The marine biodiscovery pipeline and ocean medicines of tomorrow

Marine organisms possess the capacity to produce a variety of unique and biologically potent natural products for treating human diseases, many of which are currently commercially available or are in advanced clinical trials. Here we provide a short review on progress in the field and discuss a case study of an EU-funded project, PharmaSea, which aims to discover novel products for the treatment of infections, inflammation and neurodegenerative diseases. Research in this sector is opening new doors for harnessing the potential of marine natural products with pharmaceutical properties

Sensitivity of Northern Hemisphere Cyclone Detection and Tracking Results to Fine Spatial and Temporal Resolution Using ERA5

Lagrangian detection and tracking algorithms are frequently used to study the development, distribution, and trends of extratropical cyclones. Past research shows that results from these algorithms are sensitive to both spatial and temporal resolution of the gridded input fields, with coarser resolutions typically underestimating cyclone frequency by failing to capture weak, small, and short-lived systems. The fifth-generation atmospheric reanalysis from the European Centre for Medium-Range Weather Forecasts (ERA5) offers finer resolution, and therefore more precise information regarding storm locations and development than previous global reanalyses. However, our sensitivity tests show that using ERA5 sea-level pressure fields at their finest possible resolution does not necessarily lead to better cyclone detection and tracking. If a common number of nearest neighbors is used when detecting minima in sea-level pressure (like past studies), finer spatial resolution leads to noisier fields that unrealistically break up multi-center cyclones. Using a common search distance instead (with more neighbors at finer resolution) resolves the issue without smoothing inputs. Doing this also makes cyclone frequency, lifespan, and average depth insensitive to refining spatial resolution beyond 100 km. Results using 6-h and 3-h temporal resolutions have only minor differences, but using 1-h temporal resolution with a maximum allowed propagation speed of 150 km h-1 leads to unrealistic track splitting. This can be counteracted by increasing the maximum propagation speed, but modest sensitivity to temporal resolution persists for several cyclone characteristics. Therefore, we recommend caution if applying existing algorithms to temporal resolutions finer than 3-h and careful evaluation of algorithm settings

Sources of seasonal sea-ice bias for CMIP6 models in the Hudson Bay Complex

The seasonal ice-free period in the Hudson Bay Complex (HBC) has grown longer in recent decades in response to warming, both from progressively earlier sea-ice retreat in summer and later sea-ice advance in fall. Such changes disrupt the HBC ecosystem and ice-based human activities. In this study, we compare 102 simulations from 37 models participating in phase 6 of the Coupled Model Intercomparison Project to the satellite passive microwave record and atmospheric reanalyses. We show that, throughout the HBC, models simulate an ice-free period that averages 30 d longer than in satellite observations. This occurs because seasonal sea-ice advance is unrealistically late and seasonal sea-ice retreat is unrealistically early. We find that much of the ice-season bias can be linked to a warm bias in the atmosphere that is associated with a southerly wind bias, especially in summer. Many models also exhibit an easterly wind bias during winter and spring, which reduces sea-ice convergence on the east side of Hudson Bay and impacts the spatial patterns of summer sea-ice retreat. These results suggest that, for many models, more realistic simulation of atmospheric circulation would improve their simulation of HBC sea ice

Assessment of Surgical Procedural Time, Pedicle Screw Accuracy, and Clinician Radiation Exposure of a Novel Robotic Navigation System Compared With Conventional Open and Percutaneous Freehand Techniques: A Cadaveric Investigation

STUDY DESIGN: Cadaveric study. OBJECTIVE: To evaluate accuracy, radiation exposure, and surgical time of a new robotic-assisted navigation (RAN) platform compared with freehand techniques in conventional open and percutaneous procedures. METHODS: Ten board-certified surgeons inserted 16 pedicle screws at T10-L5 (n = 40 per technique) in 10 human cadaveric torsos. Pedicle screws were inserted with (1) conventional MIS technique (L2-L5, patient left pedicles), (2) MIS RAN (L2-L5, patient right pedicles), (3) conventional open technique (T10-L1, patient left pedicles), and (4) open RAN (T10-L1, patient right pedicles). Output included (1) operative time, (2) number of fluoroscopic images, and (3) screw accuracy. RESULTS: In the MIS group, compared with the freehand technique, RAN allowed for use of larger screws (diameter: 6.6 ± 0.6 mm vs 6.3 ± 0.5 mm; length: 50.3 ± 4.1 mm vs 46.9 ± 3.5 mm), decreased the number of breaches \u3e2 mm (0 vs 7), fewer fluoroscopic images (0 ± 0 vs 108.3 ± 30.9), and surgical procedure time per screw (3.6 ± 0.4 minutes vs 7.6 ± 2.0 minutes) (all CONCLUSION: RAN significantly improved accuracy and decreased radiation exposure in comparison to freehand techniques in both conventional open and percutaneous surgical procedures in cadavers. RAN significantly increased setup time compared with both conventional procedures

Nightly treatment of primary insomnia with prolonged release melatonin for 6 months: a randomized placebo controlled trial on age and endogenous melatonin as predictors of efficacy and safety

<p>Background: Melatonin is extensively used in the USA in a non-regulated manner for sleep disorders. Prolonged release melatonin (PRM) is licensed in Europe and other countries for the short term treatment of primary insomnia in patients aged 55 years and over. However, a clear definition of the target patient population and well-controlled studies of long-term efficacy and safety are lacking. It is known that melatonin production declines with age. Some young insomnia patients also may have low melatonin levels. The study investigated whether older age or low melatonin excretion is a better predictor of response to PRM, whether the efficacy observed in short-term studies is sustained during continued treatment and the long term safety of such treatment.</p> <p>Methods: Adult outpatients (791, aged 18-80 years) with primary insomnia, were treated with placebo (2 weeks) and then randomized, double-blind to 3 weeks with PRM or placebo nightly. PRM patients continued whereas placebo completers were re-randomized 1:1 to PRM or placebo for 26 weeks with 2 weeks of single-blind placebo run-out. Main outcome measures were sleep latency derived from a sleep diary, Pittsburgh Sleep Quality Index (PSQI), Quality of Life (World Health Organzaton-5) Clinical Global Impression of Improvement (CGI-I) and adverse effects and vital signs recorded at each visit.</p> <p>Results: On the primary efficacy variable, sleep latency, the effects of PRM (3 weeks) in patients with low endogenous melatonin (6-sulphatoxymelatonin [6-SMT] ≤8 μg/night) regardless of age did not differ from the placebo, whereas PRM significantly reduced sleep latency compared to the placebo in elderly patients regardless of melatonin levels (-19.1 versus -1.7 min; P = 0.002). The effects on sleep latency and additional sleep and daytime parameters that improved with PRM were maintained or enhanced over the 6-month period with no signs of tolerance. Most adverse events were mild in severity with no clinically relevant differences between PRM and placebo for any safety outcome.</p> <p>Conclusions: The results demonstrate short- and long-term efficacy and safety of PRM in elderly insomnia patients. Low melatonin production regardless of age is not useful in predicting responses to melatonin therapy in insomnia. The age cut-off for response warrants further investigation.</p&gt

Genotype-free demultiplexing of pooled single-cell RNA-seq.

A variety of methods have been developed to demultiplex pooled samples in a single cell RNA sequencing (scRNA-seq) experiment which either require hashtag barcodes or sample genotypes prior to pooling. We introduce scSplit which utilizes genetic differences inferred from scRNA-seq data alone to demultiplex pooled samples. scSplit also enables mapping clusters to original samples. Using simulated, merged, and pooled multi-individual datasets, we show that scSplit prediction is highly concordant with demuxlet predictions and is highly consistent with the known truth in cell-hashing dataset. scSplit is ideally suited to samples without external genotype information and is available at: https://github.com/jon-xu/scSplit

Land management explains major trends in forest structure and composition over the last millennium in California's Klamath Mountains

For millennia, forest ecosystems in California have been shaped by fire from both natural processes and Indigenous land management, but the notion of climatic variation as a primary controller of the pre-colonial landscape remains pervasive. Understanding the relative influence of climate and Indigenous burning on the fire regime is key because contemporary forest policy and management are informed by historical baselines. This need is particularly acute in California, where 20th-century fire suppression, coupled with a warming climate, has caused forest densification and increasingly large wildfires that threaten forest ecosystem integrity and management of the forests as part of climate mitigation efforts. We examine climatic versus anthropogenic influence on forest conditions over 3 millennia in the western Klamath Mountains—the ancestral territories of the Karuk and Yurok Tribes—by combining paleoenvironmental data with Western and Indigenous knowledge. A fire regime consisting of tribal burning practices and lightning were associated with long-term stability of forest biomass. Before Euro-American colonization, the long-term median forest biomass was between 104 and 128 Mg/ha, compared to values over 250 Mg/ha today. Indigenous depopulation after AD 1800, coupled with 20th-century fire suppression, likely allowed biomass to increase, culminating in the current landscape: a closed Douglas fir–dominant forest unlike any seen in the preceding 3,000 y. These findings are consistent with precontact forest conditions being influenced by Indigenous land management and suggest large-scale interventions could be needed to return to historic forest biomass levels

Fine particle pH and sensitivity to NH3 and HNO3 over summertime South Korea during KORUS-AQ

Using a new approach that constrains thermodynamic modeling of aerosol composition with measured gas-to-particle partitioning of inorganic nitrate, we estimate the acidity levels for aerosol sampled in the South Korean planetary boundary layer during the NASA/NIER KORUS-AQ field campaign. The pH (mean ± 1σ = 2.43 ± 0.68) and aerosol liquid water content determined were then used to determine the chemical regime of the inorganic fraction of particulate matter (PM) sensitivity to ammonia and nitrate availability. We found that the aerosol formation is always sensitive to HNO3 levels, especially in highly polluted regions, while it is only exclusively sensitive to NH3 in some rural/remote regions. Nitrate levels are further promoted because dry deposition velocity is low and allows its accumulation in the boundary layer. Because of this, HNO3 reductions achieved by NOx controls prove to be the most effective approach for all conditions examined, and that NH3 emissions can only partially affect PM reduction for the specific season and region. Despite the benefits of controlling PM formation to reduce ammonium-nitrate aerosol and PM mass, changes in the acidity domain can significantly affect other processes and sources of aerosol toxicity (such as e.g., solubilization of Fe, Cu and other metals) as well as the deposition patterns of these trace species and reactive nitrate