Proc Natl Acad Sci U S A
September 2020
Soil erosion is a major global soil degradation threat to land, freshwater, and oceans. Wind and water are the major drivers, with water erosion over land being the focus of this work; excluding gullying and river bank erosion. Improving knowledge of the probable future rates of soil erosion, accelerated by human activity, is important both for policy makers engaged in land use decision-making and for earth-system modelers seeking to reduce uncertainty on global predictions.
View Article and Find Full Text PDFACS Synth Biol
September 2020
Developing sustainable agricultural practices will require increasing our understanding of plant-microbe interactions. To study these interactions, new genetic tools for manipulating nonmodel microbes will be needed. To help meet this need, we recently reported development of chassis-independent recombinase-assisted genome engineering (CRAGE).
View Article and Find Full Text PDFBMJ Simul Technol Enhanc Learn
August 2020
Introduction: Competitive physical performance is routinely monitored by wearable technology (biosensors), yet professional healthcare is not, despite high prevalence of trainee stress and burnout, notwithstanding the corresponding risk to patient safety. This study aimed to document the physiological stress response of UK Core Surgical Trainees (CSTs) during simulation training.
Methods: CSTs (n=20, 10 male) were fitted with Vital Scout Wellness Monitors (VivaLNK, Campbell, California, USA) for an intensive 3-day training bootcamp.
Eukaryotic organisms share many common features in terms of endomembrane trafficking. This fact has helped plant scientists to propose testable hypotheses on how plant intracellular membrane trafficking is achieved and regulated based on knowledge from yeast and mammals. However, when a new compartment has been identified in a plant cell that has a vesicle tethering complex located at a position which is completely different to its counterpart in yeast and mammalian cells, caution is demanded when interpreting possible interactions with other trafficking elements.
View Article and Find Full Text PDFContext: Melanoma treatment has substantially changed over the last several years, yet little information regarding physician's preferences around treatment exists.
Objective: Our aim is to describe the results of the CancerMPact (CMP) survey performed in 2019 about the treatment of advanced/metastatic melanoma.
Methods: CMP is a data source from Kantar, Health Division, containing data on cancer epidemiology and treatment.
Objective: To determine the utility of mild cognitive impairment (MCI) subtypes and number of impaired cognitive domains on initial assessment at predicting progression to dementia in a sample of memory clinic patients over a 20-year period.
Methods: A retrospective analysis was conducted of those presenting to a memory clinic with MCI from 1 January 1999 to 31 December 2018 inclusive. Those with MCI were broken down into one of the four subtypes using recommended cut-off scores on the Cambridge Cognitive Assessment (CAMCOG).
Introduction: A high prevalence of stress and burnout has been reported among healthcare professionals; however, the current tools utilized to quantify such metrics are not in keeping with doctors' busy lifestyles, and moreover do not comply with infection prevention policies. Given that increased stress can subsequently impact both the healthcare profession and the patient in care, this study aimed to assess the validity of a wearable biosensor to monitor and manage stress experienced by healthcare professionals.
Methods: In all, 12 healthy, male volunteers completed an incremental exercise protocol to volitional exhaustion, which aimed to induce physiological stress in a graded manner.
The plant Golgi apparatus (sensu lato: Golgi stack + Trans Golgi Network, TGN) is a highly polar and mobile key organelle lying at the junction of the secretory and endocytic pathways. Unlike its counterpart in animal cells it does not disassemble during mitosis. It modifies glycoproteins sent to it from the endoplasmic reticulum (ER), it recycles ER resident proteins, it sorts proteins destined for the vacuole from secretory proteins, it receives proteins internalised from the plasma membrane and either recycles them to the plasma membrane or retargets them to the vacuole for degradation.
View Article and Find Full Text PDFJ Am Chem Soc
June 2020
With a resurgence in interest in covalent drugs, there is a need to identify new moieties capable of cysteine bond formation that are differentiated from commonly employed systems such as acrylamide. Herein, we report on the discovery of new alkynyl benzoxazine and dihydroquinazoline moieties capable of covalent reaction with cysteine. Their utility as alternative electrophilic warheads for chemical biological probes and drug molecules is demonstrated through site-selective protein modification and incorporation into kinase drug scaffolds.
View Article and Find Full Text PDFThis study aimed to quantify core surgical trainee (CST) differential attainment (DA) related to three cohorts; white UK graduate (White UKG) versus black and minority ethnic UKG (BME UKG) versus international medical graduates (IMGs). The primary outcome measures were annual review of competence progression (ARCP) outcome, intercollegiate Membership of the Royal College of Surgeons (iMRCS) examination pass and national training number (NTN) selection. Intercollegiate Surgical Curriculum Programme (ISCP) portfolios of 264 consecutive CSTs (2010-2017, 168 white UKG, 66 BME UKG, 30 IMG) from a single UK regional post graduate medical region (Wales) were examined.
View Article and Find Full Text PDFTibialis posterior tendinopathy is a common debilitating condition seen by foot and ankle providers. Non-operative management is difficult as patients often present in later stages of the disease. This case series evaluated the combination of radial shockwave therapy and a foot core progression exercise regimen on 10 patients who had failed standard conservative treatment techniques.
View Article and Find Full Text PDFis a human opportunistic fungal pathogen whose cell wall protects it from the extracellular environment including host defenses. Chitin, an essential component of the fungal cell wall, is synthesized from UDP-GlcNAc produced in the hexosamine biosynthetic pathway. As this pathway is critical for fungal cell wall integrity, the hexosamine biosynthesis enzymes represent potential targets of antifungal drugs.
View Article and Find Full Text PDFRunning is one of the most popular sports worldwide, with many health benefits. Injuries are also common, with running-related injuries reported in up to 79% of runners annually. Extracorporeal shockwave treatment can be used to treat soft tissue conditions, with the strongest level of evidence for management of plantar fasciitis.
View Article and Find Full Text PDFJ Chem Theory Comput
May 2020
Determining conical intersection geometries is of key importance to understanding the photochemical reactivity of molecules. While many small- to medium-sized molecules can be treated accurately using multireference approaches, larger molecules require a less computationally demanding approach. In this work, minimum energy crossing point conical intersection geometries for a series of molecules have been studied using spin-flip TDDFT (SF-TDDFT), within the Tamm-Dancoff Approximation, both with and without explicit calculation of nonadiabatic coupling terms, and compared with both XMS-CASPT2 and CASSCF calculated geometries.
View Article and Find Full Text PDFMethionyl-tRNA synthetase (MetRS) is a chemically validated drug target in kinetoplastid parasites and . To date, all kinetoplastid MetRS inhibitors described bind in a similar way to an expanded methionine pocket and an adjacent, auxiliary pocket. In the current study, we have identified a structurally novel class of inhibitors containing a 4,6-diamino-substituted pyrazolopyrimidine core (the MetRS02 series).
View Article and Find Full Text PDFObjective: To evaluate whether the effects of radical treatment in men with locally advanced prostate cancer (PCa) on PCa mortality observed in randomised clinical trials are applicable on a population basis.
Patients And Methods: We conducted a population-based cohort study using the Prostate Cancer data Base Sweden of 20 350 men diagnosed between 2000 and 2016 with locally advanced PCa, defined as clinical local stage T3/T4, M0, Mx and a prostate-specific antigen level of <100 ng/mL. Cumulative PCa mortality was examined using competing risk analysis of all men with locally advanced PCa, and also including men who did not undergo radical treatment.
ER lumenal proteins have a K(H)DEL motif at their C-terminus. This is recognized by the ERD2 receptor (KDEL receptor in animals), which localizes to the Golgi apparatus and serves to capture escaped ER lumenal proteins. ERD2-ligand complexes are then transported back to the ER via COPI coated vesicles.
View Article and Find Full Text PDFPurpose: 5α-Reductase inhibitors reduced the risk of prostate cancer in 25% in 2 randomized trials but increased the risk of Gleason 8-10 at biopsy. One explanation is that 5α-reductase inhibitors induce morphological changes in prostate cancer cells similar to higher Gleason grades but without its adverse biology. We compared risk of prostate cancer death between men on 5α-reductase inhibitors and men not on 5α-reductase inhibitors before prostate cancer diagnosis in each Gleason Grade Group.
View Article and Find Full Text PDFJAMA Netw Open
February 2020
This cross-sectional study analyzes emergency department visits associated with hemodialysis by insured and uninsured patients in Texas.
View Article and Find Full Text PDFAttempts to directly drug the important oncogene KRAS have met with limited success despite numerous efforts across industry and academia. The KRAS mutant represents an "Achilles heel" and has recently yielded to covalent targeting with small molecules that bind the mutant cysteine and create an allosteric pocket on GDP-bound RAS, locking it in an inactive state. A weak inhibitor at this site was optimized through conformational locking of a piperazine-quinazoline motif and linker modification.
View Article and Find Full Text PDFTo report the results of a survey of USA physicians (CancerMPact) that treat non-small-cell lung cancer patients. 60 physicians were surveyed. Questions covered aspects of the treatment for all stages of the disease.
View Article and Find Full Text PDFThe objective was to investigate the proportion of men with metastatic prostate cancer in groups defined by T stage, Gleason Grade Group (GGG) and serum levels of prostate-specific antigen (PSA) and if PSA can be used to rule in metastatic prostate cancer when combined with T stage and GGG. We identified 102,076 men in Prostate Cancer data Base Sweden 4.0 who were diagnosed with prostate cancer in 2006-2016.
View Article and Find Full Text PDFEffects of earthworms on soil physico-hydraulic and chemical properties, herbage production and wheat growth in long-term arable soils following conversion to ley were investigated. Seven intact soil monoliths were collected from each of four arable fields. One monolith per field served as a control.
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