Janus Kinase Inhibitors and Coronavirus Disease (COVID)-19: Rationale, Clinical Evidence and Safety Issues

: We are witnessing a paradigm shift in drug development and clinical practice to fight the novel coronavirus disease (COVID-19), and a number of clinical trials have been or are being testing various pharmacological approaches to counteract viral load and its complications such as cytokine storm. However, data on the effectiveness of antiviral and immune therapies are still inconclusive and inconsistent. As compared to other candidate drugs to treat COVID-19, Janus Kinase (JAK) inhibitors, including baricitinib and ruxolitinib, possess key pharmacological features for a potentially successful repurposing: convenient oral administration, favorable pharmacokinetic profile, multifunctional pharmacodynamics by exerting dual anti-inflammatory and anti-viral effects. Baricitinib, originally approved for rheumatoid arthritis, received Emergency Use Authorization in November 2020 by the Food and Drug Administration in combination with remdesivir for the treatment of COVID-19 in hospitalized patients ≥ 2 years old who require supplemental oxygen, invasive mechanical ventilation, or extracorporeal membrane oxygenation. By July 2021, the European Medicines Agency is also expected to issue the opinion on whether or not to extend its use in hospitalised patients from 10 years of age who require supplemental oxygen. Ruxolitinib, approved for myelofibrosis, was prescribed in patients with COVID-19 within an open-label Emergency Expanded Access Plan. This review will address key milestones in the discovery and use of JAK inhibitors in COVID-19, from artificial intelligence to current clinical evidence, including real world experience, and critically appraise emerging safety issues, namely infections, thrombosis, and liver injury. An outlook to ongoing studies (clinicaltrials.gov) and unpublished pharmacovigilance data is also offered

Opportunities from Doping of Non-Critical Metal Oxides in Last Generation Light-Conversion Devices

The need to develop sustainable energy solutions is an urgent requirement for society, with the additional requirement to limit dependence on critical raw materials, within a virtuous circular economy model. In this framework, it is essential to identify new avenues for light-conversion into clean energy and fuels exploiting largely available materials and green production methods. Metal oxide semiconductors (MOSs) emerge among other species for their remarkable environmental stability, chemical tunability, and optoelectronic properties. MOSs are often key constituents in next generation energy devices, mainly in the role of charge selective layers. Their use as light harvesters is hitherto rather limited, but progressively emerging. One of the key strategies to boost their properties involves doping, that can improve charge mobility, light absorption and tune band structures to maximize charge separation at heterojunctions. In this review, effective methods to dope MOSs and to exploit the derived benefits in relation to performance enhancement in different types of devices are identified and critically compared. The work is focused specifically on the best opportunities coming from the use of non-critical raw materials, so as to contribute in defining an economically feasible roadmap for light conversion technologies based on these highly stable and widely available compounds

Lung anatomy, energy load, and ventilator-induced lung injury

High tidal volume can cause ventilator-induced lung injury (VILI), but positive end-expiratory pressure (PEEP) is thought to be protective. We aimed to find the volumetric VILI threshold and see whether PEEP is protective per se or indirectly

Optimal quantum cloning of orbital angular momentum photon qubits via Hong-Ou-Mandel coalescence

The orbital angular momentum (OAM) of light, associated with a helical structure of the wavefunction, has a great potential for quantum photonics, as it allows attaching a higher dimensional quantum space to each photon. Hitherto, however, the use of OAM has been hindered by its difficult manipulation. Here, exploiting the recently demonstrated spin-OAM information transfer tools, we report the first observation of the Hong-Ou-Mandel coalescence of two incoming photons having nonzero OAM into the same outgoing mode of a beam-splitter. The coalescence can be switched on and off by varying the input OAM state of the photons. Such effect has been then exploited to carry out the 1 \rightarrow 2 universal optimal quantum cloning of OAM-encoded qubits, using the symmetrization technique already developed for polarization. These results are finally shown to be scalable to quantum spaces of arbitrary dimension, even combining different degrees of freedom of the photons.Comment: 5 pages, 3 figure

Disentangling nonradiative recombination processes in Ge micro-crystals on Si substrates

We address nonradiative recombination pathways by leveraging surface passivation and dislocation management in μm-scale arrays of Ge crystals grown on deeply patterned Si substrates. The time decay photoluminescence (PL) at cryogenic temperatures discloses carrier lifetimes approaching 45 ns in band-gap engineered Ge micro-crystals. This investigation provides compelling information about the competitive interplay between the radiative band-edge transitions and the trapping of carriers by dislocations and free surfaces. Furthermore, an in-depth analysis of the temperature dependence of the PL, combined with capacitance data and finite difference time domain modeling, demonstrates the effectiveness of GeO2 in passivating the surface of Ge and thus in enhancing the room temperature PL emission

A Recent Class of Chemosensory Neurons Developed in Mouse and Rat

In most animal species, the vomeronasal organ ensures the individual recognition of conspecifics, a prerequisite for a successful reproduction. The vomeronasal organ expresses several receptors for pheromone detection. Mouse vomeronasal type-2 receptors (V2Rs) are restricted to the basal neurons of this organ and organized in four families. Family-A, B and D (family ABD) V2Rs are expressed monogenically (one receptor per neuron) and coexpress with either Vmn2r1 or Vmn2r2, two members of family-C V2Rs. Thus, basal neurons are characterized by specific combinations of two V2Rs. To investigate this issue, we raised antibodies against all family-C V2Rs and analyzed their expression pattern. We found that six out of seven family-C V2Rs (Vmn2r2-7) largely coexpressed and that none of the anti-Vmn2r2-7 antibodies significantly stained Vmn2r1 positive neurons. Thus, basal neurons are divided into two complementary subsets. The first subset (Vmn2r1-positive) preferentially coexpresses a distinct group of family-ABD V2Rs, whereas the second subset (Vmn2r2-7-positive) coexpresses the remaining group of V2Rs. Phylogenetic reconstruction and the analysis of genetic loci in various species reveal that receptors expressed by this second neuronal subset are recent branches of the V2R tree exclusively present in mouse and rat. Conversely, V2Rs expressed in Vmn2r1 positive neurons, are phylogenetically ancient and found in most vertebrates including rodents. Noticeably, the more recent neuronal subset expresses a type of Major Histocompatibility Complex genes only found in murine species. These results indicate that the expansion of the V2R repertoire in a murine ancestor occurred with the establishment of a new population of vomeronasal neurons in which coexists the polygenic expression of a recent group of family-C V2Rs (Vmn2r2-7) and the monogenic expression of a recent group of family-ABD V2Rs. This evolutionary innovation could provide a molecular rationale for the exquisite ability in individual recognition and mate choice of murine species