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Examining institutional data from seven cohorts of students intending to major in biology across five research-intensive institutions, this work analyzes opportunity gaps-defined as the difference between the grade received by students from the dominant and nondominant sociodemographic groups in institutions of higher education-at the course-section level across mathematics, physics, biology, and chemistry disciplines. From this analysis, we find that the majority of course sections have large opportunity gaps between female and male students, students who are Black, Latino/a/e/x, or indigenous to the United States and its territories and students who are White or Asian, first-generation and non-first-generation students, and low-income and non-low-income students. This work provides a framework to analyze equity across institutions using robust methodology, including: using multiple approaches to measure grades, quantile regression rankscores which adjust for previous academic performance, and cluster analysis. Recommendations are provided for institutions to identify faculty who have equitable course sections, automate equity analyses, and compare results to other institutions to make a change toward more equitable outcomes., Competing Interests: Conflicts of interest: The authors declare no conflicts of interest.

PDIA3 is a pleiotropic protein primarily located in the endoplasmic reticulum where it is involved in protein folding, catalyzing the formation, breakage, and rearrangement of disulfide bonds. PDIA3 is implicated in numerous pathologies such as cancer, inflammation, and neurodegeneration. Although punicalagin has been proven to be a highly promising PDIA3 inhibitor and can be used as target protein in glioblastoma, it does not have sufficient selectivity for PDIA3 and is a quite-large molecule. With the aim of finding punicalagin derivatives with a simplified structure, we selected punicalin, which lacks the hexahydroxy-diphenic acid moiety. Previous docking studies suggest that this part of the molecule is not involved in the binding with PDIA3. In this study we compared the ability of punicalin to bind and inhibit PDIA3 and PDIA1. Tryptophan fluorescence quenching and disulfide reductase activity (using both glutathione and insulin as substrates) were evaluated, demonstrating the ability of punicalin to bind and inhibit PDIA3 even to a lesser extent compared to punicalagin. On the other hand, punicalin showed a very low inhibition activity towards PDIA1, demonstrating a higher selectivity for PDIA3. Protein thermal shift assay evidenced that both proteins can be destabilized by punicalin as well as punicalagin, with PDIA3 much more sensitive. Additionally, punicalin showed a higher change in the thermal stability of PDIA3, with a shift up to 8 °C. This result could explain the presence of PDIA3 aggregates, evidenced by immunofluorescence analysis, that accumulate within treated cells and that are more evident in the presence of punicalin. The results here obtained show punicalin is able to bind both proteins but with a higher selectivity for PDIA3, suggesting the possibility of developing new molecules with a simplified structure that are still able to selectively bind and inhibit PDIA3.

Hidradenitis suppurativa (HS) is a frequent chronic inflammatory skin condition primarily affecting areas rich in apocrine sweat glands, presenting with comedones, papules, nodules, and abscesses, as well as tunnels and hypertrophic scarring. Despite its prevalence and impact on quality of life, the pathogenesis of HS remains incompletely understood. Notably, its diagnosis often suffers from delays and misidentification, therefore an improved education for healthcare providers is mandatory. Moreover, HS is frequently associated with systemic comorbidities and a multidisciplinary approach is suggested for its management. Recognizing these challenges, a group of Italian HS experts and patients convened to develop consensus guidelines via the Nominal Group Technique. Through iterative meetings and remote collaboration, they identified key areas for improvement and formulated consensus statements to guide healthcare providers in delivering optimal care. This collaborative effort highlights the importance of standardized approaches and interdisciplinary collaboration in managing HS effectively., (© 2024. The Author(s).)

Organochlorine pesticides (OCPs) are a class of environmentally persistent and bioaccumulative pollutants. Among these, β-hexachlorocyclohexane (β-HCH) is a byproduct of lindane synthesis, one of the most worldwide widespread pesticides. β-HCH cellular mechanisms inducing chemical carcinogenesis correspond to many of those inducing chemoresistance, in particular, by the activation of signal transducer and activator of transcription 3 (STAT3) signaling pathways. For this purpose, four cell lines, representative of breast, lung, prostate, and hepatocellular cancers, were treated with β-HCH, specific tyrosine kinase inhibitors (TKIs), and a STAT3 inhibitor. All cell samples were analyzed by a viability assay, immunoblotting analysis, a wound-healing assay, and a colony formation assay. The results show that β-HCH reduces the efficacy of TKIs. The STAT3 protein, in this context, plays a central role. In fact, by inhibiting its activity, the efficacy of the anticancer drug is restored. Furthermore, this manuscript aimed to draw the attention of the scientific and socio-healthcare community to the issue of prolonged exposure to contaminants and their impact on drug efficacy.

Treatment adherence, defined as the degree to which the patient actively follows the plan of care, is very difficult for subjects undergoing ketogenic dietary therapies (KDTs). This is a relevant issue because adherence to dietary therapies is considered 1 of the primary determinants of the treatment's success. This paper aimed to review the literature evidence about KDT adherence according to age and diagnosis of patients. Performed based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses method, this systematic review included clinical trials and observational studies. The risk of bias was assessed by the RoB 2.0 Cochrane tool and the quality of evidence according to the Mixed Methods Appraisal Tool system. Twenty-two articles were included, with more than half (n = 12) having average quality (2-3 stars). The studies' heterogeneity in measuring adherence and diagnosis made it difficult to compare results. Mean adherence rates were 71.5%, 66%, and 63.9% for children, adolescents, and adults, respectively. Adherence and compliance rates varied according to the follow-up period (79.7%, 66.7%, and 37.7% at 6, 24, and 36 months, respectively). The most frequent reasons for low adherence were linked to inefficacy in seizure control, adverse effects, food refusal, difficulty in preparing KDT meals or diet restrictiveness, lack of motivation, poor parental compliance, or cost of the diet. To conclude, there is a lack of standardized tools to measure adherence. Several studies highlighted the families' challenges in adhering to KDTs. These factors should be considered when creating strategies and resources on family education., Competing Interests: Author declarations All authors disclose any financial and personal relationships with other people or organizations that could inappropriately influence (bias) this work., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Ultrasound-responsive agents have shown great potential as targeted drug delivery agents, effectively augmenting cell permeability and facilitating drug absorption. This review focuses on two specific agents, microbubbles and nanodroplets, and provides a sequential overview of their drug delivery process. Particular emphasis is given to the mechanical response of the agents under ultrasound, and the subsequent physical and biological effects on the cells. Finally, the state-of-the-art in their pre-clinical and clinical implementation are discussed. Throughout the review, major challenges that need to be overcome in order to accelerate their clinical translation are highlighted., 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.)

Background: Large introductory lecture courses are frequently post-secondary students' first formal interaction with science, technology, engineering, and mathematics (STEM) disciplines. Grade outcomes in these courses are often disparate across student populations, which, in turn, has implications for student retention. This study positions such disparities as a manifestation of systemic inequities along the dimensions of sex, race/ethnicity, income, and first-generation status and investigates the extent to which they are similar across peer institutions., Results: We examined grade outcomes in a selected set of early STEM courses across six large, public, research-intensive universities in the United States over ten years. In this sample of more than 200,000 STEM course enrollments, we find that course grade benefits increase significantly with the number of systemic advantages students possess at all six institutions. The observed trends in academic outcomes versus advantage are strikingly similar across universities despite the fact that we did not control for differences in grading practices, contexts, and instructor and student populations. The findings are concerning given that these courses are often students' first post-secondary STEM experiences., Conclusions: STEM course grades are typically lower than those in other disciplines; students taking them often pay grade penalties. The systemic advantages some student groups experience are correlated with significant reductions in these grade penalties at all six institutions. The consistency of these findings across institutions and courses supports the claim that inequities in STEM education are a systemic problem, driven by factors that go beyond specific courses or individual institutions. Our work provides a basis for the exploration of contexts where inequities are exacerbated or reduced and can be used to advocate for structural change within STEM education. To cultivate more equitable learning environments, we must reckon with how pervasive structural barriers in STEM courses negatively shape the experiences of marginalized students., Supplementary Information: The online version contains supplementary material available at 10.1186/s40594-024-00474-7., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s) 2024.)