Machine learning approaches to predict TAS2R receptors for bitterants.

Bitter taste involves the detection of diverse chemical compounds by a family of G protein-coupled receptors, known as taste receptor type 2 (TAS2R). It is often linked to toxins and harmful compounds and in particular bitter taste receptors participate in the regulation of glucose homeostasis, modulation of immune and inflammatory responses, and may have implications for various diseases. Human TAS2Rs are characterized by their polymorphism and differ in localization and function. Different receptors can activate various signaling pathways depending on the tissue and the ligand. However, in vitro screening of possible TAS2R ligands is costly and time-consuming. For this reason, in silico methods to predict bitterant-TAS2R interactions could be powerful tools to help in the selection of ligands and targets for experimental studies and improve our knowledge of bitter receptor roles. Machine learning (ML) is a branch of artificial intelligence that applies algorithms to large datasets to learn from patterns and make predictions. In recent years, there has been a record of numerous taste classifiers in literature, especially on bitter/non-bitter or bitter/sweet classification. However, only a few of them exploit ML to predict which TAS2R receptors could be targeted by bitter molecules. Indeed, the shortage and incompleteness of data on receptor-ligand associations in literature make this task non-trivial. In this work, we provide an overview of the state of the art dealing with this specific investigation, focusing on three ML-based models, namely BitterX (2016), BitterSweet (2019) and BitterMatch (2022). This review aims to establish the foundation for future research endeavours focused on addressing the limitations and drawbacks of existing models.

Quantum Fluctuation Dynamics of Dispersive Superradiant Pulses in a Hybrid Light-Matter System.

We consider theoretically a driven-dissipative quantum many-body system consisting of an atomic ensemble in a single-mode optical cavity as described by the open Tavis-Cummings model. In this hybrid light-matter system, the interplay between coherent and dissipative processes leads to superradiant pulses with a buildup of strong correlations, even for systems comprising hundreds to thousands of particles. A central feature of the mean-field dynamics is a self-reversal of two spin degrees of freedom due to an underlying time-reversal symmetry, which is broken by quantum fluctuations. We demonstrate a quench protocol that can maintain highly non-Gaussian states over long timescales. This general mechanism offers interesting possibilities for the generation and control of complex fluctuation patterns, as suggested for the improvement of quantum sensing protocols for dissipative spin amplification.

Dissipation-Engineered Family of Nearly Dark States in Many-Body Cavity-Atom Systems.

Three-level atomic systems coupled to light have the capacity to host dark states. We study a system of V-shaped three-level atoms coherently coupled to the two quadratures of a dissipative cavity. The interplay between the atomic level structure and dissipation makes the phase diagram of the open system drastically different from the closed one. In particular, it leads to the stabilization of a continuous family of dark and nearly dark excited many-body states with inverted atomic populations as the steady states. The multistability of these states can be probed via their distinct fluctuations and excitation spectra, as well as the system's Liouvillian dynamics which are highly sensitive to ramp protocols. Our model can be implemented experimentally by encoding the two higher-energy modes in orthogonal density-modulated states in a bosonic quantum gas. This implementation offers prospects for potential applications like the realization of quantum optical random walks and microscopy with subwavelength spatial resolution.

Observing Dynamical Currents in a Non-Hermitian Momentum Lattice.

We report on the experimental realization and detection of dynamical currents in a spin-textured lattice in momentum space. Collective tunneling is implemented via cavity-assisted Raman scattering of photons by a spinor Bose-Einstein condensate into an optical cavity. The photon field inducing the tunneling processes is subject to cavity dissipation, resulting in effective directional dynamics in a non-Hermitian setting. We observe that the individual tunneling events are superradiant in nature and locally resolve them in the lattice by performing real-time, frequency-resolved measurements of the leaking cavity field. The results can be extended to a regime exhibiting a cascade of currents and simultaneous coherences between multiple lattice sites, where numerical simulations provide further understanding of the dynamics. Our observations showcase dynamical tunneling in momentum-space lattices and provide prospects to realize dynamical gauge fields in driven-dissipative settings.

At the peak of COVID-19 age and disease severity but not comorbidities are predictors of mortality: COVID-19 burden in Bergamo, Italy.

BACKGROUND: Findings from February 2020, indicate that the clinical spectrum of COVID-19 can be heterogeneous, probably due to the infectious dose and viral load of SARS-CoV-2 within the first weeks of the outbreak. The aim of this study was to investigate predictors of overall 28-day mortality at the peak of the Italian outbreak. METHODS: Retrospective observational study of all COVID-19 patients admitted to the main hospital of Bergamo, from February 23 to March 14, 2020. RESULTS: Five hundred and eight patients were hospitalized, predominantly male (72.4%), mean age of 66±15 years; 49.2% were older than 70 years. Most of patients presented with severe respiratory failure (median value [IQR] of PaO2/FiO2: 233 [149-281]). Mortality rate at 28 days resulted of 33.7% (N.=171). Thirty-nine percent of patients were treated with continuous positive airway pressure (CPAP), 9.5% with noninvasive ventilation (NIV) and 13.6% with endotracheal intubation. 9.5% were admitted to Semi-Intensive Respiratory Care Unit, and 18.9% to Intensive Care Unit. Risk factors independently associated with 28-day mortality were advanced age (≥78 years: odds ratio [OR], 95% confidence interval [CI]: 38.91 [10.67-141.93], P<0.001; 70-77 years: 17.30 [5.40-55.38], P<0.001; 60-69 years: 3.20 [1.00-10.20], P=0.049), PaO2/FiO2<200 at presentation (3.50 [1.70-7.20], P=0.001), need for CPAP/NIV in the first 24 hours (8.38 [3.63-19.35], P<0.001), and blood urea value at admission (1.01 [1.00-1.02], P=0.015). CONCLUSIONS: At the peak of the outbreak, with a probable high infectious dose and viral load, older age, the severity of respiratory failure and renal impairment at presentation, but not comorbidities, are predictors of 28-day mortality in COVID-19.

Overlapping two standing waves in a microcavity for a multi-atom photon interface.

We develop a light-matter interface enabling strong and uniform coupling between a chain of cold atoms and photons of an optical cavity. This interface is a fiber Fabry-Perot cavity, doubly resonant for both the wavelength of the atomic transition and for a geometrically commensurate red-detuned intracavity trapping lattice. Fulfilling the condition of a strong and uniform atom-photon coupling requires optimization of the spatial overlap between the two standing waves in the cavity. In a strong-coupling cavity, where the mode waists and Rayleigh range are small, we derive the expression of the optimal trapping wavelength, taking into account the Gouy phase. The main parameter controlling the overlap of the standing waves is the relative phase shift at the reflection on the cavity mirrors between the two wavelengths, for which we derive the optimal value. We have built a microcavity optimized according to these results, employing custom-made mirrors with engineered reflection phase for both wavelengths. We present a method to measure with high precision the relative phase shift at reflection, which allows us to determine the spatial overlap of the two modes in this cavity.

Mapping optical standing-waves of an open-access Fabry-Perot cavity with a tapered fiber.

We describe a method to map the standing-wave pattern inside an open-access Fabry-Perot optical cavity with sub-wavelength resolution by perturbing it with a commercially available tapered fiber. The method is applied to a fiber Fabry-Perot microcavity. We demonstrate its use in determining the relative position of the antinodes at two different wavelengths. In addition, we use the tapered optical fiber as a point-like source, allowing precise positioning of a microscope objective with respect to the cavity mode.

Acute and Subacute Outcome Predictors in Moderate and Severe Traumatic Brain Injury: A Retrospective Monocentric Study.

BACKGROUND: Prognostic factors affecting outcome of traumatic brain injury (TBI), despite their importance, are still under discussion. The purpose of this study was to describe risk factors of in-hospital mortality and outcome at 1 year in a homogeneously treated population of patients with moderate/severe TBI. METHODS: A total of 193 consecutive patients with moderate or severe TBI (Glasgow Coma Scale [GCS] score 13-3, including patients with initial GCS score of 13 at high risk for subsequent neurologic deterioration), admitted to the intensive care unit, were retrospectively analyzed. In-hospital mortality and unfavorable outcome at 1 year, based on a Glasgow Outcome Scale-Extended score ≤4, were considered as primary and secondary outcomes. RESULTS: At 1 year, unfavorable outcome occurred in 47.2%, including an in-hospital mortality of 19.7%. Increasing age, GCS motor score <3, coagulation disorders, and intracranial hypertension were acute risk factors of in-hospital mortality. In the 155 remaining survivors, Oxford Handicap Scale (OHS), posttraumatic cerebral infarction, cerebrospinal fluid disturbances, and length of intensive care unit stay were associated with unfavorable outcome at 1 year, in univariate analysis. A cutoff OHS score ≥3 discriminated the probability of an unfavorable outcome (area under the curve, 0.87; P < 0.001; specificity, 74%; sensitivity, 84%). Combining the effect of acute and subacute variables in a multivariate analysis, increasing age and OHS score were independent predictors of outcome. CONCLUSIONS: The results of this retrospective study confirmed age as the main acute risk factor and identified OHS as new potential subacute predictor of unfavorable outcome in moderate and severe TBI.

Dual-wavelength fiber Fabry-Perot cavities with engineered birefringence.

We present a method to engineer the frequency splitting of polarization eigenmodes in fiber Fabry-Perot (FFP) cavities. Using specific patterns of multiple CO2 laser pulses, we machine paraboloidal micromirrors with controlled elliptical shape in a large range of radii of curvature. This method is versatile and can be used to produce cavities with maximized or near-zero polarization mode splitting. In addition, we realize dual-wavelength FFP cavities with finesse exceeding 40 000 at 780 nm and at 1559 nm in the telecom range. We provide direct evidence that the birefringent frequency splitting in FFP cavities is governed only by the geometrical shape of the mirrors, and that the astigmatism of the cavity modes needs to be taken into account for specific cavities.

Extracorporeal life support in a severe Taxus baccata poisoning.

INTRODUCTION: Yew (Taxus baccata) is a conifer known to be toxic since ancient times. Taxine A and taxine B, the toxic alkaloids of Taxus, block cardiac sodium and calcium channels causing nausea, vomiting, abdominal pain, cardiac arrhythmias, respiratory distress, coma, seizures, and death in yew poisoning. CASE REPORT: A 44-year-old male farmer was admitted to the hospital because of a suspected myocardial infarction. First bradycardia and then ventricular tachycardia were present and a severe right ventricular dilatation with biventricular dysfunction was observed but with normal coronary arteriography. He was resistant to conventional therapy and, 6 h after hospital admission, extracorporeal support with membrane oxygenation was applied. The patient recovered. Nine days later, a large number of yew leaves were unexpectedly observed in his feces. Botanical and laboratory analysis confirmed the poisoning. Blood (651 ng/mL) and urinary (5.6 mcg/mL) levels of 3,5-dimethoxyphenol (metabolite of taxicatine) were greater than previously reported in lethal cases. The patient was transferred to a psychiatric unit 17 days after admission. CONCLUSIONS: Intensive treatment of severe cardiovascular symptoms with antiarrhythmic drugs, temporary pacemaker, intra-aortic balloon pump, extracorporeal membrane oxygenation, and extracorporeal life support can be life-saving even after a potentially lethal ingestion of T. baccata leaves.

Ineffectiveness of local wound anesthesia to reduce postoperative pain after median sternotomy.

Postoperative pain control still represents a major challenge in every surgical field. Bupivacaine wound infiltration is frequently used to reduce the pain related to the surgical incision itself. In this randomized study, we investigated the efficacy of bupivacaine local anesthesia after median sternotomy to reduce postoperative pain. Forty-seven patients undergoing major cardiac surgery procedures were allocated randomly to group A (bupivacaine wound infiltration 0.5%; 10 mL, followed by continuous infusion: 10 mg/24 H) or to group C (controls). Extubation time, postoperative arterial blood gases, postoperative pain (assessed by means of a visual analog scale), and morphine consumption were the endpoints of the study. Patients of group C were extubated earlier; blood gases and VAS values were similar in both group. Bupivacaine local analgesia did not improve postoperative pain control after median sternotomy.