Abstract:
:Support from human genetics increases the probability of success in drug development. However, few examples exist of successful genomically-driven drug repositioning. Given that a Mendelian form of severe enterocolitis is due to up-regulation of the interleukin-18 (IL18) signaling pathway, and pharmacologic inhibition of IL18 has been shown to reverse this enterocolitis, we undertook a Mendelian randomization study to test the causal effect of elevated IL18 levels on inflammatory bowel disease susceptibility (IBD) in 12,882 cases and 21,770 controls. Mendelian randomization is an established method to assess the role of biomarkers in disease etiology in a manner that minimizes confounding and prevents reverse causation. Using three SNPs that explained almost 7% of the variance in IL18 level, we found that each genetically predicted standard deviation increase in IL18 was associated with an increase in IBD susceptibility (odds ratio = 1.22, 95% CI = 1.11-1.34, P-value = 6 × 10-5). This association was further validated in 25,042 IBD cases and 34,915 controls (odds ratio = 1.13, 95% CI = 1.05-1.20). Recently, an anti-IL18 monoclonal antibody, which decreased free IL18 levels, was found to be safe, yet ineffective in a phase II trial for type 2 diabetes. Taken together, these genomic findings implicated IBD as an alternative indication for anti-IL18 therapy, which should be tested in randomized controlled trials.
journal_name
Sci Repjournal_title
Scientific reportsauthors
Mokry LE,Zhou S,Guo C,Scott RA,Devey L,Langenberg C,Wareham N,Waterworth D,Cardon L,Sanseau P,Davey Smith G,Richards JBdoi
10.1038/s41598-019-45747-2subject
Has Abstractpub_date
2019-06-28 00:00:00pages
9386issue
1issn
2045-2322pii
10.1038/s41598-019-45747-2journal_volume
9pub_type
杂志文章abstract::In this study, the effect of post-deposition tetrafluoromethane (CF4) plasma treatment on the physical and electrical characteristics of an In2TiO5 based electrolyte-insulator-semiconductor (EIS) sensor was investigated. Post-deposition CF4 plasma treatment typically improved the crystalline structure and repaired dan...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-019-39012-9
更新日期:2019-02-28 00:00:00
abstract::O antigen (O-Ag) in many bacteria is synthesized via the Wzx/Wzy-dependent pathway in which Wzy polymerizes lipid-linked O-Ag subunits to modal lengths regulated by Wzz. Characterization of 83 site-directed mutants of Wzy from Pseudomonas aeruginosa PAO1 (WzyPa) in topologically-mapped periplasmic (PL) and cytoplasmic...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep03441
更新日期:2013-12-06 00:00:00
abstract::The healthy adult heart primarily relies on fatty acid oxidation (FAO) for energy production but instantaneously adapts its substrate preference in response to physiological or pathological challenges. Accurate FAO measurements are crucial to investigate early metabolic (mal)adaptations. While measurements in intact c...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-018-19478-9
更新日期:2018-01-24 00:00:00
abstract::Complex Semi-Definite Programming (SDP) is introduced as a novel approach to phase retrieval enabled control of monochromatic light transmission through highly scattering media. In a simple optical setup, a spatial light modulator is used to generate a random sequence of phase-modulated wavefronts, and the resulting i...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-017-02716-x
更新日期:2017-05-31 00:00:00
abstract::With aging, less blue light reaches the retina due to gradual yellowing of the lens. This could result in reduced activation of blue light-sensitive melanopsin-containing retinal ganglion cells, which mediate non-visual light responses (e.g., the pupillary light reflex, melatonin suppression, and circadian resetting)....
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep43832
更新日期:2017-03-07 00:00:00
abstract::Choosing an option increases a person's preference for that option. This phenomenon, called choice-based learning (CBL), has been investigated separately in the contexts of internally guided decision-making (IDM, e.g., preference judgment), for which no objectively correct answer exists, and externally guided decision...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep32477
更新日期:2016-08-31 00:00:00
abstract::Dietary information is lacking in most of small to mid-sized carnivores due to their elusive predatory behaviour and versatile feeding habits. The leopard cat (LPC; Prionailurus bengalensis) and the Asiatic golden cat (AGC; Catopuma temminckii) are two important yet increasingly endangered carnivore species in the tem...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep41909
更新日期:2017-02-14 00:00:00
abstract::Fluorescence lifetime imaging microscopy (FLIM) is a key technology that provides direct insight into cell metabolism, cell dynamics and protein activity. However, determining the lifetimes of different fluorescent proteins requires the detection of a relatively large number of photons, hence slowing down total acquis...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-020-77737-0
更新日期:2020-12-02 00:00:00
abstract::Diffusion processes are widespread in biological and chemical systems, where they play a fundamental role in the exchange of substances at the cellular level and in determining the rate of chemical reactions. Recently, the classical picture that portrays diffusion as random uncorrelated motion of molecules has been re...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep14486
更新日期:2015-09-30 00:00:00
abstract::Peritoneal macrophages play a critical role in the control of infectious and inflammatory diseases. Although recent progress on murine peritoneal macrophages has revealed multiple aspects on their origin and mechanisms involved in their maintenance in this compartment, little is known on the characteristics of human p...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-018-30787-x
更新日期:2018-08-24 00:00:00
abstract::HIV-1 latency generates reservoirs that prevent viral eradication by the current therapies. To find strategies toward an HIV cure, detailed understandings of the molecular mechanisms underlying establishment and persistence of the reservoirs are needed. The cellular transcription factor KAP1 is known as a potent repre...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-021-82164-w
更新日期:2021-01-29 00:00:00
abstract::We show how adaptive protocols of quantum and private communication through bosonic Gaussian channels can be simplifed into much easier block versions that involve resource states with finite energy. This is achieved by combining an adaptive-to-block reduction technique devised earlier, based on teleportation stretchi...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-018-33332-y
更新日期:2018-10-15 00:00:00
abstract::This work highlights the possibility of using microstructured fibres with predefined doped regions to produce functional microstructures at a fibre facet with differential chemical etching. A specially designed silica microstructured fibre (MSF) that possesses specific boron-doped silica regions was fabricated for the...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep21279
更新日期:2016-02-19 00:00:00
abstract::Accumulating evidence indicates that cancer cells show specific alterations in phospholipid metabolism that contribute to tumour progression in several types of cancer, including colorectal cancer. Questions still remain as to what lipids characterize the outer edge of cancer tissues and whether those cancer outer edg...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep29935
更新日期:2016-07-20 00:00:00
abstract::Procalcitonin (PCT) is a useful marker for the diagnosis of systemic inflammatory response syndrome. In addition, PCT is affected by renal function. However, few studies have investigated the relationship between PCT and the development of acute kidney injury (AKI). Hence, we investigated whether serum PCT levels at t...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-019-41291-1
更新日期:2019-03-18 00:00:00
abstract::A mathematical model is proposed for the autonomic control of cardiovascular system, which takes into account two separated self-exciting sympathetic control loops of heart rate and peripheral vascular tone. The control loops are represented by self-exciting time-delay systems and their tone depends on activity of the...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-020-71532-7
更新日期:2020-10-05 00:00:00
abstract::Interactions between microalgae and bacteria are often obligatory for harmful algal blooms (HABs). Here, we investigated the specific bacterial communities associated with Alexandrium tamarense and Cochlodinium polykrikoides, which cause ecological and economic damage during their blooms. To this end, the bacterial me...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-018-23634-6
更新日期:2018-03-28 00:00:00
abstract::Evidence showed preventive impacts of the highly active antiretroviral therapy (HAART) on the Human Immunodeficiency Virus (HIV) transmission amomg heterosexual population, however, that is of deficit among men who have sex with men (MSM). The aim was to systematically examine the efficacy of HAART on HIV transmission...
journal_title:Scientific reports
pub_type: 杂志文章,meta分析
doi:10.1038/s41598-019-56530-8
更新日期:2020-01-23 00:00:00
abstract::Bioartificial livers (BAL) may offer acute liver failure (ALF) patients an opportunity for cure without liver transplantation. We evaluated the efficacy of a spheroid-based BAL system, containing aggregates of porcine hepatocytes, in a porcine model of ALF. ALF pigs were divided into three groups. The control group co...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-017-03424-2
更新日期:2017-06-19 00:00:00
abstract::The transition energies and formation energies of N, C, F, Cl, and S as substitutional dopants in Ag3PO4 are studied using first-principles calculations based on the hybrid Hartree-Fock density functional, which correctly reproduces the band gap and thus provides the accurate defect states. Our results show that NO an...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep12750
更新日期:2015-08-03 00:00:00
abstract::We investigated a recovery pattern in subjective and objective measures among 52 patients with cubital tunnel syndrome after anterior subcutaneous transposition of the ulnar nerve. Disabilities of the Arm, Shoulder and Hand (DASH) score (primary outcome), numbness score, grip and pinch strength, Semmes-Weinstein (SW) ...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep27497
更新日期:2016-06-06 00:00:00
abstract::Tuberous sclerosis complex (TSC) is a rare autosomal dominant disorder causing benign tumors in the brain and other vital organs. The genes implicated in disease development are TSC1 and TSC2. Here, we have performed mutational analysis followed by a genotype-phenotype correlation study based on the clinical character...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-017-16988-w
更新日期:2017-12-01 00:00:00
abstract::We investigate whether the collapse of the quantum state of a single photon split between two space-like separated places takes a nonvanishing time. We realize this by using a source of heralded single photons, then splitting the resulting single photon state and letting it propagate over distances much larger than th...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-019-48387-8
更新日期:2019-08-15 00:00:00
abstract::MCM7, a subunit of mini-chromosome maintenance proteins (MCM) complex, plays an important role in initiating DNA replication during the G1 phase and extending DNA strands during the S phase. Here, we demonstrated that MCM7 is not only sustained but maintains association with chromatin during M phase. Remarkably, MCM7 ...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-017-03148-3
更新日期:2017-06-06 00:00:00
abstract::The fungus-growing ant-microbe symbiosis is an ideal system to study chemistry-based microbial interactions due to the wealth of microbial interactions described, and the lack of information on the molecules involved therein. In this study, we employed a combination of MALDI imaging mass spectrometry (MALDI-IMS) and M...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-017-05515-6
更新日期:2017-07-17 00:00:00
abstract::Albuminuria is widely used to indicate early phases of diabetic nephropathy although it is limited by the fact that structural damage might precede albumin excretion. This necessitates identifying better biomarkers that diagnose or predict diabetic nephropathy. This is a cross-sectional hospital based study recruiting...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-017-02421-9
更新日期:2017-06-02 00:00:00
abstract::A significant advantage of a graphene biosensor is that it inherently represents a continuum of independent and aligned sensor-units. We demonstrate a nanoscale version of a micro-physiometer - a device that measures cellular metabolic activity from the local acidification rate. Graphene functions as a matrix of indep...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep06865
更新日期:2014-10-31 00:00:00
abstract::In this contribution, a complete dissertation concerning the behavior of a Long Period Grating (LPG) inscribed in a B-Ge co-doped optical fiber by means of an excimer laser and exposed to proton irradiation during a recent extensive campaign performed at the European Organization for Nuclear Research (CERN) with a flu...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-020-58049-9
更新日期:2020-01-28 00:00:00
abstract::Increasing levels of human activity threaten wildlife populations through direct mortality, habitat degradation, and habitat fragmentation. Area closures can improve habitat quality for wildlife, but may be difficult to achieve where tourism or other economic drivers are a priority. Temporal closures that limit human ...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-019-40581-y
更新日期:2019-03-07 00:00:00
abstract::The Pregnane X Receptor (PXR) is a ligand-activated transcription factor belonging to the nuclear receptor family. PXR can bind diverse drugs and environmental toxicants with different binding modes, making it an intriguing target for drug discovery. Here we investigated the binding mechanism of the SR12813 ligand to ...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-018-34373-z
更新日期:2018-11-01 00:00:00