Nightside condensation of iron in an ultrahot giant exoplanet.

Ultrahot giant exoplanets receive thousands of times Earth's insolation1,2. Their high-temperature atmospheres (greater than 2,000 kelvin) are ideal laboratories for studying extreme planetary climates and chemistry3-5. Daysides are predicted to be cloud-free, dominated by atomic species6 and much hotter than nightsides5,7,8. Atoms are expected to recombine into molecules over the nightside9, resulting in different day and night chemistries. Although metallic elements and a large temperature contrast have been observed10-14, no chemical gradient has been measured across the surface of such an exoplanet. Different atmospheric chemistry between the day-to-night ('evening') and night-to-day ('morning') terminators could, however, be revealed as an asymmetric absorption signature during transit4,7,15. Here we report the detection of an asymmetric atmospheric signature in the ultrahot exoplanet WASP-76b. We spectrally and temporally resolve this signature using a combination of high-dispersion spectroscopy with a large photon-collecting area. The absorption signal, attributed to neutral iron, is blueshifted by -11 ± 0.7 kilometres per second on the trailing limb, which can be explained by a combination of planetary rotation and wind blowing from the hot dayside16. In contrast, no signal arises from the nightside close to the morning terminator, showing that atomic iron is not absorbing starlight there. We conclude that iron must therefore condense during its journey across the nightside.

Orbital misalignment of the Neptune-mass exoplanet GJ 436b with the spin of its cool star.

The angle between the spin of a star and the orbital planes of its planets traces the history of the planetary system. Exoplanets orbiting close to cool stars are expected to be on circular, aligned orbits because of strong tidal interactions with the stellar convective envelope. Spin-orbit alignment can be measured when the planet transits its star, but such ground-based spectroscopic measurements are challenging for cool, slowly rotating stars. Here we report the three-dimensional characterization of the trajectory of an exoplanet around an M dwarf star, derived by mapping the spectrum of the stellar photosphere along the chord transited by the planet. We find that the eccentric orbit of the Neptune-mass exoplanet GJ 436b is nearly perpendicular to the stellar equator. Both eccentricity and misalignment, surprising around a cool star, can result from dynamical interactions (via Kozai migration) with a yet-undetected outer companion. This inward migration of GJ 436b could have triggered the atmospheric escape that now sustains its giant exosphere.

Clinical characteristics of patients hospitalized for COVID-19: comparison between different age groups.

BACKGROUND: To test whether known prognosticators of COVID-19 maintained their stratification ability across age groups. METHODS: We performed a retrospective study. We included all patients (n = 2225), who presented to the Emergency Department of the Careggi University Hospital for COVID-19 in the period February 2020-May 2021, and were admitted to the hospital. The following parameters were analyzed as dichotomized: 1) SpO2/FiO2 ≤ or > 214; 2) creatinine < or ≥ 1.1 mg/dL; 3) Lactic dehydrogenase (LDH) < or ≥ 250 U/mL; 4) C Reactive Protein (CRP) < or ≥ 60 mg/100 mL. We divided the study population in four subgroups, based on the quartiles of distribution of age (G1 18-57 years, G2 57-71 years, G3 72-81 years, G4 > 82). The primary end-point was in-hospital mortality. RESULTS: By the univariate analysis, the aforementioned dichotomized variables demonstrated a significant association with in-hospital mortality in all subgroups. We introduced them in a multivariate model: in G1 SpO2/FiO2 ≤ 214 (Relative Risk, RR 15.66; 95%CI 3.98-61,74), in G2 creatinine ≥ 1.1 mg/L (RR 2.87, 95%CI 1.30-6.32) and LDH ≥ 250 UI/L (RR 8.71, 95%CI 1,15-65,70), in G3 creatinine ≥ 1.1 mg/L (RR 1.98, 95%CI 1,17-3.36) and CRP ≥ 60 ng/L (RR 2.14, 95%CI 1.23-3.71), in G4 SpO2/FiO2 ≤ 214 (RR 5.15, 95%CI 2.35-11.29), creatinine ≥ 1.1 mg/L (RR 1.75, 95%CI 1.09-2.80) and CRP ≥ 60 ng/L (RR 1.82, 95%CI 1.11-2.98) were independently associated with an increased in-hospital mortality. CONCLUSIONS: A mild to moderate respiratory failure showed an independent association with an increased mortality rate only in youngest and oldest patients, while kidney disease maintained a prognostic role regardless of age.

Liquid biopsy: A promising tool for driving strategies and predicting failures in patients with classic Hodgkin lymphoma.

Classic Hodgkin lymphoma (cHL) consists of a heterogeneous group of haematological disorders that covers undifferentiated B cell neoplasms originating from germinal centre B cells. The HL molecular characterization still represents an ongoing challenge due to the low fraction of tumour Hodgkin and Reed-Sternberg cells mixed with a plethora of non-tumour haematological cells. In this scenario, next generation sequencing of liquid biopsy samples is emerging as a useful tool in HL patients' management. In this review, we aimed to overview the clinical and methodological topics regarding the implementation of molecular analysis in cHL, focusing on the role of liquid biopsy in diagnosis, follow-up, and response prediction.

A temperate rocky super-Earth transiting a nearby cool star.

M dwarf stars, which have masses less than 60 per cent that of the Sun, make up 75 per cent of the population of the stars in the Galaxy. The atmospheres of orbiting Earth-sized planets are observationally accessible via transmission spectroscopy when the planets pass in front of these stars. Statistical results suggest that the nearest transiting Earth-sized planet in the liquid-water, habitable zone of an M dwarf star is probably around 10.5 parsecs away. A temperate planet has been discovered orbiting Proxima Centauri, the closest M dwarf, but it probably does not transit and its true mass is unknown. Seven Earth-sized planets transit the very low-mass star TRAPPIST-1, which is 12 parsecs away, but their masses and, particularly, their densities are poorly constrained. Here we report observations of LHS 1140b, a planet with a radius of 1.4 Earth radii transiting a small, cool star (LHS 1140) 12 parsecs away. We measure the mass of the planet to be 6.6 times that of Earth, consistent with a rocky bulk composition. LHS 1140b receives an insolation of 0.46 times that of Earth, placing it within the liquid-water, habitable zone. With 90 per cent confidence, we place an upper limit on the orbital eccentricity of 0.29. The circular orbit is unlikely to be the result of tides and therefore was probably present at formation. Given its large surface gravity and cool insolation, the planet may have retained its atmosphere despite the greater luminosity (compared to the present-day) of its host star in its youth. Because LHS 1140 is nearby, telescopes currently under construction might be able to search for specific atmospheric gases in the future.

Dynamical Quantum Phase Transitions of the Schwinger Model: Real-Time Dynamics on IBM Quantum.

Simulating the real-time dynamics of gauge theories represents a paradigmatic use case to test the hardware capabilities of a quantum computer, since it can involve non-trivial input states' preparation, discretized time evolution, long-distance entanglement, and measurement in a noisy environment. We implemented an algorithm to simulate the real-time dynamics of a few-qubit system that approximates the Schwinger model in the framework of lattice gauge theories, with specific attention to the occurrence of a dynamical quantum phase transition. Limitations in the simulation capabilities on IBM Quantum were imposed by noise affecting the application of single-qubit and two-qubit gates, which combine in the decomposition of Trotter evolution. The experimental results collected in quantum algorithm runs on IBM Quantum were compared with noise models to characterize the performance in the absence of error mitigation.

FGFR2 testing in cholangiocarcinoma: translating molecular studies into clinical practice.

Cholangiocarcinoma (CCA) is a heterogeneous group of neoplasms burdened by a dismal prognosis. Several studies have investigated the genomic profile of CCA and identified numerous druggable genetic alterations, including FGFR2 fusions/rearrangements. Approximately 5-7% of CCAs and 10-20% of intrahepatic iCCAs harbor FGFR2 fusions. With the recent advent of FGFR-targeting therapies into clinical practice, a standardization of molecular testing for FGFR2 alterations in CCA will be necessary. In this review, we describe the technical aspects and challenges related to FGFR2 testing in routine practice, focusing on the comparison between Next-Generation Sequencing (NGS) and FISH assays, the best timing to perform the test, and on the role of liquid biopsy.

The ideal reporting of RAS testing in colorectal adenocarcinoma: a pathologists' perspective.

RAS gene mutational status represents an imperative predictive biomarker to be tested in the clinical management of metastatic colorectal adenocarcinoma. Even if it is one of the most studied biomarkers in the era of precision medicine, several pre-analytical and analytical factors may still impasse an adequate reporting of RAS status in clinical practice, with significant therapeutic consequences. Thus, pathologists should be aware on the main topics related to this molecular evaluation: (i) adopt diagnostic limit of detections adequate to avoid the interference of sub-clonal cancer cell populations; (ii) choose the most adequate diagnostic strategy according to the available sample and its qualification for molecular testing; (iii) provide all the information regarding the mutation detected, since many RAS mutation-specific targeted therapeutic approaches are in development and will enter into routine clinical practice. In this review, we give a comprehensive description of the current scenario about RAS gene mutational testing in the clinic focusing on the pathologist's role in patient selection for targeted therapies.

Think "HER2" different: integrative diagnostic approaches for HER2-low breast cancer.

This work explores the complex field of HER2 testing in the HER2-low breast cancer era, with a focus on methodological aspects. We aim to propose clear positions to scientific societies, institutions, pathologists, and oncologists to guide and shape the appropriate diagnostic strategies for HER2-low breast cancer. The fundamental question at hand is whether the necessary tools to effectively translate our knowledge about HER2 into practical diagnostic schemes for the lower spectrum of expression are available. Our investigation is centered on the significance of distinguishing between an immunohistochemistry (IHC) score 0 and score 1+ in light of the clinical implications now apparent, as patients with HER2-low breast cancer become eligible for trastuzumab-deruxtecan treatment. Furthermore, we discuss the definition of HER2-low beyond its conventional boundaries and assess the reliability of established diagnostic procedures designed at a time when therapeutic perspectives were non-existent for these cases. In this regard, we examine potential complementary technologies, such as gene expression analysis and liquid biopsy. Ultimately, we consider the potential role of artificial intelligence (AI) in the field of digital pathology and its integration into HER2 testing, with a particular emphasis on its application in the context of HER2-low breast cancer.

Refocusing Algorithm for Correlation Plenoptic Imaging.

Correlation plenoptic imaging (CPI) is a technique capable of acquiring the light field emerging from a scene of interest, namely, the combined information of intensity and propagation direction of light. This is achieved by evaluating correlations between the photon numbers measured by two high-resolution detectors. Volumetric information about the object of interest is decoded, through data analysis, from the measured four-dimensional correlation function. In this paper, we investigate the relevant aspects of the refocusing algorithm, a post-processing method that isolates the image of a selected transverse plane within the 3D scene, once applied to the correlation function. In particular, we aim at bridging the gap between existing literature, which only deals with refocusing algorithms in case of continuous coordinates, and the experimental reality, in which the correlation function is available as a discrete quantity defined on the sensors pixels.

Effect of Finite-Sized Optical Components and Pixels on Light-Field Imaging through Correlated Light.

Diffraction-limited light-field imaging has been recently achieved by exploiting light spatial correlations measured on two high-resolution detectors. As in conventional light-field imaging, the typical operations of refocusing and 3D reconstruction are based on ray tracing in a geometrical optics context, and are thus well defined in the ideal case, both conceptually and theoretically. However, some properties of the measured correlation function are influenced by experimental features such as the finite size of apertures, detectors, and pixels. In this work, we take into account realistic experimental conditions and analyze the resulting correlation function through theory and simulation. We also provide an expression to evaluate the pixel-limited resolution of the refocused images, as well as a strategy for eliminating artifacts introduced by the finite size of the optical elements.

B7-H3/CD276 Inhibitors: Is There Room for the Treatment of Metastatic Non-Small Cell Lung Cancer?

The striking clinical outcomes of antibody-based immunotherapy, through the inhibitors of cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) and the programmed cell death protein-1 (PD-1) and its ligand (PD-L1) axis, have driven research aimed at identifying further clinically relevant tumor antigens that can serve as targets in solid tumors. B7 homolog 3 protein (B7-H3, also known as CD276) is a member of the B7 family overexpressed in tumor tissues, including non-small cell lung cancer (NSCLC), while showing limited expression in normal tissues, becoming an attractive and promising target for cancer immunotherapy. B7-H3 expression in tumors has been demonstrated to be associated with poor prognosis. In addition to its role in immune modulation, B7-H3 also promotes pro-tumorigenic functions such as tumor migration, invasion, metastases, resistance, and metabolism. In this review, we will provide an overview of this newly characterized immune checkpoint molecule and its development in the management of metastatic NSCLC.

Evaluation of the Molecular Landscape in PD-L1 Positive Metastatic NSCLC: Data from Campania, Italy.

BACKGROUND: Immune-checkpoint inhibitors (ICIs) have increased and improved the treatment options for patients with non-oncogene-addicted advanced stage non-small cell lung cancer (NSCLC). However, the role of ICIs in oncogene-addicted advanced stage NSCLC patients is still debated. In this study, in an attempt to fill in the informational gap on the effect of ICIs on other driver mutations, we set out to provide a molecular landscape of clinically relevant oncogenic drivers in programmed death-ligand 1 (PD-L1) positive NSCLC patients. METHODS: We retrospectively reviewed data on 167 advanced stage NSCLC PD-L1 positive patients (≥1%) who were referred to our clinic for molecular evaluation of five driver oncogenes, namely, EGFR, KRAS, BRAF, ALK and ROS1. RESULTS: Interestingly, n = 93 (55.7%) patients showed at least one genomic alteration within the tested genes. Furthermore, analyzing a subset of patients with PD-L1 tumor proportion score (TPS) ≥ 50% and concomitant gene alterations (n = 8), we found that n = 3 (37.5%) of these patients feature clinical benefit with ICIs administration, despite the presence of a concomitant KRAS gene alteration. CONCLUSIONS: In this study, we provide a molecular landscape of clinically relevant biomarkers in NSCLC PD-L1 positive patients, along with data evidencing the clinical benefit of ICIs in patient NSCLC PD-L1 positive alterations.

A rocky planet transiting a nearby low-mass star.

M-dwarf stars--hydrogen-burning stars that are smaller than 60 per cent of the size of the Sun--are the most common class of star in our Galaxy and outnumber Sun-like stars by a ratio of 12:1. Recent results have shown that M dwarfs host Earth-sized planets in great numbers: the average number of M-dwarf planets that are between 0.5 to 1.5 times the size of Earth is at least 1.4 per star. The nearest such planets known to transit their star are 39 parsecs away, too distant for detailed follow-up observations to measure the planetary masses or to study their atmospheres. Here we report observations of GJ 1132b, a planet with a size of 1.2 Earth radii that is transiting a small star 12 parsecs away. Our Doppler mass measurement of GJ 1132b yields a density consistent with an Earth-like bulk composition, similar to the compositions of the six known exoplanets with masses less than six times that of the Earth and precisely measured densities. Receiving 19 times more stellar radiation than the Earth, the planet is too hot to be habitable but is cool enough to support a substantial atmosphere, one that has probably been considerably depleted of hydrogen. Because the host star is nearby and only 21 per cent the radius of the Sun, existing and upcoming telescopes will be able to observe the composition and dynamics of the planetary atmosphere.

Next generation sequencing in cytology.

The application of next generation sequencing (NGS) technology to cytological samples has significantly modified molecular cytopathology practice. Cytological samples represent a valid source of high-quality DNA for NGS analysis, especially for predicting patients' response to targeted treatments and for refining the risk of malignancy in indeterminate cytological diagnoses. However, several pre-analytical factors may influence the reliability of NGS clinical analysis. Here, we briefly review the challenges of NGS in cytology practice, focusing on those pre-analytical factors that may negatively affect NGS success rates and routine diagnostic applications. Finally, we address the future directions of the field.

Correlation plenoptic imaging between arbitrary planes.

We propose a novel method to perform plenoptic imaging at the diffraction limit by measuring second-order correlations of light between two reference planes, arbitrarily chosen, within the tridimensional scene of interest. We show that for both chaotic light and entangled-photon illumination, the protocol enables to change the focused planes, in post-processing, and to achieve an unprecedented combination of image resolution and depth of field. In particular, the depth of field results larger by a factor 3 with respect to previous correlation plenoptic imaging protocols, and by an order of magnitude with respect to standard imaging, while the resolution is kept at the diffraction limit. The results lead the way towards the development of compact designs for correlation plenoptic imaging devices based on chaotic light, as well as high-SNR plenoptic imaging devices based on entangled photon illumination, thus contributing to make correlation plenoptic imaging effectively competitive with commercial plenoptic devices.

Instrumentation for the detection and characterization of exoplanets.

In no other field of astrophysics has the impact of new instrumentation been as substantial as in the domain of exoplanets. Before 1995 our knowledge of exoplanets was mainly based on philosophical and theoretical considerations. The years that followed have been marked, instead, by surprising discoveries made possible by high-precision instruments. Over the past decade, the availability of new techniques has moved the focus of research from the detection to the characterization of exoplanets. Next-generation facilities will produce even more complementary data that will lead to a comprehensive view of exoplanet characteristics and, by comparison with theoretical models, to a better understanding of planet formation.

[Liquid biopsy as indication of tumour progression in lung cancer: a potential intervention in tertiary prevention]. / La biopsia liquida quale segnale di progressione tumorale nel carcinoma polmonare: potenziale di intervento in prevenzione terziaria.

In the era of personalised therapies, liquid biopsy is considered an important diagnostic tool in the clinical management of cancer patients. Tissue specimen represents the gold standard for molecular evaluation of specific gene targets alterations that lead cancer patients to benefit of a "tailed therapy" based on molecular features of the tumour. This innovative source of nucleic acids was introduced in clinical setting only for non-small-cell lung cancer (NSCLC) patients to test epidermal grow factor receptor (EGFR) mutations when tissue is not available for a number of reasons (difficult access to the lesion, the presence of other disabling pathologies, especially in elderly patients, rejection by the patient, etcetera) or to monitor acquired resistance mutation after a first line of treatment. The present study aimed at assessing the diagnostic potential of liquid biopsy in balanced tertiary screening modelling. The cases relating to 5 years of activity regarding to molecular diagnostics performed on liquid biopsy specimens in the Predictive diagnostic laboratory of the University hospital "Federico II" of Naples (Campania Region, Southern Italy) were reviewed. Laboratory data were collected through the software SPSS. Non-parametric analysis was performed in order to test the differences between "wild type" patients or not. A multivariate logistic model was performed in order to assess the effect of mutation, age, and gender on the tumour progression. The results of the revision concern 515 total cases (almost of all plasma or peripheral blood), which allowed to evaluate the liquid biopsies for women and men. The average age of the patients is 66.3 years, and the 25° percentile is 59 years. The cases are: 221 basal and 294 by progression. The cases with mutation, as expected, have an odds ratio of 4,15, compared to the basal, to have a tumour progression (95%IC 2,7-6,3), regardless of gender and age. The detected mutations were 131 from different types of pulmonary carcinomas. Working on case data, specifying the characteristics of the patients with mutations will drive a further estimate in tertiary prevention screening designs.

Visible blue-to-red 10 GHz frequency comb via on-chip triple-sum-frequency generation.

A broadband visible (VIS) blue-to-red, 10 GHz repetition rate frequency comb is generated by combined spectral broadening and triple-sum-frequency generation in an on-chip silicon nitride waveguide. Ultra-short pulses of 150 pJ pulse energy, generated via electro-optic modulation of a 1560 nm continuous-wave laser (CW), are coupled to a silicon nitride waveguide giving rise to a broadband near-infrared (NIR) supercontinuum. Modal phase matching inside the waveguide allows direct triple-sum-frequency transfer of the NIR supercontinuum into the VIS wavelength range covering more than 250 THz from below 400 to above 600 nm wavelength. This scheme directly links the mature optical telecommunication band technology to the VIS wavelength band and can find application in astronomical spectrograph calibration, as well as referencing of CW lasers.

Experimental Investigation of Quantum Decay at Short, Intermediate, and Long Times via Integrated Photonics.

The decay of an unstable system is usually described by an exponential law. Quantum mechanics predicts strong deviations of the survival probability from the exponential: Indeed, the decay is initially quadratic, while at very large times it follows a power law, with superimposed oscillations. The latter regime is particularly elusive and difficult to observe. Here we employ arrays of single-mode optical waveguides, fabricated by femtosecond laser direct inscription, to implement quantum systems where a discrete state is coupled and can decay into a continuum. The optical modes correspond to distinct quantum states of the photon, and the temporal evolution of the quantum system is mapped into the spatial propagation coordinate. By injecting coherent light states in the fabricated photonic structures and by measuring a small scattered fraction of such light with an unprecedented dynamic range, we are able to experimentally observe not only the exponential decay regime, but also the quadratic Zeno region and the power-law decay at long evolution times.