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Abstract Understanding the mechanisms of resistance to PARP inhibitors (PARPi) is a clinical priority, especially in breast cancer. We developed a novel mathematical framework accounting for intrinsic resistance to olaparib, identified by fitting the model to tumour growth metrics from breast cancer patient-derived xenograft (PDX) data. Pre-treatment transcriptomic profiles were used with the calculated resistance to identify baseline biomarkers of resistance, including potential combination targets. The model provided both a classification of responses, as well as a continuous description of resistance, allowing for more robust biomarker associations and capturing the observed variability. Thirty-six resistance gene markers were identified, including multiple homologous recombination repair (HRR) pathway genes. High WEE1 expression was also linked to resistance, highlighting an opportunity for combining PARP and WEE1 inhibitors. This framework facilitates a fully automated way of capturing intrinsic resistance, and accounts for the pharmacological response variability captured within PDX studies and hence provides a precision medicine approach.

The production of phycobiliproteins, such as cyanobacterial phycocyanins, is a growing interest due to their diverse industrial and biotechnological applications. This study focuses on optimizing phycocyanin production using the strain Potamosiphon sp. through experimental techniques and mathematical modeling in fed-batch cultures. The methodology applied includes determining the kinetic constants by linearizing the Monod equation evaluating the concentrations of biomass, C-phycocyanin (C-PC), nitrates (NO3), and phosphates (PO4). A mathematical model of periodic fed-batch feeding was subsequently established, applying mass conservation principles and evaluating the accuracy of the Monod, Contois, Moser, and Tessier models. The results indicate that phycocyanin production is highly dependent on phosphorus and nitrogen concentrations, with optimal conversion observed at specific levels of these elements (0.832 for phosphorus and 0.805 for nitrogen in terms of C-PC and biomass, respectively). The Tessier model demonstrated the highest accuracy in predicting production and optimizing operational conditions, with a Mean Squared Error (MSE) of 0.005000 for biomass production, 0.200000 for C-PC production, and 0.000010 for substrate consumption. It also achieved high R² values of 0.980 for biomass, 0.999 for C-PC production, and 0.997 for substrate consumption. It presented the lowest Akaike Information Criterion (AIC) scores, indicating its robustness and reliability in modeling these processes and manipulating cultivation conditions and providing adequate nutrition allowed for achieving growth rates of 1.23 g/L and a C-PC concentration of 37 mg/L, which are essential for industrial applications such as natural colorants and antioxidants, among others.

Abstract Background Poly (ADP-ribose) polymerase 1 and 2 (PARP1/2) inhibitors (PARPi) are targeted therapies approved for homologous recombination repair (HRR)-deficient breast, ovarian, pancreatic, and prostate cancers. Since inhibition of PARP1 is sufficient to cause synthetic lethality in tumors with homologous recombination deficiency (HRD), PARP1 selective inhibitors such as saruparib (AZD5305) are being developed. It is expected that selective PARP1 inhibition leads to a safer profile that facilitates its combination with other DNA damage repair inhibitors. Here, we aimed to characterize the antitumor activity of AZD5305 in patient-derived preclinical models compared to the first-generation PARP1/2 inhibitor olaparib and to identify mechanisms of resistance. Methods Thirteen previously characterized patient-derived tumor xenograft (PDX) models from breast, ovarian, and pancreatic cancer patients harboring germline pathogenic alterations in BRCA1, BRCA2, or PALB2 were used to evaluate the efficacy of AZD5305 alone or in combination with carboplatin or an ataxia telangiectasia and Rad3 related (ATR) inhibitor (ceralasertib) and compared it to the first-generation PARPi olaparib. We performed DNA and RNA sequencing as well as protein-based assays to identify mechanisms of acquired resistance to either PARPi. Results AZD5305 showed superior antitumor activity than the first-generation PARPi in terms of preclinical complete response rate (75% vs. 37%). The median preclinical progression-free survival was significantly longer in the AZD5305-treated group compared to the olaparib-treated group (> 386 days vs. 90 days). Mechanistically, AZD5305 induced more replication stress and genomic instability than the PARP1/2 inhibitor olaparib in PARPi-sensitive tumors. All tumors at progression with either PARPi (39/39) showed increase of HRR functionality by RAD51 foci formation. The most prevalent resistance mechanisms identified were the acquisition of reversion mutations in BRCA1/BRCA2 and the accumulation of hypomorphic BRCA1. AZD5305 did not sensitize PDXs with acquired resistance to olaparib but elicited profound and durable responses when combined with carboplatin or ceralasertib in 3/6 and 5/5 models, respectively. Conclusions Collectively, these results show that the novel PARP1 selective inhibitor AZD5305 yields a potent antitumor response in PDX models with HRD and delays PARPi resistance alone or in combination with carboplatin or ceralasertib, which supports its use in the clinic as a new therapeutic option.

Abstract Background Penicillium digitatum is a fungal plant pathogen that causes the green mold disease in harvested citrus fruits. Due to its economical relevance, many efforts have focused on the development of genetic engineering tools for this fungus. Adaptation of the CRISPR/Cas9 technology was previously accomplished with self-replicative AMA1-based plasmids for marker-free gene editing, but the resulting efficiency (10%) limited its practical implementation. In this study, we aimed to enhance the efficiency of the CRISPR/Cas9-mediated gene editing in P. digitatum to facilitate its practical use. Results Increasing the culture time by performing additional culture streaks under selection conditions in a medium that promotes slower growth rates significantly improved the gene editing efficiency in P. digitatum up to 54–83%. To prove this, we disrupted five candidate genes that were chosen based on our previous high-throughput gene expression studies aimed at elucidating the transcriptomic response of P. digitatum to the antifungal protein PdAfpB. Two of these genes lead to visual phenotypic changes (PDIG_53730/pksP, and PDIG_54100/arp2) and allowed to start the protocol optimization. The other three candidates (PDIG_56860, PDIG_33760/rodA and PDIG_68680/dfg5) had no visually associated phenotype and were targeted to confirm the high efficiency of the protocol. Conclusion Genome editing efficiency of P. digitatum was significantly increased from 10% to up to 83% through the modification of the selection methodology, which demonstrates the feasibility of the CRISPR/Cas9 system for gene disruption in this phytopathogenic fungus. Moreover, the approach described in this study might help increase CRISPR/Cas9 gene editing efficiencies in other economically relevant fungal species for which editing efficiency via CRISPR/Cas9 is still low.

This study addressed the optimization of biomass and C-phycocyanin (C-PC) concentration and its purity in the thermotolerant cyanobacterium Potamosiphon sp by adjusting key light quality parameters. Custom design and Central Composite Design experimental designs were employed, using LEDs light intensity, wavelength, and photoperiod. The results demonstrated that these lighting parameters significantly influence biomass and C-phycocyanin production, achieving up to a 100 % increase in phycocyanin accumulation and biomass production and a 50 % improvement in purity index compared to conventional white light under optimal conditions of Red:Blue light (3:1), Intensity (283 μmol m−2 s−1), and photoperiod (17.8 H light). The findings support the use of specific LEDs wavelengths that optimize the performance of production processes and the quality of products derived from cyanobacteria, such as high-value phycobiliproteins.

Stroke is the leading cause of disability and the second cause of death worldwide. The increasing burden of stroke underscores the importance of optimising rehabilitation protocols. Virtual reality (VR) can improve poststroke prognosis. A VR software combining gamification, full immersion and stroke specificity (ie, the Development and validation of a novel viRtual rEality software for improving diSability and quality of lifE in patients with sTroke (RESET) software) might substantially improve disability and quality of life (QoL). However, this technology is still very scarce. The RESET trial aims to assess the effects of an early 10-week gamified, fully immersive and stroke-specific VR intervention (ie, starting at week 3 poststroke) on disability and QoL in people with stroke in the subacute phase. People with ischaemic or haemorrhagic stroke (n=94) aged ≥18 years will be randomised to receive (1) usual care (UC), (2) commercial VR or (3) gamified, fully immersive and stroke-specific VR (RESET). The three groups will receive UC (ie, three sessions/week of 90 min of standard rehabilitation). The VR groups will additionally receive three VR sessions of 20 min per week. The outcome measures will be assessed at baseline (week 2 from stroke occurrence), week 13 (approximately 90 days from the event) and week 26 (approximately 6 months from the event). The primary outcome is disability measured with the Barthel Index. Secondary outcomes include QoL, upper-extremity and lower-extremity motor function, gross manual dexterity, handgrip strength and cognitive function. This study will unravel the effects of a gamified, fully immersive and stroke-specific VR software on disability and QoL in patients with stroke in the early subacute phase.NCT06132399.

Digital footprints (DF) offer relevant information about educational activities and processes related to strategies of academic assessment, identification of skills and psychological traits of students, and permanence and dropout trends, etc. This study analyzes scientific evidence on the use of DF in education, and shows the results of a systematic mapping of literature carried out based on the analysis of documents published in the last fifteen years (2005-2019) in two databases: Scopus and Web of Science (WoS). Findings reveal that educational research on DF is focused on learning analytics, the study of digital presence and psychometric modeling. Likewise, the article reports on the scarce investigation of DF in Massive Open Online Courses (MOOCs) environments and highlights the multiple meanings of DF as an action and as a service, beyond the generalized conception of data. These findings suggest the importance of preparing educational institutions to implement DF use and management practices in order to favor processes that range from DF curation, to cognitive evaluation, digital equity, prediction of school success and/or failure, etc. Hence, DF meanings (data, action and service) could aid to generate proper administration and policy-making actions, placed at the service of all students and their educational communities.

Introduction Alzheimer’s and Parkinson’s disease are neurodegenerative disorders with life limiting conditions. The symptomatic pharmacological therapeutic strategies unfortunately are also related to undesirable side effects. Acetylcholinesterase inhibitors administered to Alzheimer’s disease patients increase cholinergic transmission in cortex and hippocampus. Antiparkinsonian drugs increase dopaminergic system activity, to compensate for dopaminergic neurons’ degeneration in corpus striatum, therefore supplying the imbalance of these neurotransmitters in these degenerative areas.But undesirable the increase of these neurotransmitters in other cerebral and peripheral areas brings us important side effects Objectives To study Alzheimer’s cholinergic drugs and Parkinson’s dopaminergic drugs’ side effects Methods This retrospective study included 107 geriatric patients enrolled in a private long-term care institution. 79 patients with Alzheimer’s disease had mean age of 88.11 ± 5,78 years old, mean weight of 61.62 ± 13.10 kg. 28 patients with Parkinson’s disease had mean age of 84.93 ± 5.71 years old, weight mean 66.36 ± 2.83 kg. Results Alzheimer’s disease patients 41.77% (33) received. Acetylcholinesterase inhibitors (Donepezil, galantamine and rivastigmine) Psychomotor agitation and aggressive behavior 63.666% and nausea (15%) were observed in the patients treated with these drugs. The association of L-DOPA and DOPA decarboxylase inhibitors (benserazide) were administered to 53%(15) of the Parkinson’s disease patients in doses between 2.0-19.0 mg/kg/day. L-DOPA associated to catechol-O-methyltransferase inhibitor (entacapone) 3 mg/kg/day were given to 7.14% (2) patients. Bromocriptine 0.04 mg/kg/day was given to 3.57% (1) patients. Mental confusion and hallucination side effects were observed in 53.33% (8) patients treated with L-DOPA associated with the DOPA decarboxylase inhibitor (benserazide). Conclusions The increase of cholinergic activity due to the acetylcholinesterase inhibitors in the Nigro- striatal pathway could be related to psychomotor agitation in Alzheimer’s disease patients in a similar way to akathisia induced by neuroleptics. The increase of dopamine levels due to the administration of L-DOPA, in corpus striatum improved Parkinson’s disease symptoms although the increase of dopaminergic activity at mesocortical pathways may be related to confusion and hallucination observed in these patients. Adjustments in dosage of these drugs could provide improvement in these patients’ daily life conditions. Disclosure of Interest None Declared

We analyzed immune response to SARS-CoV-2 vaccination by measuring specific IgG titers and T-cell reactivity to different SARS-CoV-2 peptides in multiple sclerosis patients taking different disease-modifying treatments. Of the 88 patients included, 72 developed any kind of immune response after vaccination. Although DMTs such as fingolimod and anti-CD20+ treatments prevented patients from developing a robust humoral response to the vaccine, most of them were still able to develop a cellular response, which could be crucial for long-term immunity. It is probably advisable that all MS patients take additional/booster doses to increase their humoral and/or cellular immune response to SARS-CoV-2.

Abstract Triple‐negative breast cancer (TNBC) often develops resistance to single‐agent treatment, which can be circumvented using targeted combinatorial approaches. Here, we demonstrate that the simultaneous inhibition of LOXL2 and BRD4 synergistically limits TNBC proliferation in vitro and in vivo. Mechanistically, LOXL2 interacts in the nucleus with the short isoform of BRD4 (BRD4S), MED1, and the cell cycle transcriptional regulator B‐MyB. These interactions sustain the formation of BRD4 and MED1 nuclear transcriptional foci and control cell cycle progression at the gene expression level. The pharmacological co‐inhibition of LOXL2 and BRD4 reduces BRD4 nuclear foci, BRD4‐MED1 colocalization, and the transcription of cell cycle genes, thus suppressing TNBC cell proliferation. Targeting the interaction between BRD4S and LOXL2 could be a starting point for the development of new anticancer strategies for the treatment of TNBC.

Abstract The RAD51 test is emerging as a promising biomarker for the assessment of functional homologous recombination deficiency (HRD). Yet, the robustness and reproducibility of the immunofluorescence‐based RAD51 test, in different academic laboratories, have not been systematically investigated. Therefore, we tested the performance of the RAD51 assay in formalin‐fixed paraffin‐embedded (FFPE) high‐grade serous ovarian carcinoma (HGSOC) samples in four European laboratories. Here, we confirm that subtle differences in staining procedures result in low variability of RAD51 and γH2AX scores. However, substantial variability in RAD51 scoring was observed in some samples, likely due to complicating technical and biological features, such as high RAD51 signal‐to‐noise ratio and RAD51 heterogeneity. These results support the need to identify and perform additional quality control steps and/or automating image analysis. Altogether, resolving technical issues should be a priority, as identifying tumours with functional HRD is urgently needed to guide the individual treatment of HGSOC patients. Follow‐up studies are needed to define the key tissue quality requirements to assess HRD by RAD51 in FFPE tumour samples, as this test could help in guiding the individual treatment of HGSOC patients.

This study presents a comprehensive bibliometric analysis of research on bank erosion and control measures, utilizing the Scopus database and VOSviewer software. Key terms such as “bank”, “erosion”, “control”, and “protection” frequently appear in the literature, underscoring their importance in studies on riverbank erosion. Since 2000, scientific production has steadily increased, particularly in disciplines such as Environmental Sciences and Earth and Planetary Sciences, driven by growing concerns about climate change and sustainable water resource management. Countries with substantial research resources, such as the United States and China, lead in the production of studies, reflecting their commitment to addressing this global issue. In parallel, the evaluation of erosion mitigation practices in Colombia revealed that, although effective techniques such as gabion walls and riparian vegetation exist, 40% of respondents do not implement specific measures. This lack of implementation is attributed to insufficient knowledge, limited resources, and misconceptions about the effectiveness of these techniques. The findings highlight the need to promote proven practices and enhance professional training. Future research should focus on developing more accurate predictive models, integrating interdisciplinary approaches, and assessing the impacts of climate change on bank erosion. Addressing barriers to applying effective techniques at the local level and improving access to resources and knowledge are critical steps to reducing bank erosion and ensuring sustainable water management.

Vaccination Week in the Americas (VWA) is a yearly regional initiative that promotes the benefits of vaccination to all persons in the region. In its 22-year history, more than 1.15 billion people have been reached under the framework of VWA across more than 40 countries and territories. This review examines multiple PAHO and WHO data points, documents and reports related to measles/rubella vaccination coverage and VWA since its inception. Its goal is to document the impact that the VWA has had in maintaining and accelerating measles and rubella disease elimination, in the context of PAHO’s Disease Elimination Initiative. The results suggest that VWA’s contributions to measles and rubella elimination have been substantial. Every year, VWA promotes (a) renewed political commitment to the immunization program from the highest political authorities of Member States; (b) vaccination operations to close immunity gaps, recover under-vaccinated persons, and reach chronically underserved populations; and (c) the dissemination of messages on the benefits of vaccination through regional and national communications campaigns. VWA will continue to be an important contributor to disease elimination efforts in the Americas, even as new targets are set in response to the evolving epidemiological landscape.

Abstract Background Early identification of plasma leakage may guide treatment decisions in dengue patients. This study evaluated the value of point-of-care ultrasound (POCUS) to detect plasma leakage and predict hospitalization or referral to a higher level of care in suspected dengue patients under routine conditions at a primary care facility in Colombia. Methods We conducted a cohort study between April 2019 and March 2020 in a primary care hospital in Cali, Colombia. We prospectively included and followed 178 patients who were at least 2 years old with fever of less than 10 days and clinician-suspected dengue. A trained general practitioner performed a standardized POCUS protocol. Images were quality-rated and overread by an expert radiologist, and her results and those of the general practitioner were compared using the Kappa index. Logistic regression was used to identify factors associated with plasma leakage at enrollment and explore its prognostic value regarding hospital admission or referral to a higher level of care. Results Half (49.6%) POCUS images were of suitable quality to be interpreted. The proportion of plasma leakage reported by the radiologist was 85.1% (95% CI: 78.6–90.2%) and 47.2% by the study physician (Kappa = 0.25, 95% CI: 0.15–0.35). The most frequent ultrasound findings were ascites (hepatorenal 87.2%, splenorenal 64%, or pelvic 21.8%) and gallbladder wall thickening (10.5%). Plasma leakage was higher in subjects with thrombocytopenia (aOR = 4, 95% CI: 1.3–12.1) and lower in patients 30–59 years old (aOR = 0.1, 95% CI: 0.0–0.4) than in those 18 years old or younger. POCUS evidence of plasma leakage (aOR = 8.2, 95% CI: 2.2–29.9), thrombocytopenia (aOR = 6.3, 95% CI: 2.4–16.0) and pulse pressure (aOR = 1.1, 95% CI: 1.07–1.2) were associated with hospital admission or referral to a higher level of care. Conclusions Ultrasound is useful to detect plasma leakage in primary care and, challenges remain to guarantee high-quality images and diagnostic accuracy, for which a standardized dengue POCUS protocol and training program is needed. Graphical Abstract

Abstract Background For health professionals, gamification is a new teaching method that has achieved an important role in recent years, with excellent results in learning and knowledge acquisition. Thus, the objective of this study was to analyze the gaming experience through different gamification resources in the classroom with physiotherapy students. Methods A comparative study on gamification-based teaching resources was carried out during the first semester of the 2021–2022 academic year. A total of 33 physiotherapy students participated in this study. After the theoretical topics were taught, the participants were invited to participate in different gamification resources such as Kahoot!, Physiotherapy Party and Escape Room. The gaming experience with the different gamification resources was measured with the GAMEX scale. Results The Physiotherapy Party showed a higher score in relation to the enjoyment dimension compared to the Kahoot! and Escape Room (p = 0.004). The Escape Room presented higher scores in absorption, creative thinking, activation and dominance compared to Kahoot! and Physiotherapy Party (p

Introducción. La baja agudeza es un problema de salud pública en el mundo, que aumenta año tras año, relacionada con factores comportamentales poco saludables como el sedentarismo. La baja agudeza afecta especialmente a escolares, en quienes la visión representa uno de los sistemas más importantes para su desarrollo, tanto para el aprendizaje como para las relaciones sociales. El objetivo es establecer asociación entre baja agudeza visual y características sociodemográficas y comportamentales en una población escolar de la ciudad de Bucaramanga, Colombia. Metodología. Estudio observacional de corte transversal basado en datos recolectados de encuestas a estudiantes de una institución educativa de Bucaramanga entre los años 2006 y 2017, sobre las cuales se realizó un análisis bivariado entre características sociodemográficas y comportamentales con baja agudeza visual. Resultados. La prevalencia de baja agudeza visual fue de 33.57%, con mayor prevalencia de baja agudeza visual en mujeres y aquellos con mayor índice de masa corporal. La agudeza visual baja no tuvo asociación estadísticamente significativa con las otras variables estudiadas. Discusión. Las mujeres tienen una mayor prevalencia de baja agudeza visual. Parece existir una relación entre la actividad física y la agudeza visual. Conclusiones. Las diferencias encontradas según el sexo pueden deberse a patrones comportamentales diferentes entre hombres y mujeres, como la actividad física y el sedentarismo. Hacen falta estudios que evalúen la causalidad de la asociación entre los problemas de agudeza visual y los hábitos de vida poco saludables. Introduction. Low visual acuity is a public health problem worldwide, which is increasing year by year, and it is associated with unhealthy behavioral factors such as sedentary lifestyle. Low visual acuity particularly affects schoolchildren, whom eyesight is one of the most important abilities for their development, both in terms of learning and social interactions. The objective of this study is to establish an association between low visual acuity, sociodemographic, and behavioral characteristics of a student population in Bucaramanga, Colombia. Methodology. This was a cross-sectional observational study based on data collected from surveys of students within an educational institution sited in Bucaramanga between 2006 and 2017. A bivariate analysis was conducted between sociodemographic and behavioral characteristics and low visual acuity. Results. The prevalence of low visual acuity was 33.57%, with a higher prevalence of low visual acuity in women and those with a higher body mass index. However, low visual acuity didn’t have a statistically significant association with the other variables studied. Discussion. Women have a higher prevalence of low visual acuity. There appears to be an association between physical activity and visual acuity. Conclusions. The encountered differences according to sex may be due to different behavioral patterns between males and females, such as physical activity and sedentary lifestyle. Further studies are needed to assess the causality of the association. Introdução. A baixa acuidade é um problema de saúde pública no mundo, que aumenta a cada ano, relacionada a fatores comportamentais pouco saudáveis, como o sedentarismo. A baixa acuidade atinge especialmente as crianças em idade escolar, para as quais a visão representa um dos sistemas mais importantes para o seu desenvolvimento, tanto para a aprendizagem quanto para as relações sociais. O objetivo é estabelecer uma associação entre baixa acuidade visual e características sociodemográficas e comportamentais em uma população escolar na cidade de Bucaramanga, Colômbia. Metodologia. Estudo observacional transversal baseado em dados coletados em pesquisas com estudantes de uma instituição de ensino de Bucaramanga entre 2006 e 2017, nos quais foi realizada uma análise bivariada entre características sociodemográficas e comportamentais com baixa acuidade visual. Resultados. A prevalência de baixa acuidade visual foi de 33.57%, com maior prevalência de baixa acuidade visual em mulheres e naqueles com maior índice de massa corporal. A baixa acuidade visual não teve associação estatisticamente significativa com as demais variáveis estudadas. Discussão. As mulheres apresentam maior prevalência de baixa acuidade visual. Parece haver uma relação entre atividade física e acuidade visual. Conclusões. As diferenças encontradas segundo o sexo podem ser decorrentes de diferentes padrões comportamentais entre homens e mulheres, como atividade física e sedentarismo. Estudos são necessários para avaliar a causalidade da associação entre problemas de acuidade visual e hábitos de vida pouco saudáveis.

The RNA recognition motif (RRM) is the most common RNA-binding protein domain identified in nature. However, RRM-containing proteins are only prevalent in eukaryotic phyla, in which they play central regulatory roles. Here, we engineered an orthogonal post-transcriptional control system of gene expression in the bacterium Escherichia coli with the mammalian RNA-binding protein Musashi-1, which is a stem cell marker with neurodevelopmental role that contains two canonical RRMs. In the circuit, Musashi-1 is regulated transcriptionally and works as an allosteric translation repressor thanks to a specific interaction with the N-terminal coding region of a messenger RNA and its structural plasticity to respond to fatty acids. We fully characterized the genetic system at the population and single-cell levels showing a significant fold change in reporter expression, and the underlying molecular mechanism by assessing the in vitro binding kinetics and in vivo functionality of a series of RNA mutants. The dynamic response of the system was well recapitulated by a bottom-up mathematical model. Moreover, we applied the post-transcriptional mechanism engineered with Musashi-1 to specifically regulate a gene within an operon, implement combinatorial regulation, and reduce protein expression noise. This work illustrates how RRM-based regulation can be adapted to simple organisms, thereby adding a new regulatory layer in prokaryotes for translation control.

Death investigation on tribal lands and of American Indian/Alaska Native (AIAN) people is complex and not well documented. An analysis of data from the 2018 Census of Medical Examiner and Coroner Offices (CMEC) provides a timely update on the extent of medicolegal death investigations (MDIs) on federal and state-recognized tribal lands. An estimated 150 MEC offices serve tribal lands, however, 44 % of these offices (i.e., 4 % of MEC offices) do not track cases from tribal lands separately. MEC offices with a population of 25,000 to 250,000 that serve tribal lands had more resources and access to information to perform MDIs than all other MEC offices. Analysis also indicates that the median number of unidentified human remains cases from MECs serving tribal lands is 6 times higher than that of jurisdictions not serving tribal lands. This analysis begins to elucidate gaps in the nation's understanding of MDI on tribal lands.

Technology uses among medical examiner and coroner (MEC) offices in the United States are not well characterized, yet technology is essential to job-performing duties. Resources, operational infrastructure, and MECs' policies and procedures that affect technology use should be better understood. MEC offices need access to technologies like internet, case management systems (CMSs), databases, and advanced imaging to perform their basic duties. A current state of the technologies MEC offices use to complete a death investigation is presented by analyzing data from the 2018 Census of Medical Examiner and Coroner Offices. This analysis shows the New England division reported the most internet and CMS access. Many offices reported limited access to, and low participation in, databases for assessing and sharing case data. Offices serving populations >250,000 have more access to the internet, CMSs, databases, and advanced imaging. Although MEC office technology use has improved over time, it is still disparate.

In the United States, medical examiners and coroners (MECs) fill critical roles within our public health and public safety systems. These professionals are primarily charged with determining the cause and manner of death as they investigate deaths and respond to associated scenes and mass fatalities and can also help identify trends in public health crises through medicolegal death investigations. Despite their instrumental role, they are organized in disparate systems with varying governing structures, functions, staffing, caseload, budget, and access to resources. This paper examines data from the 2018 Census of Medical Examiner and Coroners to evaluate MEC operations in the United States. The findings show that MEC offices’ organizational and operational governance structures greatly influence resources, workloads, and access to information and services. Standalone MEC offices were generally better resourced than those affiliated with law enforcement, public health, forensic science, district attorneys, or other agencies.1

With the rise of mass fatalities and disasters, access to mass fatality and disaster planning trainings and resources available to medical examiners and coroners (MECs) in the United States should be reviewed. This paper provides a necessary update on the extent of access to these resources by analyzing data from the 2018 Census for Medical Examiner and Coroner Offices (CMEC). Results show that a high percentage of respondents have access to mass fatality and disaster planning trainings/resources; however, the access is disproportionate. Respondents in the Midwest and South—and those with smaller populations—have less access to resources, while agencies with larger budgets and more full-time staff have more access to resources. This paper discusses potential contributing factors for these disparities, but the data only begin to elucidate gaps in access to mass fatality and disaster planning trainings/resources for MECs and where further research should be conducted.

Introduction COVID-19 is associated with higher morbimortality in pregnant people compared with non-pregnant people. At present, the benefits of maternal immunisation are considered to outweigh the risks, and therefore, vaccination is recommended during pregnancy. However, additional information is needed on the safety of the vaccines in this population.Methods and analysis This a retrospective cohort nested case–control study in pregnant people who attended maternity hospitals from eight Latin American and Caribbean countries. A perinatal electronic clinical history database with neonatal and obstetric information will be used. The proportion of pregnant people immunised with COVID-19 vaccines of the following maternal and neonatal events will be described: preterm infant, small for gestational age, low birth weight, stillbirth, neonatal death, congenital malformations, maternal near miss and maternal death. Moreover, the risk of prematurity, small for gestational age and low birth weight associated with exposure to COVID-19 vaccines will be estimated. Each case will be matched with two groups of three randomly selected controls. Controls will be matched by hospital and mother’s age (±3 years) with an additional matching by delivery date and conception time in the first and second control groups, respectively. The estimated required sample size for the main analysis (exposure to any vaccine) concerning ‘non-use’ is at least 1009 cases (3027 controls) to detect an increased probability of vaccine-associated event risk of 30% and at least 650 cases (1950 controls) to detect 30% protection. Sensitivity and secondary analyses considering country, type of vaccine, exposure windows and completeness of immunisation will be reported.Ethics The study protocol was reviewed by the Ethical Review Committee on Research of the Pan American Health Organization. Patient informed consent was waived due to the retrospective design and the utilisation of anonymised data (Ref. No: PAHOERC.0546.01). Results will be disseminated in open access journals.

In the last years, many research efforts have been applied for the development of filamentous fungi as hosts for heterologous protein production. Aspergillus vadensis CBS 113365, a close relative of the industrial workhorse Aspergillus niger, has been suggested as a more suitable cell factory as it does not acidify the culture medium and produces very low levels of secreted proteases. Therefore, efficient methods and tools that allow the genetic manipulation and exploitation of this biotechnologically relevant fungus are needed. To date, only protoplast-mediated transformation and classical cloning strategies have been implemented for A. vadensis genetic modification, which decreases the exploitation capacity of this fungus at the industrial level. In this study, we have adapted and implemented an Agrobacterium tumefaciens-mediated transformation protocol for A. vadensis for the first time, and applied the FungalBraid system to genetically modify this species by means of synthetic biology. As proof of concept, we have successfully complemented and fluorescently labelled a uridine auxotrophic A. vadensis pyrA- strain and generated A. vadensis mutants carrying the Penicillium expansum-based expression cassette for the heterologous production of the antifungal protein PeAfpA from P. expansum. Even though we have yet to find the conditions that trigger PeAfpA production in this species, the implementation of the ATMT method reported here, along with the application of the FungalBraid system, will greatly aid in this task and will facilitate the exploitation of A. vadensis as a fungal workhorse for protein production for multiple biotechnological applications.

This report describes acidic microbial mats containing cyanobacteria that are strongly associated to precipitated minerals in the source area of Río Tinto. Río Tinto (Huelva, Southwestern Spain) is an extreme acidic environment where iron and sulfur cycles play a fundamental role in sustaining the extremely low pH and the high concentration of heavy metals, while maintaining a high level of microbial diversity. These multi-layered mineral deposits are stable all year round and are characterized by a succession of thick greenish-blue and brownish layers mainly composed of natrojarosite. The temperature and absorbance above and below the mineral precipitates were followed and stable conditions were detected inside the mineral precipitates. Different methodologies, scanning and transmission electron microscopy, immunological detection, fluorescence in situ hybridization, and metagenomic analysis were used to describe the biodiversity existing in these microbial mats, demonstrating, for the first time, the existence of acid-tolerant cyanobacteria in a hyperacidic environment of below pH 1. Up to 0.46% of the classified sequences belong to cyanobacterial microorganisms, and 1.47% of the aligned DNA reads belong to the Cyanobacteria clade.

El guayabo (Psidium guajava) es una especie de importancia económica en diferentes países del mundo, especialmente por la producción de frutos comestibles, su alto contenido de vitamina C y su maleabilidad para la transformación agroindustrial. La Colección Colombiana de Guayaba conservada en Agrosavia resguarda la variabilidad de esta especie y algunas relacionadas, no obstante, se tienen estudios parciales que limitan el potencial de su uso. El objetivo fue evaluar y caracterizar las variables fisicoquímicas del fruto en busca de identificar accesiones con atributos de interés agroindustrial. Para ello se evaluaron 29 descriptores (17 cuantitativos y 12 cualitativos) en frutos de las 41 accesiones que componen la colección. La información obtenida fue sometida a un análisis de componentes principales y a otro de correspondencia múltiple. En los análisis cualitativos se encontró que el germoplasma evaluado se caracteriza por tener frutos de forma convexa con cuello, pulpa de color rosado con textura granulosa, color verde predominante en el epicarpio, inserción de pedúnculo oblicua, semillas de forma oblonga y forma de ápice y fruta con ombligo en el eje polar. En los análisis cuantitativos, 20 accesiones presentaron porcentajes de pulpa entre el 97 % y el 99 %, donde el contenido de sólidos solubles totales de la población evaluada fluctuó entre 4,3 y 10,5 °Brix; la relación de vitamina C osciló entre 28,3 y 208,26 mg/100 g de muestra y el peso del fruto estuvo entre 18,84 y 363,53 g, siendo las accesiones 25, 33 y 36 seleccionadas como promisorias.

Abstract Background In yellow fever (YF) endemic areas, measles, mumps, and rubella (MMR), and YF vaccines are often co-administered in childhood vaccination schedules. Because these are live vaccines, we assessed potential immune interference that could result from co-administration. Methods We conducted an open-label, randomized non-inferiority trial among healthy 1-year-olds in Misiones Province, Argentina. Children were randomized to one of three groups (1:1:1): Co-administration of MMR and YF vaccines (MMR1YF1), MMR followed by YF vaccine four weeks later (MMR1YF2), or YF followed by MMR vaccine four weeks later (YF1MMR2). Blood samples obtained pre-vaccination and 28 days post-vaccination were tested for immunoglobulin G antibodies against measles, mumps, and rubella, and for YF virus-specific neutralizing antibodies. Non-inferiority in seroconversion was assessed using a -5% non-inferiority margin. Antibody concentrations were compared with Kruskal-Wallis tests. Results Of 851 randomized children, 738 were correctly vaccinated, had ≥ 1 follow-up sample, and were included in the intention-to-treat population. Non-inferior seroconversion was observed for all antigens (measles seroconversion: 97.9% in the MMR1YF1 group versus 96.3% in the MMR1YF2 group, a difference of 1.6% [90% CI -1.5, 4.7]; rubella: 97.9% MMR1YF1 versus 94.7% MMR1YF2, a difference of 3.3% [-0.1, 6.7]; mumps: 96.7% MMR1YF1 versus 97.9% MMR1YF2, a difference of -1.3% [-4.1, 1.5]; and YF: 96.3% MMR1YF1 versus 97.5% YF1MMR2, a difference of -1.2% [-4.2, 1.7]). Rubella antibody concentrations and YF titers were significantly lower following co-administration; measles and mumps concentrations were not impacted. Conclusion Effective seroconversion was achieved and was not impacted by the co-administration, although antibody levels for two antigens were lower. The impact of lower antibody levels needs to be weighed against missed opportunities for vaccination to determine optimal timing for MMR and YF vaccine administration. Trial Registration The study was retrospectively registered in ClinicalTrials.gov (NCT03368495) on 11/12/2017.

Background: Data management is fast becoming an essential part of scientific practice, driven by open science and FAIR (findable, accessible, interoperable, and reusable) data sharing requirements. Whilst data management plans (DMPs) are clear to data management experts and data stewards, understandings of their purpose and creation are often obscure to the producers of the data, which in academic environments are often PhD students. Methods: Within the RNAct EU Horizon 2020 ITN project, we engaged the 10 RNAct early-stage researchers (ESRs) in a training project aimed at formulating a DMP. To do so, we used the Data Stewardship Wizard (DSW) framework and modified the existing Life Sciences Knowledge Model into a simplified version aimed at training young scientists, with computational or experimental backgrounds, in core data management principles. We collected feedback from the ESRs during this exercise. Results: Here, we introduce our new life-sciences training DMP template for young scientists. We report and discuss our experiences as principal investigators (PIs) and ESRs during this project and address the typical difficulties that are encountered in developing and understanding a DMP. Conclusions: We found that the DS-wizard can also be an appropriate tool for DMP training, to get terminology and concepts across to researchers. A full training in addition requires an upstream step to present basic DMP concepts and a downstream step to publish a dataset in a (public) repository. Overall, the DS-Wizard tool was essential for our DMP training and we hope our efforts can be used in other projects.

ABSTRACT Antifungal proteins (AFPs) from filamentous fungi are promising biomolecules to control fungal pathogens. Understanding their biological role and mode of action is essential for their future application. AfpB from the citrus fruit pathogen Penicillium digitatum is highly active against fungal phytopathogens, including its native fungus. Our previous data showed that AfpB acts through a multitargeted three-stage process: interaction with the outer mannosylated cell wall, energy-dependent cell internalization, and intracellular actions that result in cell death. Here, we extend these findings by characterizing the functional role of AfpB and its interaction with P. digitatum through transcriptomic studies. For this, we compared the transcriptomic response of AfpB-treated P. digitatum wild type, a ΔafpB mutant, and an AfpB-overproducing strain. Transcriptomic data suggest a multifaceted role for AfpB. Data from the ΔafpB mutant suggested that the afpB gene contributes to the overall homeostasis of the cell. Additionally, these data showed that AfpB represses toxin-encoding genes, and they suggest a link to apoptotic processes. Gene expression and knockout mutants confirmed that genes coding for acetolactate synthase (ALS) and acetolactate decarboxylase (ALD), which belong to the acetoin biosynthetic pathway, contribute to the inhibitory activity of AfpB. Moreover, a gene encoding a previously uncharacterized extracellular tandem repeat peptide (TRP) protein showed high induction in the presence of AfpB, whereas its TRP monomer enhanced AfpB activity. Overall, our study offers a rich source of information to further advance in the characterization of the multifaceted mode of action of AFPs. IMPORTANCE Fungal infections threaten human health worldwide and have a negative impact on food security, damaging crop production and causing animal diseases. At present, only a few classes of fungicides are available due to the complexity of targeting fungi without affecting plant, animal, or human hosts. Moreover, the intensive use of fungicides in agriculture has led to the development of resistance. Therefore, there is an urgent need to develop antifungal biomolecules with new modes of action to fight human-, animal-, and plant-pathogenic fungi. Fungal antifungal proteins (AFPs) offer great potential as new biofungicides to control deleterious fungi. However, current knowledge about their killing mechanism is still limited, which hampers their potential applicability. AfpB from P. digitatum is a promising molecule with potent and specific fungicidal activity. This study further characterizes its mode of action, opening avenues for the development of new antifungals.

In the last few years, gradually more systems have relied on the Global Navigation Satellite System (GNSS) for their correct functioning. These systems include safety-critical applications such as airports or emergency services. Given the wide number of GNSS applications and the current availability of affordable and easily configurable Software-Defined Radio (SDR) devices, GNSS has become the target of numerous Radio Frequency Interference (RFI) attacks. Thus, RFI has become a real threat for GNSS and, hence, for those systems relying on it. With the purpose of detecting, characterizing, and localizing RFI not only in GNSS frequency bands but also in other daily-used frequency bands, a GNSS Interference Monitoring and Detection (GIMAD) prototype has been developed, with special emphasis on its deployment in safety-critical environments such as airports. GIMAD contemplates European Geostationary Navigation Overlay Service (EGNOS) V3 and International Civil Aviation Organization (ICAO) Ground Based Augmentation System (GBAS) RFI masks covering both in-band and out-band RFIs. In addition, GIMAD was tested in a real-field scenario.

New developments in the field of youth studies are calling for a reorientation of discourses of adolescence away from developmental tropes of transition, crisis, and dysfunction, and towards a more fluid sociocultural framework. Meg Rosoff's acclaimed novel "How I Live Now" (2004) achieves a balance that transcends the pitfalls of developmentalism and gestures towards a sociological model of adolescence. In this novel, key developmental ideas such as risk, vulnerability and liminality are not the province of the young characters, but are reframed as the defining features of the dystopic society they inhabit. Rosoff's critical revision of dominant ideas about adolescence is facilitated by her fluid use of different literary traditions ranging from adolescent realism and evacuation fiction to dystopia.

Abstract To assess severity markers and outcomes of patients with systemic sclerosis (SSc) with or without pulmonary arterial hypertension (PAH-SSc/non-PAH-SSc), and the impact of interstitial lung disease (ILD) on PAH-SSc. Non-PAH-SSc patients from the Spanish SSc registry and PAH-SSc patients from the Spanish PAH registry were included. A total of 364 PAH-SSc and 1589 non-PAH-SSc patients were included. PAH-SSc patients had worse NYHA-functional class (NYHA-FC), worse forced vital capacity (FVC) (81.2 ± 20.6% vs 93.6 ± 20.6%, P