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Measuring psychological traits with standardised questionnaires is an essential component of clinical practice and research; however, patients and participants risk fatigue from overly long and repetitive measures. When developing the short form of a questionnaire, the most widely used method for selecting an item subset uses factor analysis loadings to identify the items most closely related to the psychological construct being measured. However, this approach will tend to select highly correlated, homogeneous items and might therefore restrict the breadth of the construct examined. In this study, we will present Yarkoni's genetic algorithm for scale reduction and compare it with the classical scale reduction method. The algorithm will be applied to the shortening of three instruments for measuring self-compassion and social safeness (two unidimensional measures and a three-factor measure). We evaluated the shortened scales using correlation with long-form scores, internal reliability and the change in the correlations observed with other related constructs. Findings suggested that the classical method preserves internal reliability, but Yarkoni's genetic algorithm better maintained correlations with other constructs. An additional qualitative assessment of item content showed that the latter method led to a more heterogeneous selection of items, better preserving the full complexity of the constructs being measured., (© 2024 The Author(s). International Journal of Psychology published by John Wiley & Sons Ltd on behalf of International Union of Psychological Science.)

Introduction: Personalized medicine has revolutionized the clinical management of patients with solid tumors. However, the large volumes of molecular data derived from next-generation sequencing (NGS) and the lack of harmonized bioinformatics pipelines drastically impact the clinical management of patients with solid tumors. A possible solution to streamline the molecular interpretation and reporting of NGS data would be to adopt automated data analysis software. In this study, we tested the clinical efficiency of the Navify Mutation Profiler (nMP) software in improving the interpretation of NGS data analysis in diagnostic routine samples from patients with solid tumors., Methods: This study included one coordinating institution (Federico II University of Naples) and five other Italian institutions. Variant call format (VCF) files from reference standard samples previously tested by the coordinating institution and from n = 8 diagnostic routine samples (n = 2 from colorectal carcinoma; n = 2 from non-small cell lung cancer; n = 2 from advanced melanoma; and n = 2 from patients with gastrointestinal stromal tumors) and previously analyzed by each participating institution (n = 5) with standardized internal analysis workflows were uploaded onto the Navify ® Mutation Profiler (nMP) system (Roche Sequencing Solutions, Pleasanton, CA, USA) for automated analysis and interpretation of DNA and RNA molecular alterations analytical parameters, molecular profiling, and clinical interpretation were carried out by the nMP system and compared with the standard workflow data analyzed by the participating institutions., Results: Overall, all VCF files were successfully submitted and interpreted by the nMP system. A concordance agreement rate of 89.6% was observed between the automated and standard workflow systems. In particular, DNA and RNA molecular profiles obtained with the nMP system matched those obtained with standardized approaches in 44 out of 48 patients (91.7%) and in 11 out of 12 (91.7%) cases, respectively. In addition, the nMP system evidenced wild-type variants in 6 out of 7 (85.7%) cases., Conclusions: The nMP system represents a valid, easily manageable, and clinically useful system to interpret NGS data on diagnostic routine samples from patients with solid tumors., Competing Interests: Declarations. Conflict of Interest: Francesco Pepe has a relevant relationship (advisory fees, honoraria, travel accommodation and expenses, grants, and non-financial support) with Menarini and Roche that is unrelated to the current work. Luisella Righi reports personal fees (for speaker’s bureaus or acting as an advisor) from Roche, MSD, Boehringer Ingelheim, Eli Lilly, BMS, AstraZeneca, Amgen, and Bayer that are unrelated to the current work. Giancarlo Troncone reports personal fees (for speaker’s bureaus or acting as an advisor) from Roche, MSD, Pfizer, Boehringer Ingelheim, Eli Lilly, BMS, GSK, Menarini, AstraZeneca, Amgen, and Bayer that are unrelated to the current work. Umberto Malapelle has received personal fees (for acting as a consultant and/or speaker’s bureaus) from Boehringer Ingelheim, Roche, MSD, Amgen, Thermo Fisher Scientific, Eli Lilly, Diaceutics, GSK, Merck, AstraZeneca, Janssen, Diatech, Novartis, and Hedera that are unrelated to the current work. Umberto Malapelle is an editorial board member of Oncology and Therapy. Umberto Malapelle was not involved in the selection of peer reviewers for the manuscript nor in any of the subsequent editorial decisions. All other named authors confirm that they have no conflicts of interest to declare. Ethical Approval: Written informed consent was acquired from all patients involved in the study and documented in accordance with the general authorization for processing personal data for scientific research purposes from the Italian Data Protection Authority ( http://www.garanteprivacy.it/web/guest/home/docweb/-/docwebdisplay/export/2485392 ). All information regarding human material was managed using anonymous numerical codes, and all samples were handled in compliance with the Helsinki Declaration ( http://www.wma.net/en/30publications/10policies/b3/ )., (© 2024. The Author(s).)

Patients with health pathologies may exhibit psychological features in addition to medical symptomatology. A sample of 76 Italian women with an age range between 23 and 78 years old (mean = 50.22 ± 10.47 years) diagnosed with fibromyalgia (a disorder characterized by widespread musculoskeletal pain accompanied by fatigue, sleep, cognitive and mood issues) was examined to identify typical characteristics of their psychological profile. All patients were administered a series of questionnaires, to assess avoidance of physical touch by others; anxiety; depression; risk of developing psychotic disorders; self-criticism and perfectionism; acceptance of chronic pain; general impact of the pathology on their lives, and the predisposition to experience positive emotional states. The scores resulting from this assessment were evaluated against the normative data. Patients with fibromyalgia showed psychological dysfunction in most of the scales administered, with a significantly higher disposition to experience compassion towards others ( t = 5.94, df = 75, p < 0.001). A higher risk of psychosis was related with higher levels of depression ( B = 0.49, t = 0.20, p = 0.015), poor involvement in daily activities ( B = 0.41, t = 0.13, p = 0.002), touch avoidance (especially towards strangers, B = -0.20, t = 0.14, p = 0.01), and overall poor quality of life ( B = 0.40, t = 0.16, p = 0.01). This study may broaden the possibility to evaluate psychological features in this clinical population; it may contribute to tailoring psychological care and related treatments in the context of health services.

Competing Interests: There are no conflicts of interest.

Context: Lenvatinib is approved for the treatment of radioiodine-refractory differentiated thyroid cancer (RR-DTC). The definition of predictive factors of survival is incomplete., Objective: To identify pre- and posttreatment survival predictors in a real-life cohort of RR-DTC treated with lenvatinib., Design: Multicenter, retrospective, cohort study., Setting: 3 Italian thyroid cancer referral centers., Participants: 55 RR-DTC treated with lenvatinib., Main Outcome Measures: Progression-free survival (PFS) and overall survival (OS)., Results: Lenvatinib was the first-line kinase-inhibitor in 96.4% of subjects. Median follow-up was 48 months. Median PFS and OS were 26 [95% confidence interval (CI) 19.06-32.93] and 70 months (95% CI 36-111.99), respectively. Pretreatment setting: Eastern Cooperative Oncology Group (ECOG) performance status was independently related to PFS [P < .001; hazard ratio (HR) 18.82; 95% CI 3.65-97.08: score 0-1 as reference] and OS (P = .001; HR 6.20; 95% CI 2.11-18.20; score 0-1 as reference); radioactive iodine (RAI) avidity was independently related to PFS (P = .047; HR 3.74; 95% CI 1.01-13.76; avid disease as reference). Patients with good ECOG status (0-1) and RAI-avid disease obtained objective response in 100% of cases and achieved a median PFS of 45 months without any death upon a median follow-up of 81 months. Posttreatment setting: the best radiological response independently predicted PFS (P = .001; HR 4.6; 95% CI 1.89-11.18; partial/complete response as reference) and OS (P = .013; HR 2.94; 95% CI 1.25-6.89; partial/complete response as reference)., Conclusion: RR-DTC with good performance status and RAI-avid disease obtains the highest clinical benefit from lenvatinib. After treatment initiation, objective response was the only independent survival predictor., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

One-dimensional sub-wavelength gratings are versatile photonic platforms supporting diverse resonances, including symmetry-protected bound states in the continuum. However, practical access to these bound modes relies on their quasi-bound form, which necessitates the introduction of perturbations in either geometry or material properties. Despite having a large, finite quality factor, quasi-bound modes retain their characteristically strong field confinement. Gaining control over field localization and leakage of quasi-bound modes requires an investigation not limited to studying the degree of asymmetry and the incoming polarization. Here, we demonstrate that by carefully combining specific types of asymmetries and refractive index contrast between the grating and its surrounding environment, one can tailor field localization and Q-factor almost at will. Our findings reveal a strategic roadmap for optimizing quasi-bound mode implementation, dramatically improving their use in applications such as optical communication, sensing, and nonlinear optical processes.

Context: Growth hormone (GH) deficiency in a child with short stature is diagnosed by GH secretion provocative tests. When the test response is considered adequate, the short stature is considered idiopathic (ISS)., Objective: To determine the effect of GH provocative tests on the growth rate in children with idiopathic short stature., Design: Children with short stature with a normal response to at least one GH provocative test were enrolled. Height and growth velocity were measured prior to and after stimulus tests during the follow-up., Methods: Height, mid-parental height, body weight, and body mass index were measured. The height and growth rate were converted to percentiles and Standard Deviation Scores (SDS) using reference ranges standardized by age and sex. GH provocative tests employed arginine or clonidine as secretagogues., Results: Fourty-six children of both genders were enrolled. In thirty-six children, height was measured at the time of testing and on an average time prior to and after the tests of 210 days and 180 days respectively. After testing the children displayed a 3.4-fold increase in their estimated 90-day growth rate. The median (inter-quartile range, IQR) 90 days growth of children pre-and post-tests were 0.7 (0.2-1.0) cm and 2.4 (1.7-3.1) cm respectively with a mean 3,4-fold increase (p < 0.0001). The median (IQR) 90 days growth of children pre- and post-tests calculated as standard deviation scores (SDS) were -4.0 (-5.4--2.1) SDS and 0.1 (-1.9-1.4) SDS respectively (p < 0.0001). Ten children with ISS were observed for about 5 months before the GH provocative tests. A small increase in the growth rate was seen only in 2 out of 10 children before testing while it increased in all of them after the tests. The difference in the median growth rate at the first and the second observation was not significant (p = 0.219)., Conclusions: Two sequential somatotropic axis provocative tests increase the growth rate in children with idiopathic short stature. The duration of this effect is yet to be determined., (© 2024. The Author(s).)

We demonstrate that AlGaAs thin films and metasurfaces generate a distinct intrinsic nonlinear geometric phase in their second harmonic signals, differing significantly from previous studies on nonlinear dielectric, plasmonic, or hybrid metasurfaces. Unlike conventional observations, our study reveals that the second harmonic phase remains unaffected by the linear optical response at both pump and harmonic wavelengths, introducing a novel realm of achievable phase functions yet to be explored. Furthermore, we explore the interplay between this intrinsic nonlinear geometric phase and the geometric phase induced by rotations of nanoresonators within metasurface arrangements. Our findings extend the capabilities of nonlinear wavefront shaping metasurfaces, exploiting phase manipulation to uncover unique phenomena exclusive to the nonlinear regime., Competing Interests: Conflict of interest: Authors state no conflicts of interest., (© 2024 the author(s), published by De Gruyter, Berlin/Boston.)

Nowadays, dielectric metasurfaces are a promising platform in many different research fields such as sensing, lasing, all-optical modulation and nonlinear optics. Among all the different kinds of such thin structures, asymmetric geometries are recently attracting increasing interest. In particular, nonlinear light-matter interaction in metasurfaces constitutes a valid approach for achieving miniaturized control over light. Here, we demonstrate nonlinear asymmetric generation of light in a dielectric metasurface via second harmonic generation. By inverting the illumination direction of the pump, the nonlinear emitted power is modulated by more than one order of magnitude. Moreover, we demonstrate how a properly designed metasurface can generate two completely different images at the second harmonic when the direction of illumination is reversed. Our results may pave the way to important opportunities for the realization of compact nanophotonic devices for imaging applications by densely integrating numerous nonlinear resonators.

All-optical modulation yields the promise of high-speed information processing. In this field, metasurfaces are rapidly gaining traction as ultrathin multifunctional platforms for light management. Among the featured functionalities, they enable light-wavefront manipulation and more recently demonstrated the ability to perform light-by-light manipulation through nonlinear optical processes. Here, by employing a nonlinear periodic metasurface, we demonstrate the all-optical routing of telecom photons upconverted to the visible range. This is achieved via the interference between two frequency-degenerate upconversion processes, namely, third-harmonic and sum-frequency generation, stemming from the interaction of a pump pulse with its frequency-doubled replica. By tuning the relative phase and polarization between these two pump beams, we route the upconverted signal among the diffraction orders of the metasurface with a modulation efficiency of up to 90%. This can be achieved by concurrently engineering the nonlinear emission of the individual elements (meta-atoms) of the metasurface along with its pitch. Owing to the phase control and ultrafast dynamics of the underlying nonlinear processes, free-space all-optical routing could be potentially performed at rates close to the employed optical frequencies divided by the quality factor of the optical resonances at play. Our approach adds a further twist to optical interferometry, which is a key enabling technique employed in a wide range of applications, such as homodyne detection, radar interferometry, light detection and ranging technology, gravitational-wave detection and molecular photometry. In particular, the nonlinear character of light upconversion combined with phase sensitivity is extremely appealing for enhanced imaging and biosensing., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

In this work, phytochemical analysis on different extracts of Roccella tinctoria DC. was reported using different techniques with respect to the past. Twenty volatile and three non-volatile compounds were identified, some of which were found in this species for the first time. The methanolic extracts and their non-volatile components were then evaluated for their antitumor effects in cancerous A549 and Mz-ChA-1 cells and for their tolerability in non-cancerous BEAS-2B and H69 cells, showing IC 50 values from 94.6 µg/mL to 416.4 µg/mL, in general. The same extracts and compounds were also tested for their antifungal effects in Candida albicans, with only compound 2 being active, with an MIC 50 value of 87 µg/mL. In addition, they were tested for their anti- Candida adhesion activity, anti- Candida biofilm formation, and anti- Candida mature biofilm inhibition, with efficacy percentages generally above 50% but not for all of them. Lastly, the DF3 extract and compounds 1 - 2 were tested in vivo according to the Galleria mellonella survival assay, showing positive mortality rates above 50% at different concentrations. All these biological assays were conducted on this species for the first time. Comparisons with other lichens and compounds were also presented and discussed.

Background: MET (MET Proto-Oncogene, Receptor Tyrosine Kinase) exon 14 skipping mutation represents one of the most common MET alterations, accounting for approximately 1-3% of all mutations in advanced lung adenocarcinomas. While until 2020 no specific treatment was available for this subset of patients, as of today, three MET Tyrosine Kinase Inhibitors (TKIs) are currently approved in this setting, namely capmatinib, tepotinib and savolitinib., Objective: This article aims to provide an extensive overview of the current therapeutic standard of care for exon 14 skipped advanced Non-small Cell Lung Cancer (NSCLC) patients, alongside with mentions of the main future challenges and opportunities., Conclusion: FDA-approved MET-TKIs currently represent the best option for treating exon 14 skipped advanced NSCLC patients, thanks to their excellent efficacy profile, alongside their manageable safety and tolerability. However, we currently lack specific agents to treat patients progressing on capmatinib or tepotinib, due to a limited understanding of the mechanisms underlying both on- and off-target resistance. In this respect, on-target mutations presently constitute the most explored ones from a mechanistic point of view, and type II MET-TKIs are currently under investigation as the most promising agents capable of overcoming the acquired resistance., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Metasurfaces, composed of artificial meta-atoms of subwavelength size, can support strong light-matter interaction based on multipolar resonances and plasmonics, hence offering the great capability of empowering nonlinear generation. Recently, owing to their ability to manipulate the amplitude and phase of the nonlinear emission in the subwavelength scale, metasurfaces have been recognized as ultra-compact, flat optical components for a vast range of applications, including nonlinear imaging, quantum light sources, and ultrasensitive sensing. This review focuses on the recent progress on nonlinear metasurfaces for those applications. The principles and advances of metasurfaces-based techniques for image generation, including image encoding, holography, and metalens, are investigated and presented. Additionally, the overview and development of spontaneous photon pair generation from metasurfaces are demonstrated and discussed, focusing on the aspects of photon pair generation rate and entanglement of photon pairs. The recent blossoming of the nonlinear metasurfaces field has triggered growing interest to explore its ability to efficiently up-convert infrared images of arbitrary objects to visible images and achieve spontaneous parametric down-conversion. This recently emerged direction holds promising potential for the next-generation technology in night-vision, quantum computing, and biosensing fields., Competing Interests: Conflict of interest: Authors state no conflicts of interest., (© 2023 the author(s), published by De Gruyter, Berlin/Boston.)

In this paper, novel optimization methodologies of sub-relativistic guided interaction structures for dielectric laser particle acceleration (DLA) are presented. In particular, we focus on co-propagating geometries based on slot waveguides in continuous wave (CW) operation, where the particle flow and the direction of propagation of the accelerating field are co-linear. Since the velocity of sub-relativistic particles varies along the acceleration path, proper tapering of the waveguide geometry is required to achieve an extended acceleration region, and, thus a large energy gain. The design of an optimal taper ensuring particle-wave synchronicity and maximum energy gain is pursued through a physics-based approach, and these results are compared, for validation, with the outcomes of a downhill simplex method searching algorithm. Additionally, the application of a simplified 2D model of the accelerating slot waveguide is investigated and profitably used to get qualitative results useful for fast structure optimization. Indeed, this approach can hold significant potential for the development of novel accelerating structures, as it enables a thorough and fast exploration of the design space.

Taking into account the huge epidemiologic impact of lung cancer (in 2020, lung cancer accounted for 2,206,771 of the cases and for 1,796,144 of the cancer-related deaths, representing the second most common cancer in female patients, the most common cancer in male patients, and the second most common cancer in male and female patients) and the current lack of recommendations in terms of prognostic factors for patients selection and management, this article aims to provide an overview of the current landscape in terms of currently available immunotherapy treatments and the most promising assessed prognostic biomarkers, highlighting the current state-of-the-art and hinting at future challenges.

We investigate nonlinear THz generation from lithium niobate films and crystals of different thicknesses by optical rectification of near-infrared femtosecond pulses. A comparison between numerical studies and polarization-resolved measurements of the generated THz signal reveals a 2 orders of magnitude enhancement in the nonlinear response compared to optical frequencies. We show that this enhancement is due to optical phonon modes at 4.5 and 7.45 THz and is most pronounced for films thinner than 2 μm where optical-to-THz conversion is not limited by self-absorption. These results shed new light on the employment of thin film lithium niobate platforms for the development of new integrated broadband THz emitters and detectors. This may also open the door for further control (e.g., polarization, directivity, and spectral selectivity) of the process in nanophotonic structures, such as nanowires and metasurfaces, realized in the thin film platform. We illustrate this potential by numerically investigating optical-to-THz conversion driven by localized surface phonon-polariton resonances in sub-wavelength lithium niobate rods., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Vinca sardoa (Stearn) Pignatti, known as Sardinian periwinkle, is widely diffused in Sardinia (Italy). This species contains indole alkaloids, which are known to have a great variety of biological activities. This study investigated the antileukemic activity against a B lymphoblast cell line (SUP-B15) of V. sardoa alkaloid-rich extracts obtained from plants grown in Italy, in Iglesias (Sardinia) and Rome (Latium). All the extracts showed a good capacity to induce reductions in cell proliferation of up to 50% at the tested concentrations (1-15 µg/mL). Moreover, none of the extracts showed cytotoxicity on normal cells at all the studied concentrations.

Introduction: CTLA-4/PD-1/PD-L1- directed immune checkpoint inhibitors (ICIs) are one of the standard therapies for the treatment of advanced non-small cell lung cancer (NSCLC). However, some new classes of monoclonal antibodies are emerging as promising therapies for advanced NSCLC., Areas Covered: Therefore, this paper aims to provide a comprehensive review of the recently approved as well as emerging monoclonal antibody immune checkpoint inhibitors for the treatment of advanced NSCLC., Expert Opinion: Further and larger studies will be needed to explore the promising emerging data on new ICIs. Future phase III trials could allow us to properly assess the role of each immune checkpoints in the wider context of the tumor microenvironment and thus the best new ICIs to use, the best approach and the most effective subset of patients to select.

Somatic activating mutations of PIK3CA are associated with development of vascular malformations (VMs). Here, we describe a microfluidic model of PIK3CA -driven VMs consisting of human umbilical vein endothelial cells expressing PIK3CA activating mutations embedded in three-dimensional hydrogels. We observed enlarged, irregular vessel phenotypes and the formation of cyst-like structures consistent with clinical signatures and not previously observed in cell culture models. Pathologic morphologies occurred concomitant with up-regulation of Rac1/p21-activated kinase (PAK), mitogen-activated protein kinase cascades (MEK/ERK), and mammalian target of rapamycin (mTORC1/2) signaling networks. We observed differential effects between alpelisib, a PIK3CA inhibitor, and rapamycin, an mTORC1 inhibitor, in mitigating matrix degradation and network topology. While both were effective in preventing vessel enlargement, rapamycin failed to reduce MEK/ERK and mTORC2 activity and resulted in hyperbranching, while inhibiting PAK, MEK1/2, and mTORC1/2 mitigates abnormal growth and vascular dilation. Collectively, these findings demonstrate an in vitro platform for VMs and establish a role of dysregulated Rac1/PAK and mTORC1/2 signaling in PIK3CA -driven VMs.

Carbon quantum dots (CDs) are "small" carbon nanostructures with excellent photoluminescence properties, together with low-toxicity, high biocompatibility, excellent dispersibility in water as well as organic solvents. Due to their characteristics, CDs have been studied for a plethora of applications as biosensors, luminescent probes for photodynamic and photothermal therapy, fluorescent inks and many more. Moreover, the possibility to obtain carbon dots from biomasses and/or organic waste has strongly promoted the interest in this class of carbon-based nanoparticles, having a promising impact in the view of circular economy and sustainable processes. Within this context, electrochemistry proved to be a green, practical, and efficient method for the synthesis of high-quality CDs, with the possibility to fine-tune their characteristics by changing operational parameters. This review outlines the principal and most recent advances in the electrochemical synthesis of CDs, focusing on the electrochemical set-up optimization., Competing Interests: The authors declare no conflict of interest., (© 2023 The Authors. ChemElectroChem published by Wiley-VCH GmbH.)

RET-selective tyrosine kinase inhibitors (TKIs) selpercatinib and pralsetinib have revolutionized the landscape of RET-positive (RET+) advanced non-small cell lung cancer (NSCLC) treatment, thanks to their efficacy and safety profiles. This class of medications currently represents the standard of care for both naïve and patients that have not received selective RET-TKIs in the first-line setting. However, we presently lack a satisfactory understanding of resistance mechanism developing after selective RET-TKIs usage, as well as a specific treatment for patients progressing on selpercatinib or pralsetinib. Chemotherapy ± immunotherapy is considered as a recommended subsequent second-line regimen in these patients. Therefore, it is of paramount importance to better define and understand the resistance mechanisms triggered by RET-TKIs. With this in mind, the present review article has been conceived to provide a comprehensive overview about RET+ advanced NSCLC, both from a therapeutic and molecular point of view. Besides comparing the clinical outcome achieved in RET+ advanced NSCLC patients after multikinase inhibitors (MKIs) and/or RET-selective TKIs' administration, we focused on the molecular mechanisms accountable for their long-term resistance. Finally, a critical perspective on many of today's most debated issues and concerns is provided, with the purpose of shaping the possible pharmacological approaches for tomorrow's therapies.

Bisphenol A (BPA) is a widespread thyroid disruptor, but evidence about an association with thyroid cancer is weak. Excess body weight is a risk factor for thyroid cancer and affects activity of endocrine disruptors. Aim of the study was to investigate the association between BPA exposure and thyroid cancer, verifying the effect modification related to body weight. We performed a multicentre, cross-sectional study including consecutive patients referring for nodular goiter. The quantitative determination of BPA in serum samples was performed through high performance liquid chromatography system, coupled in tandem with ultraviolet and fluorescence detection. Ninety-six patients were included: 55 benign nodules, 41 thyroid cancers, 28 normal weight, and 68 overweight/obese. BPA was detected in 79 subjects. In the overall study population and in the group with BMI<25 kg/m 2 BPA exposure was not significantly correlated to thyroid cancer (p = 0.08 and 0.759, respectively). In the group with BMI≥25 kg/m 2 , BPA-exposed subjects showed significantly higher risk of malignancy (OR: 5.3, p = 0.028). At multivariate analysis, such association was independent of smoking, alcohol consumption, occupational exposure, and phthalates exposure (p = 0.021 and 0.016, respectively), but was lost after adjustment for the presence of metabolic syndrome (p = 0.089). In overweight/obese subjects, BPA exposure was significantly associated with higher thyroid stimulating hormone levels. Our study suggests that BPA exposure is a risk factor for thyroid cancer in overweight/obese subjects., 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 © 2022 Elsevier Ltd. All rights reserved.)

The synthesis and characterization of two tritopic ligands containing a 2,2':6',2″-terpyridine (tpy) metal binding domain and either a 3,2':6',3″- or a 4,2':6',4″-tpy domain are detailed. The synthetic routes to these ligands involved the [Pd(dppf)Cl 2 ]-catalyzed coupling of a boronic ester-functionalized 2,2':6',2″-tpy with bromo-derivatives of 3,2':6',3″-tpy or 4,2':6',4″-tpy. The 2,2':6',2″-tpy domains of the tritopic ligands preferentially bind Fe 2+ in reactions with iron(II) salts leading to the formation of two homoleptic iron(II) complexes containing two peripheral 3,2':6',3″-tpy or 4,2':6',4″-tpy metal-binding sites, respectively. These iron(II) complexes are potentially tetratopic ligands and represent expanded versions of tetra(pyridin-4-yl)pyrazine.

Background and Aim of the Work: In the Italian and also international contexts, there is a paucity of evidence testing whether a structured educational intervention delivered from remote might be useful in increasing the levels of preparedness for self-employed careers among third-year nursing students, despite freelance nursing careers are a promising component of the current labour market. This study aimed to test the effects of a structured educational program on the preparedness for self-employed careers in Italian undergraduate nursing students., Methods: The study was quasi-experimental and nonrandomized and employed a pre/post-intervention approach with convenience sampling. Data were collected before the structured education program was delivered (T0) and up to one day after the instruction was delivered (T1)., Results: In this study, 717 third-year nursing students were enrolled. The most significant difference between T0 and T1 was in the domain of knowledge about pensions and retirement issues, followed by administrative rules knowledge. There were substantial variations between T0 and T1 in the area of logistic characteristics in determining the price of a freelance nursing activity, as well as scores in the domain of care complexity in determining the price of the independent nursing occupation., Conclusions: This study proved the short-term impacts of a structured educational program on enhancing levels of preparation for self-employed professions among Italian undergraduate nursing students. This topic requires more attention as the demands of prepared healthcare workers to undertake self-employed careers necessitate a greater capacity to properly educate nursing students for self-employed occupations within their undergraduate path.

Lung cancer is the leading cause of cancer-related death worldwide. Since prognosis of early-stage non-small cell lung cancer (NSCLC) remains dismal for common relapses after curative surgery, considerable efforts are currently focused on bringing immunotherapy into neoadjuvant and adjuvant settings. Previously, perioperative chemotherapy showed only a modest but significative improvement in overall survival. The presence of broad tumor neoantigens load at primary tumor prior to surgery as well as the known immunosuppressive status following resection represent the main rationale for immunotherapy in early disease. Several trials have been conducted in recent years, leading to atezolizumab and nivolumab approval in the adjuvant and neoadjuvant setting, respectively, and perioperative immunotherapy in NSCLC remains a field of active clinical and preclinical investigation. Unanswered questions in perioperative therapy in NSCLC include the optimal sequence and timing of chemotherapy and immunotherapy, the potential of combination strategies, the role of predictive biomarkers for patient selection and the choice of useful endpoints in clinical investigation.

As of today, only two antiangiogenic monoclonal antibodies plus epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) combinations are FDA and EMA-approved and are recommended by American Society of Clinical Oncology, European Society for Medical Oncology, and National Comprehensive Cancer Network for the first-line treatment of EGFR+ advanced non-small cell lung cancer patients: erlotinib plus bevacizumab and erlotinib plus ramucirumab. However, all treated patients eventually become unresponsive to such drugs, due to several different acquired resistance mechanisms, mainly represented by T790M substitutions and MET amplifications. While osimertinib treatment in T790M+ patients still represents the only approved treatment, MET-TKIs will likely change this status quo in the near future. In fact, existing clinical data strongly support a role for MET-TKI-based combinations in EGFR+ MET-amplified patients, possibly revolutionizing our current treatment algorithm. Chemotherapy plus immunotherapy plus antiangiogenic therapy combinations could also represent another useful addition., Competing Interests: Dr. Gridelli C received honoraria as speaker bureau and advisory board member from Astra Zeneca, BMS, MSD, Roche, Sanofi, GSK, Menarini, Karyopharm, Amgen, Pfizer, Eli Lilly, Takeda, Novartis; all the other authors have no conflicts of interest to declare., (© The Author(s) 2022.)

Alectinib is a highly selective tyrosine kinase inhibitor of anaplastic lymphoma kinase (ALK) that is approved as first-line treatment in adult patients with ALK-positive non-small cell lung cancer (NSCLC) and as second-line in patients previously treated with crizotinib, and has been shown in the literature to significantly prolong progression-free survival compared to chemotherapy in patients with advanced non-small cell lung cancer. The authors describe a clinical case of a 24-year-old woman with malignant massive pleural effusion caused by ALK rearranged pulmonary adenocarcinoma with pleural and pericardial metastasis, in which, despite a dramatic clinical debut, the correct and timely management of the diagnostic and therapeutic path allowed for extraordinary therapeutic success.

Aim: ALK , ROS1 , NTRK  and RET gene fusions and MET exon 14 skipping alterations represent novel predictive biomarkers for advanced non-small-cell lung cancer (NSCLC). Therefore, testing patients for these genetic variants is crucial for choosing the best selective treatment. Over the last couple of decades, next-generation sequencing (NGS) platforms have emerged as an extremely useful tool for detecting these variants. Materials & methods: In the present study, we report our NGS molecular records produced during a year of diagnostic activity. Results: Overall, our in-house developed NGS workflow successfully analyzed n = 116/131 (88.5%) NSCLC samples. Of these, eight (6.8%) and five (4.3%) out of 116 patients harbored ALK and RET gene rearrangements, respectively: one case harbored ROS1 gene fusion (0.7%). Conclusion: Our results highlight that an RNA-based NGS analysis can reliably detect gene fusion alterations, thereby playing a pivotal role in the management of NSCLC patients.

In this paper we present the first electrochemical generation of NHC carried out in a divided flow cell. The flow cell operated in the recycle mode. The need for a divided cell derived from the anodic electroactivity of the electrogenerated carbene. In order to have NHC accumulation in the catholyte, the Nafion membrane (cell separator) was pretreated with an alkaline solution. The formation of NHC was quantified as its reaction product with elemental sulfur. The NHC was successfully used as organocatalyst in two classical umpolung reactions of cinnamaldehyde: its cyclodimerization and its oxidative esterification., (Copyright © 2022, Rocco et al.)

Agropyron repens (L.) P. Beauv. (couch grass) is a world-wide infesting rhizomatous plant with pharmacological applications. Chemical research is focused on its allelopathic and anti-inflammatory components, which are mainly present in the essential oil. Conversely, the aqueous extracts have been sparingly investigated, although the herbal tea is by far the most used formulation. To fill the gap, the metabolic profile of Agropyron repens rhizome herbal tea was investigated by electrospray ionization (ESI) tandem-mass spectrometry (MS/MS); the phenolic profile was investigated by HPLC-PDA-ESI-MS/MS. ESI-MS fingerprinting was provided, evidencing diagnostic ions for saccharides, organic acids and amino acids. The HPLC-PDA-ESI-MS/MS analysis evidenced at least 20 characteristic phenolic compounds, the most representative being caffeoyl and feruloyl quinic esters, followed by coumaric, caffeic and ferulic acids, and hesperidin among flavonoids. In addition, the essential amino acid tryptophan was identified for the first time. The results suggest new perspectives of applications for Agropyron repens rhizome.

Organ functions are highly specialized and interdependent. Secreted factors regulate organ development and mediate homeostasis through serum trafficking and inter-organ communication. Enzyme-catalysed proximity labelling enables the identification of proteins within a specific cellular compartment. Here, we report a BirA*G3 mouse strain that enables CRE-dependent promiscuous biotinylation of proteins trafficking through the endoplasmic reticulum. When broadly activated throughout the mouse, widespread labelling of proteins was observed within the secretory pathway. Streptavidin affinity purification and peptide mapping by quantitative mass spectrometry (MS) proteomics revealed organ-specific secretory profiles and serum trafficking. As expected, secretory proteomes were highly enriched for signal peptide-containing proteins, highlighting both conventional and non-conventional secretory processes, and ectodomain shedding. Lower-abundance proteins with hormone-like properties were recovered and validated using orthogonal approaches. Hepatocyte-specific activation of BirA*G3 highlighted liver-specific biotinylated secretome profiles. The BirA*G3 mouse model demonstrates enhanced labelling efficiency and tissue specificity over viral transduction approaches and will facilitate a deeper understanding of secretory protein interplay in development, and in healthy and diseased adult states.

Drug repurposing and combination therapy have been proposed as cost-effective strategies to improve Chagas disease treatment. Miltefosine (MLT), a synthetic alkylphospholipid initially developed for breast cancer and repositioned for leishmaniasis, is a promising candidate against Trypanosoma cruzi infection. This study evaluates the efficacy of MLT as a monodrug and combined with benznidazole (BZ) in both in vitro and in vivo models of infection with T. cruzi (VD strain, DTU TcVI). MLT exhibited in vitro activity on amastigotes and trypomastigotes with values of IC 50 = 0.51 µM (0.48 µM; 0,55 µM) and LC 50 = 31.17 µM (29.56 µM; 32.87 µM), respectively. Drug interaction was studied with the fixed-ration method. The sum of the fractional inhibitory concentrations (ΣFICs) resulted in ∑FIC= 0.45 for trypomastigotes and ∑FIC= 0.71 for amastigotes, suggesting in vitro synergistic and additive effects, respectively. No cytotoxic effects on host cells were observed. MLT efficacy was also evaluated in a murine model of acute infection alone or combined with BZ. Treatment was well tolerated with few adverse effects, and all treated animals displayed significantly lower mean peak parasitemia and mortality than infected non-treated controls (p<0.05). The in vivo studies showed that MLT led to a dose-dependent parasitostatic effect as monotherapy which could be improved by combining with BZ, preventing parasitemia rebound after a stringent immunosuppression protocol. These results support MLT activity in clinically relevant stages from T. cruzi , and it is the first report of positive interaction with BZ, providing further support for evaluating combined schemes using MLT and exploring synthetic alkylphospholipids as drug candidates., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Gulin, Bisio, Rocco, Altcheh, Solana and García-Bournissen.)

Aims: To develop and psychometrically validate an inventory based on two scales: awareness regarding factors for determining the prices of freelance activities and knowledge regarding freelance-related norms among nursing undergraduate students in Italy., Background: Although self-employed nursing careers are strategic to enhance employability, no valid scales for assessing nursing students' preparedness to undertake self-employed careers are available., Design: A multi-method and multi-phase design were employed. Phase one encompassed developmental tasks for generating items and phase two included a cross-sectional data collection for determining the psychometric proprieties of the developed scales and their reliability., Results: The final inventory encompassed two scales showing adequate validity and reliability after testing it on 882 Italian undergraduate nursing students. The first scale, factors for determining the prices of activities, is based on care complexity and logistic characteristic (two-factor structure). The second scale, knowledge regarding freelance-related characteristics, encompassed two domains: knowledge regarding administrative rules and pensions and retirement issues., Conclusions: The developed inventory showed adequate evidence of initial validity and reliability, useful for filling the gap given by the unavailability of valid assessments for educators who pursue measuring the nursing students' preparedness to undertake self-employed careers., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Motivated by the increasing demand to monitor the air-quality, our study proved the feasibility of a new compact and portable experimental approach based on Terahertz (THz) continuous wave high resolution spectroscopy, to detect the presence of the air's contaminants as greenhouse gases (GHG) and volatile organic compounds (VOCs). In this specific work, we first characterized, determining their molar absorption coefficient in the spectral region (0.06-1.2) THz, the pure optical response of the vapor of five VOCs: methanol, ethanol, isopropanol, 1-butanol and 2-butanol. In particular, 1-butanol and 2-butanol are characterized for the first time in literature at THz frequencies. Then we studied the optical response of their mixtures achieved with ambient air and ethanol. The results show that it is possible for a differentiation of single components by describing their spectral absorption in terms of the linear combination of pure compounds absorption. This proof of concept for this apparatus study and set-up paves the way to the use of THz Continuous wave high resolution spectroscopy for the environmental tracking of air pollutants.

Introduction: COVID-19 has disrupted the global health care system since March 2020. Lung cancer (LC) patients (pts) represent a vulnerable population highly affected by the pandemic. This multicenter Italian study aimed to evaluate whether the COVID-19 outbreak had an impact on access to cancer diagnosis and treatment of LC pts compared with pre-pandemic time., Methods: Consecutive newly diagnosed LC pts referred to 25 Italian Oncology Departments between March and December 2020 were included. Access rate and temporal intervals between date of symptoms onset and diagnostic and therapeutic services were compared with the same period in 2019. Differences between the 2 years were analyzed using the chi-square test for categorical variables and the Mann-Whitney U test for continuous variables., Results: A slight reduction (-6.9%) in newly diagnosed LC cases was observed in 2020 compared with 2019 (1523 versus 1637, P = 0.09). Newly diagnosed LC pts in 2020 were more likely to be diagnosed with stage IV disease (P < 0.01) and to be current smokers (someone who has smoked more than 100 cigarettes, including hand-rolled cigarettes, cigars, cigarillos, in their lifetime and has smoked in the last 28 days) (P < 0.01). The drop in terms of new diagnoses was greater in the lockdown period (percentage drop -12% versus -3.2%) compared with the other months included. More LC pts were referred to a low/medium volume hospital in 2020 compared with 2019 (P = 0.01). No differences emerged in terms of interval between symptoms onset and radiological diagnosis (P = 0.94), symptoms onset and cytohistological diagnosis (P = 0.92), symptoms onset and treatment start (P = 0.40), and treatment start and first radiological revaluation (P = 0.36)., Conclusions: Our study pointed out a reduction of new diagnoses with a shift towards higher stage at diagnosis for LC pts in 2020. Despite this, the measures adopted by Italian Oncology Departments ensured the maintenance of the diagnostic-therapeutic pathways of LC pts., Competing Interests: Disclosure DS received personal fees from AstraZeneca, Merck Sharp & Dohme (MSD), Boehringer Ingelheim and received travel grants from Roche, AstraZeneca, Bristol Myers Squibb (BMS), MSD. AMo received honoraria from Roche, AstraZeneca, Boehringer, Pfizer, MSD, BMS, Novartis, Lilly, Takeda. RC received fees for speaker's bureau and advisory boards participation in BMS, MSD, Roche, Pfizer, AstraZeneca, Takeda, Amgen, Boehringer, Novartis. FM received founding from AstraZeneca, Incyte and served as consultant for MSD. RB is a consultant/advisory board member for AstraZeneca, Boehringer Ingelheim, Novartis, MSD, Otsuka, Eli Lilly, Roche. All other authors have declared no conflicts of interest., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The THz spectrum (spanning from 0.3 to 30 THz) offers the potential of a plethora of applications, ranging from the imaging through non transparent media to wireless-over-fiber communications and THz-photonics. The latter framework would greatly benefit from the development of optical-to-THz wavelength converters. Exploiting Difference Frequency Generation in a nonlinear all dielectric nanoantenna, we propose a compact solution to this problem. By means of a near-infrared pump beam (at [Formula: see text]), the information signal in the optical domain (at [Formula: see text]) is converted to the THz band (at [Formula: see text]). The approach is completely transparent with respect to the modulation format, and can be easily integrated in a metasurface platform for simultaneous frequency and spatial moulding of THz beams., (© 2022. The Author(s).)

Introduction : Approximately 5% of all diagnosed non-small cell lung cancer (NSCLC) patients harbor a genetic rearrangement between the ALK and EML4 genes, representing a specific molecular, histological and clinical subgroup (ALK+ NSCLC). To date, upfront treatment with ALK-tyrosine-kinase inhibitors (ALK-TKIs) has replaced chemotherapy in the first line setting for this subset of patients with excellent results. However, all treated patients eventually develop acquired resistance mechanisms to these agents (mainly resistance mutations) and experience progression of the disease. Areas covered : This paper provides a comprehensive state-of-the-art review about first-line approved ALK-TKIs, furthermore, it discusses the most promising ALK-TKIs under development designed to overcome resistance mutations and their implications. Expert opinion : Alectinib should currently be regarded as the standard of care for the first-line treatment of ALK+ NSCLC, considering its superior efficacy and safety profile. Regarding developing agents, lorlatinib and ensartinib appear to be the most promising ones, even though the data from their trials are still immature.

Introduction: Chemo-immunotherapy combinations have revolutionized our treatment algorithm with respect to naïve advanced NSCLC; however, given the great number of developed and approved combinations, the question arises as to which combinations provide the best efficacy and safety., Areas Covered: This review assesses and discusses the available data concerning chemo-immunotherapy combinations in the treatment of naïve advanced NSCLC, as well as presenting the most promising data involving combinations currently under investigation., Expert Opinion: Pembrolizumab-containing chemo-immunotherapy combinations are associated with the most mature data available and presently represent the standard treatment in clinical practice in naïve advanced NSCLC-affected patients. The nivolumab plus ipilimumab plus short-course chemotherapy combination, more recently approved by regulatory agencies, is an appealing alternative, thanks to the reduced rate of grade 3-5 TRAEs and the limited chemotherapy administration. The new chemo-immunotherapy combinations currently under investigation will help us to better identify both the best immune checkpoints to target and the most effective combinations to administer.

Imidazolium-based dicationic ionic liquids (DILs) are gaining considerable space in the field of organocatalysis mainly due to the opportunities in offering new possible applicable structural variations. In addition to the well-known variables which made the ionic liquids (ILs) famous as the type of cation and anion used, the nature of the molecular spacer moiety turns out a further possibility to improve some physicochemical properties, for example, solubility, acidity, electrochemical behavior, and so on. For this reason, this class of ionic liquids has been considered as possible competitors to their corresponding monocationic salts in replacing common catalysts in organic synthesis, particularly in cases in which their bidentate nature could positively affect the catalytic activity. This mini-review is intended to highlight the progress carried out in the last six years in the field of organocatalysis, including DILs as such and as hybrids with polymers, nanomaterials, and composites.

Objective: The present work aims to conduct the first naturalistic empirical investigation of the process and outcome assessment of functional psychotherapy (FP) treatment. The FP model of psychotherapy is rooted in psychoanalysis and integrates the verbal communication approach founded on transference and countertransference dynamics with the analysis of bodily processes. Method: The study sample included ten patients recruited on a voluntary basis and treated by clinicians in their private practices. Each patient received FP with an average duration of 40 h (min 35 and max 42). Therapies had weekly sessions, were audio-recorded with the patient's written consent, and lasted for an average of 10 months (min 9 and max 12). Outcome and process tools included the Minnesota Multiphasic Personality Inventory-2 (MMPI-2) and the Luborsky's the Core Conflictual Relationship Theme (CCRT), used to assess therapeutic benefit, and the Metacognition Assessment Scale (MAS) and the Italian Discourse Attributes Analysis Program (IDAAP) system, used to evaluate therapeutic benefit and process. The MMPI-2 was used also in the follow-up assessment. Results: Results show that FP had a positive therapeutic outcome on the patients assessed in this study, and that the therapeutic benefits were maintained over time. Some specific features of the FP approach were found to contribute more than others to the observed therapeutic benefits. Conclusion: The current investigation constitutes a first step toward assessment of the therapeutic effectiveness of FP. Future developments should apply the methodology to a larger sample, possibly introducing different methodologies to enable detection of specific bodily oriented processes and techniques., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Rocco, Rizzi, Dell’Arciprete and Perrella.)

Epidermal growth factor receptor (EGFR) exon 20 insertions occur rarely among different cancer types, with the highest frequency reported among non-small-cell lung cancer (NSCLC) patients, particularly adenocarcinomas (ADCs). Exon 20 insertions fall back in the tyrosine kinase domain, and can be clustered into two principal groups represented by in frame insertions and three to 21 bp (corresponding to 1-7 amino acids) duplications within amino acids 762 and 774. The identification of these alterations is key for an adequate management of NSCLC patients due to the possibility to treat these patients with specific targeted therapies. Next generation sequencing (NGS) technology, able to detect several hotspot gene mutations for different patients simultaneously, is the best detection approach due to its higher sensitivity and specificity compared to other techniques. Here we reviewed the principal biological characteristics, the main detection technologies and treatment options for NSCLC patients harbouring EGFR exon 20 insertions., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Metasurfaces are versatile tools for manipulating light; however, they have received little attention as devices for the efficient control of nonlinearly diffracted light. Here, we demonstrate nonlinear wavefront control through third-harmonic generation (THG) beaming into diffraction orders with efficiency tuned by excitation of hybrid Mie-quasi-bound states in the continuum (BIC) modes in a silicon metasurface. Simultaneous excitation of the high-Q collective Mie-type modes and quasi-BIC modes leads to their hybridization and results in a local electric field redistribution. We probe the hybrid mode by measuring far-field patterns of THG and observe the strong switching between (0,-1) and (-1,0) THG diffraction orders from 1:6 for off-resonant excitation to 129:1 for the hybrid mode excitation, showing tremendous contrast in controlling the nonlinear diffraction patterns. Our results pave the way to the realization of metasurfaces for novel light sources, telecommunications, and quantum photonics.

Introduction: Lung adenocarcinomas account for approximately 40-50% of all NSCLC (Non-Small Cell Lung Cancer) cases. In addition, lung adenocarcinomas can harbor several different genetic mutations, EGFR (Epidermal Growth Factor Receptor) being the most frequent one, accounting for approximately 5-15% of all the mutations in western patients and for approximately 40-55% in Asian patients; on the other hand, EGFR mutations are uncommon in squamous histology. Approximately 90% of EGFR mutations are represented by exon 19 in-frame deletion and by the L858R exon 21-point mutation, that confer sensitivity to EGFR TKI (Tyrosine Kinase Inhibitors) treatment., Areas Covered: The authors comprehensively review the current state of the art with reference to EGFR+ NSCLC treatment and to discuss the possible future developments., Expert Opinion: Osimertinib must be considered the preferred first-line agent in EGFR+ advanced NSCLC patients thanks to its superior performances. With respect to acquired resistance mechanisms to osimertinib, the currently ongoing clinical trials will surely help us to better understand and tackle them. Globally, we strongly believe that a biomarker-driven sequential treatment algorithm is key in order to provide personalized, effective and durable therapies in the increasingly complex landscape of EGFR+ advanced NSCLC.

Reconfigurable metasurfaces have recently gained a lot of attention in applications such as adaptive meta-lenses, hyperspectral imaging and optical modulation. This kind of metastructure can be obtained by an external control signal, enabling us to dynamically manipulate the electromagnetic radiation. Here, we theoretically propose an AlGaAs device to control the second harmonic generation (SHG) emission at nanoscale upon optimized optical heating. The asymmetric shape of the used meta-atom is selected to guarantee a predominant second harmonic (SH) emission towards the normal direction. The proposed structure is concurrently excited by a pump beam at a fundamental wavelength of 1540 nm and by a continuous wave (CW) control signal above the semiconductor band gap. The optical tuning is achieved by a selective optimization of meta-atoms SH phase, which is modulated by the control signal intensity. We numerically demonstrate that the heating induced in the meta-atoms by the CW pump can be used to dynamically tune the device properties. In particular, we theoretically demonstrate a SH beam steering of 8° with respect to the vertical axis for an optimized device with average temperature increase even below 90° C.

Ankyrin proteins (ANKRD) are key mediators linking membrane and sub-membranous cytoskeletal proteins. Recent findings have highlighted a new role of ANKRD31 during spermatogenesis, elucidating its involvement in meiotic recombination and male germ cell progression. Following testicular differentiation, spermatozoa (SPZ) enter into the epididymis, where they undergo several biochemical and enzymatic changes. The epididymal epithelium is characterized by cell-to-cell junctions that are able to form the blood-epididymal barrier (BEB). This intricate epithelial structure provides the optimal microenvironment needed for epididymal sperm maturation. To date, no notions have been reported regarding a putative role of ANKRD31 in correct BEB formation. In our work, we generated an Ankrd31 knockout male mouse model ( Ankrd31 -/- ) and characterized its reproductive phenotype. Ankrd31 -/- mice were infertile and exhibited oligo-astheno-teratozoospermia (a low number of immotile SPZ with abnormal morphological features). In addition, a complete deregulation of BEB was found in Ankrd31 -/- , due to cell-to-cell junction anomalies. In order to suggest that BEB deregulation may depend on Ankrd31 gene deletion, we showed the physical interaction among ANKRD31 and some epithelial junction proteins in wild-type (WT) epididymides. In conclusion, the current work shows a key role of ANKRD31 in the control of germ cell progression as well as sperm and epididymal integrity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Manfrevola, Martinez, Coutton, Rocco, Reynaud, Le Vern, Froment, Beauclair, Aubert, Pierantoni, Chianese and Guillou.)

Introduction : Landscape of Extensive Stage (ES)-SCLC treatment has been unchanged over the years. Chemotherapy, mostly based on cisplatin and etoposide, remained the standard-of-care for patients with ES-SCLC for almost 40 years. Recently, immune check points inhibitors have emerged marking a turning point for ES-SCLC treatment Areas covered : Aim of the paper is to discuss ICIs impact on ES-SCLC treatment algorithms, review current clinical trials, and explore future perspectives. Expert opinion : A growing body of evidence supports ICI-containing regimens as a new mainstay of ES-SCLC treatment. Whether subgroups of SCLC patients may have greater survival benefits from ICIs treatment needs to be better defined. Understanding the impact of tumor microenvironment and identifying reliable predictive and/or prognostic biomarkers will be fundamental to move toward a personalized treatment approach leading to improved survival.

Coordination networks formed between Co(NCS) 2 and 4'-substituted-[1,1'-biphenyl]-4-yl-3,2':6',3"-terpyridines in which the 4'-group is Me ( 1 ), H ( 2 ), F ( 3 ), Cl ( 4 ) or Br ( 5 ) are reported. [Co( 1 ) 2 (NCS) 2 ] n ·4.5 n CHCl 3 , [Co( 2 ) 2 (NCS) 2 ] n ·4.3 n CHCl 3 , [Co( 3 ) 2 (NCS) 2 ] n ·4 n CHCl 3 , [Co( 4 ) 2 (NCS) 2 ] n , and [Co( 5 ) 2 (NCS) 2 ] n · n CHCl 3 are 2D-networks directed by 4-connecting cobalt nodes. Changes in the conformation of the 3,2':6',3"-tpy unit coupled with the different peripheral substituents lead to three structure types. In [Co( 1 ) 2 (NCS) 2 ] n ·4.5 n CHCl 3 , [Co( 2 ) 2 (NCS) 2 ] n ·4.3 n CHCl 3 , [Co( 3 ) 2 (NCS) 2 ] n ·4 n CHCl 3 , cone-like arrangements of [1,1'-biphenyl]-4-yl units pack through pyridine…arene π-stacking, whereas Cl…π interactions are dominant in the packing in [Co( 4 ) 2 (NCS) 2 ] n . The introduction of the Br substituent in ligand 5 switches off both face-to-face π-stacking and halogen…π-interactions, and the packing interactions are more subtly controlled. Assemblies with organic linkers 1 - 3 are structurally similar and the lattice accommodates CHCl 3 molecules in distinct cavities; thermogravimetric analysis confirmed that half the solvent in [Co( 3 ) 2 (NCS) 2 ] n ·4 n CHCl 3 can be reversibly removed.

The ideal management of bronchoesophageal fistulas is a debated topic. While open surgical repair remains the most definitive treatment, not all patients are fit for surgery. In this communication, we present a patient who developed a bronchoesophageal fistula 1 year after an Ivor Lewis esophagectomy that involved the native oesophagus and right mainstem bronchus. Endoluminal vacuum therapy was successful at closing this benign bronchoesophageal fistula., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2021. No commercial re-use. See rights and permissions. Published by BMJ.)