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The Mars2020 Perseverance Rover landed successfully on the Martian surface on the Jezero Crater floor (18.44°N, 77.45°E) at Martian solar longitude, $L_s$, $\sim$5 in February 2021. Since then it has produced highly valuable environmental measurements with a versatile scientific payload including the MEDA (Mars Environmental Dynamics Analyzer) suite of environmental sensors. One of the MEDA systems is the PS pressure sensor system which weighs 40 grams and has an estimated absolute accuracy of better than 3.5 Pa and a resolution of 0.13 Pa. We present initial results from the first 414 sols of Martian atmospheric surface pressure observations by the PS whose performance was found to meet its specifications. Observed sol-averaged atmospheric pressures follow an anticipated pattern of pressure variation in the course of the advancing season and are consistent with data from other landing missions. The observed diurnal pressure amplitude varies by $\sim$2-5 \% of the sol-averaged pressure, with absolute amplitude 10-35 Pa in an approximately direct relationship with airborne dust. During a regional dust storm, which began at $L_s~135^\circ$ the diurnal pressure amplitude roughly doubles. The diurnal pressure variations were found to be remarkably sensitive to the seasonal evolution of the atmosphere. In particular analysis of the diurnal pressure signature revealed diagnostic information likely related to the regional scale structure of the atmosphere. Comparison of Perseverance pressure observations to data from other landers reveals the global scale seasonal behaviour of Mars’ atmosphere.

Clouds on Mars are primary elements for understanding the past and present climate of the planet. Cloud particles can affect the energy balance of the planet, and so the atmospheric dynamic, as well as influence the vertical distribution of dust particles through dust scavenging. The dust scavenging by clouds has critical consequences in the water cycle of the planet; e.g. regions in the atmosphere with insufficient quantity of dust particles (or condensation nuclei) can inhibit the formation of H2O clouds and thus lead to the presence of water vapor in excess of saturation. The study of these interactions requires observations whose analysis allows us to infer simultaneously the properties of both the clouds and dust. To address these observations, the Radiation and Dust Sensor (RDS) is part of the Mars Environmental Dynamics Analyzer (MEDA) payload onboard of the Mars 2020 rover Perseverance.In this work we analysed the RDS observations made during twilight in the period Ls 39◦-262◦ to characterize the clouds above ∼ 30 km over the Perseverance rover site. From the ratio between the irradiance measured at zenith at 450 nm and 750 nm, we inferred that from Ls= 39◦ to 150◦ (referred as the cloudy period), water ice is the main constituent of the detected high-altitude aerosol layers. For Ls 150◦-262◦ dust is the main aerosol present. A total of 161 twilights were analysed in the cloudy period with a radiative transfer code in spherical geometry. Among other results we found: i) signatures of clouds or hazes on the RDS signals in the 58 % of the twilights; ii) most of the clouds were at altitudes between 40 km and 50 km and with particle sizes between 0.6 μm and 2 μm (in effective radius); iii) the cloud activity at sunrise is slightly higher that at sunset (65 % against 52 %), likely due to the differences in temperature; iv) the cloudiest time in Perseverance site and with the greatest cloud opacities is in Ls 120◦-150◦; and v) a notable decrease in the cloud activity around the aphelion (Ls ∼ 70◦), along with lower cloud altitudes and opacities. The drop in cloud activity around Ls ∼ 70◦ indicates lower concentrations of water vapor or cloud nuclei (dust) around this period in the Martian mesosphere. In this presentation, we will discuss the implications of our results on the water cycle of the planet.

Pressure measurements by the MEDA sensor on board Perseverance Rover show oscillations in a wide range of temporal scales, from the seasonal evolution of average pressure to rapid fluctuations on the scale of a few seconds. In this work, we profit from an entire Martian Year of pressure measurements to analyse the seasonal and daily evolution of rapid fluctuations, a signature of atmospheric turbulence. We find that during the full Martian year, fluctuations are enhanced at convective hours of the day, but the intensity of fluctuations is modulated through the seasons. At nighttime, the first half of the Martian years is characterized by an almost complete absence of fluctuations with an especially calm period in the early morning, while bursts of fluctuation become common in the dusty season. We also analyse the change of the daily pattern induced by regional dust storms at Jezero. We study the power spectra of the fluctuations to try to infer information about different turbulent regimes at the surface layer and their dependence on local time and season. Finally, we explore possible correlations with the dust load of the atmosphere and the temperature gradients, and we look at the origin of nighttime bursts of turbulence.

The Thermal Infrared Sensor (TIRS; Sebastián et al., 2021; Martínez et al., 2023) is one of the six sensor packages of the Mars Environmental Dynamics Analyzer (MEDA; Rodríguez-Manfredi et al., 2021), which in turn is one of the seven science instruments on board Perseverance. Here we show a summary of TIRS scientific highlights during the first Martian year of operations. In particular, TIRS is providing the first in situ determination of the surface radiative budget, direct determination of broadband albedo and thermal inertia (Martínez et al., 2023; Savijärvi et al., 2022), and around-the-clock determination of aerosol opacities (Smith et al., 2023). In addition, TIRS is providing ground-truth to orbital retrievals of thermal inertia and albedo, as well as geophysical characterization of the uppermost surface of the regolith during Phobos and Deimos eclipses. In synergy with other instruments, TIRS is being used to determine vertical profiles of temperature (Munguira et al., 2023), to detect dust lifting from sudden changes in albedo (Vicente-Retortillo et al., 2023), and to assess changes in the water content of the Martian soil (Hausrath et al., 2023), including the potential formation of frost. TIRS observations are critical to achieve MEDA’s first programmatic objective (validate global atmospheric models by measuring the radiative surface budget in preparation for future human exploration). Also, TIRS observations are important in support of flights of Ingenuity and therefore for the design and operations of future drones. References: Hausrath, E. M. et al. (2023), The SuperCam team and the Regolith working group, An Examination of Soil Crusts on the Floor of Jezero crater, Mars, Journal of Geophysical Research: Planets (accepted). Martínez, G. M. et al. (2023), Surface Energy Budget, Albedo and Thermal Inertia at Jezero Crater, Mars, as Observed from the Mars 2020 MEDA Instrument, Journal of Geophysical Research: Planets (accepted). Munguira, A. et al. (2023), Near Surface Atmospheric Temperatures at Jezero from Mars 2020 MEDA measurements, Journal of Geophysical Research: Planets (under review). Rodriguez-Manfredi, J.A. et al. (2021), The Mars Environmental Dynamics Analyzer, MEDA. A suite of environmental sensors for the Mars 2020 mission, Spa. Sci. Rev., 217(3), 1-86. Savijärvi, H. I. et al. (2022), Surface energy fluxes and temperatures at Jezero crater, Mars, Journal of Geophysical Research: Planets: e2022JE007438. Sebastián, E. et al. (2021), Thermal calibration of the MEDA-TIRS radiometer onboard NASA's Perseverance rover, Acta Astronautica, 182,144-159. Smith, M. D. et al. (2023), Diurnal and Seasonal Variations of Aerosol Optical Depth Observed by MEDA/TIRS at Jezero Crater, Mars, Journal of Geophysical Research: Planets (accepted). Vicente-Retortillo, A. et al. (2023), Dust Lifting Through Changes in Albedo at Jezero Crater, Mars, Journal of Geophysical Research: Planets (under review).

A better understanding of the thermodynamics of heavy precipitation events is necessary towards improving weather and climate models and quantifying the impact of climate variability on precipitation. However, there are limited observations available to assess the thermodynamics model structure within heavy precipitation conditions.In 2009, the Earth Observation Group at ICE-CSIC/IEEC conceived the polarimetric radio occultations (GNSS-PRO) technique with the aim to obtain simultaneous measurements of the vertical structure of precipitation and its associated thermodynamic state. Based on the standard GNSS radio occultation technique (GNSS-RO), polarimetric RO consists of an identical instrument working at two orthogonal linear polarizations (H,V) instead of the conventional circularly polarized antenna. This allows us to measure the differential phase delay at both ports, hypothesized to be positive in the presence of asymmetric hydrometeors (large raindrops, snowflakes, ice aggregates). This technique is being tested for the first time on the proof-of-concept mission Radio Occultations and Heavy Precipitation (ROHP) aboard PAZ satellite, operating since 2018. The results of the first 4 years of PRO observations already showed sensitivity to heavy precipitation and its associated cloud structures.Such technique provides high quality thermodynamic observations of water vapor, temperature and pressure with high vertical resolution, along with the vertical measurements of the phase delay linked to the precipitation structure. This study focuses on comparing these observations with the simulations based on the outputs of several operational models and reanalysis for a set of selected cases. The main objectives of the study are: (1) To check if the models reproduce the main features of the actual data; (2) to assess whether different models/schemes result in different GNSS PRO observables, and whether these differences are larger than the measurement uncertainty; and (3) to examine the utility of PAZ GNSS PRO observations for model validation and diagnosis.This effort provides insight on future methods to assimilate the PRO profile alongside other conventional (non-polarimetric) RO data, including work towards building a forward operator. The exercise includes comparisons with ECWMF operational model, ERA-5 reanalysis, the operational NWP at the Japan Meteorological Agency, and a near-real-time implementation of the WRF regional model over the northeastern Pacific produced at the Center for Western Weather and Water Extremes (CW3E) called West WRF, forced with ECMWF and GFS.

We use data from the MEDA instrument on Mars 2020 to study the evolution of atmospheric and surface temperatures at Jezero. The measurements correspond to four height levels from the surface to ~40 m and together they allow us to examine multiple aspects of the near-surface meteorology at Jezero. We extend the analysis of near-surface temperatures of Munguira et al. (JGR:Planets 2023), which covered the period from Ls 13º to Ls 203º, over a full Martian year. We show the seasonal evolution of temperatures, including temperature fluctuations and thermal gradients, which are affected by the properties of the terrain traversed by Perseverance. We will focus on a physical description of the thermal processes that take place in the Convective Boundary Layer at Jezero. We compare near-surface temperatures with the atmospheric opacity around-the-clock retrieved by Smith et al. (2022) and with daily averages of optical depth measured by MastCam-Z (Bell et al. 2022). After Ls 203º, atmospheric waves coming across Jezero predicted by atmospheric models are expected to contribute to shaping temperatures producing thermal oscillations on time-scales of a few sols. This effect is accompanied by an enhanced variability of atmospheric opacity and both effects contribute to produce a higher variability on temperatures. References:[1] Munguira, A. et al. (2023). Near Surface Atmospheric Temperatures at Jezero from Mars 2020 MEDA Measurements. JGR: Planets.[2] Smith, M.D. et al. (2022). Diurnal and Seasonal Variations of Aerosol Optical Depth Observed by MEDA/TIRS at Jezero Crater, Mars. In Seventh international workshop on the Mars atmosphere: Modelling and observations (pp. 14-17).[3] Bell, J.F. et al. (2022). Geological, multispectral, and meteorological imaging results from the mars 2020 perseverance rover in jezero crater. Science Advances, 8 (47), eabo4856. doi: 10.1126/sciadv.abo485

After one year of surface operations at Jezero, the MEDA meteorological sensors have captured the signals produced by the close approach of hundreds of vortices and dust devils over different seasons and terrains. Here we update findings on the vortex and Dust Devils published in Hueso et al. (JGR: Planets, 2023). That work analyzed MEDA data from spring to early autumn identifying vortices as pressure drops and later characterizing them from the ensemble of MEDA measurements. In this updated analysis we show that, in winter, declining surface temperatures and smaller vertical gradients result in a wane of vortex activity. This decreased activity affects more the frequency of intense vortices (Δp >1.5 Pa) without showing a stiff decay in the total number of vortices (Δp>0.5 Pa). In this contribution we concentrate on the specific aspects of the thermodynamics of the vortices from temperature measurements obtained by MEDA that characterize the vertical thermal gradient at the time of the vortex passage. In addition, when vortices approach the rover closely in a favorable geometry (coming from the front of the vortex) we measure the increased temperatures inside the vortex. We also explore the increased nighttime vortex activity found on some sols, when pressure drops equivalent to those created by daytime vortices appear in the early morning before sunrise, with clusters of nighttime activity in winter and early spring.

Any oncological treatment must aim at maximizing patient survival with the best quality of life and not merely at eliminating the tumor. Since the liver has a vital function, any radical treatment severely compromising liver function will result in a shortening of life expectancy, rather than a prolongation. Furthermore, even non-severe liver damage may imply the risk of impeding the opportunity to receive further effective therapies. This is particularly important in the case of hepatocellular carcinoma (HCC), since this tumor is associated with underlying cirrhosis in the majority of patients, and cirrhosis itself is not only a potentially lethal disease and independent prognostic factor in HCC, but it also makes liver function fragile. Accordingly, some information about liver dysfunction is included in most staging systems for HCC, in an attempt to suggest treatments that the functional liver reserve can adequately tolerate. Unfortunately, the prediction of functional liver damage in the case of antitumor treatments is very challenging and still suboptimal in any given specific patient. Moreover, while the assessment of the functional reserve has been sufficiently elucidated in the surgical setting to avoid postoperative liver failure, it has instead been less clarified for non-surgical therapies, despite the fact that this aspect appears to have become of particular relevance today, when several lines of effective non-surgical treatments, including systemic therapies, have become available. The present article will a) critically review the implications of the assessment of liver functional reserve in patients with HCC, b) illustrate the different available tools to assess the liver functional reserve and c) discuss the role of functional assessment in the setting of each type of non-surgical therapy for HCC.

The following supporting information can be downloaded at: https:// www.mdpi.com/article/10.3390/foods12071505/s1, Table S1: Calibration ranges, curves, regression coefficients and LOD and LOQ of the standard molecules., This study was supported by the Spanish Ministry of Science and Innovation within the project ACTIVE HONEY: Innovative formulations of main bee products using natural ingredients. 2019–2022. (EXP 00116482/INNO-20182004), funded by the Technological Center for the Industrial Development (CDTI)., A comprehensive characterization of the phytochemicals present in a blackberry fruit extract by HPLC-TOF-MS has been carried out. The main compounds in the extract were ursane-type terpenoids which, along with phenolic compounds, may be responsible for the bioactivity of the extract. In vitro antioxidant capacity was assessed through Folin-Ciocalteu (31.05 +/- 4.9 mg GAE/g d.w.), FRAP (637.8 +/- 3.2 mu mol Fe2+/g d.w.), DPPH (IC50 97.1 +/- 2.4 mu g d.w./mL) and TEAC (576.6 +/- 8.3 mu mol TE/g d.w.) assays. Furthermore, the extract exerted remarkable effects on in vitro cellular antioxidant activity in HUVEC cells at a concentration of 5 mg/mL. Antimicrobial activity of the extract was also tested. Most sensible microorganisms were Gram-positive bacteria, such as E. faecalis, B. cereus and Gram-negative E. coli (MBC of 12.5 mg/mL). IC50 values against colon tumoral cells HT-29 (4.9 +/- 0.2 mg/mL), T-84 (5.9 +/- 0.3 mg/mL) and SW-837 (5.9 +/- 0.2 mg/mL) were also obtained. Furthermore, blackberry extract demonstrated anti-inflammatory activity inhibiting the secretion of pro-inflammatory IL-8 cytokines in two cellular models (HT-29 and T-84) in a concentration-dependent manner. These results support that blackberry fruits are an interesting source of bioactive compounds that may be useful in the prevention and treatment of different diseases, mainly related to oxidative stress., Spanish Ministry of Science and Innovation within the project ACTIVE HONEY: Innovative formulations of main bee products using natural ingredients. 2019-2022 - Technological Center for the Industrial Development (CDTI) EXP 00116482/INNO-20182004

Purpose: Clinically useful molecular markers predicting the clinical course of patients diagnosed with non–muscle-invasive bladder cancer are needed to improve treatment outcome. Here, we validated four previously reported gene expression signatures for molecular diagnosis of disease stage and carcinoma in situ (CIS) and for predicting disease recurrence and progression.Experimental Design: We analyzed tumors from 404 patients diagnosed with bladder cancer in hospitals in Denmark, Sweden, England, Spain, and France using custom microarrays. Molecular classifications were compared with pathologic diagnosis and clinical outcome.Results: Classification of disease stage using a 52-gene classifier was found to be highly significantly correlated with pathologic stage (P < 0.001). Furthermore, the classifier added information regarding disease progression of Ta or T1 tumors (P < 0.001). The molecular 88-gene progression classifier was highly significantly correlated with progression-free survival (P < 0.001) and cancer-specific survival (P = 0.001). Multivariate Cox regression analysis showed the progression classifier to be an independently significant variable associated with disease progression after adjustment for age, sex, stage, grade, and treatment (hazard ratio, 2.3; P = 0.007). The diagnosis of CIS using a 68-gene classifier showed a highly significant correlation with histopathologic CIS diagnosis (odds ratio, 5.8; P < 0.001) in multivariate logistic regression analysis.Conclusion: This multicenter validation study confirms in an independent series the clinical utility of molecular classifiers to predict the outcome of patients initially diagnosed with non–muscle-invasive bladder cancer. This information may be useful to better guide patient treatment.

Supplementary Table 2 from Gene Expression Signatures Predict Outcome in Non–Muscle-Invasive Bladder Carcinoma: A Multicenter Validation Study

Supplementary Figures S1-S2 from Gene Expression Signatures Predict Outcome in Non–Muscle-Invasive Bladder Carcinoma: A Multicenter Validation Study

Supplementary Table 1 from Gene Expression Signatures Predict Outcome in Non–Muscle-Invasive Bladder Carcinoma: A Multicenter Validation Study

Metabolic dysfunction–associated fatty liver disease (MAFLD) is nowadays considered the liver manifestation of metabolic syndrome. Its prevalence is increasing worldwide in parallel to the epidemic of diabetes and obesity. MAFLD includes a wide spectrum of liver injury including simple steatosis and non-alcoholic steatohepatitis (NASH) that may lead to serious complications such as liver cirrhosis and liver cancer. The complexity of its pathophysiology and the intricate mechanisms underlying disease progression explains the huge variety of molecules targeting diverse biological mechanisms that have been tested in preclinical and clinical settings in the last two decades. Thanks to the large number of clinical trials of the last few years, most of them still ongoing, the pharmacotherapy scenario of MAFLD is rapidly evolving. The three major components of MAFLD, steatosis, inflammation, and fibrosis seem to be safely targeted with different agents at least in a large proportion of patients. Likely, in the next few years more than one drug will be approved for the treatment of MAFLD at different disease stages. The aim of this review is to synthesize the characteristics and the results of the most advanced clinical trials for the treatment of NASH to evaluate the recent advances of pharmacotherapy in this disease.

The Mars Environmental Dynamics Analyzer (MEDA) instrument, on board the NASA’s Mars 2020 Perseverance rover, includes a number of sensors to characterize the Martian atmosphere. One of this sensors is the Radiation and Dust Sensor (RDS) that measures the solar irradiance at different wavelengths and geometries. We analyzed the RDS observations made during twilight for the period between sol 71 and 492 of the mission (Ls 39◦-262◦) to characterize the clouds over the Perseverance rover site. Using the ratio between the irradiance at zenith at 450 and 750 nm, we inferred that the main constituent of the detected high-altitude aerosol layers was ice from Ls= 39◦ to 150◦ (cloudy period), an dust from Ls 150◦-262◦. A total of 161 twilights were analyzed in the cloudy period using a radiative transfer code and we found: i) signatures of clouds/hazes in the signals in the 58 % of the twilights; ii) most of the clouds had altitudes between 40-50 km, suggesting water ice composition, and had particle sizes between 0.6 and 2 μm; iii) the cloud activity at sunrise is slightly higher that at sunset, likely due to the differences in temperature; iv) the time period with more cloud detections and with the greatest cloud opacities is during Ls 120◦-150◦; and v) a notable decrease in the cloud activity around the aphelion, along with lower cloud altitudes and opacities. This decrease in cloud activity indicates lower concentrations of water vapor or cloud condensation nuclei (dust) around this period in the Martian mesosphere.

The present work is focused on the development of an analytical platform to elucidate the metabolic pathway of PTSO from onion, an organosulfur compound well-known for its functional and technological properties and its potential application in animal and human nutrition. This analytical platform consisted of the use of gas chromatography–mass spectrometry (GC-MS) and ultra-high performance liquid chromatography quadrupole with time-of-flight MS (UHPLC-Q-TOF-MS) in order to monitor volatile and non-volatile compounds derived from the PTSO. For the extraction of the compounds of interest, two different sample treatments were developed: liquid–liquid extraction (LLE) and salting-out assisted liquid–liquid extraction (SALLE) for GC–MS and UHPLC-Q-TOF-MS analysis, respectively. Once the analytical platform was optimised and validated, an in vivo study was planned to elucidate PTSO metabolisation, revealing the presence of dipropyl disulfide (DPDS) in liver samples with concentrations between 0.11 and 0.61 µg g−1. The DPDS maximum concentration in the liver was observed at 0.5 h after the intake. DPDS was also present in all plasma samples with concentrations between 2.1 and 2.4 µg mL−1. In regard to PTSO, it was only found in plasma at times above 5 h (0.18 µg mL−1). Both PTSO and DPDS were excreted via urine 24 h after ingestion., Spanish MICINN (PGC2018-098363-B-100), the University of Murcia (R-1328/2018), European Commission (FEDER/ERDF), CIBEREHD is funded by the Instituto de Salud Carlos III

Following the successful launch of the Spanish PAZ mission the proof of concept experiment ¿Radio Occultation and Heavy Precipitation with PAZ¿ (ROHP-PAZ) started operating in May 2018. The ROHP-PAZ observations demonstrated that precise measurements of the phase shift between horizontal and vertical polarizations from Global Navigation Satellite System (GNSS) L-band signals are sensitive to oriented hydrometeors along the ray paths. While this differential phase shift measurement as a function of time has proven very useful, the regular radio occultation (RO) intermediate products from different polarized channels, such as bending angle and phase retrievals on the domain of impact parameter, have never been exploited. In this research, we studied the characteristics of polarimetric phase and bending angle difference retrieved by the radio-holographic (RH) method to mitigate atmospheric multipath effect and to explore their use in data assimilation. To validate RH approach in polarimetric retrievals, we performed end-to-end simulations where the hydrometeors are modeled by the effective refractivity with different horizontal extents. The simulation results demonstrate that the strong precipitation (>15 mm h^-1) with 40-km horizontal extent can be detected with the retrieved bending angle shift. The calibration process on the impact parameter domain has also been developed to extract the differential phase and bending angle shift from the actual polarimetric RO data. Statistics from the PAZ data shows that the mean retrieved RH polarimetric phase shift with various horizontal extent is approximately proportional to the tangent point location rain rate at a ratio of 0.02 rad (mm h^-1)^-1, It is supported by NASA ROSES Earth Science U.S. Participating Investigator Program 14-ESUSPI14-0014. The GNSS PRO experiment aboard PAZ is funded by the Spanish Grant MCI RTI2018-099008-B-C21/AEI/10.13039/501100011033/ERDF. E.C. is member of the EUMETSAT ROM SAF.