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We investigated the capacitance of a forward-biased silicon pn diode using impedance spectroscopy. Despite extensive research spanning decades, no single model in the literature adequately describes the impedance behavior for bias up to the built-in voltage. By employing the 1N4007 diode as a case study, we analyzed the impedance over a wide frequency range, from 1 Hz to 1 MHz. Our analysis reveals that impedance can be effectively studied by combining two models. In both models, the depletion capacitance is assumed to be an ideal capacitor with a value independent of frequency. One model accounts for diffusion processes, while the other addresses interfacial effects, as well as potential and capacitance distributions across the junction. This approach offers valuable insights into the complex capacitance behavior of pn junctions as a function of the bias voltage. Measurements of depletion and diffusion capacitances, as well as of the diode transit time can be achieved from a set of impedance spectroscopy data. [ABSTRACT FROM AUTHOR]

BackgroundLeft bundle branch (LBB) pacing could achieve cardiac resynchronization therapy (CRT) in patients who cannot be resynchronized via the placement of the left ventricle (LV) lead into the coronary sinus. LBB pacing could improve cardiovascular outcomes in heart failure (HF) patients with LBB block who are affected by type 2 diabetes mellitus (T2DM).Study hypothesisLBB pacing could increase the number of CRT responders and lead to the best clinical outcomes in HF patients with T2DM, inducing cardiac remodeling and improving left ventricle ejection fraction (LVEF) via microRNA (miR) modulation.MethodsIn a multicenter observational study, we enrolled 334 HF patients with LBB block and an indication to receive LBB pacing for CRT. In these patients, we evaluated the CRT responder rate, clinical outcomes, and miR expression at 1 year of follow-up.ResultsAt 1 year of follow-up, we had 223 responders (66.8%), 132 hospitalizations for HF (39.5%), 24 cardiac deaths (7.2%), and 37 all-cause deaths (11.1%), with a higher rate of HF hospitalizations (77 (69.4%) vs 55 (24.7%), p < 0.05), and cardiac deaths (13 (11.7% vs 11 (4.9%), p < 0.05) in non-responders vs responders. At the end of follow-up, we found the lowest expression of miR-26, miR-29, miR-30, miR-92, and miR-145 in LBB-pacing non-responders vs responders (p < 0.05), and a direct correlation between miR-30 (0.340, [0.833–1.915]; p 0.001), the 6-minute-walking test (6MWT; 0.168, [0.008–0.060]; p 0.011), angiotensin-receptor-neprilysin inhibitors (ARNI; 0.157, [0.183–4.877]; p 0.035), sodium-glucose-transporter-2 inhibitors (0.245, [2.242–7.283]; p 0.001), and LVEF improvements. C reactive protein (CRP) inversely correlated with LVEF improvement (−0.220, [-(0.066–0.263)]; p 0.001). ARNI (1.373, CI 95% [1.007–1.872], p 0.045), miR-30 (2.713, CI 95% [1.543–4.769], p 0.001), and 6MWT (1.288, CI 95% [1.084–1.998], p 0.001) were predictors of LBB pacing responders at 1 year of follow-up.ConclusionLBB-pacing responders evidenced miR modulation, which was linked to significant improvement of the cardiac pump. Specifically, miR-30 was linked to cardiac pump improvement and predicted responders at 1 year of follow-up in patients with T2DM.

Abstract The central role of the microbiota as a pivotal factor regulating anti-tumor immune responses has recently been appreciated. Increasing evidence has put a spotlight on the connection of microbiota to T cells, by showing impaired effector and/or memory responses in germ-free (GF) mice or in the presence of dysbiotic communities, and association with tumor growth and overall survival (OS). These observations also have significant implications for anti-tumor therapy and vaccination, suggesting that the communication between T cells and the microbiota involves soluble mediators (microbiota-derived metabolites) that influence various functions of T cells. In addition, there is growing appreciation of the role of bacterial translocation into the peritumoral milieu from the intestinal tract, as well as of locally developed tumor microbial communities, spatially separated from the gut microbiota, in shaping the tumor microbiome. Collectively, these findings have added new support to the idea that tonic inputs mirroring the existence of tumor microbiome could regulate the function of tumor-infiltrating T cells and tissue-resident memory T (TRM) cells. In this review, we focus on recent advances and aspects of these active areas of investigation and provide a comprehensive overview of the unique mechanisms that play a pivotal role in the regulation of anti-tumor immunity by the microbiota, some of which could be of particular relevance for addressing problems caused by tumor heterogeneity. It is our hope that this review will provide a theoretical foundation for future investigations in this area.

Abstract The characterization of particle accelerator induced neutron fields is challenging but fundamental for research and industrial activities, including radiation protection, neutron metrology, developments of neutron detectors for nuclear and high-energy physics, decommissioning of nuclear facilities, and studies of neutron damage on materials and electronic components. This work reports on the study of a novel approach to the experimental characterization of neutron spectra at two complex accelerator environments, namely the CERF, a high-energy mixed reference field at CERN in Geneva, and the Bern medical cyclotron laboratory, a facility used for multi-disciplinary research activities, and for commercial radioisotope production for nuclear medicine. Measurements were performed through an innovative active neutron spectrometer called DIAMON, a device developed to provide in real time neutron energy spectra without the need of guess distributions. The intercomparison of DIAMON measurements with reference data, Monte Carlo simulations, and with the well-established neutron monitor Berthold LB 6411, has been found to be highly satisfactory in all conditions. It was demonstrated that DIAMON is an almost unique device able to characterize neutron fields induced by hadrons at 120 GeV/c as well as by protons at 18 MeV colliding with different materials. The accurate measurement of neutron spectra at medical cyclotrons during routine radionuclide production for nuclear medicine applications is of paramount importance for the facility decommissioning. The findings of this work are the basis for establishing a methodology for producing controlled proton-induced neutron beams with medical cyclotrons.

A time series is a sequence of time-ordered data, and it is generally used to describe how a phenomenon evolves over time. Time series forecasting, estimating future values of time series, allows the implementation of decision-making strategies. Deep learning, the currently leading field of machine learning, applied to time series forecasting can cope with complex and high-dimensional time series that cannot be usually handled by other machine learning techniques. The aim of the work is to provide a review of state-of-the-art deep learning architectures for time series forecasting, underline recent advances and open problems, and also pay attention to benchmark data sets. Moreover, the work presents a clear distinction between deep learning architectures that are suitable for short-term and long-term forecasting. With respect to existing literature, the major advantage of the work consists in describing the most recent architectures for time series forecasting, such as Graph Neural Networks, Deep Gaussian Processes, Generative Adversarial Networks, Diffusion Models, and Transformers.

Abstract Phospholipid scramblase 1 (PLSCR1) is the most studied protein of the scramblase family. Originally, it was identified as a membrane protein involved in maintaining plasma membrane asymmetry. However, studies conducted over the past few years have shown the involvement of PLSCR1 in several other cellular pathways. Indeed, PLSCR1 is not only embedded in the plasma membrane but is also expressed in several intracellular compartments where it interacts with a diverse repertoire of effectors, mediators, and regulators contributing to distinct cellular processes. Although most PLSCR1 interactors are thought to be cell-type specific, PLSCR1 often exerts its regulatory functions through shared mechanisms, including the trafficking of different molecules within intracellular vesicles such as endosomes, liposomes, and phagosomes. Intriguingly, besides endogenous proteins, PLSCR1 was also reported to interact with exogenous viral proteins, thereby regulating viral uptake and spread. This review aims to summarize the current knowledge about the multiple roles of PLSCR1 in distinct cellular pathways. Video Abstract

The study of the effects of the radiation dose on devices and materials is a topic of high interest in several fields, including radiobiology, space missions, microelectronics, and high energy physics. In this paper, a new method, based on radiochromic film dosimetry, is proposed for real-time dose assessment in radiation hardness assurance tests. This method allows for correlating the radiation dose at which devices are exposed to the radiation effects (malfunctioning and/or breakdown). In previous studies, it has already been demonstrated that a system, based on optical fibers and a spectrometer, allows for the real-time dose assessment of radiochromic films. The current study not only validates our previous results, but shows that it is possible to apply the new method to an actual radiation environment for the real-time measurement of the dose delivered to a device in radiation hardness assurance tests. This new dosimeter can be used in different radiation environments for a wide dose range, from a few Gy to a few MGy. This high sensitivity can be reached by changing the radiochromic film type and/or the parameters used for the analysis.

Pseudomonas aeruginosa (PA) is a major Gram-negative opportunistic pathogen causing several serious acute and chronic infections in the nosocomial and community settings. PA eradication has become increasingly difficult due to its remarkable ability to evade antibiotics. Therefore, epidemiological studies are needed to limit the infection and aim for the correct treatment. The present retrospective study focused on PA presence among samples collected at the San Giovanni di Dio and Ruggi D’Aragona University Hospital in Salerno, Italy; its resistance profile and relative variations over the eight years were analyzed. Bacterial identification and antibiotic susceptibility tests were performed by VITEK® 2. In the 2015–2019 and 2020–2022 timeframes, respectively, 1739 and 1307 isolates of PA were obtained from respiratory samples, wound swabs, urine cultures, cultural swabs, blood, liquor, catheter cultures, vaginal swabs, and others. During 2015–2019, PA strains exhibited low resistance against amikacin (17.2%), gentamicin (25.2%), and cefepime (28.3%); moderate resistance against ceftazidime (34.4%), imipenem (34.6%), and piperacillin/tazobactam (37.7%); and high resistance against ciprofloxacin (42.4%) and levofloxacin (50.6%). Conversely, during the 2020–2022 era, PA showed 11.7, 21.1, 26.9, 32.6, 33.1, 38.7, and 39.8% resistance to amikacin, tobramycin, cefepime, imipenem, ceftazidime, ciprofloxacin, and piperacillin/tazobactam, respectively. An overall resistance-decreasing trend was observed for imipenem and gentamicin during 2015–2019. Instead, a significant increase in resistance was recorded for cefepime, ceftazidime, and imipenem in the second set of years investigated. Monitoring sentinel germs represents a key factor in optimizing empirical therapy to minimize the spread of antimicrobial resistance.

IgE-mediated release of proinflammatory mediators and cytokines from basophils and mast cells is a central event in allergic disorders. Several groups of investigators have demonstrated the presence of autoantibodies against IgE and/or FcεRI in patients with chronic spontaneous urticaria. By contrast, the prevalence and functional activity of anti-IgE autoantibodies in atopic dermatitis (AD) are largely unknown. We evaluated the ability of IgG anti-IgE from patients with AD to induce the in vitro IgE-dependent activation of human basophils and skin and lung mast cells. Different preparations of IgG anti-IgE purified from patients with AD and rabbit IgG anti-IgE were compared for their triggering effects on the in vitro release of histamine and type 2 cytokines (IL-4, IL-13) from basophils and of histamine and lipid mediators (prostaglandin D2 and cysteinyl leukotriene C4) from human skin and lung mast cells. One preparation of human IgG anti-IgE out of six patients with AD induced histamine release from basophils, skin and lung mast cells. This preparation of human IgG anti-IgE induced the secretion of cytokines and eicosanoids from basophils and mast cells, respectively. Human monoclonal IgE was a competitive antagonist of both human and rabbit IgG anti-IgE. Human anti-IgE was more potent than rabbit anti-IgE for IL-4 and IL-13 production by basophils and histamine, prostaglandin D2 and leukotriene C4 release from mast cells. Functional anti-IgE autoantibodies rarely occur in patients with AD. When present, they induce the release of proinflammatory mediators and cytokines from basophils and mast cells, thereby possibly contributing to sustained IgE-dependent inflammation in at least a subset of patients with this disorder.

A two-dimensional beam monitoring detector named π2 has been developed and tested at the Bern University Hospital, using an 18 MeV proton beam provided by a medical cyclotron. This non-destructive device utilises a scintillating compound (P47 phosphor) coated onto a thin aluminium foil that is angled at 45∘ with respect to the beam axis. The scintillating light produced when the beam passes through the foil is captured by a CMOS camera, resulting in a two-dimensional image of the beam profile. Custom software is then used to analyse the image and extract valuable information about the beam’s position, shape, and intensity. The focus of the experimental work was on characterising the performance of the π2 with the 18 MeV proton beam. The linearity of the detector’s output signal was evaluated for proton fluxes ranging from 2·1010cm−2·s−1 to 5·1011cm−2·s−1. Furthermore, the beam profiles measured with the π2 were found to be consistent with reference measurements obtained using alternative beam monitors. Additionally, the experiments also involved studying the beam scattering caused by the foil and scintillating layer. Finally, in a long-term radiation test, the detector demonstrated a stable response up to an integrated proton flux of 3·1015cm−2. The π2 is currently being used at the Bern cyclotron for monitoring beams in the development of new methods for medical radioisotope production and for radiation hardness studies. The π2 has potential applications in several fields that involve the use of accelerated ions, such as cancer particle therapy, medical radioisotope production and radiation hardness studies.

Trazodone is a serotonin antagonist/reuptake inhibitor, approved for treating major depressive disorder (MDD). Oral formulations are widely studied and marketed in several countries worldwide while there is little evidence to support use of parenteral formulation. Our narrative review summarizes pharmacological properties and clinical data concerning use of parenteral trazodone in mood disorders. PubMed and Web of Science were used to identify the most relevant literature. The main evidence concerns four studies evaluating efficacy in major depressive disorder and indicates that trazodone was well tolerated and effective. Off-label use in agitation associated with bipolar disorder is also reported in three studies, although prescription of concomitant treatment, as a confounding factor, may have influenced outcome measures. The limited available evidence supports parenteral trazodone use in major depressive disorder and suggests that trazodone is a suitable option in patients at high risk of treatment-emergent mania (TEM). [ABSTRACT FROM AUTHOR]

The production of medical radioisotopes for theranostics is essential for the development of personalized nuclear medicine. Among them, radiometals can be used to label proteins and peptides and their supply in quantity and quality suitable for clinical applications represents a scientific challenge. A research program is ongoing at the Bern medical cyclotron, where an IBA Cyclone 18/18 HC is in operation. The cyclotron provides 18 MeV proton beams up to 150 μA and is equipped with a Solid Target Station (STS) and a 6 m Beam Transport Line (BTL), ending in a separate bunker with independent access. A novel magnetic target coin was realized to bombard isotope-enriched materials in the form of compressed powders, together with a compact focalization system to enhance the irradiation procedure. For an optimized production yield with the required radionuclidic purity, novel methods were developed to precisely measure the extracted beam energy and the involved reaction cross sections. In particular, a target station was realized to measure nuclear cross sections using materials in the form of powder deposited on an aluminium disc by sedimentation, bombarded by a monitored flat beam.

44Sc is a promising radionuclide for positron emission tomography (PET) in nuclear medicine. As a part of the implementation of a production site for 44Sc, precise knowledge of the activity of the product is necessary. At the Paul Scherrer Institute (PSI) and the University of Bern (UniBE), 44Sc is produced by enriched 44CaO-target irradiation with a cyclotron. The two sites use different techniques for activity measurement, namely a dose calibrator at the PSI and a gamma-ray spectrometry system at UniBE and PSI. In this work, the 44Sc was produced at the PSI, and samples of the product were prepared in dedicated containers for onsite measurements at PSI, UniBE, and the Institute of Radiation Physics (IRA) in Lausanne for precise activity measurement using primary techniques and for the calibration of the reference ionization chambers. An accuracy of 1% was obtained for the activity measurement, allowing for a precise calibration of the dose calibrator and gamma-ray spectrometry of the two production sites. Each production site now has the capability of measuring 44Sc activity with an accuracy of 2%.