even beating the early attention-based supervised model.