Featured
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Matters Arising
| Open AccessFormal reply to “Alternative lengthening of telomeres is not synonymous with mutations in ATRX/DAXX”
- Lars Feuerbach
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Article
| Open AccessPoint-of-care bulk testing for SARS-CoV-2 by combining hybridization capture with improved colorimetric LAMP
Current SARS-CoV-2 diagnostic methods are sensitive yet poorly suited to testing whole communities on a regular basis. Here the authors present Cap-iLAMP that tests gargle lavage samples with an improved colorimetric RT-LAMP.
- Lukas Bokelmann
- , Olaf Nickel
- & Stephan Riesenberg
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Article
| Open AccessExploring beyond clinical routine SARS-CoV-2 serology using MultiCoV-Ab to evaluate endemic coronavirus cross-reactivity
Serology is an important way to monitor SARS-CoV-2 infection in the population and support vaccine development. Here the authors develop a multiplex immunoassay including spike and nucleocapsid proteins of SARS-CoV-2 and the endemic human coronaviruses with high specificity and sensitivity.
- Matthias Becker
- , Monika Strengert
- & Nicole Schneiderhan-Marra
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Matters Arising
| Open AccessReply to ‘Hypothermic machine perfusion before viability testing of previously discarded human livers’
- Hynek Mergental
- , Richard W. Laing
- & Darius F. Mirza
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Article
| Open AccessFacilitation of molecular motion to develop turn-on photoacoustic bioprobe for detecting nitric oxide in encephalitis
Nitric oxide plays key roles in regulating many pathological processes and it is important to monitor NO and related diseases. Here, the authors report on the development of a molecular motion based NO responsive photoacoustic probe and demonstrate application in detecting encephalitis in vivo.
- Ji Qi
- , Leyan Feng
- & Ben Zhong Tang
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Article
| Open AccessA multiplex chemiluminescent immunoassay for serological profiling of COVID-19-positive symptomatic and asymptomatic patients
Antibody responses to SARS-CoV-2 may be important biomarkers for assessing the risk for viral transmission. Here the authors present serological antibody profiling results of COVID-19 patients using a new multiplex assay to show distinct kinetics and dynamics of IgG, IgM and IgA responses in patients with different disease severity.
- Allison N. Grossberg
- , Lilia A. Koza
- & Daniel A. Linseman
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Article
| Open AccessA glucose meter interface for point-of-care gene circuit-based diagnostics
Getting synthetic biology circuit-based sensors into field applications is still a challenge. Here the authors combine a circuit sensor with a glucose meter for small analyte and nucleic acid detection.
- Evan Amalfitano
- , Margot Karlikow
- & Keith Pardee
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Article
| Open AccessInterplay between chromosomal alterations and gene mutations shapes the evolutionary trajectory of clonal hematopoiesis
Patients with solid cancers have high rates of clonal haematopoiesis associated with increased risk of secondary leukemias. Here, by using peripheral blood sequencing data from patients with solid non-hematologic cancer, the authors profile the landscape of mosaic chromosomal alterations and gene mutations, defining patients at high risk of leukemia progression.
- Teng Gao
- , Ryan Ptashkin
- & Elli Papaemmanuil
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Article
| Open AccessSex-dimorphic genetic effects and novel loci for fasting glucose and insulin variability
Sex differences in fasting glucose and insulin have been identified, but the genetic loci underlying these differences have not. Here, the authors perform a meta-analysis of genome-wide association studies to detect sex-specific and sex-dimorphic loci associated with fasting glucose and insulin.
- Vasiliki Lagou
- , Reedik Mägi
- & Inga Prokopenko
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Article
| Open AccessAnalysis of SARS-CoV-2 antibodies in COVID-19 convalescent blood using a coronavirus antigen microarray
COVID-19 diagnosis is commonly performed by PCR testing, however, serologic methods are more accurate and versatile for monitoring disease burden and epidemiology. Here the authors report a protein microarray with antigens from SARS-CoV-2, SARS-CoV, MERS-CoV as well as common human respiratory viruses.
- Rafael R. de Assis
- , Aarti Jain
- & Saahir Khan
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Article
| Open AccessConcordant peripheral lipidome signatures in two large clinical studies of Alzheimer’s disease
The onset and pathology of Alzheimer’s disease (AD) is associated with changes to lipid metabolism. Here, the authors analysed 569 lipids from 32 classes and subclasses in two independent patient cohorts to identify key lipid pathways to link the plasma lipidome with AD and the future onset of AD.
- Kevin Huynh
- , Wei Ling Florence Lim
- & Peter J. Meikle
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Article
| Open AccessDistinct signatures of gut microbiome and metabolites associated with significant fibrosis in non-obese NAFLD
Nonalcoholic fatty liver disease (NAFLD) is associated with obesity but also found in individuals without obesity. Here, gut microbiome analysis using a biopsy-proven NAFLD cohort reveal distinct signatures of microbiome-metabolites associated with significant fibrosis in patients with NAFLD without obesity.
- Giljae Lee
- , Hyun Ju You
- & GwangPyo Ko
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Article
| Open AccessUltra-sensitive and rapid detection of nucleic acids and microorganisms in body fluids using single-molecule tethering
Culture-based diagnostic methods for microorganism detection are time-consuming but still the gold standard for conditions such as sepsis. Here the authors present an amplification and purification-free method to detect microorganisms in bodily fluids with high sensitivity: Single MOLecule Tethering (SMOLT).
- Wen-Chih Cheng
- , Troy Horn
- & Alfredo Celedon
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Article
| Open AccessSARS-CoV-2 seroprevalence and neutralizing activity in donor and patient blood
Highly accurate antibody tests for SARS-CoV-2 are needed for surveillance in low-prevalence populations. Here, the authors find seroprevalence of less than 1% in two San Francisco Bay Area populations at the beginning of April, and that seroreactivity is generally predictive of in vitro neutralising activity.
- Dianna L. Ng
- , Gregory M. Goldgof
- & Charles Y. Chiu
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Article
| Open AccessPurification of HCC-specific extracellular vesicles on nanosubstrates for early HCC detection by digital scoring
Extracellular vesicles (EVs) are present in circulation at relatively early stages of disease, providing potential opportunities for early cancer diagnosis. Here, the authors report a covalent chemistry-based hepatocellular carcinoma (HCC)-specific EV purification system for early detection of HCC by performing digital scoring on the purified EVs.
- Na Sun
- , Yi-Te Lee
- & Yazhen Zhu
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Article
| Open AccessDeep neural networks enable quantitative movement analysis using single-camera videos
In the context of diseases impairing movement, quantitative assessment of motion is critical to medical decision-making but is currently possible only with expensive motion capture systems and trained personnel. Here, the authors present a method for predicting clinically relevant motion parameters from an ordinary video of a patient.
- Łukasz Kidziński
- , Bryan Yang
- & Michael H. Schwartz
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Article
| Open AccessMachine learning-based prediction of acute coronary syndrome using only the pre-hospital 12-lead electrocardiogram
Diagnosing a heart attack requires excessive testing and prolonged observation, which frequently requires hospital admission. Here the authors report a machine learning-based system based exclusively on ECG data that can help clinicians identify 37% more heart attacks during initial screening.
- Salah Al-Zaiti
- , Lucas Besomi
- & Ervin Sejdić
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Article
| Open AccessTransplantation of discarded livers following viability testing with normothermic machine perfusion
The shortage of viable donated livers limits patient access to liver transplantation. Here the authors report the use of normothermic machine perfusion to help identify viable organs from livers discarded based on current clinical criteria, which are then transplanted to recipients in a single-arm clinical trial.
- Hynek Mergental
- , Richard W. Laing
- & Darius F. Mirza
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Article
| Open AccessComprehensive aptamer-based screening identifies a spectrum of urinary biomarkers of lupus nephritis across ethnicities
Developing noninvasive diagnostic biomarkers for lupus nephritis (LN) diagnosis is an important clinical goal. Here the authors identify urinary proteins correlated with active LN and disease severity, which differ across ethnicities but collectively outperform the current clinical method.
- Samantha Stanley
- , Kamala Vanarsa
- & Chandra Mohan
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Article
| Open AccessScavenger receptor-A is a biomarker and effector of rheumatoid arthritis: A large-scale multicenter study
Scavenger receptor-A (SR-A) is mostly expressed by myeloid cells and has been attributed a variety of biological functions. Here the authors assess SR-A as a biomarker for diagnosis of rheumatoid arthritis (RA) using large-scale training and validation cohorts and show that modulating SR-A levels can alter progression of collagen-induced arthritis in mice.
- Fanlei Hu
- , Xiang Jiang
- & Zhanguo Li
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Article
| Open AccessRe-definition of claudin-low as a breast cancer phenotype
In breast cancer, the claudin-low breast cancer subtype is remarkably diverse. Here, the authors propose that claudin-low is not a classical intrinsic breast cancer subtype, but rather a complex additional phenotype that can occur across intrinsic subtypes.
- Christian Fougner
- , Helga Bergholtz
- & Therese Sørlie
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Article
| Open AccessComputational analysis of pathological images enables a better diagnosis of TFE3 Xp11.2 translocation renal cell carcinoma
Translocation renal cell carcinoma is an aggressive form of renal cancer that is often misdiagnosed to other subtypes. Here the authors demonstrated that by using machine learning and H&E stained whole-slide images, an accurate diagnose of this particular type of renal cancer can be achieved.
- Jun Cheng
- , Zhi Han
- & Jie Zhang
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Article
| Open AccessCerebrospinal fluid p-tau217 performs better than p-tau181 as a biomarker of Alzheimer’s disease
Cerebrospinal fluid (CSF) p-tau181 (tau phosphorylated at threonine 181) is an established biomarker of Alzheimer’s disease (AD) reflecting abnormal tau metabolism in the AD brain. Here the authors demonstrate that CSF p-tau217 shows better performance as an AD biomarker than p-tau181.
- Shorena Janelidze
- , Erik Stomrud
- & Oskar Hansson
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Article
| Open AccessGPR56/ADGRG1 is associated with response to antidepressant treatment
It is not fully understood why some patients respond or do not respond to antidepressant treatment. Here the authors show that in the blood of individuals with depression, GPR56 expression increases in responders to antidepressant treatment, but not in non-responders.
- Raoul Belzeaux
- , Victor Gorgievski
- & Gustavo Turecki
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Article
| Open AccessA generalizable 29-mRNA neural-network classifier for acute bacterial and viral infections
Diagnosing acute infections based on transcriptional host response shows promise, but generalizability is wanting. Here, the authors use a co-normalization framework to train a classifier to diagnose acute infections and apply it to independent data on a targeted diagnostic platform.
- Michael B. Mayhew
- , Ljubomir Buturovic
- & Timothy E. Sweeney
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Article
| Open AccessA case report of multiple primary prostate tumors with differential drug sensitivity
Prostate cancer is often a multifocal disease but how best to manage this clinically remains unclear. Here, the authors report a single case study of a patient with two genetically diverse tumours which showed differential response to therapy.
- Scott Wilkinson
- , Stephanie A. Harmon
- & Adam G. Sowalsky
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Article
| Open AccessMetabolic dysregulation in vitamin E and carnitine shuttle energy mechanisms associate with human frailty
Risk of age-related chronic disorders and decrease in resilience is associated with ageing. Here the authors analyse the human blood metabolome and identify metabolites associated with frailty.
- Nicholas J. W. Rattray
- , Drupad K. Trivedi
- & Royston Goodacre
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Article
| Open AccessEvaluation of integrin αvβ6 cystine knot PET tracers to detect cancer and idiopathic pulmonary fibrosis
Knottin is a cystine knot peptide. Here, the authors develop a knottin-based tracer for positron emission tomography and demonstrate its ability to detect cancer and idiopathic pulmonary fibrosis through selective binding to integrin αvβ6.
- Richard H. Kimura
- , Ling Wang
- & Sanjiv S. Gambhir
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Article
| Open AccessSynthetic molecular recognition nanosensor paint for microalbuminuria
Microalbuminuria, a clinical marker associated with cancer and hypertension, defined by low albumin levels in the urine, is normally detected by immunoassay. Herein, a nanosensor paint was developed using a polymer to mimic fatty acid binding to albumin, transduced by carbon nanotube fluorescence.
- Januka Budhathoki-Uprety
- , Janki Shah
- & Daniel A. Heller
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Article
| Open AccessThe generation and use of recombinant extracellular vesicles as biological reference material
There is no universal reference material to develop extracellular vesicle (EV) separation methods and carry out calibration and normalization. Here the authors use HIV-derived gag proteins to assemble recombinant fluorescent EV as a trackable reference material resembling the physical and biochemical properties of sample EV.
- Edward Geeurickx
- , Joeri Tulkens
- & An Hendrix
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Article
| Open AccessZero-field nuclear magnetic resonance of chemically exchanging systems
Zero-field nuclear magnetic resonance can identify species and collective behaviors in mixtures without applied magnetic fields. Here the authors demonstrate its use for resolving proton exchange in ammonium and for the detection of hyperpolarized pyruvic acid, an important imaging biomarker.
- Danila A. Barskiy
- , Michael C. D. Tayler
- & Alexander Pines
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Article
| Open AccessMetabolite changes in blood predict the onset of tuberculosis
The tuberculosis pandemic requires new methods for diagnosing and containing infections prior to active disease. Here, the authors performed a multi-site observational study within sub-Saharan Africa and present serum and plasma metabolic signatures that can predict the onset of active TB with a high degree of sensitivity and specificity.
- January Weiner 3rd
- , Jeroen Maertzdorf
- & Sarah Zalwango
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Article
| Open AccessEpigenetically reprogrammed methylation landscape drives the DNA self-assembly and serves as a universal cancer biomarker
DNA methylation is an epigenetic modification that control genetic programs. Here, the authors found that the methylation landscape influences the physicochemical properties of DNA and that it can serve as a universal cancer biomarker, and developed a one-step assay for the detection of cancer DNA.
- Abu Ali Ibn Sina
- , Laura G. Carrascosa
- & Matt Trau
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Article
| Open AccessComprehensive human cell-type methylation atlas reveals origins of circulating cell-free DNA in health and disease
The methylation status of circulating cell-free DNA (cfDNA) can be informative about recent cell death events. Here the authors present an approach to determine the tissue origins of cfDNA, using a reference methylation atlas of 25 human tissues and cell types, and find that cfDNA from patients reveals tissue contributions that agree with clinical findings.
- Joshua Moss
- , Judith Magenheim
- & Yuval Dor
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Article
| Open AccessEnhanced mRNA FISH with compact quantum dots
FISH-based techniques to image and count mRNA in single cells can be limited by the photophysical properties of organic dyes. Here the authors develop photostable quantum dot FISH probes for multiplexed imaging.
- Yang Liu
- , Phuong Le
- & Andrew M. Smith
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Article
| Open AccessCerebello-thalamo-cortical hyperconnectivity as a state-independent functional neural signature for psychosis prediction and characterization
Brain function alterations in schizophrenia and other psychotic disorders remain poorly understood. Here, the authors discover that increased neural connectivity in the cerebello-thalamo-cortical circuitry predicts psychosis in those at high risk, and is present in people with schizophrenia.
- Hengyi Cao
- , Oliver Y. Chén
- & Tyrone D. Cannon
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Article
| Open AccessPreDicta chip-based high resolution diagnosis of rhinovirus-induced wheeze
Rhinovirus (RV) infections can trigger acute exacerbations of respiratory diseases. Here, Niespodziana et al. develop a PreDicta chip that identifies the culprit RV strain from small blood samples and show that RV-A and RV-C strains are associated with most severe symptoms.
- Katarzyna Niespodziana
- , Katarina Stenberg-Hammar
- & Rudolf Valenta
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Article
| Open AccessRecurrent rearrangements of FOS and FOSB define osteoblastoma
FOS has been linked to bone tumour pathogenesis, and viral homologue v-fos causes osteosarcoma in mice. Here, the authors report rearrangement of FOS and its paralogue FOSB in osteoblastoma and osteoid osteoma, revealing human bone tumours that are defined by mutations of FOS and FOSB.
- Matthew W. Fittall
- , William Mifsud
- & Sam Behjati
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Article
| Open AccessVariability in the location of high frequency oscillations during prolonged intracranial EEG recordings
High frequency oscillations (HFO) are a promising biomarker for identifying epileptogenic zones without the need to monitor spontaneous seizure episodes. Here the authors report that there is much variability in the location of HFOs offering a note of caution toward using HFO locations from short recordings as a guide for surgery.
- Stephen V. Gliske
- , Zachary T. Irwin
- & William C. Stacey
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Article
| Open AccessNon-invasive detection of human cardiomyocyte death using methylation patterns of circulating DNA
The detection of cardiomyocyte death is a critical aspect in the diagnosis and monitoring of heart diseases. Here the authors show that cardiomyocyte-specific methylation patterns of circulating cell-free DNA may serve as a biomarker of cardiac cell death in infarcted and septic patients.
- Hai Zemmour
- , David Planer
- & Yuval Dor
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Article
| Open AccessDynamic network biomarker indicates pulmonary metastasis at the tipping point of hepatocellular carcinoma
Biomarkers of the tipping point before metastasis in hepatocellular carcinoma (HCC) could help stratify patient treatment. Here, the authors study dynamic network biomarkers to identify CALM3 as a potential suppressor of metastasis, the level of which can predict overall survival and relapse-free survival in postoperative HCC.
- Biwei Yang
- , Meiyi Li
- & Jinglin Xia
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Article
| Open AccessNovel peptide probes to assess the tensional state of fibronectin fibers in cancer
The extracellular matrix is under variable strain, but we lack the tools to detect differences in strain. Here the authors develop a probe based on a bacterial fibronectin-binding peptide that binds to relaxed fibronectin fibrils and detects relaxed matrix in cell culture, tissue slices and in vivo.
- Simon Arnoldini
- , Alessandra Moscaroli
- & Viola Vogel
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Article
| Open AccessWhole blood stabilization for the microfluidic isolation and molecular characterization of circulating tumor cells
The current FDA-approved whole blood stabilization method for circulating tumor cell (CTC) isolation suffers from RNA degradation. Here the authors combine hypothermic preservation and antiplatelet strategies to stabilize whole blood up to 72 h without compromising CTC yield and RNA integrity.
- Keith H. K. Wong
- , Shannon N. Tessier
- & Mehmet Toner
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Article
| Open AccessTranscriptional signature of human pro-inflammatory TH17 cells identifies reduced IL10 gene expression in multiple sclerosis
CD4+ T cells secreting interleukin-17 (TH17) have diverse functions in modulating autoimmune diseases. Here the authors show via transcriptome analyses that a subset of human TH 17 co-expressing interferon-γ (TH1/17) has a molecular signature similar to “pathogenic” mouse TH 17 but distinct from “non-pathogenic” mouse TH 17.
- Dan Hu
- , Samuele Notarbartolo
- & Howard L. Weiner
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Article
| Open AccessEarliest accumulation of β-amyloid occurs within the default-mode network and concurrently affects brain connectivity
Abnormal levels of Aβ42 in the cerebrospinal fluid occur prior to a positive amyloid PET scan in the brain of individuals with Alzheimer’s disease and here the authors use this temporal pattern to identify individuals with very early stage AD. They show that Aβ fibrils start to accumulate in some of the regions of the default mode network and affect brain connectivity before neurodegeneration occurs.
- Sebastian Palmqvist
- , Michael Schöll
- & Oskar Hansson
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Article
| Open AccessNon-invasive assessment of hepatic mitochondrial metabolism by positional isotopomer NMR tracer analysis (PINTA)
Liver mitochondrial metabolism plays an important role for glucose and lipid homeostasis and its alterations contribute to metabolic disorders, including fatty liver and diabetes. Here Perry et al. develop a method for the measurement of hepatic fluxes by using lactate and glucose tracers in combination with NMR spectroscopy.
- Rachel J. Perry
- , Liang Peng
- & Gerald I. Shulman
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Article
| Open AccessIn vivo quantitative imaging of tumor pH by nanosonophore assisted multispectral photoacoustic imaging
Background optical absorption of several biomolecules impedes an effective in vivo pH imaging in tumors. Here, the authors developed a visible light-based in vivo pH mapping method by coupling photoacoustic imaging and pH-responsive modified nanoparticles that selectively target tumor cells.
- Janggun Jo
- , Chang H. Lee
- & Xueding Wang
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Article
| Open AccessBiochemical phosphates observed using hyperpolarized 31P in physiological aqueous solutions
Real-time monitoring of phosphate metabolism and distribution in the live body without ionizing radiation is highly desirable. Here, the authors show dissolution-dynamic nuclear polarization technology can enable nuclear magnetic resonance detection of hyperpolarized 31P of important biological phosphates in aqueous solutions.
- Atara Nardi-Schreiber
- , Ayelet Gamliel
- & Rachel Katz-Brull
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Article
| Open AccessDiagnosing peri-implant disease using the tongue as a 24/7 detector
Early detection of gum inflammation caused by dental implants helps prevent tissue damage. Here, the authors present a peptide sensor that generates a bitter taste when cleaved by proteases present in peri-implant disease, embed it in a chewing gum, and compare the probe to existing sensors using patient saliva.
- J. Ritzer
- , T. Lühmann
- & L. Meinel