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Protein function hinges on small shifts of three-dimensional structure. Elevating temperature or pressure may provide experimentally accessible insights into such shifts, but the effects of these distinct perturbations on protein structures have not been compared in atomic detail. To quantitatively explore these two axes, we report the first pair of structures at physiological temperature versus. high pressure for the same protein, STEP (PTPN5). We show that these perturbations have distinct and surprising effects on protein volume, patterns of ordered solvent, and local backbone and side-chain conformations. This includes interactions between key catalytic loops only at physiological temperature, and a distinct conformational ensemble for another active-site loop only at high pressure. Strikingly, in torsional space, physiological temperature shifts STEP toward previously reported active-like states, while high pressure shifts it toward a previously uncharted region. Altogether, our work indicates that temperature and pressure are complementary, powerful, fundamental macromolecular perturbations. A multi-perturbation crystallographic study on the atypical phosphatase STEP reveals that temperature and pressure are powerful macromolecular perturbations, with distinct effects on protein backbone, side-chain conformations, and ordered solvent. [ABSTRACT FROM AUTHOR]

The article discusses the importance of teaching and transmitting classical authors in psychoanalysis. Recognized authors, Silvina Ferreira dos Santos and Gonzalo López Musa, discuss how to reinterpret the ideas of classical authors in light of current reality. The impact of technology on the transmission of psychoanalytic knowledge is also mentioned. The article addresses challenges in transmission and training in psychoanalysis, the inclusion of diverse authors, and the importance of working with basic concepts. The responsibility of transmitters, the influence of institutions, and the importance of thinking in terms of metapsychologies are also discussed. Additionally, it talks about how historical and social moments can affect the training and practice of psychoanalysis. The text also discusses the importance of reflecting on practices and foundations in the field of psychoanalysis, the influence of institutions on the transmission of knowledge, and the possibility of remote training. The importance of freedom and adaptability in the practice of psychoanalysis is highlighted. The text also discusses the importance of maintaining a clinical perspective in teaching, the need to create spaces for dialogue and sharing experiences, and the importance of generating curiosity and events in the teaching act. Furthermore, the importance of personal involvement in academic work and the transmission of psychoanalysis, the importance of group discussion and evaluation, and concern about the trivialization of psychoanalysis on social media are highlighted. The article also raises concerns about the naturalization of the virtual among analysts and the importance of establishing an ethical framework and setting in the virtual environment. The importance of creating conditions for intimacy and analytical work both in the office and in the virtual environment, and the importance of not considering the virtual as inferior or deficient, are emphasized. [Extracted from the article]

Erythroderma, an inflammatory skin condition characterized by widespread erythema with variable degrees of exfoliation, pustulation, or vesiculobullous formation, is associated with high morbidity and mortality. Determining the underlying cause of erythroderma frequently presents a diagnostic challenge, which may contribute to the condition’s relatively poor prognosis. This review covers the clinical presentation, pathophysiology, diagnosis, and treatment of erythroderma. It discusses similarities and differences among the many underlying etiologies of the condition and differences between erythrodermic and non-erythrodermic presentations of the same dermatosis. Finally, this article explores current research that may provide future tools in the diagnosis and management of erythroderma. [ABSTRACT FROM AUTHOR]

Correctly allocating times to the main activities of a manager is a crucial task that directly affects the possibility of success for any company. Decision support based on state-of-the-art methods can lead to better performance in this activity. However, allocating times to managerial activities is not straightforward; the decision support should provide a flexible recommendation so the manager can make a final decision while ensuring robustness. This paper describes and assesses a novel approach where a search for the best distribution of the manager's time is performed by an intelligent decision support system. The approach consists of eliciting manager preferences to define the value of the manager's main activities and, by using a portfolio-like optimization based on differential evolution, obtaining the best time allocation. Aiming at applicability in practical scenarios, the approach can deal with many activities, group decisions, cope with imprecision, vagueness, ill-determination, and other types of uncertainty. We present evidence of the approach's applicability exploiting a real case study with the participation of several managers. The approach is assessed through the satisfaction level of each manager. [ABSTRACT FROM AUTHOR]

Background Patients with lymphoid malignancies are at risk for poor coronavirus disease 2019 (COVID-19)-related outcomes and have reduced vaccine-induced immune responses. Currently, a 3-dose primary regimen of mRNA vaccines is recommended in the United States for immunocompromised hosts. Methods A prospective cohort study of healthy adults (n  = 27) and patients with lymphoid malignancies (n  = 94) was conducted, with longitudinal follow-up through completion of a 2- or 3-dose primary mRNA COVID vaccine series, respectively. Humoral responses were assessed in all participants, and cellular immunity was assessed in a subset of participants. Results The rate of seroconversion (68.1% vs 100%) and the magnitude of peak anti-S immunoglobulin G (IgG) titer (median anti-S IgG = 32.4, IQR = 0.48–75.0 vs median anti-S IgG = 72.6, IQR 51.1–100.1; P  = .0202) were both significantly lower in patients with lymphoid malignancies compared to the healthy cohort. However, peak titers of patients with lymphoid malignancies who responded to vaccination were similar to healthy cohort titers (median anti-S IgG = 64.3; IQR, 23.7–161.5; P  = .7424). The third dose seroconverted 7 of 41 (17.1%) patients who were seronegative after the first 2 doses. Although most patients with lymphoid malignancies produced vaccine-induced T-cell responses in the subset studied, B-cell frequencies were low with minimal memory cell formation. Conclusions A 3-dose primary mRNA series enhanced anti-S IgG responses to titers equivalent to healthy adults in patients with lymphoid malignancies who were seropositive after the first 2 doses and seroconverted 17.1% who were seronegative after the first 2 doses. T-cell responses were present, raising the possibility that the vaccines may confer some cell-based protection even if not measurable by anti-S IgG. [ABSTRACT FROM AUTHOR]