9,551 results match your criteria Nature medicine[Journal]


Single-dose CRISPR-Cas9 therapy extends lifespan of mice with Hutchinson-Gilford progeria syndrome.

Nat Med 2019 Feb 18. Epub 2019 Feb 18.

Salk Institute for Biological Studies, La Jolla, CA, USA.

Hutchinson-Gilford progeria syndrome (HGPS) is a rare lethal genetic disorder characterized by symptoms reminiscent of accelerated aging. The major underlying genetic cause is a substitution mutation in the gene coding for lamin A, causing the production of a toxic isoform called progerin. Here we show that reduction of lamin A/progerin by a single-dose systemic administration of adeno-associated virus-delivered CRISPR-Cas9 components suppresses HGPS in a mouse model. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41591-019-0343-4DOI Listing
February 2019

Development of a CRISPR/Cas9-based therapy for Hutchinson-Gilford progeria syndrome.

Nat Med 2019 Feb 18. Epub 2019 Feb 18.

Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Instituto Universitario de Oncología del Principado de Asturias, Universidad de Oviedo, Oviedo, Spain.

CRISPR/Cas9-based therapies hold considerable promise for the treatment of genetic diseases. Among these, Hutchinson-Gilford progeria syndrome, caused by a point mutation in the LMNA gene, stands out as a potential candidate. Here, we explore the efficacy of a CRISPR/Cas9-based approach that reverts several alterations in Hutchinson-Gilford progeria syndrome cells and mice by introducing frameshift mutations in the LMNA gene. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41591-018-0338-6DOI Listing
February 2019

Long-term evaluation of AAV-CRISPR genome editing for Duchenne muscular dystrophy.

Nat Med 2019 Feb 18. Epub 2019 Feb 18.

Department of Biomedical Engineering, Duke University, Durham, NC, USA.

Duchenne muscular dystrophy (DMD) is a monogenic disorder and a candidate for therapeutic genome editing. There have been several recent reports of genome editing in preclinical models of Duchenne muscular dystrophy, however, the long-term persistence and safety of these genome editing approaches have not been addressed. Here we show that genome editing and dystrophin protein restoration is sustained in the mdx mouse model of Duchenne muscular dystrophy for 1 year after a single intravenous administration of an adeno-associated virus that encodes CRISPR (AAV-CRISPR). Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41591-019-0344-3DOI Listing
February 2019

Neoadjuvant anti-PD-1 immunotherapy promotes a survival benefit with intratumoral and systemic immune responses in recurrent glioblastoma.

Nat Med 2019 Feb 11. Epub 2019 Feb 11.

Department of Medical and Molecular Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.

Glioblastoma is the most common primary malignant brain tumor in adults and is associated with poor survival. The Ivy Foundation Early Phase Clinical Trials Consortium conducted a randomized, multi-institution clinical trial to evaluate immune responses and survival following neoadjuvant and/or adjuvant therapy with pembrolizumab in 35 patients with recurrent, surgically resectable glioblastoma. Patients who were randomized to receive neoadjuvant pembrolizumab, with continued adjuvant therapy following surgery, had significantly extended overall survival compared to patients that were randomized to receive adjuvant, post-surgical programmed cell death protein 1 (PD-1) blockade alone. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41591-018-0337-7DOI Listing
February 2019
2 Reads

Evaluation and accurate diagnoses of pediatric diseases using artificial intelligence.

Nat Med 2019 Feb 11. Epub 2019 Feb 11.

Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.

Artificial intelligence (AI)-based methods have emerged as powerful tools to transform medical care. Although machine learning classifiers (MLCs) have already demonstrated strong performance in image-based diagnoses, analysis of diverse and massive electronic health record (EHR) data remains challenging. Here, we show that MLCs can query EHRs in a manner similar to the hypothetico-deductive reasoning used by physicians and unearth associations that previous statistical methods have not found. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41591-018-0335-9DOI Listing
February 2019
1 Read

Neoadjuvant nivolumab modifies the tumor immune microenvironment in resectable glioblastoma.

Nat Med 2019 Feb 11. Epub 2019 Feb 11.

Centro de Investigación Biomedica en Red de Oncología (CIBERONC), Madrid, Spain.

Glioblastoma is the most common primary central nervous system malignancy and has a poor prognosis. Standard first-line treatment, which includes surgery followed by adjuvant radio-chemotherapy, produces only modest benefits to survival. Here, to explore the feasibility, safety and immunobiological effects of PD-1 blockade in patients undergoing surgery for glioblastoma, we conducted a single-arm phase II clinical trial (NCT02550249) in which we tested a presurgical dose of nivolumab followed by postsurgical nivolumab until disease progression or unacceptable toxicity in 30 patients (27 salvage surgeries for recurrent cases and 3 cases of primary surgery for newly diagnosed patients). Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41591-018-0339-5DOI Listing
February 2019
1 Read

Immune and genomic correlates of response to anti-PD-1 immunotherapy in glioblastoma.

Nat Med 2019 Feb 11. Epub 2019 Feb 11.

Department of Systems Biology, Columbia University, New York, NY, USA.

Immune checkpoint inhibitors have been successful across several tumor types; however, their efficacy has been uncommon and unpredictable in glioblastomas (GBM), where <10% of patients show long-term responses. To understand the molecular determinants of immunotherapeutic response in GBM, we longitudinally profiled 66 patients, including 17 long-term responders, during standard therapy and after treatment with PD-1 inhibitors (nivolumab or pembrolizumab). Genomic and transcriptomic analysis revealed a significant enrichment of PTEN mutations associated with immunosuppressive expression signatures in non-responders, and an enrichment of MAPK pathway alterations (PTPN11, BRAF) in responders. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41591-019-0349-yDOI Listing
February 2019
27.363 Impact Factor

Author Correction: Metformin inhibits gluconeogenesis via a redox-dependent mechanism in vivo.

Nat Med 2019 Feb 7. Epub 2019 Feb 7.

Department of Medicine, Yale University School of Medicine, New Haven, CT, USA.

In the version of this article originally published, the V and V flux data shown in Fig. 6e,f were inadvertently duplicated from Fig. 5j,k. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41591-018-0220-6DOI Listing
February 2019

Adding to the checkpoint blockade armamentarium.

Nat Med 2019 Feb;25(2):203-205

Merck, Rahway, NJ, USA.

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41591-019-0350-5DOI Listing
February 2019

No guts, no research glory.

Authors:
Eran Elinav

Nat Med 2019 Feb;25(2):196

Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41591-019-0342-5DOI Listing
February 2019

A life exposed (and better for it).

Authors:
Kjersti Aagaard

Nat Med 2019 Feb;25(2):195

Department of Obstetrics & Gynecology and Division of Maternal-Fetal Medicine, Baylor College of Medicine and Texas Children's Hospital, Houston, TX, USA.

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41591-019-0341-6DOI Listing
February 2019

Precision epidemiology for infectious disease control.

Nat Med 2019 Feb 6;25(2):206-211. Epub 2019 Feb 6.

Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA.

Advances in genomics and computing are transforming the capacity for the characterization of biological systems, and researchers are now poised for a precision-focused transformation in the way they prepare for, and respond to, infectious diseases. This includes the use of genome-based approaches to inform molecular diagnosis and individual-level treatment regimens. In addition, advances in the speed and granularity of pathogen genome generation have improved the capability to track and understand pathogen transmission, leading to potential improvements in the design and implementation of population-level public health interventions. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41591-019-0345-2DOI Listing
February 2019

Biomarkers for Alzheimer's disease beyond amyloid and tau.

Nat Med 2019 Feb;25(2):201-203

Dementia Research Centre, Box 16, National Hospital for Neurology and Neurosurgery, London, UK.

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41591-019-0348-zDOI Listing
February 2019

Positive selection.

Nat Med 2019 Feb;25(2):192-194

Nature Medicine, .

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41591-019-0351-4DOI Listing
February 2019

Transmission of Aβ seeds.

Authors:
Hannah Stower

Nat Med 2019 Feb;25(2):197

Nature Medicine, .

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41591-019-0364-zDOI Listing
February 2019

Personalizing metabolic disease therapies.

Authors:
Hannah Stower

Nat Med 2019 Feb;25(2):197

Nature Medicine, .

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41591-019-0365-yDOI Listing
February 2019

Sequencing for rapid response to Lassa fever.

Authors:
Hannah Stower

Nat Med 2019 Feb;25(2):197

Nature Medicine, .

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41591-019-0363-0DOI Listing
February 2019

Exome sequencing for chronic kidney disease diagnosis.

Authors:
Hannah Stower

Nat Med 2019 Feb;25(2):197

Nature Medicine, .

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41591-019-0361-2DOI Listing
February 2019

Detecting opioid overdoses with smartphones.

Authors:
Hannah Stower

Nat Med 2019 Feb;25(2):197

Nature Medicine, .

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41591-019-0362-1DOI Listing
February 2019

A framework for responsibility.

Authors:

Nat Med 2019 Feb;25(2):191

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41591-019-0352-3DOI Listing
February 2019

Publisher Correction: ApoE attenuates unresolvable inflammation by complex formation with activated C1q.

Nat Med 2019 Feb 4. Epub 2019 Feb 4.

Institute for Cardiovascular Prevention (IPEK), Ludwig-Maximilians-University, Munich, Germany.

In the version of this article originally published, a sentence was erroneously included in the author contributions, and information regarding second shared authorship was missing from the author contributions. The following should not have been included in the author contributions: "C.W. Read More

View Article

Download full-text PDF

Source
http://www.nature.com/articles/s41591-019-0378-6
Publisher Site
http://dx.doi.org/10.1038/s41591-019-0378-6DOI Listing
February 2019
2 Reads
27.363 Impact Factor

Gene therapy for retinal dystrophy.

Nat Med 2019 Feb;25(2):198-199

Sorbonne Université, INSERM, CNRS, Institut de la Vision, Paris, France.

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41591-019-0346-1DOI Listing
February 2019

Publisher Correction: Cannabinoid CB receptors in the amygdalar cholecystokinin glutamatergic afferents to nucleus accumbens modulate depressive-like behavior.

Nat Med 2019 Feb;25(2):350

Center for Neuroscience and Department of Neurology of Second Affiliated Hospital, NHC and CAMS Key Laboratory of Medical Neurobiology, Joint Institute for Genetics and Genome Medicine between Zhejiang University and University of Toronto, Zhejiang University School of Medicine, Hangzhou, China.

In the version of this article originally published, there were several errors in Fig. 4. In Fig. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41591-019-0372-zDOI Listing
February 2019
2 Reads

Publisher Correction: Calibration of CAR activation potential directs alternative T cell fates and therapeutic potency.

Nat Med 2019 Jan 28. Epub 2019 Jan 28.

Center for Cell Engineering and Immunology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

In the version of this article originally published, there was an error in the legend for Extended Data Fig. 7. The legend for panel f was originally: "f, FACS analysis of IL7R, CD62L and CD45RA expression on TRAC-1928ζ and TRAC-1XX CAR T cells at day 63 post CAR infusion (representative for at least n = 3 mice per group in one independent experiment). Read More

View Article

Download full-text PDF

Source
http://www.nature.com/articles/s41591-019-0360-3
Publisher Site
http://dx.doi.org/10.1038/s41591-019-0360-3DOI Listing
January 2019
2 Reads

ApoE attenuates unresolvable inflammation by complex formation with activated C1q.

Nat Med 2019 Jan 28. Epub 2019 Jan 28.

Institute for Cardiovascular Prevention (IPEK), Ludwig-Maximilians-University, Munich, Germany.

Apolipoprotein-E (ApoE) has been implicated in Alzheimer's disease, atherosclerosis, and other unresolvable inflammatory conditions but a common mechanism of action remains elusive. We found in ApoE-deficient mice that oxidized lipids activated the classical complement cascade (CCC), resulting in leukocyte infiltration of the choroid plexus (ChP). All human ApoE isoforms attenuated CCC activity via high-affinity binding to the activated CCC-initiating C1q protein (K~140-580 pM) in vitro, and C1q-ApoE complexes emerged as markers for ongoing complement activity of diseased ChPs, Aβ plaques, and atherosclerosis in vivo. Read More

View Article

Download full-text PDF

Source
http://www.nature.com/articles/s41591-018-0336-8
Publisher Site
http://dx.doi.org/10.1038/s41591-018-0336-8DOI Listing
January 2019
7 Reads
27.363 Impact Factor

Protection against tuberculosis by mucosal BCG administration.

Nat Med 2019 Feb;25(2):199-201

South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease & Molecular Medicine and Division of Immunology, Department of Pathology, University of Cape Town, Cape Town, South Africa.

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41591-019-0347-0DOI Listing
February 2019

Non-invasive prenatal sequencing for multiple Mendelian monogenic disorders using circulating cell-free fetal DNA.

Nat Med 2019 Jan 28. Epub 2019 Jan 28.

Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.

Current non-invasive prenatal screening is targeted toward the detection of chromosomal abnormalities in the fetus. However, screening for many dominant monogenic disorders associated with de novo mutations is not available, despite their relatively high incidence. Here we report on the development and validation of, and early clinical experience with, a new approach for non-invasive prenatal sequencing for a panel of causative genes for frequent dominant monogenic diseases. Read More

View Article

Download full-text PDF

Source
http://www.nature.com/articles/s41591-018-0334-x
Publisher Site
http://dx.doi.org/10.1038/s41591-018-0334-xDOI Listing
January 2019
5 Reads

Current and future influenza vaccines.

Nat Med 2019 Feb 28;25(2):212-220. Epub 2019 Jan 28.

Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo, Japan.

Although antiviral drugs and vaccines have reduced the economic and healthcare burdens of influenza, influenza epidemics continue to take a toll. Over the past decade, research on influenza viruses has revealed a potential path to improvement. The clues have come from accumulated discoveries from basic and clinical studies. Read More

View Article

Download full-text PDF

Source
http://www.nature.com/articles/s41591-018-0340-z
Publisher Site
http://dx.doi.org/10.1038/s41591-018-0340-zDOI Listing
February 2019
3 Reads

Identification of preexisting adaptive immunity to Cas9 proteins in humans.

Nat Med 2019 Feb 28;25(2):249-254. Epub 2019 Jan 28.

Department of Pediatrics, Stanford University, Stanford, CA, USA.

The CRISPR-Cas9 system is a powerful tool for genome editing, which allows the precise modification of specific DNA sequences. Many efforts are underway to use the CRISPR-Cas9 system to therapeutically correct human genetic diseases. The most widely used orthologs of Cas9 are derived from Staphylococcus aureus and Streptococcus pyogenes. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41591-018-0326-xDOI Listing
February 2019
1 Read
27.363 Impact Factor

Publisher Correction: Cardiologist-level arrhythmia detection and classification in ambulatory electrocardiograms using a deep neural network.

Nat Med 2019 Jan 24. Epub 2019 Jan 24.

Department of Computer Science, Stanford University, Stanford, CA, USA.

In the version of this article originally published, the x axis labels in Fig. 1a were incorrect. The labels originally were 'Specificity,' but should have been '1 - Specificity. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41591-019-0359-9DOI Listing
January 2019

Author Correction: Sequestration of T cells in bone marrow in the setting of glioblastoma and other intracranial tumors.

Nat Med 2019 Jan 22. Epub 2019 Jan 22.

Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, NC, USA.

In the version of this article originally published, the figure callout in this sentence was incorrect: "Furthermore, in S1P1-KI mice themselves, whereas PD-1 blockade was ineffectual as monotherapy, the effects of 4-1BB agonism and checkpoint blockade proved additive, with the combination prolonging median survival and producing a 50% long-term survival rate (Fig. 6f)." The callout should have been to Supplementary Fig. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41591-019-0355-0DOI Listing
January 2019
1 Read
27.363 Impact Factor

Development of a gene-editing approach to restore vision loss in Leber congenital amaurosis type 10.

Nat Med 2019 Feb 21;25(2):229-233. Epub 2019 Jan 21.

Editas Medicine, Cambridge, MA, USA.

Leber congenital amaurosis type 10 is a severe retinal dystrophy caused by mutations in the CEP290 gene. We developed EDIT-101, a candidate genome-editing therapeutic, to remove the aberrant splice donor created by the IVS26 mutation in the CEP290 gene and restore normal CEP290 expression. Key to this therapeutic, we identified a pair of Staphylococcus aureus Cas9 guide RNAs that were highly active and specific to the human CEP290 target sequence. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41591-018-0327-9DOI Listing
February 2019
1 Read

Serum neurofilament dynamics predicts neurodegeneration and clinical progression in presymptomatic Alzheimer's disease.

Nat Med 2019 Feb 21;25(2):277-283. Epub 2019 Jan 21.

German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany.

Neurofilament light chain (NfL) is a promising fluid biomarker of disease progression for various cerebral proteopathies. Here we leverage the unique characteristics of the Dominantly Inherited Alzheimer Network and ultrasensitive immunoassay technology to demonstrate that NfL levels in the cerebrospinal fluid (n = 187) and serum (n = 405) are correlated with one another and are elevated at the presymptomatic stages of familial Alzheimer's disease. Longitudinal, within-person analysis of serum NfL dynamics (n = 196) confirmed this elevation and further revealed that the rate of change of serum NfL could discriminate mutation carriers from non-mutation carriers almost a decade earlier than cross-sectional absolute NfL levels (that is, 16. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41591-018-0304-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6367005PMC
February 2019
9 Reads

Microbial network disturbances in relapsing refractory Crohn's disease.

Nat Med 2019 Feb 21;25(2):323-336. Epub 2019 Jan 21.

Maurice Müller Laboratories, Department for Biomedical Research, University of Bern, Bern, Switzerland.

Inflammatory bowel diseases (IBD) can be broadly divided into Crohn's disease (CD) and ulcerative colitis (UC) from their clinical phenotypes. Over 150 host susceptibility genes have been described, although most overlap between CD, UC and their subtypes, and they do not adequately account for the overall incidence or the highly variable severity of disease. Replicating key findings between two long-term IBD cohorts, we have defined distinct networks of taxa associations within intestinal biopsies of CD and UC patients. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41591-018-0308-zDOI Listing
February 2019
10 Reads

Prevention of tuberculosis infection and disease by local BCG in repeatedly exposed rhesus macaques.

Nat Med 2019 Feb 21;25(2):255-262. Epub 2019 Jan 21.

Biomedical Primate Research Centre, Rijswijk, the Netherlands.

Tuberculosis (TB) remains the deadliest infectious disease, and the widely used Bacillus Calmette-Guérin (BCG) vaccine fails to curb the epidemic. An improved vaccination strategy could provide a cost-effective intervention to break the transmission cycle and prevent antimicrobial resistance. Limited knowledge of the host responses critically involved in protective immunity hampers the development of improved TB vaccination regimens. Read More

View Article

Download full-text PDF

Source
http://www.nature.com/articles/s41591-018-0319-9
Publisher Site
http://dx.doi.org/10.1038/s41591-018-0319-9DOI Listing
February 2019
6 Reads

Intrabone hematopoietic stem cell gene therapy for adult and pediatric patients affected by transfusion-dependent ß-thalassemia.

Nat Med 2019 Feb 21;25(2):234-241. Epub 2019 Jan 21.

San Raffaele Telethon Institute for Gene Therapy (SR-TIGET), IRCCS San Raffaele Scientific Institute, Milan, Italy.

ß-thalassemia is caused by ß-globin gene mutations resulting in reduced (β) or absent (β) hemoglobin production. Patient life expectancy has recently increased, but the need for chronic transfusions in transfusion-dependent thalassemia (TDT) and iron chelation impairs quality of life. Allogeneic hematopoietic stem cell (HSC) transplantation represents the curative treatment, with thalassemia-free survival exceeding 80%. Read More

View Article

Download full-text PDF

Source
http://www.nature.com/articles/s41591-018-0301-6
Publisher Site
http://dx.doi.org/10.1038/s41591-018-0301-6DOI Listing
February 2019
4 Reads

Deciphering the genomic, epigenomic, and transcriptomic landscapes of pre-invasive lung cancer lesions.

Nat Med 2019 Jan 21. Epub 2019 Jan 21.

Lungs for Living Research Centre, UCL Respiratory, University College London, London, UK.

The molecular alterations that occur in cells before cancer is manifest are largely uncharted. Lung carcinoma in situ (CIS) lesions are the pre-invasive precursor to squamous cell carcinoma. Although microscopically identical, their future is in equipoise, with half progressing to invasive cancer and half regressing or remaining static. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41591-018-0323-0DOI Listing
January 2019
1 Read

Small-molecule targeting of brachyury transcription factor addiction in chordoma.

Nat Med 2019 Feb 21;25(2):292-300. Epub 2019 Jan 21.

Broad Institute of Harvard and MIT, Cambridge, MA, USA.

Chordoma is a primary bone cancer with no approved therapy. The identification of therapeutic targets in this disease has been challenging due to the infrequent occurrence of clinically actionable somatic mutations in chordoma tumors. Here we describe the discovery of therapeutically targetable chordoma dependencies via genome-scale CRISPR-Cas9 screening and focused small-molecule sensitivity profiling. Read More

View Article

Download full-text PDF

Source
http://www.nature.com/articles/s41591-018-0312-3
Publisher Site
http://dx.doi.org/10.1038/s41591-018-0312-3DOI Listing
February 2019
12 Reads

Cannabinoid CB receptors in the amygdalar cholecystokinin glutamatergic afferents to nucleus accumbens modulate depressive-like behavior.

Nat Med 2019 Feb 14;25(2):337-349. Epub 2019 Jan 14.

Center for Neuroscience and Department of Neurology of Second Affiliated Hospital, NHC and CAMS Key Laboratory of Medical Neurobiology, Joint Institute for Genetics and Genome Medicine between Zhejiang University and University of Toronto, Zhejiang University School of Medicine, Hangzhou, China.

Major depressive disorder is a devastating psychiatric disease that afflicts up to 17% of the world's population. Postmortem brain analyses and imaging studies of patients with depression have implicated basal lateral amygdala (BLA) dysfunction in the pathophysiology of depression. However, the circuit and molecular mechanisms through which BLA neurons modulate depressive behavior are largely uncharacterized. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41591-018-0299-9DOI Listing
February 2019
2 Reads

Healthy infants harbor intestinal bacteria that protect against food allergy.

Nat Med 2019 Jan 14. Epub 2019 Jan 14.

Department of Pathology and Committee on Immunology, The University of Chicago, Chicago, IL, USA.

There has been a striking generational increase in life-threatening food allergies in Westernized societies. One hypothesis to explain this rising prevalence is that twenty-first century lifestyle practices, including misuse of antibiotics, dietary changes, and higher rates of Caesarean birth and formula feeding have altered intestinal bacterial communities; early-life alterations may be particularly detrimental. To better understand how commensal bacteria regulate food allergy in humans, we colonized germ-free mice with feces from healthy or cow's milk allergic (CMA) infants. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41591-018-0324-zDOI Listing
January 2019
1 Read

Blood-brain barrier breakdown is an early biomarker of human cognitive dysfunction.

Nat Med 2019 Feb 14;25(2):270-276. Epub 2019 Jan 14.

Department of Physiology and Neuroscience, Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.

Vascular contributions to cognitive impairment are increasingly recognized as shown by neuropathological, neuroimaging, and cerebrospinal fluid biomarker studies. Moreover, small vessel disease of the brain has been estimated to contribute to approximately 50% of all dementias worldwide, including those caused by Alzheimer's disease (AD). Vascular changes in AD have been typically attributed to the vasoactive and/or vasculotoxic effects of amyloid-β (Aβ), and more recently tau. Read More

View Article

Download full-text PDF

Source
http://www.nature.com/articles/s41591-018-0297-y
Publisher Site
http://dx.doi.org/10.1038/s41591-018-0297-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6367058PMC
February 2019
6 Reads
27.363 Impact Factor

Tumor-educated B cells selectively promote breast cancer lymph node metastasis by HSPA4-targeting IgG.

Nat Med 2019 Feb 14;25(2):312-322. Epub 2019 Jan 14.

National Key Laboratory of Medical Immunology & Institute of Immunology, Second Military Medical University, Shanghai, China.

Primary tumors may create the premetastatic niche in secondary organs for subsequent metastasis. Humoral immunity contributes to the progression of certain cancers, but the roles of B cells and their derived antibodies in premetastatic niche formation are poorly defined. Using a mouse model of spontaneous lymph node metastasis of breast cancer, we show that primary tumors induced B cell accumulation in draining lymph nodes. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41591-018-0309-yDOI Listing
February 2019
1 Read
27.363 Impact Factor

Translation control of the immune checkpoint in cancer and its therapeutic targeting.

Nat Med 2019 Feb 14;25(2):301-311. Epub 2019 Jan 14.

Department of Urology, University of California, San Francisco, San Francisco, CA, USA.

Cancer cells develop mechanisms to escape immunosurveillance, among which modulating the expression of immune suppressive messenger RNAs is most well-documented. However, how this is molecularly achieved remains largely unresolved. Here, we develop an in vivo mouse model of liver cancer to study oncogene cooperation in immunosurveillance. Read More

View Article

Download full-text PDF

Source
http://www.nature.com/articles/s41591-018-0321-2
Publisher Site
http://dx.doi.org/10.1038/s41591-018-0321-2DOI Listing
February 2019
33 Reads
27.363 Impact Factor

Biomimetic 3D-printed scaffolds for spinal cord injury repair.

Nat Med 2019 Feb 14;25(2):263-269. Epub 2019 Jan 14.

Department of Neuroscience, University of California San Diego, La Jolla, CA, USA.

Current methods for bioprinting functional tissue lack appropriate biofabrication techniques to build complex 3D microarchitectures essential for guiding cell growth and promoting tissue maturation. 3D printing of central nervous system (CNS) structures has not been accomplished, possibly owing to the complexity of CNS architecture. Here, we report the use of a microscale continuous projection printing method (μCPP) to create a complex CNS structure for regenerative medicine applications in the spinal cord. Read More

View Article

Download full-text PDF

Source
http://www.nature.com/articles/s41591-018-0296-z
Publisher Site
http://dx.doi.org/10.1038/s41591-018-0296-zDOI Listing
February 2019
7 Reads

High-performance medicine: the convergence of human and artificial intelligence.

Authors:
Eric J Topol

Nat Med 2019 Jan 7;25(1):44-56. Epub 2019 Jan 7.

Department of Molecular Medicine, Scripps Research, La Jolla, CA, USA.

The use of artificial intelligence, and the deep-learning subtype in particular, has been enabled by the use of labeled big data, along with markedly enhanced computing power and cloud storage, across all sectors. In medicine, this is beginning to have an impact at three levels: for clinicians, predominantly via rapid, accurate image interpretation; for health systems, by improving workflow and the potential for reducing medical errors; and for patients, by enabling them to process their own data to promote health. The current limitations, including bias, privacy and security, and lack of transparency, along with the future directions of these applications will be discussed in this article. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41591-018-0300-7DOI Listing
January 2019

Medicine in the digital age.

Authors:

Nat Med 2019 Jan;25(1)

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41591-018-0322-1DOI Listing
January 2019

A call for deep-learning healthcare.

Nat Med 2019 Jan;25(1):14-15

Bakar Computational Health Sciences Institute, University of California San Francisco, San Francisco, CA, USA.

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41591-018-0320-3DOI Listing
January 2019

The practical implementation of artificial intelligence technologies in medicine.

Nat Med 2019 Jan 7;25(1):30-36. Epub 2019 Jan 7.

Department of Thoracic Surgery/Oncology, First Affiliated Hospital of Guangzhou Medical University, China State Key Laboratory and National Clinical Research Center for Respiratory Disease, Guangzhou, China.

The development of artificial intelligence (AI)-based technologies in medicine is advancing rapidly, but real-world clinical implementation has not yet become a reality. Here we review some of the key practical issues surrounding the implementation of AI into existing clinical workflows, including data sharing and privacy, transparency of algorithms, data standardization, and interoperability across multiple platforms, and concern for patient safety. We summarize the current regulatory environment in the United States and highlight comparisons with other regions in the world, notably Europe and China. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41591-018-0307-0DOI Listing
January 2019
2 Reads

A guide to deep learning in healthcare.

Nat Med 2019 Jan 7;25(1):24-29. Epub 2019 Jan 7.

Google Research, San Jose, CA, USA.

Here we present deep-learning techniques for healthcare, centering our discussion on deep learning in computer vision, natural language processing, reinforcement learning, and generalized methods. We describe how these computational techniques can impact a few key areas of medicine and explore how to build end-to-end systems. Our discussion of computer vision focuses largely on medical imaging, and we describe the application of natural language processing to domains such as electronic health record data. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41591-018-0316-zDOI Listing
January 2019
1 Read