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Abstract Intratumoral cellular heterogeneity necessitates multi-targeting therapies for improved clinical benefits in advanced malignancies. However, systematic identification of patient-specific treatments that selectively co-inhibit cancerous cell populations poses a combinatorial challenge, since the number of possible drug-dose combinations vastly exceeds what could be tested in patient cells. Here, we describe a machine learning approach, scTherapy, which leverages single-cell transcriptomic profiles to prioritize multi-targeting treatment options for individual patients with hematological cancers or solid tumors. Patient-specific treatments reveal a wide spectrum of co-inhibitors of multiple biological pathways predicted for primary cells from heterogenous cohorts of patients with acute myeloid leukemia and high-grade serous ovarian carcinoma, each with unique resistance patterns and synergy mechanisms. Experimental validations confirm that 96% of the multi-targeting treatments exhibit selective efficacy or synergy, and 83% demonstrate low toxicity to normal cells, highlighting their potential for therapeutic efficacy and safety. In a pan-cancer analysis across five cancer types, 25% of the predicted treatments are shared among the patients of the same tumor type, while 19% of the treatments are patient-specific. Our approach provides a widely-applicable strategy to identify personalized treatment regimens that selectively co-inhibit malignant cells and avoid inhibition of non-cancerous cells, thereby increasing their likelihood for clinical success.

Abstract Unraveling the precursory signals of potentially destructive earthquakes is crucial to understand the Earth’s crust dynamics and to provide reliable seismic warnings. Earthquake precursors are ambiguous, but recent experimental studies suggest that robust warning signs may precede large seismic events in the short (day-to-months) term. Here, we show that the M6.4-M7.1 2019 Ridgecrest sequence (California) and the M7.1 2018 Anchorage earthquake (Alaska) were preceded by up to ~3 months of tectonic unrest on regional scales, as evidenced by abnormal low-magnitude seismicity spreading over the ~15-25% of Southern California and Southcentral Alaska. This precursory unrest has been discovered with an algorithm that integrates an innovative random forest machine learning approach and statistical features built from earthquake catalogs. Supported by a novel suite of finite element solid mechanics models, we propose that precursory, abnormal, low-magnitude seismicity arises if the pore fluid pressure within large fault segments escalates significantly as they approach failure, which leads to major uneven changes in the regional stress field. Our findings and method may open up new perspectives for surveillance agencies to anticipate when a region approaches an earthquake of great magnitude weeks to months before it occurs.

We analysed all the Holocene structures defining the Fremrinamar Fissure Swarm (FFS), in the Northern Volcanic Zone of Iceland, through the interpretation of aerial photos, orthomosaics and Digital Surface Models (DSMs), and field surveys. We measured the strike, dip, length and kinematics of 761 normal faults and reconstructed the slip profile of 76 main faults (length >2 km), with the purpose of evaluating the overall direction of along-axis rift propagation. We also measured the strike of 146 eruptive fissures and 1,128 extension fractures. A total of 421 faults dip towards the east and 340 dip towards the west, mainly striking N0°-10°E. Maximum fault length is 14.2 km, and W-dipping faults are longer than E-dipping faults. The majority of eruptive fissures strike N10°-20°E, and are concentrated in the southern part of the FFS, around the Fremrinamar central volcano. Extension fractures mainly strike N0°-10°E, with a maximum length of 2,508 m. We evaluated the variation of strike, fracture density and spacing along the FFS, and observed a change of its trend from NNE-SSW in the central-southern part, to NNW-SSE in the northern part. We interpret this evidence as the effect of the intersection with the Grimsey Lineament. The tapering of fault slip profiles indicates a main northward propagation of the rift, and thus of the deformation, interpreted as the effect of lateral propagation of dykes from the magma chamber below the central volcano towards the north. Such interpretation is also supported by the distribution of normal faults, vertical offset and dilation values, and also by the rift width, which tend to decrease towards the north.

Abstract The most widely used test for the diagnosis of SARS-CoV-2 infection is a PCR test. PCR has very high sensitivity and is able to detect very low amounts of RNA. However, many individuals receiving a positive test result in a context of a PCR-based surveillance might be infected with SARS-CoV-2, but they are not contagious at the time of the test. The question arises regards if the cost effective, portable rapid antigen tests (RATs) have a better performance than PCR in identification of infectious individuals. In this direction, we examined the diagnostic performance of RATs from 14 different manufacturers in 400 clinical samples with known rRT-PCR cycles threshold (cT) and 50 control samples. Substantial variability was observed in the limit of detection (LOD) of different RATs (cT = 26.8–34.7). The fluorescence-based RAT exhibited a LOD of cT = 34.7. The use of the most effective RATs leads to true positive rates (sensitivities) of 99.1% and 90.9% for samples with cT ≤ 30 and cT ≤ 33, respectively, percentages that can guarantee a sensitivity high enough to identify contagious patients. RAT testing may also substantially reduce the quarantine period for infected individuals without compromising personal or public safety.

The concepts of CO2 emission, global warming, climate change, and their environmental impacts are of utmost importance for the understanding and protection of the ecosystems. Among the natural sources of gases into the atmosphere, the contribution of geogenic sources plays a crucial role. However, while subaerial emissions are widely studied, submarine outgassing is not yet well understood. In this study, we review and catalog 122 literature and unpublished data of submarine emissions distributed in ten coastal areas of the Aegean Sea. This catalog includes descriptions of the degassing vents through in situ observations, their chemical and isotopic compositions, and flux estimations. Temperatures and pH data of surface seawaters in four areas affected by submarine degassing are also presented. This overview provides useful information to researchers studying the impact of enhanced seawater CO2 concentrations related either to increasing CO2 levels in the atmosphere or leaking carbon capture and storage systems.

This work is aimed at reviewing the current state of the art in geosite selection, assessment, and communication. We first highlight the main papers that have defined paramount concepts such as geodiversity, geoheritage, and geosites. We then delve into the theoretical principles and guidelines that have been proposed over the last twenty years by researchers who have thoroughly illustrated how to individuate and assess geosites. In doing so, we illustrate notable field examples of applications of qualitative and quantitative assessments of geosites in places such as Serbia, India, Iceland, Ecuador, Sardinia (Italy), Egypt, Tasmania (Australia), and Brazil. The third part of this work is dedicated to illustrating a list (by no means exhaustive) of works that have tried to come up with innovative tools, strategies, and solutions to promote and communicate geosites. From our work, it appears that geosites can be extremely effective as fully fledged outreach tools capable of bridging the gap between Earth science and the lay public.

The Cheb Basin (Czech Republic) is characterized by emanations of magma-derived gases and repeated occurrences of mid-crustal earthquake swarms with small to intermediate magnitudes (ML < 4.5). Associated intense mantle degassing occurs at the Hartoušov Mofette, a representative site for the Cheb Basin. Here, we performed 14 sampling campaigns between June 2019 and March 2020. Gas samples of fluids ascending in two boreholes (F1, ∼28 m depth and F2, ∼108 m depth) and from a nearby natural mofette were analyzed for their chemical (CO2, N2, O2, Ar, He, CH4, and H2) and isotope compositions (noble gases and CO2). CO2 concentrations were above 99.1% in most samples, while O2 and N2 were below 0.6%. He ranged from 19 to 34 μmol/mol and CH4 was mostly below 12 μmol/mol. Isotope compositions of helium and carbon in CO2 ranged from 5.39 to 5.86 RA and from −2.4 to −1.3 ‰ versus VPDB, respectively. Solubility differences of the investigated gases resulted in fluctuations of their chemical compositions. These differences were accompanied by observed changes of gas fluxes in the field and at the monitoring station for F1. Variations in solubilities and fluxes also impacted the chemical concentration of the gases and the δ13C values that were also likely influenced by Fischer-Tropsch type reactions. The combination of (a) the Bernard ratio, (b) CH4/3He distributions, (c) P-T conditions, (d) heat flow, and (e) the sedimentary regime led to the hypothesis that CH4 may be of mixed biogenic and volcanic/geothermal origin with a noticeable atmospheric contribution. The drilling of a third borehole (F3) with a depth of ∼238 m in August 2019 has been crucial for providing insights into the complex system of Hartoušov Mofette.

Fluid anomalies were often considered as possible precursors before earthquakes. However, fluid properties at the surface can change for a variety of reasons, including environmental changes near the surface, the response of the superficial fluid system to loads associated with the mechanical nucleation of earthquake fractures, or as a result of transients in fluid flow from the depths. A key problem is to understand the origin of the anomaly and to distinguish between different causes. We present a new approach to monitor geochemical and geophysical fluid properties along a vertical profile in a set of drillings from a depth of a few hundred meters to the surface. This setup can provide hints on the origin of temporal variations, as the migration direction and speed of properties can be measured. In addition, potential admixtures of fluids from a deep crustal or mantle origin with meteoric fluids can be better quantified. A prototype of a multi-level gas monitoring system comprising flow and pressure probes, as well as monitoring of fluid-geochemical properties and stable isotopes is being implemented in a mofette field with massive CO2 (up to 97 tons per day) degassing. The mofette is believed a gas emission site where CO2 ascends through crustal-scale conduits from as deep as the upper mantle, and may therefore provide a natural window to ongoing magmatic processes at mantle depth. Fluids from three adjacent boreholes—30, 70, and 230 m deep—will be continuously monitored at high sampling rates.