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People now commonly interact with Artificial Intelligence (AI) agents. How do these interactions shape how humans perceive each other? In two preregistered studies (total N = 1,261), we show that people evaluate other humans more harshly after interacting with an AI (compared with an unrelated purported human). In Study 1, participants who worked on a creative task with AIs (versus purported humans) subsequently rated another purported human's work more negatively. Study 2 replicated this effect and demonstrated that the results hold even when participants believed their evaluation would not be shared with the purported human. Exploratory analyses of participants' conversations show that prior to their human evaluations they were more demanding, more instrumental and displayed less positive affect towards AIs (versus purported humans). These findings point to a potentially worrisome side effect of the exponential rise in human-AI interactions., (© The Author(s) 2024. Published by Oxford University Press on behalf of National Academy of Sciences.)

Vaults are eukaryotic ribonucleoproteins consisting of 78 copies of the major vault protein (MVP), which assemble into a nanoparticle with an about 60 nm volume-based size, enclosing other proteins and RNAs. Regardless of their physiological role(s), vaults represent ideal, natural hollow nanoparticles, which are produced by the assembly of the sole MVP. Here, we have expressed in Komagataella phaffi and purified an MVP variant carrying a C-terminal Z peptide (vault-Z), which can tightly bind an antibody's Fc portion, in view of targeted delivery. Via surface plasmon resonance analysis, we could determine a 2.5 nM affinity to the monoclonal antibody Trastuzumab (Tz)/vault-Z 1:1 interaction. Then, we characterized the in-solution interaction via co-incubation, ultracentrifugation, and analysis of the pelleted proteins. This showed virtually irreversible binding up to an at least 10:1 Tz/vault-Z ratio. As a proof of concept, we labeled the Fc portion of Tz with a fluorophore and conjugated it with the nanoparticle, along with either Tz or Cetuximab, another monoclonal antibody. Thus, we could demonstrate antibody-dependent, selective uptake by the SKBR3 and MDA-MB 231 breast cancer cell lines. These investigations provide a novel, flexible technological platform that significantly extends vault-Z's applications, in that it can be stably conjugated with finely adjusted amounts of antibodies as well as of other molecules, such as fluorophores, cell-targeting peptides, or drugs, using the Fc portion as a scaffold.

Nanomedicine provides various opportunities for addressing medical challenges associated with drug bioavailability, stability, and efficacy. In particular, oral nanoparticles (NPs) represent an alternative strategy to enhance the solubility and stability of active ingredients through the gastrointestinal tract. The nanocarriers could be used for both local and systemic targeting, enabling controlled release of encapsulated drugs. This approach allows more efficient therapies. In this work, we aim to develop reliable oral solid dosage forms incorporating NPs produced by either one pot synthesis or continuous production, following protocols that yield highly consistent outcomes, promoting their technology transfer and clinical use. Microfluidics technology was selected to allow an automated and highly productive synthetic approach suitable for the highly throughput production. In particular, innovative systems, which combine advantage of NPs and solid dosage formulation, were designed, developed, and characterized demonstrating the possibility to obtaining oral administration. The resulting NPs were thus carried on oral dosage forms, i.e., pellets and minitablets. NPs resulted stable after dosage forms manufacturing, leading to confidence also on protection of encapsulated drugs. Indomethacin was used as a tracer to test biopharmaceutical behaviour. Anti-inflammatories or cytotoxic chemotherapeutics could be vehiculated leading to a breakthrough in the treatment of severe diseases allowing the oral administration of these drugs. We believe that the advancement achieved with the results of our work paves the way for the progression of nanoproducts into clinical transition processes., 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 © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

The use of co-processed materials for Orally Disintegrating Tablets (ODT) preparation by direct compression is well consolidated. However, the evaluation of their potential for ODT preparation by 3D printing technology remains almost unexplored. The present study aimed to estimate the use of commercially available co-processed excipients, conventionally applied in compression protocols, for the preparation of ODTs with binder jetting-3D printing technology. The latter was selected among the 3D printing techniques because the deposition of multiple powder layers allows for obtaining highly porous and easily disintegrating dosage forms. The influence of some process parameters, including layer thickness, type of waveform and spread speed, on the physical and mechanical properties of the prototypes printed were evaluated. Our results suggested that binder jetting-3D printing technology could benefit from the co-processed excipients for the preparation of solid dosage forms. The process optimization conducted with the experiments reported in this work indicated that additional excipients were needed to improve the physical properties of the resulting ODTs., 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 Author(s). Published by Elsevier B.V. All rights reserved.)

COVID-19 remains a leading cause of mortality in the United States, despite the widespread availability of vaccines. Conventional wisdom ties failure to vaccinate primarily to vaccine-skeptic beliefs (e.g. conspiracy theories, partisanship). Yet in this research, we find that vaccination is also hindered by travel distance to vaccine sites (a form of friction , or structural barriers). In study 1, Californians living farther from vaccine sites had lower vaccination rates, and this effect held regardless of partisanship. In study 2, Chicago zip codes saw an uptick in vaccination following vaccine site opening. These results proved robust in multiverse analyses accounting for a wide range of covariates, outcomes, and distance indicators. COVID-19 vaccination is hampered not only by vaccine hesitancy but also by structural barriers like distance. Efforts to boost vaccination could benefit from minimizing friction., (© The Author(s) 2023. Published by Oxford University Press on behalf of National Academy of Sciences.)

The vault nanoparticle is a eukaryotic assembly consisting of 78 copies of the 99-kDa major vault protein. They generate two cup-shaped symmetrical halves, which in vivo enclose protein and RNA molecules. Overall, this assembly is mainly involved in pro-survival and cytoprotective functions. It also holds a remarkable biotechnological potential for drug/gene delivery, thanks to its huge internal cavity and the absence of toxicity/immunogenicity. The available purification protocols are complex, partly because they use higher eukaryotes as expression systems. Here, we report a simplified procedure that combines human vault expression in the yeast Komagataella phaffii , as described in a recent report, and a purification process we have developed. This consists of RNase pretreatment followed by size-exclusion chromatography, which is far simpler than any other reported to date. Protein identity and purity was confirmed by SDS-PAGE, Western blot and transmission electron microscopy. We also found that the protein displayed a significant propensity to aggregate. We thus investigated this phenomenon and the related structural changes by Fourier-transform spectroscopy and dynamic light scattering, which led us to determine the most suitable storage conditions. In particular, the addition of either trehalose or Tween-20 ensured the best preservation of the protein in native, soluble form.

Whether or not someone turns out to vote depends on their beliefs (such as partisanship or sense of civic duty) and on friction -external barriers such as long travel distance to the polls. In this exploratory study, we tested whether people underestimate the effect of friction on turnout and overestimate the effect of beliefs. We surveyed a representative sample of eligible US voters before and after the 2020 election ( n = 1,280). Participants' perceptions consistently underemphasized friction and overemphasized beliefs (mean d = 0.94). In participants' open-text explanations, 91% of participants listed beliefs, compared with just 12% that listed friction. In contrast, turnout was shaped by beliefs only slightly more than friction. The actual belief-friction difference was about one-fourth the size of participants' perceptions (d = 0.24). This bias emerged across a range of survey measures (open- and close-ended; other- and self-judgments) and was implicated in downstream consequences such as support for friction-imposing policies and failing to plan one's vote.

In California, the metamorphic blueschist occurrences within the Franciscan Complex are commonly composed of glaucophane, which can be found with a fibrous habit. Fibrous glaucophane's potential toxicity/pathogenicity has never been determined and it has not been considered by the International Agency for Research on Cancer (IARC) as a potential carcinogen to date. Notwithstanding, outcrops hosting fibrous glaucophane are being excavated today in California for building/construction purposes (see for example the Calaveras Dam Replacement Project - CDRP). Dust generated by these excavation activities may expose workforces and the general population to this potential natural hazard. In this work, the potential toxicity/pathogenicity of fibrous glaucophane has been determined using the fibre potential toxicity index (FPTI). This model has been applied to a representative glaucophane-rich sample collected at San Anselmo, Marin County (CA, USA), characterized using a suite of experimental techniques to determine morphometric, crystal-chemical parameters, surface reactivity, biodurability and related parameters. With respect to the asbestos minerals, the FPTI of fibrous glaucophane is remarkably higher than that of chrysotile, and comparable to that of tremolite, thus supporting the application of the precautionary approach when excavating fibrous glaucophane-rich blueschist rocks. Because fibrous glaucophane can be considered a potential health hazard, just like amphibole asbestos, it should be taken into consideration in the standard procedures for the identification and assessment of minerals fibres in soil and air samples., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Hypoparathyroidism is a rare disease characterized by low serum calcium levels and absent or deficient parathyroid hormone level. Regarding the epidemiology of chronic hypoparathyroidism, there are limited data in Italy and worldwide. Therefore, the purpose of this study was to build a unique database of patients with chronic hypoparathyroidism, derived from the databases of 16 referral centers for endocrinological diseases, affiliated with the Italian Society of Endocrinology, and four centers for endocrine surgery with expertise in hypoparathyroidism, to conduct an epidemiological analysis of chronic hypoparathyroidism in Italy. The study was approved by the Institutional Review Board. A total of 537 patients with chronic hypoparathyroidism were identified. The leading etiology was represented by postsurgical hypoparathyroidism (67.6%), followed by idiopathic hypoparathyroidism (14.6%), syndromic forms of genetic hypoparathyroidism (11%), forms of defective PTH action (5.2%), non-syndromic forms of genetic hypoparathyroidism (0.9%), and, finally, other forms of acquired hypoparathyroidism, due to infiltrative diseases, copper or iron overload, or ionizing radiation exposure (0.7%). This study represents one of the first large-scale epidemiological assessments of chronic hypoparathyroidism based on data collected at medical and/or surgical centers with expertise in hypoparathyroidism in Italy. Although the study presents some limitations, it introduces the possibility of a large-scale national survey, with the final aim of defining not only the prevalence of chronic hypoparathyroidism in Italy, but also standards for clinical and therapeutic approaches.

Thyroid angiosarcoma is an uncommon thyroid carcinoma and its incidence is the highest in the European Alpine regions. Thyroid angiosarcoma is also a very aggressive tumor that can rapidly spread to the cervical lymph nodes, lungs, and brain or can metastasize to the duodenum, small boewl, and large bowel. Although it is histologically well defined, clear-cut separation between the angiosarcoma and anaplastic thyroid carcinoma is difficult. A 49-year-old Caucasian female patient, born and resident in Southern Italy (Calabria), in an iodine-sufficient area, was admitted to the Surgery Department because she presented with a painless mass in the anterior region of neck enlarged rapidly in the last three months. After total thyroidectomy and right cervical lymphadenectomy, postoperative histological examination revealed the presence of a thyroid angiosarcoma with positive staining for CD31 and for both Factor VIII-related antigen and Vimentin and only partially positive for staining pancytokeratin and presence of metastasis in cervical, supraclavicular, mediastinal and paratracheal lymph nodes. The patient started adjuvant chemotherapy and she was treated for 6 cycles with Doxorubicin, Dacarbazine, Ifosfamide, and Mesna (MAID). After 22 months from surgery, the patient is still alive without both local and systemic recurrence of the disease.

Aim: Reporting our experience with NIM-response 2.0 and 3.0 system in a series of 127 thyroidectomies., Materials of Study: 127 patients were operated at the "Magna Graecia" University (Catanzaro) from 2009 September to 2010 December, using the technique of IntraOperative NeuroMonitoring (IONM). For each patient the surgeon charge filled in a "questionnaire" assessing his/her compliance with the apparatus., Results: We report 0.8% permanent and 0.4% transient recurrent laryngeal nerve paralysis. All surgeons have been fully satisfied from IONM technique., Discussion: A recurrent laryngeal nerve lesion may occur in patients operated on total thyroidectomy between 5-8% for transient palsies and 1-3% for the permanent ones. The use of IONM seems to contribute to a reduction of transient paralysis, even if this method is still not widely accepted Nevertheless the compliance of the surgeons with IONM seems to develop very highly., Conclusions: NIM-response is helpful in protecting recurrent laryngeal nerve function. Advantages were observed in reduction of postoperative dysphonia and in improving the surgeon's confidence in performing a total thyroidectomy.