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Most of the ongoing projects aimed at the development of specific therapies and vaccines against COVID-19 use the SARS-CoV-2 spike (S) protein as the main target. The binding of the spike protein with the ACE2 receptor (ACE2) of the host cell constitutes the first and key step for virus entry. During this process, the receptor binding domain (RBD) of the S protein plays an essential role, since it contains the receptor binding motif (RBM), responsible for the docking to the receptor. So far, mostly biochemical methods are being tested in order to prevent binding of the virus to ACE2. Here we show, with the help of atomistic simulations, that external electric fields of easily achievable and moderate strengths can dramatically destabilise the S protein, inducing long-lasting structural damage. One striking field-induced conformational change occurs at the level of the recognition loop L3 of the RBD where two parallel beta sheets, believed to be responsible for a high affinity to ACE2, undergo a change into an unstructured coil, which exhibits almost no binding possibilities to the ACE2 receptor. We also show that these severe structural changes upon electric-field application also occur in the mutant RBDs corresponding to the variants of concern (VOC) B.1.1.7 (UK), B.1.351 (South Africa) and P.1 (Brazil). Remarkably, while the structural flexibility of S allows the virus to improve its probability of entering the cell, it is also the origin of the surprising vulnerability of S upon application of electric fields of strengths at least two orders of magnitude smaller than those required for damaging most proteins. Our findings suggest the existence of a clean physical method to weaken the SARS-CoV-2 virus without further biochemical processing. Moreover, the effect could be used for infection prevention purposes and also to develop technologies for in-vitro structural manipulation of S. Since the method is largely unspecific, it can be suitable for application to other mutations in S, to other proteins of SARS-CoV-2 and in general to membrane proteins of other virus types. The SARS-CoV-2 Spike protein is essential for viral infectivity and binds to the host receptor ACE2. Here, the authors present MD simulations of the Spike protein and its variants of concern and observe that the Spike protein is destabilised by moderate static electric fields, and undergoes field-induced conformational changes that hinder binding to ACE2.

The COVID-19 outbreak has affected the lives of millions of people by causing a dramatic impact on many health care systems and the global economy. This devastating pandemic has brought together communities across the globe to work on this issue in an unprecedented manner. This case study describes the steps and methods employed in the conduction of a remote online health hackathon centered on challenges posed by the COVID-19 pandemic. It aims to deliver a clear implementation road map for other organizations to follow. This 4-day hackathon was conducted in April 2020, based on six COVID-19-related challenges defined by frontline clinicians and researchers from various disciplines. An online survey was structured to assess: (1) individual experience satisfaction, (2) level of interprofessional skills exchange, (3) maturity of the projects realized, and (4) overall quality of the event. At the end of the event, participants were invited to take part in an online survey with 17 (+5 optional) items, including multiple-choice and open-ended questions that assessed their experience regarding the remote nature of the event and their individual project, interprofessional skills exchange, and their confidence in working on a digital health project before and after the hackathon. Mentors, who guided the participants through the event, also provided feedback to the organizers through an online survey. A total of 48 participants and 52 mentors based in 8 different countries participated and developed 14 projects. A total of 75 mentorship video sessions were held. Participants reported increased confidence in starting a digital health venture or a research project after successfully participating in the hackathon, and stated that they were likely to continue working on their projects. Of the participants who provided feedback, 60% (n=18) would not have started their project without this particular hackathon and indicated that the hackathon encouraged and enabled them to progress faster, for example, by building interdisciplinary teams, gaining new insights and feedback provided by their mentors, and creating a functional prototype. This study provides insights into how online hackathons can contribute to solving the challenges and effects of a pandemic in several regions of the world. The online format fosters team diversity, increases cross-regional collaboration, and can be executed much faster and at lower costs compared to in-person events. Results on preparation, organization, and evaluation of this online hackathon are useful for other institutions and initiatives that are willing to introduce similar event formats in the fight against COVID-19.

This report presents our experience with T therapy in a cohort of T-deficient men on active surveillance （AS） for Gleason 3 ＋ 3 and Gleason 3 ＋ 4 prostate cancer （PCa）. A retrospective chart review identified 28 men with T deficiency who underwent T therapy （T group） for at least 6 months while on AS for PCa. A comparison group of 96 men on AS for PCa with untreated T deficiency （no-T group） was identified at the same institution. The AS protocol followed a modified Epstein criteria and allowed inclusion of men with a single core of low-volume Gleason 3 ＋ 4 PCa. Mean age was 59.5 and 61.3 years, and mean follow-up was 38.9 and 42.4 months for the T and no-T groups, respectively. Of all 28 men in the T group, 3 （10.7%） men developed an increase in Gleason score while on AS. Of 22 men in the T group with Gleason 3 ＋ 3 disease, 7 （31.8%） men developed biopsy progression including 3 men （13.6%） who developed Gleason 3 ＋ 4 PCa. Of 6 men with Gleason 3 ＋ 4 disease at baseline, 2 （33.3%） men developed an increase in tumor volume, and none developed upgrading beyond Gleason 3 ＋ 4. All 96 men in the no-T group had Gleason 3 ＋ 3 disease at baseline and, 43 （44.7%） developed biopsy progression, including 9 men （9.38%） with upgrading to Gleason 7 （3 ＋ 4）. Biopsy progression rates were similar for both groups and historical controls. Biopsy progression in men on AS appears unaffected by T therapy over 3 years. Prospective placebo-controlled trials of T therapy in T-deficient men on AS should be considered given the symptomatic benefits experienced by treated men.

Gender Incongruence refers to the discordance between biological sex and gender identity. Although it is possible to find literature reviews about the etiology of Gender Incongruence, almost all of these correspond to non-systematic narrative reviews, so they do not make explicit the methodology used in the collection and analysis of sources, even less its levels of evidence. In order to remedy this, we will conduct a scoping review to answer the question: what are the factors associated with gender incongruence and what level of evidence is there for each factor in the scientific literature? We will conduct a scoping review according to the methodology specified in the JBI Manual for Evidence Synthesis (Chapter 11) and the PRISMA extension for scoping reviews (PRISMA-ScR). Four databases will be reviewed to identify papers that match our search criteria, followed by a screening of titles and abstracts, the complete reading of those articles that have not been excluded, and the coding of these using the data extraction instrument developed for this research (see S1 Appendix). Data extracted will be analyzed in terms of frequency counts of factors, types of factors and levels of evidence for each factor. Results will be presented in tabular or diagrammatic forms supported by a narrative summary. The present review will help to map the factors associated with incongruence between biological sex and gender identity, specifying their levels of evidence. This evidence-based knowledge will be useful for clinicians evaluating gender incongruence, especially given that international guidelines recommend careful assessment of factors that may interfere with the clarity of gender identity development and decision making.

Until recently, developing health technologies was time-consuming and expensive, and often involved patients, doctors, and other health care professionals only as passive recipients of the end product. So far, users have been minimally involved in the ideation and creation stages of digital health technologies. In order to best address users' unmet needs, a transdisciplinary and user-led approach, involving cocreation and direct user feedback, is required. In this context, hackathon events have become increasingly popular in generating enthusiasm for user-centered innovation. This case study describes preparatory steps and the performance of a health hackathon directly involving patients and health care professionals at all stages. Feasibility and outcomes were assessed, leading to the development of systematic recommendations for future hackathons as a vehicle for bottom-up innovation in health care. A 2-day hackathon was conducted in February 2017 in Berlin, Germany. Data were collected through a field study. Collected field notes were subsequently discussed in 15 informal meetings among the research team. Experiences of conducting two further hackathons in December 2017 and November 2018 were included. In total, 30 participants took part, with 63% (19/30) of participants between 25 and 34 years of age, 30% (9/30) between 35 and 44 years of age, and 7% (2/30) younger than 25 years of age. A total of 43% (13/30) of the participants were female. The participation rate of medical experts, including patients and health care professionals, was 30% (9/30). Five multidisciplinary teams were formed and each tackled a specific health care problem. All presented projects were apps: a chatbot for skin cancer recognition, an augmented reality exposure-based therapy (eg, for arachnophobia), an app for medical neighborhood connectivity, a doctor appointment platform, and a self-care app for people suffering from depression. Patients and health care professionals initiated all of the projects. Conducting the hackathon resulted in significant growth of the digital health community of Berlin and was followed up by larger hackathons. Systematic recommendations for conducting cost-efficient hackathons (n≤30) were developed, including aspects of community building, stakeholder engagement, mentoring, themes, announcements, follow-up, and timing for each step. This study shows that hackathons are effective in bringing innovation to health care and are more cost- and time-efficient and potentially more sustainable than traditional medical device and digital product development. Our systematic recommendations can be useful to other individuals and organizations that want to establish user-led innovation in academic hospitals by conducting transdisciplinary hackathons.

About 1 out of 200 Sun-like stars has a planet with an orbital period shorter than one day: an ultrashort-period planet 1 , 2 . All of the previously known ultrashort-period planets are either hot Jupiters, with sizes above 10 Earth radii ( R ⊕ ), or apparently rocky planets smaller than 2  R ⊕ . Such lack of planets of intermediate size (the ‘hot Neptune desert’) has been interpreted as the inability of low-mass planets to retain any hydrogen/helium (H/He) envelope in the face of strong stellar irradiation. Here we report the discovery of an ultrashort-period planet with a radius of 4.6  R ⊕ and a mass of 29  M ⊕ , firmly in the hot Neptune desert. Data from the Transiting Exoplanet Survey Satellite 3 revealed transits of the bright Sun-like star LTT 9779 every 0.79 days. The planet’s mean density is similar to that of Neptune, and according to thermal evolution models, it has a H/He-rich envelope constituting 9.0 − 2.9 + 2.7 % of the total mass. With an equilibrium temperature around 2,000 K, it is unclear how this ‘ultrahot Neptune’ managed to retain such an envelope. Follow-up observations of the planet’s atmosphere to better understand its origin and physical nature will be facilitated by the star’s brightness ( V mag  = 9.8). LTT 9779 b is Neptune-sized planet rotating around its star with a period of 0.79 days and an equilibrium temperature of 2,000 K. It is not clear how it retained its atmospheric envelope, which contains ~10% of H/He, as it should have been photoevaporated by now.

The article focuses on the case of Plegaria a un labrador by Víctor Jara and its social biography as a song to show how the utopia of a classless society converges with the idea of the kingdom of God on earth in the Nueva Canción Chilena.

Functional constipation is a common gastrointestinal disorder influenced by dietary, anthropometric, and demographic factors. However, the combined impact of these factors on constipation symptoms remains underexplored, particularly within the Peruvian population. To assess the association of nutritional knowledge, fiber-rich food consumption, body mass index (BMI), and sex with functional constipation symptoms in Peruvian adults. A cross-sectional study was conducted among 404 Peruvian adults selected through non-probability sampling. Nutritional knowledge (assessed using the Dietary Fiber Habits and Knowledge Questionnaire), fiber-rich food consumption (measured with the Block Instrument), BMI (self-reported and calculated), and constipation symptoms (evaluated using the Rome III International Diagnostic Questionnaire) were analyzed. Hierarchical regression analysis was performed to evaluate the impact of the variables on constipation symptoms. The hierarchical regression analysis, conducted in four blocks, demonstrated a progressive increase in the explained variance. In the fourth block, nutritional knowledge (β = − 0.173, p  = 0.006, CI [− 0.296, − 0.050]) and consumption of high-fiber foods (β = − 0.227, p  < 0.001, CI [− 0.351, − 0.103]) were associated with a reduction in constipation symptoms, while BMI (β = 0.230, p  < 0.001, CI [0.108, 0.353]) and being female (β = 0.153, p  = 0.014, CI [0.031, 0.274]) were associated with an increase in symptoms. The final model accounted for 16.4% of the total variance (adjusted R 2 = 0.164), with fiber consumption contributing to a 5.2% increase in explained variance (∆R 2 = 0.052). These findings underscore the importance of implementing public health educational and dietary strategies to address constipation through preventive and personalized approaches.

Mosquito-borne flaviviruses represent a public health challenge due to the high-rate endemic infections, severe clinical outcomes, and the potential risk of emerging global outbreaks. Flavivirus disease pathogenesis converges on cellular factors from vectors and hosts, and their interactions are still unclear. Exosomes and microparticles are extracellular vesicles released from cells that mediate the intercellular communication necessary for maintaining homeostasis; however, they have been shown to be involved in disease establishment and progression. This review focuses on the roles of extracellular vesicles in the pathogenesis of mosquito-borne flavivirus diseases: how they contribute to viral cycle completion, cell-to-cell transmission, and cellular responses such as inflammation, immune suppression, and evasion, as well as their potential use as biomarkers or therapeutics (antiviral or vaccines). We highlight the current findings concerning the functionality of extracellular vesicles in different models of dengue virus, Zika virus, yellow fever virus, Japanese encephalitis virus, and West Nile virus infections and diseases. The available evidence suggests that extracellular vesicles mediate diverse functions between hosts, constituting novel effectors for understanding the pathogenic mechanisms of flaviviral diseases.

Artificial intelligence (AI) is rapidly transforming higher education, yet limited empirical evidence exists on how students experience the emotional, cognitive, and ethical tensions associated with AI, particularly in Latin American contexts. This study addresses this gap by examining patterns of adoption, perceived usefulness, and the ambivalent experiences that arise when engaging with AI tools for academic learning. A questionnaire combining closed and open-ended questions was administered to 170 engineering students from a Chilean public university. A mixed-methods design was used to analyse the data: quantitative analyses identified adoption patterns and perceived usefulness, while qualitative thematic analysis captured emerging emotional, ethical, and motivational tensions. The results showed high adoption (73.5%), driven by the pragmatic usefulness of saving time, understanding concepts, and improving work. Although the overall perception was positive, a deep ambivalence was identified, with enthusiasm and confidence coexisting with ethical (plagiarism), cognitive (dependence), and technical (reliability) concerns. It is concluded that the effective integration of AI transcends technological access and requires an institutional strategy that promotes critical digital literacy, clear policies, and support programmes that address competency and gender gaps, ensuring ethical and equitable adoption that enhances learning without compromising the development of critical thinking.