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Background: In people living with HIV (PLWH) with HCV infection, liver and non-liver-related mortality significantly decreased after receiving direct acting antivirals (DAAs). We aimed to assess main causes and predictors of mortality after sustained virological response (SVR) induced by DAAs., Methods: Retrospective study in antiretroviral treatment-experienced PLWH with HCV infection, followed at San Raffaele Hospital, Milan, Italy, who achieved SVR after DAAs. Kaplan-Meier analysis and log-rank test were used to estimate cumulative probability of death for any cause. Cox proportional hazards model was used to estimate adjusted hazard ratio (aHR) of death and the corresponding 95% confidence interval (95%CI); Baseline variables included in the model were: age, diabetes, hepatocellular carcinoma (HCC), α-fetoprotein (AFP), ALBI grade., Results: Among 663 people included with a median follow-up of 4.4 years (IQR=3.5-5.5), 49 died. Overall 5-year cumulative probability of death was 8.0% (95%CI=5.5%-10.4%); 63.2% (n=31/49) died from non-liver-related events [mainly non-liver malignancies (18/49) and cardiovascular events (7/49)].-. At multivariate analysis, death was more likely in older people [aHR (adjusted Hazard Ratio) (5-year older)=1.46, 95%CI=1.16-1.83, p=0.0009], and in people with diabetes [aHR=2.98, 95%CI=1.55-5.71, p=0.001], ALBI grade ≥2 [aHR=2.13, 95%CI=1.17-3.90, p=0.014] and AFP ≥3.4 ng/mL [aHR=1.96, 95%CI=1.01; 3.84, p=0.049]., Conclusions: In our cohort, non-liver-related events and malignancies were the most common cause of death after HCV eradication. Diabetes, ALBI grade ≥2 and AFP≥ 3.4 ng/L were associated with higher risk of death. In PLWH after HCV eradication, regardless of liver disease stage, surveillance of non-liver events, particularly malignancies, should be recommended., Competing Interests: Conflicts of interest: Castagna Antonella has received personal fees for advisory boards, speaker panels, and educational materials from Gilead Sciences, ViiV Healthcare, Janssen-Cilag, Merck Sharp & Dohme, and Theratechnologies; the other authors do not have any disclosures to report., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

The urbanized area of Rome is largely built over volcanic deposits, characterized by a significant radionuclides content and consequently a high radon emanation potential. An accurate monitoring of workplaces and residential dwellings constitutes a first step towards mitigating the indoor radon exposure. Since radon diffusion dynamics involves complex interactions among many environmental parameters on different time scales, a proper assessment of radon concentration variations can be better achieved by means of active monitoring approaches. We present here the results of 1 year of continuous measurements conducted in six premises (five apartments and a basement) at different floors of the same building in the Esquilino district, in the historical center of Rome. Collecting annual series of radon concentration enables us to identify fluctuations over a seasonal scale, with radon generally decreasing in the warm season. The simultaneous tracking of different floors should cancel the influence of geogenic radon and of building characteristics like age, typology, and construction materials. While the basement shows the highest radon concentration, indicating a major contribution from the ground, we observe indoor radon levels comparable at all the upper floors, questioning the common belief that high-risk exposure be limited to the lowest storeys. The use of active devices makes it possible to discriminate between average indoor radon measured during the day and overnight, when residents are more likely to be at home. Our analysis provides the characterization of the dynamics of the gas emanation and transport inside the buildings and of its temporal fluctuations, in relation to the environmental and meteorological conditions. Since the experiment was performed in the Roman urban contest, we cannot ignore the specificity of the retrieved data, affected not only by endogenous factors like life habits relative to ventilation and conditioning of the apartments, but also by exogenous factors, among which the warmer microclimate compared to the surrounding suburban and rural areas, due to the effects of urbanization (urban heat island effect)., (© 2024. The Author(s).)

Background and rationale. Pleural mesothelioma (PM) is a rare and aggressive neoplasm that originates from the pleural mesothelium and whose onset is mainly linked to exposure to asbestos, which cannot be attacked with truly effective therapies with consequent poor prognosis. The rationale of this study is based on the use of mesenchymal stromal cells (MSCs) as a vehicle for chemotherapy drugs to be injected directly into the pathological site, such as the pleural cavity. Study design. The study involves the use of a conventional chemotherapeutic drug, Paclitaxel (PTX), which is widely used in the treatment of different types of solid tumors, including PM, although some limitations are related to pharmacokinetic aspects. The use of PTX-loaded MSCs to treat PM should provide several potential advantages over the systemically administered drug as reduced toxicity and increased concentration of active drug in the tumor-surrounding context. The PACLIMES trial explores the safety and toxicity of the local administration of Paclimes in chemonaive patients, candidates for pleurectomy. The secondary objective is to find the effective Paclimes dose for subsequent phase II studies and to observe and record the antitumor activity. Future direction . The experimental pre-clinical background and rationale are discussed as well.

Manipulating physical properties through ion migration in complex oxide thin films is an emerging research direction to achieve tunable materials for advanced applications. While the reduction of complex oxides has been widely reported, few reports exist on the modulation of physical properties through a direct hydrogenation process. Here, we report an unusual mechanism for hydrogen-induced topotactic phase transitions in perovskite La 0.7 Sr 0.3 CoO 3 thin films. Hydrogenation is performed upon annealing in a pure hydrogen gas environment, offering a direct understanding of the role that hydrogen plays at the atomic scale in these transitions. Topotactic phase transformations from the perovskite (P) to hydrogenated-brownmillerite (H-BM) phase can be induced at temperatures as low as 220 °C, while at higher hydrogenation temperatures (320-400 °C), the progression toward more reduced phases is hindered. Density functional theory calculations suggest that hydroxyl bonds are formed with the introduction of hydrogen ions, which lower the formation energy of oxygen vacancies of the neighboring oxygen, enabling the transition from the P to H-BM phase at low temperatures. Furthermore, the impact on the magnetic and electronic properties of the hydrogenation temperature is investigated. Our research provides a potential pathway for utilizing hydrogen as a basis for low-temperature modulation of complex oxide thin films, with potential applications in neuromorphic computing., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Electronic defects in semiconductors form the basis for emerging quantum technologies, but many defect centers are difficult to access at the single-particle level. A method for probing optically inactive spin defects would reveal semiconductor physics at the atomic scale and advance the study of new quantum systems. We exploit the intrinsic correlation between the charge and spin states of defect centers to measure the charge populations and dynamics of single substitutional nitrogen spin defects in diamond. By probing their steady-state spin population, read out at the single-defect level with a nearby nitrogen vacancy center, we directly measure the defect ionization-corroborated by first-principles calculations-an effect we do not have access to with traditional coherence-based quantum sensing.

Background: Thymic carcinoma (TC) is a rare tumor with aggressive behavior. Chemotherapy with carboplatin plus paclitaxel represents the treatment of choice for advanced disease. Antiangiogenic drugs, including ramucirumab, have shown activity in previously treated patients. The RELEVENT trial was designed to evaluate the activity and safety of ramucirumab plus chemotherapy as first-line treatment in advanced TC., Patients and Methods: This phase II trial was conducted within the Italian TYME network. Eligible patients had treatment-naïve advanced TC. They received ramucirumab, carboplatin and paclitaxel for six cycles, followed by ramucirumab maintenance until disease progression or intolerable toxicity. Primary endpoint was objective response rate (ORR) according to RECIST v1.1 as assessed by the investigator. Secondary endpoints were progression-free survival (PFS), overall survival (OS) and safety. Centralized radiologic review was carried out., Results: From November 2018 to June 2023, 52 patients were screened and 35 were enrolled. Median age was 60.8 years, 71.4% of patients were male and 85.7% had Masaoka-Koga stage IVB. The Eastern Cooperative Oncology Group performance status was 0 in 68.5% and 1 in 31.4% of patients. At the present analysis carried out some months after the interim analysis (earlier than expected) on 35 patients, ORR was 80.0% [95% confidence interval (CI) 63.1% to 91.6%]. At the centralized radiological review of 33/35 assessable patients, ORR was 57.6% (95% CI 39.2% to 74.5%). After a median follow-up of 31.6 months, median PFS was 18.1 months (95% CI 10.8-52.3 months) and median OS was 43.8 months (95% CI 31.9 months-not reached). Thirty-two out of 35 patients (91.4%) experienced at least one treatment-related adverse event (AE), of which 48.6% were AE ≥ grade 3., Conclusions: In previously untreated advanced TC, the addition of ramucirumab to carboplatin and paclitaxel showed the highest activity compared to historical controls, with a manageable safety profile. Despite the small number of patients, given the rarity of the disease, the trial results support the consideration of this combination as first-line treatment in TC., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The brown marmorated stink bug, Halyomorpha halys (Stål, 1855) (Hemiptera: Pentatomidae) is an invasive pest that causes economic damage on crops, decreasing fruit yield and quality. Conventional insecticides are frequently used to reduce infestations, but these are often with a limited residual effect, besides being costly and detrimental to nontarget organisms and the environment. In integrated pest management, novel strategies against H. halys are proposed, such as the use of alternative substances with an effect on insect behaviour and mobility. As one of the oldest multi-site fungicides applied against fungal pathogens and as an insecticide and acaricide to control scales and mites, sulfur is proposed here to reduce H. halys infestation in fruit orchards., Results: Field experiments were performed to evaluate the effect of repeated wettable sulfur applications on H. halys in apple and pear orchards. Sulfur-induced plant phytotoxicity effects and quanti-qualitative parameters on apple fruits were also recorded. Halyomorpha halys infestation was significantly reduced in sulfur-treated compared to untreated pears and apples. Furthermore, sulfur sprays reduced fruit damage caused by H. halys. Besides, sulfur-mediated phytotoxicity such as symptoms on leaves and fruit drop were not observed. Fruit quality was not influenced by sulfur treatments., Conclusions: Wettable sulfur seems to be a promising formulation given the low phytotoxicity, considering the technical aspects for an effective use of sulfur-based products to counteract H. halys in pome fruit orchards. © 2024 The Author(s). Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry., (© 2024 The Author(s). Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.)

Recent neurophysiological studies provide inconsistent results of frontoparietal network (FPN) stimulation for altering working memory (WM) capacity. This study aimed to boost WM capacity by manipulating the activity of the FPN via dual-site high-definition transcranial direct current stimulation. Forty-eight participants were randomly assigned to three stimulation groups, receiving either simultaneous anodal stimulation of the frontal and parietal areas (double stimulation), or stimulation of the frontal area only (single stimulation), or the placebo stimulation (sham) to frontal and parietal areas. After the stimulation, we used an operation span task to test memory accuracy, mathematical accuracy, time of calculation and memorizing, and recall response time across the three groups. The results revealed an enhancement of memory accuracy and a reduction of time of calculation in the double stimulation group compared with that in others. In addition, recall response time was significantly decreased in the double and single stimulation groups compared with that in sham. No differences in mathematical accuracy were observed. Our results confirm the pivotal role of the FPN in WM and suggest its functional dissociation, with the frontal component more implicated in the retrieval stage and the parietal component in the processing and retention stages., Competing Interests: The authors declare no competing financial interests., (Copyright © 2024 Otstavnov et al.)

Introduction: To assess the effectiveness of novel HIV curative strategies, "cure" trials require periods of closely monitored antiretroviral therapy (ART) analytical treatment interruptions (ATIs). We performed a systematic review and meta-analysis to identify the impact of ATI with or without novel therapeutics in cure-related studies on the time to viral re-suppression following ART restart., Methods: Medline, Embase and Web of Science databases were searched for human studies involving ATIs from 1 January 2015 till 22 April 2024. The primary outcome was time to first viral re-suppression (plasma HIV viral load [VL] <50 copies/ml) stratified by receipt of interventional drug with ATI (IA) or ATI-only groups. Random-effects proportional meta-analysis and multivariable Cox proportional hazards analysis were performed using R., Results: Of 1073 studies screened, 13 were included that met the inclusion criteria with VL data available after restarting ART (n = 213 participants). There was no difference between time to viral suppression in IA or ATI-only cohorts (p = 0.22). For 87% of participants, viral suppression within 12 weeks of ART restart was achieved, and all eventually had at least one VL <50 copies/ml during follow-up. After adjusting for covariables, while participants in the IA cohort were associated with less rapid suppression (adjusted hazard ratio [aHR] 0.61, 95% CI 0.40-0.94, p = 0.026), other factors include greater log VL at ART restart (aHR 0.56, 95% CI 0.46-0.68, p<0.001), duration since HIV diagnosis (aHR 0.93, 95% CI 0.89-0.96) and longer intervals between HIV VL monitoring (aHR 0.66, 95% CI 0.59-0.74, p<0.001). However, the use of integrase inhibitors was associated with more rapid viral suppression (aHR 1.74, 95% CI 1.16-2.59)., Discussion: When designing studies involving ATIs, information on time to viral re-suppression after restarting ART is important to share with participants, and should be regularly monitored and reported, to assess the impact and safety of specific trial interventions in ATI studies., Conclusions: The majority of participants achieved viral suppression after restarting ART in ATI studies. ART regimens containing integrase inhibitors and frequent VL monitoring should be offered for people restarting ART after ATI studies to ensure rapid re-suppression., (© 2024 The Author(s). Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of International AIDS Society.)

Biofouling on marine surfaces causes immense material and financial harm for maritime vessels and related marine industries. Previous reports have shown the effectiveness of amphiphilic coating systems based on poly(dimethylsiloxane) (PDMS) against such marine foulers. Recent studies on biofouling mechanisms have also demonstrated acidic microenvironments in biofilms and stronger adhesion at low-pH conditions. This report presents the design and utilization of amphiphilic polymer coatings with buffer functionalities as an active disruptor against four different marine foulers. Specifically, this study explores both neutral and zwitterionic buffer systems for marine coatings, offering insights into coating design. Overall, these buffer systems were found to improve foulant removal, and unexpectedly were the most effective against the diatom Navicula incerta .

Introduction: The use of telemedicine and ultrasound is emerging and novel in the field of community paramedicine. However, there is a paucity of data supporting its use and even less evidence that shows a morbidity and mortality benefit. This case highlights a unique way to diagnose a common medical emergency, which can lead to a good outcome., Case Report: We describe the use of lung point-of-care ultrasound by a trained community paramedic that led to the identification of a pneumothorax in an 86-year-old male at a scheduled home visit. The images were interpreted over telehealth in real-time by an emergency physician, and the patient was transported to the emergency department where the diagnosis was confirmed by chest radiography. He underwent chest tube placement and was discharged five days later after returning to his baseline., Conclusion: Despite minimal data to support or refute the use of paramedic tele-ultrasound, this case highlights a unique opportunity to expand the use of telemedicine and ultrasound in community paramedicine to improve patient outcomes., Competing Interests: Conflicts of Interest: By the CPC-EM article submission agreement, all authors are required to disclose all affiliations, funding sources and financial or management relationships that could be perceived as potential sources of bias. The authors disclosed none.

We demonstrate nearly a microsecond of spin coherence in Er 3+ ions doped in cerium dioxide nanocrystal hosts, despite a large gyromagnetic ratio and nanometric proximity of the spin defect to the nanocrystal surface. The long spin coherence is enabled by reducing the dopant density below the instantaneous diffusion limit in a nuclear spin-free host material, reaching the limit of a single erbium spin defect per nanocrystal. We observe a large Orbach energy in a highly symmetric cubic site, further protecting the coherence in a qubit that would otherwise rapidly decohere. Spatially correlated electron spectroscopy measurements reveal the presence of Ce 3+ at the nanocrystal surface, which likely acts as extraneous paramagnetic spin noise. Even with these factors, defect-embedded nanocrystal hosts show tremendous promise for quantum sensing and quantum communication applications, with multiple avenues, including core-shell fabrication, redox tuning of oxygen vacancies, and organic surfactant modification, available to further enhance their spin coherence and functionality in the future.

The electronic properties and optical response of ice and water are intricately shaped by their molecular structure, including the quantum mechanical nature of the hydrogen atoms. Despite numerous previous studies, a comprehensive understanding of the nuclear quantum effects (NQEs) on the electronic structure of water and ice at finite temperatures remains elusive. Here, we utilize molecular simulations that harness efficient machine-learning potentials and many-body perturbation theory to assess how NQEs impact the electronic bands of water and hexagonal ice. By comparing path-integral and classical simulations, we find that NQEs lead to a larger renormalization of the fundamental gap of ice, compared to that of water, ultimately yielding similar bandgaps in the two systems, consistent with experimental estimates. Our calculations suggest that the increased quantum mechanical delocalization of protons in ice, relative to water, is a key factor leading to the enhancement of NQEs on the electronic structure of ice.

High Latitude fjords can serve as sediment trap, bearing different type of proxies, from geochemical to micropaleontological ones, making them exceptional tools for paleoenvironmental reconstruction. However, some unconventional proxies can be present and can be used to depict a comprehensive and exhaustive interpretation of past changes. Here, studying a sediment core in Edisto Inlet (Ross Sea, Antarctica) we used irregular echinoid spines and ophiuroids (Ophionotus victoriae) ossicles to trace environmental changes throughout the last 3.6 kyrs BP. Irregular echinoids can serve as proxy for the organic matter content, while O. victoriae ossicles can be used as proxy for steady sea-ice cycle along with organic deposition events. O. victoriae release a high number of ossicles, making estimation about the population quite challenging; still, presence data, can be easily collected. By applying Generative Additive Models to the stratigraphical distribution of these data, we detected an environmental phase that was previously unnoticed by other traditional proxies: the Ophiuroid Optimum (2-1.5 kyrs BP). In conclusion, here we demonstrate how echinoderm presence can be used as a valuable source of information, while proving the potential of modelling binary data to detect long-term trend in Holocene stratigraphical records., (© 2024. The Author(s).)

We propose a new approach to simulate the decoherence of a central spin coupled to an interacting dissipative spin bath with cluster-correlation expansion techniques. We benchmark the approach on generic 1D and 2D spin baths and find excellent agreement with numerically exact simulations. Our calculations show a complex interplay between dissipation and coherent spin exchange, leading to increased central spin coherence in the presence of fast dissipation. Finally, we model near-surface nitrogen-vacancy centers in diamond and show that accounting for bath dissipation is crucial to understanding their decoherence. Our method can be applied to a variety of systems and provides a powerful tool to investigate spin dynamics in dissipative environments.

Background: Radiomics is a quantitative approach that allows the extraction of mineable data from medical images. Despite the growing clinical interest, radiomics studies are affected by variability stemming from analysis choices. We aimed to investigate the agreement between two open-source radiomics software for both contrast-enhanced computed tomography (CT) and contrast-enhanced magnetic resonance imaging (MRI) of lung cancers and to preliminarily evaluate the existence of radiomic features stable for both techniques., Methods: Contrast-enhanced CT and MRI images of 35 patients affected with non-small cell lung cancer (NSCLC) were manually segmented and preprocessed using three different methods. Sixty-six Image Biomarker Standardisation Initiative-compliant features common to the considered platforms, PyRadiomics and LIFEx, were extracted. The correlation among features with the same mathematical definition was analyzed by comparing PyRadiomics and LIFEx (at fixed imaging technique), and MRI with CT results (for the same software)., Results: When assessing the agreement between LIFEx and PyRadiomics across the considered resampling, the maximum statistically significant correlations were observed to be 94% for CT features and 95% for MRI ones. When examining the correlation between features extracted from contrast-enhanced CT and MRI using the same software, higher significant correspondences were identified in 11% of features for both software., Conclusions: Considering NSCLC, (i) for both imaging techniques, LIFEx and PyRadiomics agreed on average for 90% of features, with MRI being more affected by resampling and (ii) CT and MRI contained mostly non-redundant information, but there are shape features and, more importantly, texture features that can be singled out by both techniques., Relevance Statement: Identifying and selecting features that are stable cross-modalities may be one of the strategies to pave the way for radiomics clinical translation., Key Points: • More than 90% of LIFEx and PyRadiomics features contain the same information. • Ten percent of features (shape, texture) are stable among contrast-enhanced CT and MRI. • Software compliance and cross-modalities stability features are impacted by the resampling method., (© 2024. The Author(s).)

Virtually noiseless due to the scarcity of spinful nuclei in the lattice, simple oxides hold promise as hosts of solid-state spin qubits. However, no suitable spin defect has yet been found in these systems. Using high-throughput first-principles calculations, we predict spin defects in calcium oxide with electronic properties remarkably similar to those of the NV center in diamond. These defects are charged complexes where a dopant atom - Sb, Bi, or I - occupies the volume vacated by adjacent cation and anion vacancies. The predicted zero phonon line shows that the Bi complex emits in the telecommunication range, and the computed many-body energy levels suggest a viable optical cycle required for qubit initialization. Notably, the high-spin nucleus of each dopant strongly couples to the electron spin, leading to many controllable quantum levels and the emergence of atomic clock-like transitions that are well protected from environmental noise. Specifically, the Hanh-echo coherence time increases beyond seconds at the clock-like transition in the defect with 209 Bi. Our results pave the way to designing quantum states with long coherence times in simple oxides, making them attractive platforms for quantum technologies., (© 2024. The Author(s).)

Background: Control of the zoonotic food-borne parasite Fasciola hepatica remains a major challenge in humans and livestock. It is estimated that annual economic losses due to fasciolosis can reach US$3.2 billion in agriculture and livestock. Moreover, the wide distribution of drug-resistant parasite populations and the absence of a vaccine threaten sustainable control, reinforcing the need for novel flukicides., Methods: The present work analyses the flukicidal activity of a total of 70 benzimidazole derivatives on different stages of F. hepatica. With the aim to select the most potent ones, and screenings were first performed on eggs at decreasing concentrations ranging from 50 to 5 µM and then on adult worms at 10 µM. Only the most effective compounds were also evaluated using a resistant isolate of the parasite., Results: After the first screenings at 50 and 10 µM, four hit compounds (BZD31, BZD46, BZD56, and BZD59) were selected and progressed to the next assays. At 5 µM, all hit compounds showed ovicidal activities higher than 71% on the susceptible isolate, but only BZD31 remained considerably active (53%) when they were tested on an albendazol-resistant isolate, even with values superior to the reference drug, albendazole sulfoxide. On the other hand, BZD59 displayed a high motility inhibition when tested on adult worms from an albendazole-resistant isolate after 72 h of incubation., Conclusions: BZD31 and BZD59 compounds could be promising candidates for the development of fasciolicidal compounds or as starting point for the new synthesis of structure-related compounds., (© 2024. The Author(s).)

We present a theoretical study of the formation of self-trapped excitons (STEs) and the associated broadband emission in metal-halide perovskites Cs 4 SnBr 6 and Cs 2 AgInCl 6 , using time-dependent density functional theory (TDDFT) with the dielectric-dependent hybrid (DDH) functional. Our approach allows for an accurate description of the excitonic effect and geometry relaxation in the electronic excited states and yields optical gap, STE emission energy, and emission spectra in reasonable agreement with experiments. We point out the significance of considering geometry relaxations in the electronic excited state by showing that the exciton-phonon coupling computed in the ground-state atomic geometry is insufficient to describe the physical properties of STEs. Overall, we find that TDDFT with the DDH hybrid functional is a suitable approach for the study of the formation of STEs in perovskite and provides insights for designing metal-halide perovskites with tailored emission properties.

All-polymer solar cells (all-PSCs) offer improved morphological and mechanical stability compared with those containing small-molecule-acceptors (SMAs). They can be processed with a broader range of conditions, making them desirable for printing techniques. In this study, we report a high-performance polymer acceptor design based on bithiazole linker (PY-BTz) that are on par with SMAs. We demonstrate that bithiazole induces a more coplanar and ordered conformation compared to bithiophene due to the synergistic effect of non-covalent backbone planarization and reduced steric encumbrances. As a result, PY-BTz shows a significantly higher efficiency of 16.4% in comparison to the polymer acceptors based on commonly used thiophene-based linkers (i.e., PY-2T, 9.8%). Detailed analyses reveal that this improvement is associated with enhanced conjugation along the backbone and closer interchain π-stacking, resulting in higher charge mobilities, suppressed charge recombination, and reduced energetic disorder. Remarkably, an efficiency of 14.7% is realized for all-PSCs that are solution-sheared in ambient conditions, which is among the highest for devices prepared under conditions relevant to scalable printing techniques. This work uncovers a strategy for promoting backbone conjugation and planarization in emerging polymer acceptors that can lead to superior all-PSCs., (© 2024. The Author(s).)

Benzimidazole heterocycles are of great importance in medicinal chemistry due to their applicability to a wide range of pharmacological targets, therefore representing a prototypical "privileged structure". In photopharmacology, azoheteroarene photoswitches have emerged as valuable tools for a variety of applications due to the high tuneability of their photophysical properties. Benzimidazole-based photoswitches could therefore enable the optically-controlled investigation of many pharmacological targets and find application in materials science. Here we report a combined experimental and computational investigation of such arylazobenzimidazoles, which allowed us to identify derivatives with near-quantitative bidirectional photoswitching using visible light and highly tuneable Z -isomer stability. We further demonstrate that arylazobenzimidazoles bearing a free benzimidazole N-H group not only exhibit efficient bidirectional photoswitching, but also excellent thermal Z -isomer stability, contrary to previously reported fast-relaxing Z -isomers of N-H azoheteroarenes. Finally, we describe derivatives which can be reversibly isomerized with cyan and red light, thereby enabling significantly "red-shifted" photocontrol over prior azoheteroarenes. The understanding gained in this study should enable future photopharmacological efforts by employing photoswitches based on the privileged benzimidazole structure., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Background: Specific components of lipid profile seem to differently impact on immune activity against cancer and unraveling their prognostic role in patients with solid cancer treated with immune checkpoint inhibitors (ICIs) is needed., Materials and Methods: We retrospectively collected baseline clinicopathological characteristics including circulating lipid profile (total cholesterol [TC], triglycerides [TG], low-density lipoproteins [LDL], high-density lipoproteins [HDL]) of patients with consecutive solid cancer treated with ICIs, and we investigated their role in predicting clinical outcomes., Results: At a median follow-up of 32.9 months, among 430 enrolled patients, those with TC ≥ 200 mg/dl showed longer median progression-free survival (mPFS; 6.6 vs. 4.7 months, P = .4), although not reaching statistical significance, and significantly longer median overall survival (mOS; 19.4 vs. 10.8 months, P = .02) compared to those with TC < 200 mg/dl. Conversely, patients with TG ≥150 mg/dl displayed shorter PFS (3.4 vs. 5.1 months, P = .02) and OS (7.1 vs. 12.9 months, P = .009) compared to those with TG <150 mg/dl. TC and TG were then combined in a "LIPID score" identifying three subgroups: good-risk (GR) (TC ≥200 mg/dl and TG <150 mg/dl), intermediate-risk (IR) (TC <200 mg/dl and TG <150 mg/dl or TC ≥200 mg/dl and TG ≥150 mg/dl) and poor-risk (PR) (TC <200 mg/dl and TG ≥150 mg/dl). The mPFS of GR, IR, and PR groups was 7.8, 4.3, and 2.5 months, respectively (P = .005); mOS of GR, IR, and PR was 20.4, 12.4, and 5.3 months, respectively (P < .001). At multivariable analysis, the PR profile represented an independent poor prognostic factor for both PFS and OS., Conclusions: We developed a lipid score that defined subgroups of patients with cancer who differently benefit from ICIs. Further mechanistic insights are warranted to clarify the prognostic and predictive role of lipid profile components in patients treated with ICIs., (© The Author(s) 2023. Published by Oxford University Press.)

Introduction: Despite several therapeutic efforts, lung cancer remains a highly lethal disease. Novel therapeutic approaches encompass immune-checkpoint inhibitors, targeted therapeutics and antibody-drug conjugates, with different results. Several studies have been aimed at identifying biomarkers able to predict benefit from these therapies and create a prediction model of response, despite this there is a lack of information to help clinicians in the choice of therapy for lung cancer patients with advanced disease. This is primarily due to the complexity of lung cancer biology, where a single or few biomarkers are not sufficient to provide enough predictive capability to explain biologic differences; other reasons include the paucity of data collected by single studies performed in heterogeneous unmatched cohorts and the methodology of analysis. In fact, classical statistical methods are unable to analyze and integrate the magnitude of information from multiple biological and clinical sources (eg, genomics, transcriptomics, and radiomics)., Methods and Objectives: APOLLO11 is an Italian multicentre, observational study involving patients with a diagnosis of advanced lung cancer (NSCLC and SCLC) treated with innovative therapies. Retrospective and prospective collection of multiomic data, such as tissue- (eg, for genomic, transcriptomic analysis) and blood-based biologic material (eg, ctDNA, PBMC), in addition to clinical and radiological data (eg, for radiomic analysis) will be collected. The overall aim of the project is to build a consortium integrating different datasets and a virtual biobank from participating Italian lung cancer centers. To face with the large amount of data provided, AI and ML techniques will be applied will be applied to manage this large dataset in an effort to build an R-Model, integrating retrospective and prospective population-based data. The ultimate goal is to create a tool able to help physicians and patients to make treatment decisions., Conclusion: APOLLO11 aims to propose a breakthrough approach in lung cancer research, replacing the old, monocentric viewpoint towards a multicomprehensive, multiomic, multicenter model. Multicenter cancer datasets incorporating common virtual biobank and new methodologic approaches including artificial intelligence, machine learning up to deep learning is the road to the future in oncology launched by this project., Competing Interests: Disclosures Arsela Prelaj certifies that all conflicts of interest reported can be considered outside the present paper: consulting or advisory role for BMS, AstraZeneca; had travel, accommodations, or other expenses paid or reimbursed by Roche, Italfarmaco; principal investigator of Spectrum Pharmaceuticals. Alessandra Laura Giulia Pedrocchi holds shares of Agade srl. Giuseppe Lo Russo has received fees for acting as a consultant from Roche, Novartis, BMS, MSD, AstraZeneca, Takeda, Amgen, Sanofi, Italfarmaco, Pfizer; has received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Roche, Novartis, BMS, MSD, AstraZeneca, Takeda, Amgen, Sanofi, has received support for attending meetings and/or travel from Roche, BMS, MSD; has participated on data safety monitoring board or advisory board for Roche, Novartis, BMS, MSD, AstraZeneca, Sanofi, has acted as principal investigator in sponsored clinical trials for Roche, Novartis, BMS, MSD, AstraZeneca, GSK, Amgen, Sanofi. Rossana Berardi has received fees for acting as a consultant, for lectures and/or for participating to advisory board from BI, EISAI, GSK, Italfarmaco, Otsuka, Lilly, MSD; has received funding to Institution from AZ, BMS, Pfizer, Novartis, Roche; AMGEN. Giulia Galli declares the following conflicts of interest: Italpharma (advisory board); Roche (travel accommodation); Astra Zeneca, BMS, MSD (honoraria for lectures). Federica Bertolini has received consultant fees from MSD, Astra-Zeneca, Lilly, Eisai, Sanofi and speakers fee from BMS, MSD, Astra Zeneca. Filippo de Braud reports a patent for PCT/IB2020/055956 pending and a patent for IT201900009954 pending; and Roche, EMD Serono, NMS Nerviano Medical Science, Sanofi, MSD, Novartis, Incyte, BMS, Menarini Healthcare Research & Pharmacoepidemiology, Merck Group, Pfizer, Servier, AMGEN, Incyte. No disclosures were reported by the other authors., (Copyright © 2023 Elsevier Inc. All rights reserved.)

By directly altering microscopic interactions, pressure provides a powerful tuning knob for the exploration of condensed phases and geophysical phenomena 1 . The megabar regime represents an interesting frontier, in which recent discoveries include high-temperature superconductors, as well as structural and valence phase transitions 2-6 . However, at such high pressures, many conventional measurement techniques fail. Here we demonstrate the ability to perform local magnetometry inside a diamond anvil cell with sub-micron spatial resolution at megabar pressures. Our approach uses a shallow layer of nitrogen-vacancy colour centres implanted directly within the anvil 7-9 ; crucially, we choose a crystal cut compatible with the intrinsic symmetries of the nitrogen-vacancy centre to enable functionality at megabar pressures. We apply our technique to characterize a recently discovered hydride superconductor, CeH 9 (ref.  10 ). By performing simultaneous magnetometry and electrical transport measurements, we observe the dual signatures of superconductivity: diamagnetism characteristic of the Meissner effect and a sharp drop of the resistance to near zero. By locally mapping both the diamagnetic response and flux trapping, we directly image the geometry of superconducting regions, showing marked inhomogeneities at the micron scale. Our work brings quantum sensing to the megabar frontier and enables the closed-loop optimization of superhydride materials synthesis., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

One of the major drawbacks of current treatments for neglected tropical diseases is the low safety of the drugs used and the emergence of resistance. Leishmaniasis is a group of neglected diseases caused by protozoa of the trypanosomatidae family that lacks preventive vaccines and whose pharmacological treatments are scarce and unsafe. Combination therapy is a strategy that could solve the above-mentioned problems, due to the participation of several mechanisms of action and the reduction in the amount of drug necessary to obtain the therapeutic effect. In addition, this approach also increases the odds of finding an effective drug following the repurposing strategy. From the previous screening of two collections of repositioning drugs, we found that pyrvinium pamoate had a potent leishmanicidal effect. For this reason, we decided to combine it separately with two clinically used leishmanicidal drugs, miltefosine and paromomycin. These combinations were tested in axenic amastigotes of Leishmania infantum obtained from bone marrow cells and in intramacrophagic amastigotes obtained from primary cultures of splenic cells, both cell types coming from experimentally infected mice. Some of the combinations showed synergistic behavior, especially in the case of the combination of pyrvinium pamoate with paromomycin, and exhibited low cytotoxicity and good tolerability on intestinal murine organoids, which reveal the potential of these combinations for the treatment of leishmaniasis.

We investigated the impact of quantum vibronic coupling on the electronic properties of solid-state spin defects using stochastic methods and first-principles molecular dynamics with a quantum thermostat. Focusing on the negatively charged nitrogen-vacancy center in diamond as an exemplary case, we found a significant dynamic Jahn-Teller splitting of the doubly degenerate single-particle levels within the diamond's band gap, even at 0 K, with a magnitude exceeding 180 meV. This pronounced splitting leads to substantial renormalizations of these levels and, subsequently, of the vertical excitation energies of the doubly degenerate singlet and triplet excited states. Our findings underscore the pressing need to incorporate quantum vibronic effects into first-principles calculations, particularly when comparing computed vertical excitation energies with experimental data. Our study also reveals the efficiency of stochastic thermal line sampling for studying phonon renormalizations of solid-state spin defects.

We investigate the Raman spectra of liquid water in contact with a semiconductor surface using first-principles molecular dynamics simulations. We focus on a hydrogenated silicon-water interface and compute the Raman spectra from time correlation functions of the polarizability. We establish a relationship between Raman spectral signatures and structural properties of the liquid at the interface, and we identify the vibrational impacts of an applied electric field. We show that negative bias leads to a reduction of the number of hydrogen bonds (HBs) formed between the surface and the topmost water layer and an enhancement of the HB interactions between water molecules. Instead, positive bias leads to an enhancement of both the HB interactions between water and the surface and between water molecules, creating a semi-ordered interfacial layer. Our work provides molecular-level insights into electrified semiconductor/water interfaces and the identification of specific structural features through Raman spectroscopy.

The realization of quantum sensors using spin defects in semiconductors requires a thorough understanding of the physical properties of the defects in the proximity of surfaces. We report a study of the divacancy (V Si V C ) in 3C-SiC, a promising material for quantum applications, as a function of surface reconstruction and termination with -H, -OH, -F and oxygen groups. We show that a V Si V C close to hydrogen-terminated (2 × 1) surfaces is a robust spin-defect with a triplet ground state and no surface states in the band gap and with small variations of many of its physical properties relative to the bulk, including the zero-phonon line and zero-field splitting. However, the Debye-Waller factor decreases in the vicinity of the surface and our calculations indicate it may be improved by strain-engineering. Overall our results show that the V Si V C close to SiC surfaces is a promising spin defect for quantum applications, similar to its bulk counterpart.

In the absence of a vaccine, there is a need to find new drugs for the treatment of neglected tropical diseases, such as leishmaniasis, that can overcome the many drawbacks of those currently used. These disadvantages include cost, the need to maintain a cold chain, the route of administration, the associated adverse effects and the generation of resistance. In this work we have evaluated the antileishmanial effect of 1,5- and 1,8-substituted fused naphthyridines through in vitro and ex vivo assays, using genetically modified axenic and intramacrophagic Leishmania infantum amastigotes. The toxicity of these compounds has been tested in the mammalian host cell using murine splenic macrophages, as well as in murine intestinal organoids (miniguts) in order to assess their potential for oral administration. The 1,8- derivatives showed greater leishmanicidal activity and the presence of a nitrogen atom in the fused ring to the naphthyridine was important to increase the activity of both types of molecules. The aromatization of the pyridine ring also had marked differences in the activity of the compounds.

Objective: Fly-catching syndrome (FCS) is a rare condition typically characterized by episodes during which affected dogs bite or lick the air and jump for no apparent reason. Among veterinary literature, obsessive-compulsive disorders, focal epileptic seizures, and underlying gastrointestinal diseases were considered the most likely triggering causes. Recently, gluten-sensitive dyskinesia has been described in dogs, but it has never been reported to be associated to FCS., Animal: A 6-year-old male French Bulldog., Clinical Presentation, Progression, and Procedures: The dog was presented for a 2-month history of episodes characterized by sudden onset of jumping while trying to catch something in the air without impaired consciousness or autonomic signs. The episodes could be interrupted by the owner and lasted several minutes. The dog suffered from chronic gastrointestinal signs. The neurological examination was within normal limits except for the episodes suggestive of FCS during the consultation. The serological test for anti-gliadin immunoglobulin G (AG IgG) and anti-transglutaminase-2 immunoglobulin A (ATG-2 IgA) antibodies resulted above the reference range (3.092 and 0.929, respectively; normal range < 0.6)., Treatment and Outcome: An exclusively gluten-free diet was started. Complete resolution of the episodes was reported during a 3-month follow-up., Clinical Relevance: To the authors' knowledge, this is the first report of FCS associated to positive AG IgG and ATG-2 IgA antibodies responsive to a gluten-free diet. The typical manifestation of the episodes and response to diet support the hypothesis that FCS may be associated to gastrointestinal disorders. However, more studies are needed in order to confirm this hypothesis.

We present a formulation of spin-conserving and spin-flip hybrid time-dependent density functional theory (TDDFT), including the calculation of analytical forces, which allows for efficient calculations of excited state properties of solid-state systems with hundreds to thousands of atoms. We discuss an implementation on both GPU- and CPU-based architectures along with several acceleration techniques. We then apply our formulation to the study of several point defects in semiconductors and insulators, specifically the negatively charged nitrogen-vacancy and neutral silicon-vacancy centers in diamond, the neutral divacancy center in 4H silicon carbide, and the neutral oxygen-vacancy center in magnesium oxide. Our results highlight the importance of taking into account structural relaxations in excited states in order to interpret and predict optical absorption and emission mechanisms in spin defects.

Pleural mesothelioma is an aggressive disease with diffuse nature, low median survival, and prolonged latency presenting difficulty in prognosis, diagnosis, and treatment. Here, we review all these aspects to underline the progress being made in its investigation and to emphasize how much work remains to be carried out to improve prognosis and treatment.

Background: Bone-targeted agents (BTA), such as denosumab (DN) and zoledronic acid (ZA), have historically reduced the risk of skeletal related events in cancer patients with bone metastases (BM), with no improvement in survival outcomes. In the immunotherapy era, BM have been associated with poor prognosis upon immune-checkpoint inhibitors (ICI). Currently, the impact of bone tumor burden on survival upon BTAs in advanced non-small cell lung cancer (aNSCLC) patients treated with ICI remains unknown., Methods: Data from ICI-treated aNSCLC patients with BM (4/2013-5/2022) in one institution were retrospectively collected. BTA-ICI concurrent treatment was defined as BTA administration at any time before or within 90 days from ICI start. High bone tumor burden (HBTB) was defined as ≥ 3 sites of BM. Median OS (mOS) was estimated with Kaplan-Meier. Aikaike's information criterion (AIC) was used to select the best model for data analysis adjusted for clinical variables., Results: Of 134 patients included, 51 (38 %) received BTA. At a mFU of 39.6 months (m), BTA-ICIs concurrent treatment did not significantly impact on mOS [8.3 m (95% CI 3.9-12.8) versus (vs) 6.8 m (95% CI 4.0-9.6) p = 0.36]; these results were confirmed after adjustment for clinical variables selected by AIC. A multivariate model showed a significant interaction between BTA use and HBTB or radiation therapy to BM. In subgroup analyses, only HBTB confirmed to be associated with significantly longer mOS [8.3 m (95% CI 2.4-14.2) vs 3.5 m (95% CI 2.9-4.1), p = 0.003] and mPFS [3.0 m (95% CI 1.6-4.4) vs 1.8 m (95% CI 1.6-2.0) p = 0.001] upon BTA-ICI concurrent treatment, with the most pronounced OS benefit observed for DN-ICI concurrent regimen [15.2 m (95% CI 0.1-30.7) vs 3.5 m (95% CI 2.9-4.1) p = 0.002]., Conclusions: In the immunotherapy era, HBTB can identify patients experiencing survival benefit with BTA, especially with DN-ICI combination. HBTB should be included as a stratification factor in the upcoming trials assessing BTA and ICI combinations in patients with aNSCLC and BM., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: SM declares personal fees from Italfarmaco, Sanofi and MSD outside the submitted work. EZ declares personal fees from AMGEN, outside the submitted work CP declares personal fees from BMS and MSD, outside the submitted work. AP declares personal fees from Astrazeneca, Roche, BMS. GG declares travel accommodation from Roche and personal fees from Italfarmaco, Astra Zeneca, BMS, MSD outside the submitted work. MCG declares personal financial interests with the following organizations: AstraZeneca, MSD International GmbH, BMS, Boehringer Ingelheim Italia S.p.A, Celgene, Eli Lilly, Ignyta, Incyte, Inivata, MedImmune, Novartis, Pfizer, Roche, Takeda; she also declares Institutional financial interests with the following organizations: Eli Lilly, MSD, Pfizer (MISP), AstraZeneca, MSD International GmbH, BMS, Boehringer Ingelheim Italia S.p.A, Celgene, Ignyta, Incyte, Inivata, MedImmune, Novartis, Pfizer, Roche, Takeda, Tiziana, Foundation Medicine; at the end, she has received research funding from the following organizations: AIRC, AIFA, Italian Moh, TRANSCAN. FdB provided consultation, attended advisory boards and/or provided lectures for the following organizations, from whom received honoraria or education grants: Amgen, AstraZeneca, Boehringer-Ingelheim, BMS, Eli Lilly, F. Hoffmann-La Roche, Ignyta, Merck Sharp and Dohme, Merck Serono, Novartis, Pfizer. GLR declares personal fees from MSD, TAKEDA; GSK; AMGEN; PFIZER; SANOFI; JANSEN; Eli Lilly, BMS, Roche, Italfarmaco, Novartis and AstraZeneca, outside the submitted work. DS declares personal fees from AstraZeneca, MSD, Boehringer Ingelheim and BMS, outside the submitted work. RF declares personal fees from MSD and Beigene outside the submitted work. The other authors report no conflict of interest. ., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objectives: To estimate the association between SSc clinical phenotypes and quantitative occupational exposure to crystalline silica, chlorinated solvents, trichloroethylene, and pesticides using job-exposure matrices., Methods: In the VISS-EXPOSITION transversal study, data on declarative occupational exposure to crystalline silica, solvents, and pesticides were retrieved. In parallel, the Lifetime Occupational History was evaluated using a questionnaire and cursus laboris for SSc patients followed at Bordeaux University Hospital (France). Using job-exposure matrices, we assessed patients' occupational exposure in relation to relevant clinical phenotypic forms of the disease., Results: Toxic exposure to crystalline silica and pesticides is underestimated by patients. Non-biased job-exposure matrices retrieved more exposed patients than the declarative assessment (10.1% of patients by job-exposure matrices versus 6.3% by declaration for crystalline silica and 25.9% versus 12.2% for pesticides). Patients overestimate their solvent exposure (7.9% for chlorinated solvents and 4.8% for trichlorethylene assessed by job-exposure matrices and 24.4% declarative exposure to solvents at large). Clinical form evaluation revealed a nonsignificant trend toward an increased risk of crystalline silica occupational exposure in the pulmonary fibrotic group of SSc patients (OR 3.12 CI 95% [0.80-12.15]). We also observed a nonsignificant trend toward elevated OR (OR 2.89 CI 95% [0.93-8.95]) for chlorinated solvent occupational exposure and the vascular phenotype of SSc. Of note, pesticide occupational exposure evaluation represents one of the largest to date in SSc patients., Conclusion: This study emphasizes that many exposed SSc patients are unaware of their occupational exposure. Job-exposure matrices allow better exposure screening for SSc secondary prevention and occupational exposure compensation., Clinical Trial Registration: clinicaltrials.gov, https://www.clinicaltrials.gov, NCT03543956., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Photoanodes used in a water-splitting photoelectrochemical cell are almost always paired with an oxygen evolution catalyst (OEC) to efficiently utilize photon-generated holes for water oxidation because the surfaces of photoanodes are typically not catalytic for the water oxidation reaction. Suppressing electron-hole recombination at the photoanode/OEC interface is critical for the OEC to maximally utilize the holes reaching the interface for water oxidation. In order to explicitly demonstrate and investigate how the detailed features of the photoanode/OEC interface affect interfacial charge transfer and photocurrent generation for water oxidation, we prepared two BiVO 4 (010)/FeOOH photoanodes with different Bi:V ratios at the outermost layer of the BiVO 4 interface (close to stoichiometric vs Bi-rich) while keeping all other factors in the bulk BiVO 4 and FeOOH layers identical. The resulting two photoanodes show striking differences in the photocurrent onset potential and photocurrent density for water oxidation. The ambient pressure X-ray photoelectron spectroscopy results show that these two BiVO 4 (010)/FeOOH photoanodes show drastically different Fe 2+ :Fe 3+ ratios in FeOOH both in the dark and under illumination with water, demonstrating the immense impact of the interfacial composition and structure on interfacial charge transfer. Using computational studies, we reveal the effect of the surface Bi:V ratio on the hydration of the BiVO 4 surface and bonding with the FeOOH layer, which in turn affect the band alignments between BiVO 4 and FeOOH. These results explain the atomic origin of the experimentally observed differences in electron and hole transfer and solar water oxidation performance of the two photoanodes having different interfacial compositions.

Peptides are at the cutting edge of contemporary research for new potent, selective, and safe therapeutical agents. Their rise has reshaped the pharmaceutical landscape, providing solutions to challenges that traditional small molecules often cannot address. A wide variety of natural and modified peptides have been obtained and studied, and many others are advancing in clinical trials, covering multiple therapeutic areas. As the demand for peptide-based therapies grows, so does the need for sustainable and environmentally friendly synthesis methods. Traditional peptide synthesis, while effective, often involves environmentally draining processes, generating significant waste and consuming vast resources. The integration of green chemistry offers sustainable alternatives, prioritizing eco-friendly processes, waste reduction, and energy conservation. This review delves into the transformative potential of applying green chemistry principles to peptide synthesis by discussing relevant examples of the application of such approaches to the production of active pharmaceutical ingredients (APIs) with a peptide structure and how these efforts are critical for an effective green transition era in the pharmaceutical field.

Carbonate formation presents a major challenge to energy storage applications based on low-temperature CO 2 electrolysis and recyclable metal-air batteries. While direct electrochemical oxidation of (bi)carbonate represents a straightforward route for carbonate management, knowledge of the feasibility and mechanisms of direct oxidation is presently lacking. Herein, we report the isolation and characterization of the bis(triphenylphosphine)iminium salts of bicarbonate and peroxybicarbonate, thus enabling the examination of their oxidation chemistry. Infrared spectroelectrochemistry combined with time-resolved infrared spectroscopy reveals that the photoinduced oxidation of HCO 3 - by an Ir(III) photoreagent results in the generation of the short-lived bicarbonate radical in less than 50 ns. The highly acidic bicarbonate radical undergoes proton transfer with HCO 3 - to furnish the carbonate radical anion and H 2 CO 3 , leading to the eventual release of CO 2 and H 2 O, thus accounting for the appearance of H 2 O and CO 2 in both electrochemical and photochemical oxidation experiments. The back reaction of the carbonate radical subsequently oxidizes the Ir(II) photoreagent, leading to carbonate. In the absence of this back reaction, dimerization of the carbonate radical provides entry into peroxybicarbonate, which we show undergoes facile oxidation to O 2 and CO 2 . Together, the results reported identify tangible pathways for the design of catalysts for the management of carbonate in energy storage applications.

Numerous field and laboratory studies have been conducted to investigate the relationship between radon variation and seismic events, as well as the complex link between radon emission and rock deformation mechanisms. However, a clear understanding of this correspondence and systematic observations of these phenomena are still lacking, and recent experimental studies have yet to yield conclusive results. In this study, we investigate the possible relationships between radon migration dynamics and rock deformation at the micro-scale through laboratory experiments using the SHIVA apparatus under shear stress-controlled conditions and simultaneous high-resolution radon measurements. We studied the behaviour of three different lithologies to show that radon emission varies in response to rock deformation and this variation is highly dependent on the mineralogy and microstructure. This study represents the first attempt to define radon gas as an indicator of transient and rapid rock deformation at the micro-scale., (© 2023. Springer Nature Limited.)

The full realization of spin qubits for quantum technologies relies on the ability to control and design the formation processes of spin defects in semiconductors and insulators. We present a computational protocol to investigate the synthesis of point-defects at the atomistic level, and we apply it to the study of a promising spin-qubit in silicon carbide, the divacancy (VV). Our strategy combines electronic structure calculations based on density functional theory and enhanced sampling techniques coupled with first principles molecular dynamics. We predict the optimal annealing temperatures for the formation of VVs at high temperature and show how to engineer the Fermi level of the material to optimize the defect's yield for several polytypes of silicon carbide. Our results are in excellent agreement with available experimental data and provide novel atomistic insights into point defect formation and annihilation processes as a function of temperature., (© 2023. Springer Nature Limited.)

Electronic structure calculations based on density functional theory (DFT) have successfully predicted numerous ground-state properties of a variety of molecules and materials. However, exchange and correlation functionals currently used in the literature, including semilocal and hybrid functionals, are often inaccurate to describe the electronic properties of heterogeneous solids, especially systems composed of building blocks with large dielectric mismatch. Here, we present a dielectric-dependent range-separated hybrid functional, screened-exchange range-separated hybrid (SE-RSH), for the investigation of heterogeneous materials. We define a spatially dependent fraction of exact exchange inspired by the static Coulomb-hole and screened-exchange (COHSEX) approximation used in many-body perturbation theory, and we show that the proposed functional accurately predicts the electronic structure of several nonmetallic interfaces, three- and two-dimensional, pristine, and defective solids and nanoparticles.

The optical spectra of neutral oxygen vacancies (F 0 centers) in the bulk MgO lattice are investigated using density matrix embedding theory. The impurity Hamiltonian is solved with the complete active space self-consistent field and second-order n -electron valence state perturbation theory (NEVPT2-DMET) multireference methods. To estimate defect-localized vertical excitation energies at the nonembedding and thermodynamic limits, a double extrapolation scheme is employed. The extrapolated NEVPT2-DMET vertical excitation energy value of 5.24 eV agrees well with the experimental absorption maxima at 5.03 eV, whereas the excitation energy value of 2.89 eV at the relaxed triplet defect-localized state geometry overestimates the experimental emission at 2.4 eV by only nearly 0.5 eV, indicating the involvement of the triplet-singlet decay pathway.

The unique self-assembly properties of unimer micelles are exploited for the preparation of fluorescent nanocarriers embedding hydrophobic fluorophores. Unimer micelles are constituted by a (meth)acrylate copolymer with oligoethyleneglycol and perflurohexylethyl side chains (PEGMA90- co -FA10) in which the hydrophilic and hydrophobic comonomers are statistically distributed along the polymeric backbone. Thanks to hydrophobic interactions in water, the amphiphilic copolymer forms small nanoparticles (<10 nm), with tunable properties and functionality. An easy procedure for the encapsulation of a small hydrophobic molecule (C153 fluorophore) within unimer micelles is presented. UV-vis, fluorescence, and fluorescence anisotropy spectroscopic experimental data demonstrate that the fluorophore is effectively embedded in the nanocarriers. Moreover, the nanocarrier positively contributes to preserve the good emissive properties of the fluorophore in water. The efficacy of the dye-loaded nanocarrier as a fluorescent probe is tested in two-photon imaging of thick ex vivo porcine scleral tissue., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Objective: Several studies showed that transcranial direct current stimulation (tDCS) enhances cognition in patients with mild cognitive impairment (MCI), however, whether tDCS leads to additional gains when combined with cognitive training remains unclear. This study aims to compare the effects of a concurrent tDCS-cognitive training intervention with either tDCS or cognitive training alone on a group of patients with MCI., Methods: The study was a 3-parallel-arm study. The intervention consisted of 20 daily sessions of 20 minutes each. Patients (n = 62) received anodal tDCS to the left dorsolateral prefrontal cortex, cognitive training on 5 cognitive domains (orientation, attention, memory, language, and executive functions), or both. To examine intervention gains, we examined global cognitive functioning, verbal short-term memory, visuospatial memory, and verbal fluency pre- and post-intervention., Results: All outcome measures improved after the intervention in the 3 groups. The improvement in global cognitive functioning and verbal fluency was significantly larger in patients who received the combined intervention. Instead, the intervention gain in verbal short-term memory and visuospatial memory was similar across the 3 groups., Discussion: tDCS, regardless of the practicalities, could be an efficacious treatment in combination with cognitive training given the increased effectiveness of the combined treatment., Conclusions: Future studies will need to consider individual differences at baseline, including genetic factors and anatomical differences that impact the electric field generated by tDCS and should also consider the feasibility of at-home treatments consisting of the application of tDCS with cognitive training.

Introduction: Thymic malignancies are rare tumors with few therapeutic options. The STYLE trial was aimed to evaluate activity and safety of sunitinib in advanced or recurrent type B3 thymoma (T) and thymic carcinoma (TC)., Methods: In this multicenter, Simon 2 stages, phase 2 trial, patients with pretreated T or TC were enrolled in two cohorts and assessed separately. Sunitinib was administered 50 mg daily for 4 weeks, followed by a 2-week rest period (schedule 4/2), until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR). Progression-free survival, overall survival, disease control rate and safety were secondary endpoints., Results: From March 2017 to January 2022, 12 patients with T and 32 patients with TC were enrolled. At stage 1, ORR was 0% (90% confidence interval [CI]: 0.0-22.1) in T and 16.7% (90% CI: 3.1-43.8) in TC, so the T cohort was closed. At stage 2, the primary endpoint was met for TC with ORR of 21.7% (90% CI: 9.0%-40.4%). In the intention-to-treat analysis, disease control rate was 91.7% (95% CI: 61.5%-99.8%) in Ts and 89.3% (95% CI: 71.8%-97.7%) in TCs. Median progression-free survival was 7.7 months (95% CI: 2.4-45.5) in Ts and 8.8 months (95% CI: 5.3-11.1) in TCs; median overall survival was 47.9 months (95% CI: 4.5-not reached) in Ts and 27.8 months (95% CI: 13.2-53.2) in TCs. Adverse events occurred in 91.7% Ts and 93.5% TCs. Grade 3 or greater treatment-related adverse events were reported in 25.0% Ts and 51.6% TCs., Conclusions: This trial confirms the activity of sunitinib in patients with TC, supporting its use as a second-line treatment, albeit with potential toxicity that requires dose adjustment., (Copyright © 2023 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Measuring the thermal conductivity (κ) of water at extreme conditions is a challenging task, and few experimental data are available. We predict κ for temperatures and pressures relevant to the conditions of the Earth mantle, between 1,000 and 2,000 K and up to 22 GPa. We employ close to equilibrium molecular dynamics simulations and a deep neural network potential fitted to density functional theory data. We then interpret our results by computing the equation of state of water on a fine grid of points and using a simple model for κ. We find that the thermal conductivity is weakly dependent on temperature and monotonically increases with pressure with an approximate square-root behavior. In addition, we show how the increase of κ at high pressure, relative to ambient conditions, is related to the corresponding increase in the sound velocity. Although the relationships between the thermal conductivity, pressure and sound velocity established here are not rigorous, they are sufficiently accurate to allow for a robust estimate of the thermal conductivity of water in a broad range of temperatures and pressures, where experiments are still difficult to perform.

Radon ( 222 Rn) is the second most common cause of lung cancer after smoking. As radon poses a significant risk to human health, radon-affected areas should be identified to ensure people's awareness of risk and remediation. The primary goal of this research was to investigate the local natural radioactivity (in soils, groundwater, and indoors) because of the presence of tuff outcrops (from middle-lower Pleistocene volcanic activity) that naturally produce radioactive gas radon at Cerveteri (Rome, Central Italy). The results of the radon survey highlighted moderate (>16,000 Bq/m 3 ) but localized anomalies in soils in correspondence with a funerary site pertaining to the Etruscan Necropolis of Cerveteri, which extends over a volcanic rock plateau. Indoor radon measurements were performed at several tuff-made dwellings, and the results showed medium-low (<200 Bq/m 3 ) values of indoor radon except for some cases exceeding the reference level (>300 Bq/m 3 ) recommended by the 2013/59 Euratom Directive. Although no clinical data exist regarding the health effects of thoron ( 220 Rn) on humans, the study of 220 Rn average activity concentration in the soil gas survey reveals new insights for the interpretation of radon sources that can affect dwellings, even taking into account the considerable difference in the half-lives of 222 Rn and 220 Rn.

In the past years cancer treatments have drastically changed, mainly due to the development of immune checkpoint inhibitors capable of immune modulation in vivo, thus providing major clinical benefit in a number of malignancies. Simultaneously, considerable technical refinements have opened new prospects for the development of immune cell-based medicinal products and unprecedented success with chimeric antigen receptor (CAR)-T cells targeting B-cell hematologic malignancies has been obtained. However, T cell therapies introduced and performed in the field of solid tumors have produced so far only limited responses in selected patient populations. This standstill is attributable to the difficulty in identifying target antigens which are homogeneously expressed by all tumor cells while absent from normal tissues, and the limited T cell persistence and proliferation in a hostile tumor microenvironment that favors immune escape. Replicating the results observed in hematology is a major scientific challenge in solid tumors, and ongoing translational and clinical research is focused on obtaining insight into the mechanisms of tumor recognition and evasion, and how to improve the efficacy of cellular therapies, also combining them with immune checkpoint inhibitors or other agents targeting either the cancer cell or the tumor environment. This paper provides an overview of current adaptive T cell therapy approaches in solid tumors, the research performed to increase their efficacy and safety, and results from ongoing clinical trials.

We present a study of molecular crystals, focused on the effect of nuclear quantum motion and anharmonicity on their electronic properties. We consider a system composed of relatively rigid molecules, a diamondoid crystal, and one composed of floppier molecules, NAI-DMAC, a thermally activated delayed fluorescence compound. We compute fundamental electronic gaps at the density functional theory (DFT) level of theory, with the Perdew-Burke-Erzenhof (PBE) and strongly constrained and approximately normed (SCAN) functionals, by coupling first-principles molecular dynamics with a nuclear quantum thermostat. We find a sizable zero-point renormalization (ZPR) of the band gaps, which is much larger in the case of diamondoids (0.6 eV) than for NAI-DMAC (0.22 eV). We show that the frozen phonon (FP) approximation, which neglects intermolecular anharmonic effects, leads to a large error (∼50%) in the calculation of the band gap ZPR. Instead, when using a stochastic method, we obtain results in good agreement with those of our quantum simulations for the diamondoid crystal. However, the agreement is worse for NAI-DMAC where intramolecular anharmonicities contribute to the ZPR. Our results highlight the importance of accurately including nuclear and anharmonic quantum effects to predict the electronic properties of molecular crystals.

Microplastics are a prolific environmental contaminant. Curbing microplastic pollution requires an array of globally relevant interventions, including source-reduction and curative measures. A novel, nature-based solution to microplastics is proposed, in which mussels are deployed in aquatic ecosystems to act as microplastic biofilters, removing waterborne microplastics and repackaging them into biodeposits that are subsequently captured and removed. Blue mussels (Mytilus edulis) were used to establish the feasibility of such an approach. In the laboratory, mussels were exposed to representative microplastics in a flume tank; at an initial concentration of 1000 microplastics L -1 , mussels reduced waterborne microplastic concentrations at an average rate of 40,146 microplastics kg -1 h -1 . Mussel faeces sank irrespective of microplastic content, with average sinking velocities of 223-266 m day -1 . Modelling predicts ∼3 × 10 9 mussels deployed on ropes at the mouths of estuaries could remove 4% of waterborne microplastics discharged from rivers. Mussels were successfully deployed in a prototype biodeposit collection system in an urban marina, with 5.0 kg of mussels removing and repackaging 239.9 ± 145.9 microplastics and anthropogenic particles day -1 into their faeces. These results provide impetus for further development of nature-based solutions targeting plastic debris., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)