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In this text, I argue that the legislative process has a legal nature, as opposed to its more apparent political facet, and that breaches of procedural lawmaking rules are incompatible with such a characterization. To defend such a viewpoint, I approach the topic in three parts.The first part addresses legislatures’ procedural rules’ force of law, navigating through U.S. and Brazilian cases. Against views that take legislative procedural rules as non-mandatory and merely coordinating tools, I develop my argument upon Hans Kelsen’s and H.L.A. Hart’s theorizations and state that these provisions belong to (hard) law. Hence, though legal interpretation challenges may blur the distinction between the political and legal facets, I affirm that legislative procedures have the force of law and, as such, are binding.The second part deals with justification and overseeing mechanisms. I argue that there are several reasons why lawmakers should abide by the legislative procedural rules. First, it is a matter of the rule of law, meaning that the participants in the lawmaking process have the right to play according to the pertinent provisions. Second, compliance with the established procedures safeguards participation and the flow of diverse opinions and, thus, democratic representativeness. Third, rules’ observance fosters transparency, shedding light on a bill and its motives. Finally, I state that compliance with procedural rules should result from enforcing tools managed by legislators and third parties, such as non-partisan officers in legislatures and, under some restraints, the judiciary.The third part addresses a specific situation: the enactment of executive decrees, provisional measures, directives, or anything similar, with the force of law, to address emergencies. I defend that the misuse or abuse of these expedited lawmaking instruments is incompatible with the legal nature of the legislative process. First, I analyze the ancient Roman Republic’s approach to the circumvention of serious menaces and the theories of John Locke, Carl Schmitt, and Santi Romano in this regard. Then, I assess how governments in Brazil, Italy, and the United States usually take advantage of those instruments not to address threats but to bypass the burdens of ordinary legislative procedures. To avoid such an outcome, I argue that legislatures should enhance their oversight capacity under emergencies or pressing situations while simultaneously providing the judiciary with more specific reviewing standards.

© 2022 Elsevier Ltd. All rights reserved., The coverage of SARS-CoV-2 vaccination in large parts of the world, together with the high number of breakthrough infections, especially following the emergence of Omicron subvariants, makes hybrid immunity (resulting from vaccine and infection) common. Hybrid immunity, particularly after BA.1 or BA.2 infection, confers substantial protection against the BA.5 infection. However, although the waning of protection afforded by natural infection in non-vaccinated individuals or by vaccination has been well documented, the stability of hybrid immunity, specifically against the BA.5 subvariant, now dominant in many countries, has not been thoroughly addressed.

© Author(s) (or their employer(s)) 2022.This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See http://creativecommons.org/licenses/by-nc/4.0/., Background: Inhibiting programmed cell death protein 1 (PD-1) or PD-ligand 1 (PD-L1) has shown exciting clinical outcomes in diverse human cancers. So far, only monoclonal antibodies are approved as PD-1/PD-L1 inhibitors. While significant clinical outcomes are observed on patients who respond to these therapeutics, a large proportion of the patients do not benefit from the currently available immune checkpoint inhibitors, which strongly emphasize the importance of developing new immunotherapeutic agents. Methods: In this study, we followed a transdisciplinary approach to discover novel small molecules that can modulate PD-1/PD-L1 interaction. To that end, we employed in silico analyses combined with in vitro, ex vivo, and in vivo experimental studies to assess the ability of novel compounds to modulate PD-1/PD-L1 interaction and enhance T-cell function. Results: Accordingly, in this study we report the identification of novel small molecules, which like anti-PD-L1/PD-1 antibodies, can stimulate human adaptive immune responses. Unlike these biological compounds, our newly-identified small molecules enabled an extensive infiltration of T lymphocytes into three-dimensional solid tumor models, and the recruitment of cytotoxic T lymphocytes to the tumor microenvironment in vivo, unveiling a unique potential to transform cancer immunotherapy. Conclusions: We identified a new promising family of small-molecule candidates that regulate the PD-L1/PD-1 signaling pathway, promoting an extensive infiltration of effector CD8 T cells to the tumor microenvironment., C and RCA are supported by the Fundação para a Ciência e a Tecnologia, Ministério da Ciência, Tecnologia e Ensino Superior (FCT-MCTES) (PhD grants PD/BD/128238/2016 (RCA) and SFRH/BD/131969/2017 (BC)). The authors thank the funding received from the European Structural & Investment Funds through the COMPETE Programme and from National Funds through FCT under the Programme grant LISBOA-01-0145-FEDER016405 - SAICTPAC/0019/2015 (HF and RCG). HFF and RCA received additional support from FCT-MCTES (UIDB/04138/2020, PTDC/BTM-SAL/4350/2021 and UTAPEXPL/NPN/0041/2021; EXPL/MED-QUI/1316/2021, respectively). The MultiNano@MBM project was supported by The Israeli Ministry of Health, and FCTMCTES, under the frame of EuroNanoMed-II (ENMed/0051/2016; HF and RS-F). HF and RS-F thank the generous financial support from ‘La Caixa’ Foundation under the framework of the Healthcare Research call 2019 (NanoPanther; LCF/PR/HR19/52160021), as well as CaixaImpulse (Co-Vax; LCF/TR/CD20/52700005). MP thanks the financial support from Liga Portuguesa Contra o Cancro – Nucleo Regional do Sul and ‘iNOVA4Health – UIDB/04462/2020’, a program financially supported by Fundação para a Ciência e Tecnologia/Ministério da Educação e Ciência. RS-F thanks the following funding agencies for their generous support: the European Research Council (ERC) Advanced Grant Agreement No. (835227)–3DBrainStrom, ERC PoC Grant Agreement no. 862580 – 3DCanPredict, The Israel Science Foundation (Grant No. 1969/18), The Melanoma Research Alliance (MRA Established Investigator Award n°615808), the Israel Cancer Research Fund (ICRF) Professorship award (n° PROF-18-682), and the Morris Kahn Foundation.