200,193 results match your criteria Cambridge Journal Of Regions Economy And Society[Journal]


Signatures of adaptation to a monocot host in the plant-parasitic cyst nematode Heterodera sacchari.

Plant J 2020 Jul 4. Epub 2020 Jul 4.

The James Hutton Institute, Invergowrie, Dundee, DD2 5DA, UK.

Interactions between plant-parasitic nematodes and their hosts are mediated by effectors; secreted proteins that manipulate the plant to the benefit of the pathogen. To understand the role of effectors in host adaptation in nematodes we analysed the transcriptome of Heterodera sacchari, a cyst nematode parasite of rice and sugarcane. A multi-gene phylogenetic analysis showed that H. Read More

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http://dx.doi.org/10.1111/tpj.14910DOI Listing

Examining the Role of Genetic Risk and Longitudinal Transmission Processes Underlying Maternal Parenting and Psychopathology and Children's ADHD Symptoms and Aggression: Utilizing the Advantages of a Prospective Adoption Design.

Behav Genet 2020 Jul 4. Epub 2020 Jul 4.

Prevention Science Institute, University of Oregon, Eugene, OR, USA.

Although genetic factors may contribute to initial liability for ADHD onset, there is growing evidence of the potential importance of the rearing environment on the developmental course of ADHD symptomatology. However, associations between family-level variables (maternal hostility, maternal depressive symptoms) and child behaviors (developmental course of ADHD and aggression) may be explained by genes that are shared by biologically related parents and children. Furthermore, ADHD symptoms and aggression commonly co-occur: it is important to consider both simultaneously to have a better understanding of processes underlying the developmental course of ADHD and aggression. Read More

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http://dx.doi.org/10.1007/s10519-020-10006-yDOI Listing

Lung cancer screening eligibility and utilization among transgender patients: an analysis of the 2017-2018 United States Behavioral Risk Factor Surveillance System survey.

Nicotine Tob Res 2020 Jul 5. Epub 2020 Jul 5.

Department of Radiology, Massachusetts General Hospital, Boston, MA, USA.

Introduction: Transgender and gender diverse (TGD) persons disproportionately face many health disparities including a higher risk of lung cancer. Lung cancer screening (LCS) using low-dose chest CT has reduced lung cancer mortality in eligible high-risk smokers across several large trials yet utilization of LCS remains low. TGD persons may be less likely to receive recommended cancer screening compared to cisgender populations. Read More

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http://dx.doi.org/10.1093/ntr/ntaa127DOI Listing

Local rotation invariance in 3D CNNs.

Med Image Anal 2020 Jun 20;65:101756. Epub 2020 Jun 20.

Institute of Information Systems, University of Applied Sciences Western Switzerland (HES-SO), Sierre, Switzerland; Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland.

Locally Rotation Invariant (LRI) image analysis was shown to be fundamental in many applications and in particular in medical imaging where local structures of tissues occur at arbitrary rotations. LRI constituted the cornerstone of several breakthroughs in texture analysis, including Local Binary Patterns (LBP), Maximum Response 8 (MR8) and steerable filterbanks. Whereas globally rotation invariant Convolutional Neural Networks (CNN) were recently proposed, LRI was very little investigated in the context of deep learning. Read More

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http://dx.doi.org/10.1016/j.media.2020.101756DOI Listing

Prevalence and predictors of general psychiatric disorders and loneliness during COVID-19 in the United Kingdom.

Psychiatry Res 2020 Jun 30;291:113267. Epub 2020 Jun 30.

University of Cambridge, Centre for Business Research, Judge Business School, 11-12 Trumpington Street, Cambridge CB2 1AG, USA. Electronic address:

Despite ample research on the prevalence of specific psychiatric disorders during COVID-19, we know little about the broader psychological impact of the pandemic on a wider population. The study investigates the prevalence and predictors of general psychiatric disorders measured by the 12-item General Health Questionnaire (GHQ-12) and frequency of loneliness during COVID-19 in the United Kingdom, a country heavily hit by the pandemic. We analyzed 15,530 respondents of the first large-scale, nationally representative survey of COVID-19 in a developed country, the first wave of Understanding Society COVID-19 Study. Read More

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http://dx.doi.org/10.1016/j.psychres.2020.113267DOI Listing

Nanostructured-membrane electron phase plates.

Ultramicroscopy 2020 Jun 25;217:113053. Epub 2020 Jun 25.

Research Laboratory of Electronics, Massachusetts Institute of Technology, Cambridge, MA 02139, United States.

Electron beams can acquire designed phase modulations by passing through nanostructured material phase plates. These phase modulations enable electron wavefront shaping and benefit electron microscopy, spectroscopy, lithography, and interferometry. However, in the fabrication of electron phase plates, the typically used focused-ion-beam-milling method limits the fabrication throughput and hence the active area of the phase plates. Read More

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http://dx.doi.org/10.1016/j.ultramic.2020.113053DOI Listing

Apathy and its impact on carer burden and psychological wellbeing in primary progressive aphasia.

J Neurol Sci 2020 Jun 30;416:117007. Epub 2020 Jun 30.

The University of Sydney, School of Psychology, Sydney, NSW, Australia; The University of Sydney, Brain & Mind Centre, Sydney, NSW, Australia. Electronic address:

Objective: While patients with primary progressive aphasia (PPA) typically present with predominant language impairment, behavioural symptoms, such as apathy, are often under-recognised. We aimed to systematically characterise apathy across the three recognised subtypes of PPA, plus atypical right-lateralised presentations of semantic dementia, and to evaluate the impact of apathy on carer burden and psychological wellbeing.

Methods: Baseline assessments from 114 PPA patients were included: 31 left semantic dementia (left SD) 16 right semantic dementia (right SD), 30 progressive nonfluent aphasia (PNFA) and 37 logopenic progressive aphasia (LPA). Read More

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http://dx.doi.org/10.1016/j.jns.2020.117007DOI Listing

Leveraging epigenetics to examine differences in developmental trajectories of social attention: A proof-of-principle study of DNA methylation in infants with older siblings with autism.

Infant Behav Dev 2020 Jul 2;60:101409. Epub 2020 Jul 2.

Department of Psychology, Cambridge University, UK.

Preliminary evidence suggests that changes in DNA methylation, a widely studied epigenetic mechanism, contribute to the etiology of Autism Spectrum Disorder (ASD). However, data is primarily derived from post-mortem brain samples or peripheral tissue from adults. Deep-phenotyped longitudinal infant cohorts are essential to understand how epigenetic modifications relate to early developmental trajectories and emergence of ASD symptoms. Read More

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http://dx.doi.org/10.1016/j.infbeh.2019.101409DOI Listing

Freshly isolated primary human proximal tubule cells as an in vitro model for the detection of renal tubular toxicity.

Toxicology 2020 Jul 2:152535. Epub 2020 Jul 2.

Drug Safety Research and Evaluation, Takeda Pharmaceutical International Co., Cambridge, MA USA. Electronic address:

Drug induced kidney injury (DIKI) is a common reason for compound attrition in drug development pipelines with proximal tubule epithelial cells (PTECs) most commonly associated with DIKI. Here, we investigated freshly isolated human (hPTECs) as an in vitro model for assessing renal tubular toxicity. The freshly isolated hPTECs were first characterized to confirm gene expression of important renal transporters involved in drug handling which was further corroborated by confirming the functional activity of organic cation transporter 2 and organic anion transporter 1 by using transporter specific inhibitors. Read More

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http://dx.doi.org/10.1016/j.tox.2020.152535DOI Listing

Nanovehicles for co-delivery of anticancer agents.

Drug Discov Today 2020 Jul 2. Epub 2020 Jul 2.

Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Dermatology, Harvard Medical School, Boston, MA 02115, USA; Laser Research Centre, Faculty of Health Science, University of Johannesburg, Doornfontein 2028, South Africa. Electronic address:

Effective cancer treatment remains a significant challenge in human healthcare. Although many different types of cancer therapy have been tested, scientists have now concluded that combinations of drugs, or drugs plus gene therapy, can target multiple pathways to fight cancer. Nanovehicles can increase drug uptake inside tumor cells, improve biodistribution and accumulation at tumor sites. Read More

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http://dx.doi.org/10.1016/j.drudis.2020.06.027DOI Listing

The origin of the heartbeat and theories of muscle contraction. Physiological concepts and conflicts in the 19th century.

Prog Biophys Mol Biol 2020 Jul 2. Epub 2020 Jul 2.

Zentrum für konstruktive Erziehungswissenschaften, Christian-Albrechts-Universität Kiel, Germany.

The origin of the incessant rhythmical heartbeat and the mechanism of muscle contraction have fascinated scientists over centuries. This short review outlines physiological explanations that were discussed in the 19th century starting with Albrecht von Haller (1708-1777), an 18th century physiologist who proposed that the heart has an intrinsic irritability. He argued that under normal conditions the inflow of blood stimulates the heart muscle to contract by mechanical touch and distension. Read More

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http://dx.doi.org/10.1016/j.pbiomolbio.2020.05.009DOI Listing

Contact Tracing to Manage COVID-19 Spread-Balancing Personal Privacy and Public Health.

Mayo Clin Proc 2020 Jul 3;95(7):1320-1322. Epub 2020 May 3.

MIT Media Lab, Massachusetts Institute of Technology, Cambridge, MA.

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http://dx.doi.org/10.1016/j.mayocp.2020.04.031DOI Listing

Ethnic and regional variations in hospital mortality from COVID-19 in Brazil: a cross-sectional observational study.

Lancet Glob Health 2020 Jul 2. Epub 2020 Jul 2.

The Alan Turing Institute, London, UK; Cambridge Centre for Artificial Intelligence in Medicine, Cambridge, UK; Department of Applied Mathematics and Theoretical Physics and Department of Population Health, University of Cambridge, Cambridge, UK; Department of Electrical and Computer Engineering, University of California Los Angeles, Los Angeles, CA, USA.

Background: Brazil ranks second worldwide in total number of COVID-19 cases and deaths. Understanding the possible socioeconomic and ethnic health inequities is particularly important given the diverse population and fragile political and economic situation. We aimed to characterise the COVID-19 pandemic in Brazil and assess variations in mortality according to region, ethnicity, comorbidities, and symptoms. Read More

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http://dx.doi.org/10.1016/S2214-109X(20)30285-0DOI Listing

Ambulatory management of primary spontaneous pneumothorax: an open-label, randomised controlled trial.

Lancet 2020 Jul;396(10243):39-49

Oxford Respiratory Trials Unit, University of Oxford, Oxford, UK.

Background: Primary spontaneous pneumothorax occurs in otherwise healthy young patients. Optimal management is not defined and often results in prolonged hospitalisation. Data on efficacy of ambulatory options are poor. Read More

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http://dx.doi.org/10.1016/S0140-6736(20)31043-6DOI Listing

Immune Cell Associations with Cancer Risk.

iScience 2020 Jun 20;23(7):101296. Epub 2020 Jun 20.

ProCURE, Catalan Institute of Oncology, Bellvitge Institute for Biomedical Research (IDIBELL), L'Hospitalet del Llobregat, Barcelona, Catalonia 08908, Spain. Electronic address:

Proper immune system function hinders cancer development, but little is known about whether genetic variants linked to cancer risk alter immune cells. Here, we report 57 cancer risk loci associated with differences in immune and/or stromal cell contents in the corresponding tissue. Predicted target genes show expression and regulatory associations with immune features. Read More

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http://dx.doi.org/10.1016/j.isci.2020.101296DOI Listing

Triboelectric Nanogenerator versus Piezoelectric Generator at Low Frequency (<4 Hz): A Quantitative Comparison.

iScience 2020 Jun 20;23(7):101286. Epub 2020 Jun 20.

Department of Chemistry and Biochemistry and California NanoSystems Institute, University of California, Los Angeles (UCLA), Loss Angeles, CA, USA; Department of Materials Science and Engineering, UCLA, Los Angeles, CA, USA.

Triboelectric nanogenerators (TENGs) and piezoelectric generators (PGs) are generally considered the two most common approaches for harvesting ambient mechanical energy that is ubiquitous in our everyday life. The main difference between the two generators lies in their respective working frequency range. Despite the remarkable progress, there has been no quantitative studies on the operating frequency band of the two generators at frequency values below 4 Hz, typical of human motion. Read More

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http://dx.doi.org/10.1016/j.isci.2020.101286DOI Listing

Selective adsorption of organic anions in a flow cell with asymmetric redox active electrodes.

Water Res 2020 May 20;182:115963. Epub 2020 May 20.

Department of Chemical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA, 02139, USA. Electronic address:

Electrochemically mediated adsorption is an emerging technology that utilizes redox active (or Faradaic) materials and has exhibited high salt adsorption capacity and superb ion selectivity. Here, we use a redox polymer polyvinylferrocene (PVFc) as the anode and a conducting polymer polypyrrole doped with a large anionic surfactant (pPy-DBS) as the cathode for selective electrochemical removal of inorganic and organic components. We fabricated a flow system with alternating adsorption/desorption steps incorporating an electrosorption cell and inline probes (ultraviolet-visible spectroscopy, conductivity and pH sensors) to demonstrate on-the-fly quantification of the ion adsorption performance. Read More

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http://dx.doi.org/10.1016/j.watres.2020.115963DOI Listing

Exudative Retinal Detachment in Ocular Inflammatory Diseases: Risk and Predictive Factors.

Am J Ophthalmol 2020 Jul 1. Epub 2020 Jul 1.

Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts; Department of Ophthalmology, Massachusetts Eye and Ear, Boston, Massachusetts; MyungSung Christian Medical Center (MCM) Eye Unit, MCM General Hospital and MyungSung Medical School, Addis Ababa, Ethiopia.

Purpose: To evaluate the risk/risk factors for exudative retinal detachment (ERD) in ocular inflammatory diseases.

Design: Retrospective cohort study.

Methods: Patients with non-infectious ocular inflammation had been followed longitudinally between 1978-2007 at four US subspecialty uveitis centers. Read More

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http://dx.doi.org/10.1016/j.ajo.2020.06.019DOI Listing

Development of Brain Targeting Peptide Based MMP-9 Inhibiting Nanoparticles for the Treatment of Brain Diseases with Elevated MMP-9 Activity.

J Pharm Sci 2020 Jul 1. Epub 2020 Jul 1.

School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Liverpool, L3 3AF, UK. Electronic address:

Latent and active levels of cerebral matrix metalloproteinase 9 (MMP-9) are elevated in neurological diseases and brain injuries, contributing to neurological damage and poor clinical outcomes. This study aimed developing peptide-based nanoparticles with ability to cross the blood-brain-barrier (BBB) and inhibit MMP-9. Three amphiphilic peptides were synthesised containing brain-targeting ligands (HAIYPRH or CKAPETALC) conjugated with MMP-9 inhibiting peptide (CTTHWGFTLC) linked by glycine (spacer) at the N-terminus, and the peptide sequences were conjugated at the N- terminus to cholesterol. Read More

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http://dx.doi.org/10.1016/j.xphs.2020.06.021DOI Listing

IMPLICON: an ultra-deep sequencing method to uncover DNA methylation at imprinted regions.

Nucleic Acids Res 2020 Jul 4. Epub 2020 Jul 4.

Epigenetics Programme, Babraham Institute, Cambridge CB22 3AT, UK.

Genomic imprinting is an epigenetic phenomenon leading to parental allele-specific expression. Dosage of imprinted genes is crucial for normal development and its dysregulation accounts for several human disorders. This unusual expression pattern is mostly dictated by differences in DNA methylation between parental alleles at specific regulatory elements known as imprinting control regions (ICRs). Read More

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http://dx.doi.org/10.1093/nar/gkaa567DOI Listing

Seeing red? Colour biases of foraging birds are context dependent.

Anim Cogn 2020 Jul 3. Epub 2020 Jul 3.

Department of Zoology, University of Cambridge, Cambridge, UK.

Colours are commonly used as visual cues when measuring animals' cognitive abilities. However, animals can have innate biases towards certain colours that depend on ecological and evolutionary contexts, therefore potentially influencing their performance in experiments. For example, when foraging, the colour red can advertise profitable fruits or act as a warning signal about chemically defended prey, and an individual's propensity to take food of that colour may depend on experience, age or physical condition. Read More

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http://dx.doi.org/10.1007/s10071-020-01407-xDOI Listing

The Genome3D Consortium for Structural Annotations of Selected Model Organisms.

Methods Mol Biol 2020 ;2165:27-67

Institute of Structural and Molecular Biology, University College London, London, UK.

Genome3D consortium is a collaborative project involving protein structure prediction and annotation resources developed by six world-leading structural bioinformatics groups, based in the United Kingdom (namely Blundell, Murzin, Gough, Sternberg, Orengo, and Jones). The main objective of Genome3D serves as a common portal to provide both predicted models and annotations of proteins in model organisms, using several resources developed by these labs such as CATH-Gene3D, DOMSERF, pDomTHREADER, PHYRE, SUPERFAMILY, FUGUE/TOCATTA, and VIVACE. These resources primarily use SCOP- and/or CATH-based protein domain assignments. Read More

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http://dx.doi.org/10.1007/978-1-0716-0708-4_3DOI Listing
January 2020

Pharmacokinetics, Safety, and Tolerability of a 2-Month Dose Interval Regimen of the Long-Acting Injectable Antipsychotic Aripiprazole Lauroxil: Results From a 44-Week Phase I Study.

CNS Drugs 2020 Jul 3. Epub 2020 Jul 3.

CNS Network, LLC, Garden Grove, CA, USA.

Background: Aripiprazole lauroxil (AL) is a long-acting injectable antipsychotic approved for treatment of schizophrenia in adults. Approved AL doses and dosing regimens include 441 mg monthly, 662 mg monthly, and 882 mg monthly or every 6 weeks (q6wk), as well as the most recently approved dose, 1064 mg, administered every 2 months.

Objective: Pharmacokinetics, safety, and tolerability of an AL regimen with a dose interval of every 2 months (1064 mg) were compared with two other regimens available as monthly and q6wk options. Read More

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http://dx.doi.org/10.1007/s40263-020-00745-1DOI Listing

Correction of cilia structure and function alleviates multi-organ pathology in Bardet-Biedl Syndrome mice.

Hum Mol Genet 2020 Jul 3. Epub 2020 Jul 3.

Rare and Neurologic Diseases Research, Sanofi, 49 New York Avenue, Framingham, MA 01701.

Bardet-Biedl syndrome (BBS) is a pleiotropic autosomal recessive ciliopathy affecting multiple organs. The development of potential disease-modifying therapy for BBS will require concurrent targeting of multi-systemic manifestations. Here, we show for the first time that monosialodihexosylganglioside accumulates in Bbs2-/- cilia, indicating impairment of glycosphingolipid (GSL) metabolism in BBS. Read More

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http://dx.doi.org/10.1093/hmg/ddaa138DOI Listing

TCF12 haploinsufficiency causes autosomal dominant Kallmann syndrome and reveals network-level interactions between causal loci.

Hum Mol Genet 2020 Jul 3. Epub 2020 Jul 3.

Center for Human Disease Modeling, Duke University, Durham NC 27701, USA.

Dysfunction of the gonadotropin-releasing hormone (GnRH) axis causes a range of reproductive phenotypes resulting from defects in the specification, migration and/or function of GnRH neurons. To identify additional molecular components of this system, we initiated a systematic genetic interrogation of families with isolated gonadotropin-releasing hormone (GnRH) deficiency (IGD). Here we report thirteen families (twelve autosomal dominant, and one autosomal recessive) with an anosmic form of IGD (Kallmann syndrome; KS) with loss-of-function mutations in TCF12, a locus also known to cause syndromic and non-syndromic craniosynostosis. Read More

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http://dx.doi.org/10.1093/hmg/ddaa120DOI Listing

Structural insight into mitochondrial β-barrel outer membrane protein biogenesis.

Nat Commun 2020 Jul 3;11(1):3290. Epub 2020 Jul 3.

Laboratory of Molecular Biology, National Institute of Diabetes & Digestive & Kidney Diseases, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD, 20892, USA.

In mitochondria, β-barrel outer membrane proteins mediate protein import, metabolite transport, lipid transport, and biogenesis. The Sorting and Assembly Machinery (SAM) complex consists of three proteins that assemble as a 1:1:1 complex to fold β-barrel proteins and insert them into the mitochondrial outer membrane. We report cryoEM structures of the SAM complex from Myceliophthora thermophila, which show that Sam50 forms a 16-stranded transmembrane β-barrel with a single polypeptide-transport-associated (POTRA) domain extending into the intermembrane space. Read More

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http://dx.doi.org/10.1038/s41467-020-17144-1DOI Listing

Rapid activation of distinct members of multigene families in Plasmodium spp.

Commun Biol 2020 Jul 3;3(1):351. Epub 2020 Jul 3.

School of Biological Sciences, Nanyang Technological University, Singapore, Singapore.

The genomes of Plasmodium spp. encode a number of different multigene families that are thought to play a critical role for survival. However, with the exception of the P. Read More

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http://dx.doi.org/10.1038/s42003-020-1081-3DOI Listing

Assessment of polygenic architecture and risk prediction based on common variants across fourteen cancers.

Nat Commun 2020 Jul 3;11(1):3353. Epub 2020 Jul 3.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.

Genome-wide association studies (GWAS) have led to the identification of hundreds of susceptibility loci across cancers, but the impact of further studies remains uncertain. Here we analyse summary-level data from GWAS of European ancestry across fourteen cancer sites to estimate the number of common susceptibility variants (polygenicity) and underlying effect-size distribution. All cancers show a high degree of polygenicity, involving at a minimum of thousands of loci. Read More

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http://dx.doi.org/10.1038/s41467-020-16483-3DOI Listing

Megaevolutionary dynamics and the timing of evolutionary innovation in reptiles.

Nat Commun 2020 Jul 3;11(1):3322. Epub 2020 Jul 3.

Department of Organismic and Evolutionary Biology & Museum of Comparative Zoology, Harvard University, Cambridge, MA, 02138, USA.

The origin of phenotypic diversity among higher clades is one of the most fundamental topics in evolutionary biology. However, due to methodological challenges, few studies have assessed rates of evolution and phenotypic disparity across broad scales of time to understand the evolutionary dynamics behind the origin and early evolution of new clades. Here, we provide a total-evidence dating approach to this problem in diapsid reptiles. Read More

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http://dx.doi.org/10.1038/s41467-020-17190-9DOI Listing

Salmonella-based platform for efficient delivery of functional binding proteins to the cytosol.

Commun Biol 2020 Jul 3;3(1):342. Epub 2020 Jul 3.

IMBA, Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Vienna, Austria.

Protein-based affinity reagents (like antibodies or alternative binding scaffolds) offer wide-ranging applications for basic research and therapeutic approaches. However, whereas small chemical molecules efficiently reach intracellular targets, the delivery of macromolecules into the cytosol of cells remains a major challenge; thus cytosolic applications of protein-based reagents are rather limited. Some pathogenic bacteria have evolved a conserved type III secretion system (T3SS) which allows the delivery of effector proteins into eukaryotic cells. Read More

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http://dx.doi.org/10.1038/s42003-020-1072-4DOI Listing

Rationally inattentive intertemporal choice.

Nat Commun 2020 Jul 3;11(1):3365. Epub 2020 Jul 3.

Department of Psychology, Harvard University, Cambridge, MA, USA.

Discounting of future rewards is traditionally interpreted as evidence for an intrinsic preference in favor of sooner rewards. However, temporal discounting can also arise from internal uncertainty in value representations of future events, if one assumes that noisy mental simulations of the future are rationally combined with prior beliefs. Here, we further develop this idea by considering how simulation noise may be adaptively modulated by task demands, based on principles of rational inattention. Read More

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http://dx.doi.org/10.1038/s41467-020-16852-yDOI Listing

Predicting and affecting response to cancer therapy based on pathway-level biomarkers.

Nat Commun 2020 Jul 3;11(1):3296. Epub 2020 Jul 3.

Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.

Identifying robust, patient-specific, and predictive biomarkers presents a major obstacle in precision oncology. To optimize patient-specific therapeutic strategies, here we couple pathway knowledge with large-scale drug sensitivity, RNAi, and CRISPR-Cas9 screening data from 460 cell lines. Pathway activity levels are found to be strong predictive biomarkers for the essentiality of 15 proteins, including the essentiality of MAD2L1 in breast cancer patients with high BRCA-pathway activity. Read More

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http://dx.doi.org/10.1038/s41467-020-17090-yDOI Listing

Effects of climate change on the movement of future landfalling Texas tropical cyclones.

Nat Commun 2020 Jul 3;11(1):3319. Epub 2020 Jul 3.

Department of Earth, Environmental and Planetary Sciences, Rice University, Houston, 77004, TX, USA.

The movement of tropical cyclones (TCs), particularly around the time of landfall, can substantially affect the resulting damage. Recently, trends in TC translation speed and the likelihood of stalled TCs such as Harvey have received significant attention, but findings have remained inconclusive. Here, we examine how the June-September steering wind and translation speed of landfalling Texas TCs change in the future under anthropogenic climate change. Read More

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http://dx.doi.org/10.1038/s41467-020-17130-7DOI Listing

Stable machine-learning parameterization of subgrid processes for climate modeling at a range of resolutions.

Nat Commun 2020 Jul 3;11(1):3295. Epub 2020 Jul 3.

Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.

Global climate models represent small-scale processes such as convection using subgrid models known as parameterizations, and these parameterizations contribute substantially to uncertainty in climate projections. Machine learning of new parameterizations from high-resolution model output is a promising approach, but such parameterizations have been prone to issues of instability and climate drift, and their performance for different grid spacings has not yet been investigated. Here we use a random forest to learn a parameterization from coarse-grained output of a three-dimensional high-resolution idealized atmospheric model. Read More

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http://dx.doi.org/10.1038/s41467-020-17142-3DOI Listing

Antagonistic odor interactions in olfactory sensory neurons are widespread in freely breathing mice.

Nat Commun 2020 Jul 3;11(1):3350. Epub 2020 Jul 3.

Department of Molecular & Cellular Biology, Harvard University, Cambridge, MA, 02138, USA.

Odor landscapes contain complex blends of molecules that each activate unique, overlapping populations of olfactory sensory neurons (OSNs). Despite the presence of hundreds of OSN subtypes in many animals, the overlapping nature of odor inputs may lead to saturation of neural responses at the early stages of stimulus encoding. Information loss due to saturation could be mitigated by normalizing mechanisms such as antagonism at the level of receptor-ligand interactions, whose existence and prevalence remains uncertain. Read More

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http://dx.doi.org/10.1038/s41467-020-17124-5DOI Listing

Silencing hepatic MCJ attenuates non-alcoholic fatty liver disease (NAFLD) by increasing mitochondrial fatty acid oxidation.

Nat Commun 2020 Jul 3;11(1):3360. Epub 2020 Jul 3.

Department of Medicine, Immunobiology Division, University of Vermont, Burlington, VT, 05405, USA.

Nonalcoholic fatty liver disease (NAFLD) is considered the next major health epidemic with an estimated 25% worldwide prevalence. No drugs have yet been approved and NAFLD remains a major unmet need. Here, we identify MCJ (Methylation-Controlled J protein) as a target for non-alcoholic steatohepatitis (NASH), an advanced phase of NAFLD. Read More

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http://dx.doi.org/10.1038/s41467-020-16991-2DOI Listing

Transcriptomic and cellular decoding of regional brain vulnerability to neurogenetic disorders.

Nat Commun 2020 Jul 3;11(1):3358. Epub 2020 Jul 3.

Developmental Neurogenomics Unit, National Institute of Mental Health, Bethesda, MD, USA.

Neurodevelopmental disorders have a heritable component and are associated with region specific alterations in brain anatomy. However, it is unclear how genetic risks for neurodevelopmental disorders are translated into spatially patterned brain vulnerabilities. Here, we integrated cortical neuroimaging data from patients with neurodevelopmental disorders caused by genomic copy number variations (CNVs) and gene expression data from healthy subjects. Read More

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http://dx.doi.org/10.1038/s41467-020-17051-5DOI Listing

Diamond Blackfan anemia is mediated by hyperactive Nemo-like kinase.

Nat Commun 2020 Jul 3;11(1):3344. Epub 2020 Jul 3.

Division of Hematology/Oncology, Department of Pediatrics, Stanford University, Stanford, CA, 94305, USA.

Diamond Blackfan Anemia (DBA) is a congenital bone marrow failure syndrome associated with ribosomal gene mutations that lead to ribosomal insufficiency. DBA is characterized by anemia, congenital anomalies, and cancer predisposition. Treatment for DBA is associated with significant morbidity. Read More

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http://dx.doi.org/10.1038/s41467-020-17100-zDOI Listing

Let's talk about sex.

Sci Immunol 2020 Jul;5(49)

Broad Institute of MIT and Harvard, Cambridge, MA, USA. Brigham and Women's Hospital, Boston, MA, USA.

Complement gene variation drives sex biases in autoimmune disease. Read More

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http://dx.doi.org/10.1126/sciimmunol.abd4828DOI Listing

Long-term efficacy of olipudase alfa in adults with acid sphingomyelinase deficiency (ASMD): Further clearance of hepatic sphingomyelin is associated with additional improvements in pro- and anti-atherogenic lipid profiles after 42 months of treatment.

Mol Genet Metab 2020 Jun 24. Epub 2020 Jun 24.

Clinical Development, Sanofi Genzyme, Cambridge, MA, United States of America.

The liver is a major site of lipoprotein synthesis and metabolism. Liver manifestations of chronic visceral ASMD include hepatomegaly, fibrosis, elevated liver enzymes and a pro-atherogenic lipid profile. Measurements of sphingomyelin (SM) levels in liver biopsies and lyso-SM in plasma were used as pharmacodynamic biomarkers. Read More

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http://dx.doi.org/10.1016/j.ymgme.2020.06.010DOI Listing

British Gynaecological Cancer Society (BGCS) vulval cancer guidelines: Recommendations for practice.

Eur J Obstet Gynecol Reprod Biol 2020 Jun 8. Epub 2020 Jun 8.

Gynaecologic Oncology, Imperial College London Faculty of Medicine, London, SW7 2DD, UK.

The purpose of this guideline is to collate evidence and propose evidence-based guidelines for the diagnosis and management of adult patients with vulva carcinoma treated in the UK. Malignant melanoma may present via similar routes and will be discussed. The reader is referred to the Ano-uro-genital Mucosal Melanoma Full Guideline [1] for more detailed recommendations. Read More

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http://dx.doi.org/10.1016/j.ejogrb.2020.05.054DOI Listing

Paravalvular leakage in transcatheter mitral valve replacement: Bringing simulation theory one step closer to reality.

J Cardiovasc Comput Tomogr 2020 Jun 26. Epub 2020 Jun 26.

Royal Papworth Hospital, Cambridge, UK.

Transcatheter mitral valve replacement (TMVR) has emerged as a promising technique for the treatment of these patients with severe mitral valve disease and high or prohibitive surgical risk. Early experience with TMVR has shown a high rate of technical success and promising reductions in the severity of mitral regurgitation sustained out to 1 year post procedure. Despite this, procedural complications remain high, with the most common and significant of these being valve embolization, left ventricualr outflow tract (LVOT) obstruction and paravalvular leakage (PVL). Read More

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http://dx.doi.org/10.1016/j.jcct.2020.06.196DOI Listing

Percutaneous Dilatational Tracheostomy in Coronavirus Disease 2019 Extracorporeal Membrane Oxygenation Patients: A Case Series.

J Cardiothorac Vasc Anesth 2020 Jun 12. Epub 2020 Jun 12.

Department of Anesthesia and Intensive Care, Royal Papworth Hospital, Cambridge, UK.

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http://dx.doi.org/10.1053/j.jvca.2020.06.024DOI Listing

Evaluation of Point-of-Care ACT Coagulometers and Anti-Xa Activity During Cardiopulmonary Bypass.

J Cardiothorac Vasc Anesth 2020 Jun 12. Epub 2020 Jun 12.

Division of Clinical Haematology and Blood Transfusion, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.

Objective: The activated clotting time (ACT) is used worldwide to confirm safe heparin anticoagulation for cardiopulmonary bypass. For the present study, the performances of 2 commonly used ACT devices were compared with each other and with anti-Xa levels throughout the surgical procedure in order to understand whether they can be used interchangeably.

Design: Prospective study. Read More

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http://dx.doi.org/10.1053/j.jvca.2020.06.027DOI Listing

The Role of Astrocytes in Remyelination.

Trends Neurosci 2020 Jul 1. Epub 2020 Jul 1.

Wellcome - MRC Cambridge Stem Cell Institute, Jeffrey Cheah Biomedical Campus, University of Cambridge, Puddicombe Way, Cambridge, CB2 0AW, UK. Electronic address:

Remyelination is the regeneration of myelin sheaths following demyelination. This regenerative process is critical for the re-establishment of axonal conduction velocity and metabolic support to the axons. Successful remyelination in the CNS generally depends on the activation, proliferation, and differentiation of oligodendrocyte progenitor cells (OPCs). Read More

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http://dx.doi.org/10.1016/j.tins.2020.05.006DOI Listing

Toxin-Mediated siRNA Delivery.

Trends Pharmacol Sci 2020 Jun 30. Epub 2020 Jun 30.

Center for Nanomedicine and Division of Engineering in Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA; Harvard Medical School, Boston, MA 02115, USA. Electronic address:

AB toxins with built-in cell targeting and endosomal escape mechanisms are attractive intracellular delivery vehicles. However, their compatibility with nucleic-acid-based therapeutics is not fully explored. Arnold et al. Read More

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http://dx.doi.org/10.1016/j.tips.2020.06.006DOI Listing

Renal Cell Carcinoma: The Evolving Role of Imaging in the 21st Century.

Semin Ultrasound CT MR 2020 Aug 15;41(4):344-350. Epub 2020 May 15.

Department of Radiology, Royal Free Hospital, London, UK; Department of Radiology, University College London Hospitals NHS Foundation Trust, London, UK. Electronic address:

Kidney lesions are commonly an incidental finding on cross sectional studies carried out for a variety of reasons. The detection of renal cell carcinoma (RCC) has increased accordingly. There are a variety of different contrast-enhanced CT imaging protocols that have been developed to help diagnose and stage RCC. Read More

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http://dx.doi.org/10.1053/j.sult.2020.05.002DOI Listing

Quantile normalization of single-cell RNA-seq read counts without unique molecular identifiers.

Genome Biol 2020 Jul 3;21(1):160. Epub 2020 Jul 3.

Department of Data Sciences, Dana-Farber Cancer Institute, Boston, MA, USA.

Single-cell RNA-seq (scRNA-seq) profiles gene expression of individual cells. Unique molecular identifiers (UMIs) remove duplicates in read counts resulting from polymerase chain reaction, a major source of noise. For scRNA-seq data lacking UMIs, we propose quasi-UMIs: quantile normalization of read counts to a compound Poisson distribution empirically derived from UMI datasets. Read More

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http://dx.doi.org/10.1186/s13059-020-02078-0DOI Listing

Constructing an automatic diagnosis and severity-classification model for acromegaly using facial photographs by deep learning.

J Hematol Oncol 2020 Jul 3;13(1):88. Epub 2020 Jul 3.

Guangdong Provincial Key Laboratory of Brain-inspired Intelligent Computation, Department of Computer Science and Engineering, Southern University of Science and Technology, Shenzhen, 518055, China.

Due to acromegaly's insidious onset and slow progression, its diagnosis is usually delayed, thus causing severe complications and treatment difficulty. A convenient screening method is imperative. Based on our previous work, we herein developed a new automatic diagnosis and severity-classification model for acromegaly using facial photographs by deep learning on the data of 2148 photographs at different severity levels. Read More

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http://dx.doi.org/10.1186/s13045-020-00925-yDOI Listing

Novel multiplex real-time PCR assays reveal a high prevalence of diarrhoeagenic Escherichia coli pathotypes in healthy and diarrhoeal children in the south of Vietnam.

BMC Microbiol 2020 Jul 3;20(1):192. Epub 2020 Jul 3.

Cambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID) Department of Medicine, Cambridge Biomedical Campus, University of Cambridge, Cambridge, CB2 0AW, UK.

Background: Diarrhoeagenic Escherichia coli (DEC) infections are common in children in low-middle income countries (LMICs). However, detecting the various DEC pathotypes is complex as they cannot be differentiated by classical microbiology. We developed four multiplex real-time PCR assays were to detect virulence markers of six DEC pathotypes; specificity was tested using DEC controls and other enteric pathogens. Read More

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http://dx.doi.org/10.1186/s12866-020-01878-5DOI Listing