Faculty (United Kingdom)

BACKGROUND: Men with high serum prostate specific antigen usually undergo transrectal ultrasound-guided prostate biopsy (TRUS-biopsy). TRUS-biopsy can cause side-effects including bleeding, pain, and infection. Multi-parametric magnetic resonance imaging (MP-MRI) used as a triage test might allow men to avoid unnecessary TRUS-biopsy and improve diagnostic accuracy. METHODS: We did this multicentre, paired-cohort, confirmatory study to test diagnostic accuracy of MP-MRI and TRUS-biopsy against a reference test (template prostate mapping biopsy [TPM-biopsy]). Men with prostate-specific antigen concentrations up to 15 ng/mL, with no previous biopsy, underwent 1·5 Tesla MP-MRI followed by both TRUS-biopsy and TPM-biopsy. The conduct and reporting of each test was done blind to other test results. Clinically significant cancer was defined as Gleason score ≥4 + 3 or a maximum cancer core length 6 mm or longer. This study is registered on ClinicalTrials.gov, NCT01292291. FINDINGS: Between May 17, 2012, and November 9, 2015, we enrolled 740 men, 576 of whom underwent 1·5 Tesla MP-MRI followed by both TRUS-biopsy and TPM-biopsy. On TPM-biopsy, 408 (71%) of 576 men had cancer with 230 (40%) of 576 patients clinically significant. For clinically significant cancer, MP-MRI was more sensitive (93%, 95% CI 88-96%) than TRUS-biopsy (48%, 42-55%; p<0·0001) and less specific (41%, 36-46% for MP-MRI vs 96%, 94-98% for TRUS-biopsy; p<0·0001). 44 (5·9%) of 740 patients reported serious adverse events, including 8 cases of sepsis. INTERPRETATION: Using MP-MRI to triage men might allow 27% of patients avoid a primary biopsy and diagnosis of 5% fewer clinically insignificant cancers. If subsequent TRUS-biopsies were directed by MP-MRI findings, up to 18% more cases of clinically significant cancer might be detected compared with the standard pathway of TRUS-biopsy for all. MP-MRI, used as a triage test before first prostate biopsy, could reduce unnecessary biopsies by a quarter. MP-MRI can also reduce over-diagnosis of clinically insignificant prostate cancer and improve detection of clinically significant cancer. FUNDING: PROMIS is funded by the UK Government Department of Health, National Institute of Health Research-Health Technology Assessment Programme, (Project number 09/22/67). This project is also supported and partly funded by UCLH/UCL Biomedical Research Centre and The Royal Marsden and Institute for Cancer Research Biomedical Research Centre and is coordinated by the Medical Research Council Clinical Trials Unit (MRC CTU) at UCL. It is sponsored by University College London (UCL).

Capacitive deionization (CDI) is a promising technology for water desalination that has seen tremendous advances over the past five years.

New achievements in the realm of nanoscience and innovative techniques of nanomedicine have moved micro/nanoparticles (MNPs) to the point of becoming actually useful for practical applications in the near future. Various differences between the extracellular and intracellular environments of cancerous and normal cells and the particular characteristics of tumors such as physicochemical properties, neovasculature, elasticity, surface electrical charge, and pH have motivated the design and fabrication of inventive "smart" MNPs for stimulus-responsive controlled drug release. These novel MNPs can be tailored to be responsive to pH variations, redox potential, enzymatic activation, thermal gradients, magnetic fields, light, and ultrasound (US), or can even be responsive to dual or multi-combinations of different stimuli. This unparalleled capability has increased their importance as site-specific controlled drug delivery systems (DDSs) and has encouraged their rapid development in recent years. An in-depth understanding of the underlying mechanisms of these DDS approaches is expected to further contribute to this groundbreaking field of nanomedicine. Smart nanocarriers in the form of MNPs that can be triggered by internal or external stimulus are summarized and discussed in the present review, including pH-sensitive peptides and polymers, redox-responsive micelles and nanogels, thermo- or magnetic-responsive nanoparticles (NPs), mechanical- or electrical-responsive MNPs, light or ultrasound-sensitive particles, and multi-responsive MNPs including dual stimuli-sensitive nanosheets of graphene. This review highlights the recent advances of smart MNPs categorized according to their activation stimulus (physical, chemical, or biological) and looks forward to future pharmaceutical applications.

The InterPro database (http://www.ebi.ac.uk/interpro/) is a freely available resource that can be used to classify sequences into protein families and to predict the presence of important domains and sites. Central to the InterPro database are predictive models, known as signatures, from a range of different protein family databases that have different biological focuses and use different methodological approaches to classify protein families and domains. InterPro integrates these signatures, capitalizing on the respective strengths of the individual databases, to produce a powerful protein classification resource. Here, we report on the status of InterPro as it enters its 15th year of operation, and give an overview of new developments with the database and its associated Web interfaces and software. In particular, the new domain architecture search tool is described and the process of mapping of Gene Ontology terms to InterPro is outlined. We also discuss the challenges faced by the resource given the explosive growth in sequence data in recent years. InterPro (version 48.0) contains 36,766 member database signatures integrated into 26,238 InterPro entries, an increase of over 3993 entries (5081 signatures), since 2012.

Neurotransmission in the hippocampus is modulated variously through presynaptic metabotropic glutamate receptors (mGluRs). To establish the precise localization of presynaptic mGluRs in the rat hippocampus, we used subtype-specific antibodies for eight mGluRs (mGluR1–mGluR8) for immunohistochemistry combined with lesioning of the three major hippocampal pathways: the perforant path, mossy fiber, and Schaffer collateral. Immunoreactivity for group II (mGluR2) and group III (mGluR4a, mGluR7a, mGluR7b, and mGluR8) mGluRs was predominantly localized to presynaptic elements, whereas that for group I mGluRs (mGluR1 and mGluR5) was localized to postsynaptic elements. The medial perforant path was strongly immunoreactive for mGluR2 and mGluR7a throughout the hippocampus, and the lateral perforant path was prominently immunoreactive for mGluR8 in the dentate gyrus and CA3 area. The mossy fiber was labeled for mGluR2, mGluR7a, and mGluR7b, whereas the Schaffer collateral was labeled only for mGluR7a. Electron microscopy further revealed the spatial segregation of group II and group III mGluRs within presynaptic elements. Immunolabeling for the group III receptors was predominantly observed in presynaptic active zones of asymmetrical and symmetrical synapses, whereas that for the group II receptor (mGluR2) was found in preterminal rather than terminal portions of axons. Target cell-specific segregation of receptors, first reported for mGluR7a (Shigemoto et al., 1996), was also apparent for the other group III mGluRs, suggesting that transmitter release is differentially regulated by 2-amino-4-phosphonobutyrate-sensitive mGluRs in individual synapses on single axons according to the identity of postsynaptic neurons.

Polyoxometalate (POM)-based metal-organic framework (MOF) materials contain POM units and generally generate MOF materials with open networks. POM-based MOF materials, which utilize the advantages of both POMs and MOFs, have received increasing attention, and much effort has been devoted to their preparation and relevant applications over the past few decades. They have good prospects in catalysis owing to the electronic and physical properties of POMs that are tunable by varying constituent elements. In this review, we present recent developments in porous POM-based MOF materials, including their classification, synthesis strategies, and applications, especially in the field of catalysis.

L. (turmeric) rhizome, has been used for centuries for culinary and food coloring purposes, and as an ingredient for various medicinal preparations, widely used in Ayurveda and Chinese medicine. In recent decades, their biological activities have been extensively studied. Thus, this review aims to offer an in-depth discussion of curcumin applications for food and biotechnological industries, and on health promotion and disease prevention, with particular emphasis on its antioxidant, anti-inflammatory, neuroprotective, anticancer, hepatoprotective, and cardioprotective effects. Bioavailability, bioefficacy and safety features, side effects, and quality parameters of curcumin are also addressed. Finally, curcumin's multidimensional applications, food attractiveness optimization, agro-industrial procedures to offset its instability and low bioavailability, health concerns, and upcoming strategies for clinical application are also covered.

Entry and progression through mitosis has traditionally been linked directly to the activity of cyclin-dependent kinase 1 (Cdk1). In this study we utilized low doses of the Cdk1-specific inhibitor, RO3306 from early G 2 phase onwards. Addition of low doses of RO3306 in G 2 phase induced minor chromosome congression and segregation defects. In contrast, mild doses of RO3306 during G 2 phase resulted in cells entering an aberrant mitosis, with cells fragmenting centrosomes and failing to fully disassemble the nuclear envelope. Cells often underwent cytokinesis and metaphase simultaneously, despite the presence of an active spindle assembly checkpoint, which prevented degradation of cyclin B1 and securin, resulting in the random partitioning of whole chromosomes. This highly aberrant mitosis produced a significant increase in the proportion of viable polyploid cells present up to 3 days post-treatment. Furthermore, cells treated with medium doses of RO3306 were only able to reach the threshold of Cdk1 substrate phosphorylation required to initiate nuclear envelope breakdown, but failed to reach the levels of phosphorylation required to correctly complete pro-metaphase. Treatment with low doses of Okadaic acid, which primarily inhibits PP2A, rescued the mitotic defects and increased the number of cells that completed a normal mitosis. This supports the current model that PP2A is the primary phosphatase that counterbalances the activity of Cdk1 during mitosis. Taken together these results show that continuous and subtle disruption of Cdk1 activity from G 2 phase onwards has deleterious consequences on mitotic progression by disrupting the balance between Cdk1 and PP2A.

An overview of high-entropy materials for energy applications, including H₂ catalysis and storage, CO₂ conversion, O₂ catalysis and electrochemical energy storage, is given and the challenges and opportunities within this field are discussed.

<italic>Cannabis sativa</italic>L. is a prolific, but not exclusive, producer of a diverse group of isoprenylated resorcinyl polyketides collectively known as phytocannabinoids.

INTRODUCTION: The COVID-19 pandemic is this century's largest public health emergency and its successful management relies on the effective dissemination of factual information. As a social media platform with billions of daily views, YouTube has tremendous potential to both support and hinder public health efforts. However, the usefulness and accuracy of most viewed YouTube videos on COVID-19 have not been investigated. METHODS: A YouTube search was performed on 21 March 2020 using keywords 'coronavirus' and 'COVID-19', and the top 75 viewed videos from each search were analysed. Videos that were duplicates, non-English, non-audio and non-visual, exceeding 1 hour in duration, live and unrelated to COVID-19 were excluded. Two reviewers coded the source, content and characteristics of included videos. The primary outcome was usability and reliability of videos, analysed using the novel COVID-19 Specific Score (CSS), modified DISCERN (mDISCERN) and modified JAMA (mJAMA) scores. RESULTS: Of 150 videos screened, 69 (46%) were included, totalling 257 804 146 views. Nineteen (27.5%) videos contained non-factual information, totalling 62 042 609 views. Government and professional videos contained only factual information and had higher CSS than consumer videos (mean difference (MD) 2.21, 95% CI 0.10 to 4.32, p=0.037); mDISCERN scores than consumer videos (MD 2.46, 95% CI 0.50 to 4.42, p=0.008), internet news videos (MD 2.20, 95% CI 0.19 to 4.21, p=0.027) and entertainment news videos (MD 2.57, 95% CI 0.66 to 4.49, p=0.004); and mJAMA scores than entertainment news videos (MD 1.21, 95% CI 0.07 to 2.36, p=0.033) and consumer videos (MD 1.27, 95% CI 0.10 to 2.44, p=0.028). However, they only accounted for 11% of videos and 10% of views. CONCLUSION: Over one-quarter of the most viewed YouTube videos on COVID-19 contained misleading information, reaching millions of viewers worldwide. As the current COVID-19 pandemic worsens, public health agencies must better use YouTube to deliver timely and accurate information and to minimise the spread of misinformation. This may play a significant role in successfully managing the COVID-19 pandemic.

A low-cost CoMoP@C electrocatalyst exhibits high efficiency and stable HER performance superior to commercial 20% Pt/C, and can directly work in seawater for the HER with a Faradaic efficiency of 92.5%.

During the last decade, two-dimensional materials (2DMs) have attracted great attention due to their unique chemical and physical properties, which make them appealing platforms for diverse applications in opto-electronic devices, energy generation and storage, and sensing. Among their various extraordinary properties, 2DMs possess high surface area-to-volume ratios and ultra-high surface sensitivity to the environment, which are key characteristics for applications in chemical sensing. Furthermore, 2DMs' superior electrical and optical properties, combined with their excellent mechanical characteristics such as robustness and flexibility, make these materials ideal components for the fabrication of a new generation of high-performance chemical sensors. Depending on the specific device, 2DMs can be tailored to interact with various chemical species at the non-covalent level, making them powerful platforms for fabricating devices exhibiting a high sensitivity towards detection of various analytes including gases, ions and small biomolecules. Here, we will review the most enlightening recent advances in the field of chemical sensors based on atomically-thin 2DMs and we will discuss the opportunities and the challenges towards the realization of novel hybrid materials and sensing devices.

van Tulder, Maurits W. PhD; Assendelft, Willem J. J. MD, PhD; Koes, Bart W. PhD; Bouter, Lex M. PhD the Editorial Board of the Cochrane Collaboration Back Review Group Author Information

Abstract Recent developments in Artificial Intelligence (AI) have generated great expectations for the future impact of AI in education and learning (AIED). Often these expectations have been based on misunderstanding current technical possibilities, lack of knowledge about state‐of‐the‐art AI in education, and exceedingly narrow views on the functions of education in society. In this article, we provide a review of existing AI systems in education and their pedagogic and educational assumptions. We develop a typology of AIED systems and describe different ways of using AI in education and learning, show how these are grounded in different interpretations of what AI and education is or could be, and discuss some potential roadblocks on the AIED highway.

Using anesthetized and paralyzed monkeys, we have studied the visual response properties of neurons in the cortical area surrounding the middle temporal area (MT) in the superior temporal sulcus (STS). Systematic electrode penetrations revealed that there is a functionally distinct region where three classes of directionally selective cells with large receptive fields cluster. This region is anteriorly adjoined to the dorsal two-thirds of MT, has a width of 4–5 mm mediolaterally, and therefore may correspond to the dorsal part of the medial superior temporal area (MST), which was previously defined as a MT-recipient zone. One class of cells responded to a straight movement of patterns in the frontoparallel plane with directional selectivity (D cells: 217/422, 51.4%). The second class of cells selectively responded to an expanding or contracting size change of patterns (S cells: 66/422, 15.7%). These cells responded neither to a change in width of a slit of any orientation or any length, nor to a change in brightness. The third class of cells responded only to a rotation of patterns in one direction (R cells: 58/422, 13.7%). A majority of these cells (41/58) responded to the clockwise or counterclockwise rotation of patterns in the frontoparallel plane (Rf cells), while the rest responded to a rotation of patterns in depth (Rd cells). We will suggest that these cells acquire the ability to discover whole events of visual motion-- i.e., unidirectional straight movement, size change (radial movement), and rotation--by integrating elemental motion information extracted by MT cells. The receptive fields of D, S, and Rf cells can be constructed by converging signals of MT cells, the preferred directions of which are arranged in parallel (D cells), radially (S cells), and circularly (Rf cells). The receptive fields of Rd cells can be constructed, in turn, by the convergence of signals of S cells.

The building block modular approach that lies behind coordination polymers (CPs) and metal-organic frameworks (MOFs) results not only in a plethora of materials that can be obtained but also in a vast array of material properties that could be aimed at. Optical properties appear to be particularly predetermined by the character of individual structural units and by the intricate interplay between them. Indeed, the "design principles" shaping the optical properties of these materials seem to be well explored for luminescence and second-harmonic generation (SHG) phenomena; these have been covered in numerous previous reviews. Herein, we shine light on CPs and MOFs as optical media for state-of-the-art photonic phenomena such as multi-photon absorption, triplet-triplet annihilation (TTA) and stimulated emission. In the first part of this review we focus on the nonlinear optical (NLO) properties of CPs and MOFs, with a closer look at the two-photon absorption property. We discuss the scope of applicability of most commonly used measurement techniques (Z-scan and two-photon excited fluorescence (TPEF)) that can be applied for proper determination of the NLO properties of these materials; in particular, we suggest recommendations for their use, along with a discussion of the best reporting practices of NLO parameters. We also outline design principles, employing both intramolecular and intermolecular strategies, that are necessary for maximizing the NLO response. A review of recent literature on two-, three- and multi-photon absorption in CPs and MOFs is further supplemented with application-oriented processes such as two-photon 3D patterning and data storage. Additionally, we provide an overview of the latest achievements in the field of frequency doubling (SHG) and tripling (third-harmonic generation, THG) in these materials. Apart from nonlinear processes, in the next sections we also target the photonic properties of MOFs that benefit from their porosity, and resulting from this their ability to serve as containers for optically-active molecules. Thus, we survey dye@MOF composites as novel media in which efficient upconversion via triplet energy migration (TEM) occurs as well as materials for stimulated emission and multi-photon pumped lasing. Prospects for producing lasing as an intrinsic property of MOFs has also been discussed. Overall, further development of the optical processes highlighted herein should allow for realization of various photonic, data storage, biomedical and optoelectronic applications.

BACKGROUND: Deoxygenated sickle hemoglobin (HbS) polymerization drives the pathophysiology of sickle cell disease. Therefore, direct inhibition of HbS polymerization has potential to favorably modify disease outcomes. Voxelotor is an HbS polymerization inhibitor. METHODS: In a multicenter, phase 3, double-blind, randomized, placebo-controlled trial, we compared the efficacy and safety of two dose levels of voxelotor (1500 mg and 900 mg, administered orally once daily) with placebo in persons with sickle cell disease. The primary end point was the percentage of participants who had a hemoglobin response, which was defined as an increase of more than 1.0 g per deciliter from baseline at week 24 in the intention-to-treat analysis. RESULTS: -thalassemia), and approximately two thirds were receiving hydroxyurea at baseline. In the intention-to-treat analysis, a significantly higher percentage of participants had a hemoglobin response in the 1500-mg voxelotor group (51%; 95% confidence interval [CI], 41 to 61) than in the placebo group (7%; 95% CI, 1 to 12). Anemia worsened between baseline and week 24 in fewer participants in each voxelotor dose group than in those receiving placebo. At week 24, the 1500-mg voxelotor group had significantly greater reductions from baseline in the indirect bilirubin level and percentage of reticulocytes than the placebo group. The percentage of participants with an adverse event that occurred or worsened during the treatment period was similar across the trial groups. Adverse events of at least grade 3 occurred in 26% of the participants in the 1500-mg voxelotor group, 23% in the 900-mg voxelotor group, and 26% in the placebo group. Most adverse events were not related to the trial drug or placebo, as determined by the investigators. CONCLUSIONS: In this phase 3 randomized, placebo-controlled trial involving participants with sickle cell disease, voxelotor significantly increased hemoglobin levels and reduced markers of hemolysis. These findings are consistent with inhibition of HbS polymerization and indicate a disease-modifying potential. (Funded by Global Blood Therapeutics; HOPE ClinicalTrials.gov number, NCT03036813.).

Drug delivery technology has a wide spectrum, which is continuously being upgraded at a stupendous speed. Different fabricated nanoparticles and drugs possessing low solubility and poor pharmacokinetic profiles are the two major substances extensively delivered to target sites. Among the colloidal carriers, nanolipid dispersions (liposomes, deformable liposomes, virosomes, ethosomes, and solid lipid nanoparticles) are ideal delivery systems with the advantages of biodegradation and nontoxicity. Among them, nano-structured lipid carriers and solid lipid nanoparticles (SLNs) are dominant, which can be modified to exhibit various advantages, compared to liposomes and polymeric nanoparticles. Nano-structured lipid carriers and SLNs are non-biotoxic since they are biodegradable. Besides, they are highly stable. Their (nano-structured lipid carriers and SLNs) morphology, structural characteristics, ingredients used for preparation, techniques for their production, and characterization using various methods are discussed in this review. Also, although nano-structured lipid carriers and SLNs are based on lipids and surfactants, the effect of these two matrixes to build excipients is also discussed together with their pharmacological significance with novel theranostic approaches, stability and storage.

STUDY DESIGN: The authors developed a diagnostic double-blindfolded survey using placebo-controlled local anesthetic blocks. OBJECTIVE: To determine the prevalence of cervical zygapophysial joint pain among patients with chronic neck pain (more than 3 months' duration) after whiplash injury. SUMMARY OF BACKGROUND DATA: The prevalence of cervical zygapophysial joint pain after whiplash has been studied by means of comparative local anesthetic blocks. The concern is that such blocks may be compromised by placebo responses and that prevalence estimates based on such blocks may exaggerate the importance of this condition. METHODS: Sixty-eight consecutive patients referred for chronic neck pain after whiplash were studied. Patients with dominant headache were first screened with the use of comparative blocks of the C2-C3 zygapophysial joint. Patients who had positive responses concluded investigations. Those who did not experience pain relief together with the patients with dominant neck pain proceeded to undergo placebo-controlled local anesthetic blocks. Two different local anesthetics and a placebo injection of normal saline were administered in random order and under double-blindfolded conditions. A positive diagnosis was made if the patient's pain was completely and reproducibly relieved by each local anesthetic but not by the placebo injection. RESULTS: Among patients with dominant headache, comparative blocks revealed that the prevalence of C2-C3 zygapophysial joint pain was 50%. Among those without C2-C3 zygapophysial joint pain, placebo-controlled blocks revealed the prevalence of lower cervical zygapophysial joint pain to be 49%. Overall, the prevalence of cervical zygapophysial joint pain (C2-C3 or below) was 60% (95% confidence interval, 46%, 73%). CONCLUSION: Cervical zygapophysial joint pain is common among patients with chronic neck pain after whiplash. This nosologic entity has survived challenge with placebo-controlled, diagnostic investigations and has proven to be of major clinical importance.