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The hallmark of keratoconus is central or paracentral stromal thinning, accompanied by apical protrusion and irregular astigmatism. Patients typically experience variable reductions in visual acuity, image distortion, and increased sensitivity to glare and light. The latter becomes of major interest when patients with keratoconus present with a cataract which contributes to a further visual decline. PURPOSE: To present a case report of a patient who underwent cataract surgery, with implantation of an intraocular implant called pinhole and correction of an irregular corneal astigmatism as a result of keratoconus. METHODS: A report of a rare case, the first implantation of XtraFocus implant in Bulgaria for the correction of keratoconus combined with cataract. RESULTS: All necessary measurements were performed using an iTrace aberrometer and IOL Master 700. The cataract removal was performed by standard phacoemulsification followed by implantation of a pinhole implant in the capsular bag. No complications related to the position of the implant were observed in the postoperative period. Optimal correction of the distance vision and near vision was achieved, and the results were monitored within six months after surgery. CONCLUSION: The pinhole implant was securely positioned in the capsular bag. Well tolerated by the patient, the implant played a key role in effectively overcoming the irregular corneal astigmatism. There is a significant improvement in visual acuity with results satisfying the patient's high expectations.

Purpose: This study assessed the correlation between corneal sensitivity and subjective symptoms in patients with chronic corneal ulcers before and after treatment. Methods: Corneal sensitivity was measured with Cochet-Bonnet aesthesiometry in twenty patients with mean age of53 years SD±20.65. Impression cytology was used to assess conjunctivalization, inflammation and keratinization. The epithelial integrity and stromal reaction were determined by anterior segment OCT. Treatment included either conservative measures or surgical ocular surface reconstruction. A questionnaire on subjective symptoms was implemented in order to obtain comparable data about their severity and effect on everyday life. Results: Mean corneal aesthesiometry was 143.03±81.68 mm/grms before treatment and 72.48±72.80 mm/grms on follow-up (p=0.001). An inverse correlation between age and corneal sensitivity was observed before treatment (p=0.002), but not after (p=0.102). Anterior segment OCT on follow-up demonstrated epithelialized corneal surface, reduced stromal reaction and scar tissue preventing further melting. All tested subjective symptoms demonstrated significant change after treatment except driving. Spearman’s analysis demonstrated a correlation between corneal sensitivity and pain (p=0.033), hyperemia (p=0.009) and driving (p=0.043). The change in corneal sensitivity correlated with tearing reduction (p=0.046) and prolonged tolerance to phone use (p=0.044). Conclusions: Cochet-Bonnet aesthesiometry is a useful diagnostic tool for evaluating corneal nerve function and monitoring the effect of treatment.

Purpose: To determine whether the wearing time of contact lenses affects the condition of the meibomian glands and the tear film breakup time. Material and methods: This is a cross-sectional study involving 150 eyes ( 75 patients) with an age between 18 to 65 years. Five groups were allocated, with distribution criteria being the soft contact lenses wearing time: up to 5 years, from 6 to 10 years, from 11 to 20 years and more than 20 years. All subjects used soft contact lenses daily, at least 5 hours a day and 4 days a week. All patients underwent a thorough ophthalmic examination and non invasive tear film breakup time (NIBUT), and meibomian gland loss (MGL) investigated with Oculus Keratograph 5 M. Results: A statistically significant relation with the soft contact lenses wearing time has been found for the indicator MGL,% (U) (p = 0.025). In the general study of male and female patients, a significant association was only observed in female patients (p = 0.04). A statistically significant relation to the soft contact lenses wearing time has been found for the indicators NIBUT 1, s ( P=0.035) и NIBUT Av, s ( P=0.023). The same relation has been found only in female patients - NIBUT 1, s ( P=0.035] и NIBUT Av, s ( P=0.023). Conclusion: Long-term contact lenses wearing is proportional to the change in gland function and may contribute to the development of dry eye syndrome.

Keratoconus is observed in cases of impaired corneal biochemical activity, leading to secondary thinning and ectasia. Usually the onset is in the second – third decade of life. The acute corneal hydrops occurs when intraocular aqueous passes through a rupture of Descemet membrane (DM) and is characterized with stromal edema. Estimated frequency is 2.5 – 3.0% among the keratoconus patient. Eye rubbing is the major risk factor. In most cases the hydrops persists for 2 -4 months. The resolution is cicatrix/scar formation, but there is a risk for complications such as vascularization, infection and corneal perforation. We present a case of a 23 year old male patient, presenting with complains of reduced and blurry vision in the right eye and photophobia. Visual acuity and full ophthalmological examination was done. UBM was performed of the right eye. The patient received conservative therapy. The acute corneal hydrops occurs when intraocular aqueous passes through a rupture of Descemet membrane (DM) and is characterized with stromal edema. The treatment could be conservative or surgical. The conservative therapy includes topical lubricants, antibiotics, cycloplegics, hyperosmotic solutions, antiglaucoma drugs, topical corticosteroids and nonsteroid anti-inflammatory drugs. Surgical treatment includes intracameral injection of air or gas, but the definitive treatment is penetrating keratoplasty. We describe a newly diagnosed patient with keratoconus, who presents with rare complication - acute corneal hydrops. Differential diagnosis in cases of young patients with acute onset of keratitis, especially young males, should be made with acute corneal hydrops.

Abstract SETD8 is a methyltransferase that is overexpressed in several cancers, which monomethylates H4K20 as well as other non-histone targets such as PCNA or p53. We here report novel SETD8 inhibitors, which were discovered while trying to identify chemicals that prevent 53BP1 foci formation, an event mediated by H4K20 methylation. Consistent with previous reports, SETD8 inhibitors induce p53 expression, although they are equally toxic for p53 proficient or deficient cells. Thermal stability proteomics revealed that the compounds had a particular impact on nucleoli, which was confirmed by fluorescent and electron microscopy. Similarly, Setd8 deletion generated nucleolar stress and impaired ribosome biogenesis, supporting that this was an on-target effect of SETD8 inhibitors. Furthermore, a genome-wide CRISPR screen identified an enrichment of nucleolar factors among those modulating the toxicity of SETD8 inhibitors. Accordingly, the toxicity of SETD8 inhibition correlated with MYC or mTOR activity, key regulators of ribosome biogenesis. Together, our study provides a new class of SETD8 inhibitors and a novel biomarker to identify tumors most likely to respond to this therapy.

Abstract The Polynomial Affine Gravity is an alternative gravitational model, where the interactions are mediated solely by the affine connection, instead of the metric tensor. In this paper, we explore the space of solutions to the field equations when the torsion fields are turned on, in a homogeneous and isotropic (cosmological) scenario. We explore various metric structures that emerge in the space of solutions.

Mexico City emits several thousands of tons of particle matter from transportation and other economic sectors. We collected PM2.5 samples from January to March 2015. The chemical analyses showed that PM2.5 is made up of 39% organic carbon, 12% elemental carbon, 23% metals (Al, Si, S, P, and K), and 5% heavy metals (Pb, Cr, Mn, Zn, and Hg). Ca and Fe were also present in trace concentrations, probably due to the resuspension of soils. Nitrate, sulfate, and ammonium suggest that the southwest of Mexico City, specifically the sampling site, receives more oxidated pollutants from vehicle emissions than other emissions. The chemical analyses show no significant changes in the composition or concentration of particle matter compared to previous studies.

El uso continuo de fertilizantes nitrogenados en exceso genera riesgos ambientales al aumentar en el suelo la acumulación, volatilización y lixiviación de nitratos, que provocan pérdidas y baja eficiencia en la utilización de N. En este estudio, el objetivo fue evaluar la aplicación de nanocompuestos nitrogenados (NCN) como fertilizante de liberación lenta en el suelo y su efecto en el crecimiento del cultivo de lechuga. El NCN se preparó por la sorción de un surfactante catiónico en una arcilla de bentonita. El estudio se realizó en columnas de suelo, los tratamientos evaluados fueron relaciones de NCN y fertilizante convencional (FC) 25/0, 50/0, 75/0 y 100/0, 0/100, 25/75, 50/50 y 75/25. Las variables evaluadas fueron: peso fresco, biomasa seca, área foliar, conductividad eléctrica, concentración de NO3- en lixiviado y hoja, unidades SPAD y NDVI, además de la liberación del NCN en agua desionizada. Los resultados obtenidos indican que después de 40 días los tratamientos con NCN igualaron al control excepto el tratamiento 25/0 que redujo las variables peso fresco 20% y el área foliar 18% con respecto al control 0/100. Los valores de SPAD y NVDI no tuvieron diferencias significativas entre tratamientos. Las relaciones NCN/FC 0/100, 50/50 y 75/25 aumentaron 19% la concentración de nitratos en hojas. El tratamiento 100/0 aumentó biomasa seca total con 48%, 87% el volumen radical y 73% la biomasa seca de raíz. Los resultados de la liberación en agua desionizada confirmaron que el NCN libera gradualmente nitratos y en mayor cantidad que lo calculado. Finalmente, se concluye que el material nanocompuesto tiene el potencial de usarse como fertilizante de lenta liberación al aumentar crecimiento, por lo que podría ser una alternativa para reducir el uso de fertilizantes convencionales y disminuir las pérdidas de nitrógeno en suelo.

On May 26, 2023, the Kinabalu UNESCO Global Geopark obtained the UNESCO Global Geopark status, and it was awarded the UNESCO Triple Crown recognition, making it the third geopark globally to receive this honour. Kinabalu UNESCO Global Geopark is located in Sabah, Malaysian Borneo, and it is the nation's second geopark site. Our study aims to investigate the mediating effect of support for geopark development on the relationship between economic, socio-cultural benefits, and perceived costs of geopark development on community well-being. A total of 301 participants, including those from the Kinabalu UNESCO Global Geopark's three areas of Kota Marudu, Ranau and Kota Belud, participated in the study. The findings indicate that community well-being is positively impacted by economic, sociocultural, and support for geopark development. Moreover, the support for geopark development mediates the relationship between economic and socio-cultural benefits towards community well-being. However, the study reveals that perceived costs of geopark development does not have significant effect on both relationships. Our study suggests that the local community recognizes the benefits of Kinabalu UNESCO Global Geopark in the form of income generation and opportunities for employment. However, because the geopark is still in an early stage of development, it is possible that the local community has not yet become aware of its negative aspects. The study proposes thorough and comprehensive guidelines and policies to be put in place to ensure the sustainability of the geopark regions as well as to continuously improve community well-being.

El creciente compromiso de las empresas con el cumplimiento de los Objetivos de Desarrollo Sostenible de la Agenda 2030 de Naciones Unidas plantea la interrogante sobre cuáles son los beneficios que las empresas pueden obtener de ese compromiso. El objetivo de este trabajo es estudiar la relación entre ese compromiso y la generación de dos tipos de beneficios para las empresas: los económicos y los relacionados con el desempeño de los recursos humanos. Se utilizó información relevada mediante un cuestionario, que fue respondido por una muestra de empresas que participaron en un programa de autoevaluación de la Responsabilidad Social Empresaria. El cuestionario incluye indicadores sobre: 1) aplicación de prácticas específicas relacionadas con los Objetivos de Desarrollo Sostenible; 2) desempeño corporativo (económico y en materia de recursos humanos); 3) protección de los intereses de los accionistas y de la sostenibilidad de la empresa. Para validar los índices construidos con base en los indicadores se utilizó el Alfa de Cronbach y el análisis factorial. La relación entre ellos se estudió mediante correlaciones simples y correlaciones parciales. Se encontró correlación positiva entre compromiso con esos objetivos y desempeño corporativo, y que ese compromiso no implica desproteger los intereses de los accionistas o poner en riesgo la sostenibilidad de la empresa. Además de contribuir al desarrollo en este campo de investigación, estos resultados aportan argumentos a las instituciones que promueven la Agenda 2030 y a los directivos de empresas interesados en involucrar a sus empresas con esta agenda.

This study compares the Melbourne Decision-Making Questionnaire (MDMQ) and the General Decision-Making Style questionnaire (GDMS), two of the most widely used decision-making questionnaires in the literature, in a large age- and sex-weighted general population sample of 714 men (45.7%) and 848 women (54.3%) between 18 and 90 years old. The objective was to evaluate the convergent and construct validity between several aspects of these decision-making style questionnaires. The results indicate that the two questionnaires replicate the factorial structure of four and five factors reported in the original studies, respectively, through exploratory and confirmatory procedures in our cross-cultural context. The domains of both questionnaires that represent a strong or large correlation are Vigilance with Rational (0.50), and Hypervigilance, Buck-passing, and Procrastination with Avoidant (0.45, 0.52, and 0.60). A Structural Equations Model (SEM) between both questionnaires indicates that both latent factors formed by the domains of the MDMQ and the GDMS obtain a correlation of 0.96. It is concluded that the two questionnaires measure similar aspects of the decision-making construct.

Abstract We analyse the asymptotic symmetries of electromagnetism non-minimally coupled to scalar fields, with non-minimal couplings of the Fermi type that occur in extended supergravity models. Our study is carried out at spatial infinity where minimal and non-minimal couplings exhibit very different asymptotic properties: while the former generically cannot be neglected at infinity, the latter can. Electromagnetic non-minimal couplings are in that respect similar to gravitational minimal couplings, which are also asymptotically subdominant. Because the non-minimally interacting model is asymptotic to the free one, its asymptotic symmetries are the same as the ones of the free theory, i.e., described by angle-dependent u(1) gauge transformations. We also analyse the duality symmetry and show that it is broken to its compact subgroup by the asymptotic conditions. Finally, we consider logarithmic gauge transformations and use them to simplify the symmetry algebra.

Abstract COVID-19 is associated with increased risk for cognitive decline but very little is known regarding the neural mechanisms of this risk. We enrolled 49 adults (55% female, mean age = 30.7 ± 8.7), 25 with and 24 without a history of COVID-19 infection. We administered standardized tests of cognitive function and acquired brain connectivity data using MRI. The COVID-19 group demonstrated significantly lower cognitive function (W = 475, p

The performance of the porous gas bearing depends on the geometric characteristics, material, fluid properties, and the properties of the porous media, which is a restrictor that controls the gas flow. Its application in industrial environments must support higher loads, higher supply pressure, and, consequently, higher pressure in the lubricant fluid film. Because porous media has a relatively low elastic modulus, it is necessary to consider its deformation when designing porous gas bearings. The design of porous gas bearings is a multi-objective problem in engineering because the optimization objectives commonly are to maximize the load capacity or static stiffness coefficient and minimize the airflow; these objectives conflict. This work presents a multi-objective optimization algorithm based on the nature-inspired Flower Pollination Algorithm enhanced with Non-Dominated Sorting Genetic Algorithm II. The algorithm is applied to optimize the design of a porous gas bearing, maximizing the resultant force and the static stiffness coefficient and minimizing the airflow. The results indicate a better performance of the Multi-Objective Flower Pollination Algorithm than the Multi-Objective Cuckoo Search. The results show a relatively short running time of 6 min for iterations and a low number of iterations of 50.

p-Coumaric acid (p-CA) is a valuable compound with applications in food additives, cosmetics, and pharmaceuticals. However, traditional production methods are often inefficient and unsustainable. This study focuses on enhancing p-CA production efficiency through the heterologous expression of tyrosine ammonia-lyase (TAL) from Rhodobacter sphaeroides in Pseudomonas putida KT2440. TAL catalyzes the conversion of L-tyrosine into p-CA and ammonia. We engineered P. putida KT2440 to express TAL in a fed-batch fermentation system. Our results demonstrate the following: (i) successful integration of the TAL gene into P. putida KT2440 and (ii) efficient bioconversion of L-tyrosine into p-CA (1381 mg/L) by implementing a pH shift from 7.0 to 8.5 during fed-batch fermentation. This approach highlights the viability of P. putida KT2440 as a host for TAL expression and the successful coupling of fermentation with the pH-shift-mediated bioconversion of L-tyrosine. Our findings underscore the potential of genetically modified P. putida for sustainable p-CA production and encourage further research to optimize bioconversion steps and fermentation conditions.

The lack of information creates problems for Colombian small-scale farmers, as it impedes them from selling at fair prices and knowing efficient production techniques. Around the world, many technological interventions have proven helpful in reducing information asymmetries. Therefore, we proposed a technological scheme based on a genetic algorithm and a natural language processor (NLP) that enables producers to obtain knowledge through information processing. Also, we ran fieldwork in twenty municipalities and a survey among 500 Colombian cocoa small-scale farmers in different regions in Colombia. This fieldwork helps us determine small-scale farmers' necessities, market conditions, and the relevance of an Artificial Intelligence (AI) tool. The results have shown that AI methodologies could improve the economic conditions of small farmers by providing access to information on prices, weather, and production techniques. The fieldwork evidence that a technological tool is a good option only if there are dynamic trade cycles. AI tools could transmit and process information to become producers' knowledge and help them evolve into collective strategies. The methodology, which combines genetic algorithms, NLP, and fieldwork for cocoa farming, is a novelty that contributes to information asymmetry reduction. We contributed to the literature about adopting AI tools to develop cocoa small-scale farming better.

Abstract Given a manifold M $$ \mathbbm{M} $$ admitting a maximally supersymmetric consistent truncation, we show how to formulate new consistent truncations by restricting to a set of Kaluza-Klein modes on M $$ \mathbbm{M} $$ invariant under some subgroup of the group of isometries of M $$ \mathbbm{M} $$ . These truncations may involve either finite or infinite sets of modes. We provide their global description using exceptional generalised geometry to construct a ‘deformed’ generalised parallelisation starting with that on M $$ \mathbbm{M} $$ . This allows us to explicitly embed known consistent truncations directly into exceptional generalised geometry/exceptional field theory, and to obtain the equations governing situations where the consistent truncation retains an infinite tower of modes.

Abstract Background Herbal medicines used for male sexual disorders are widespread across the globe and have been noted as likely candidates for adulteration. To assure access to safe and quality herbal products, this study aimed at sampling some herbal capsules indicated for male vitality for quality analytical checks. Methods Herbal capsules sampled from two regions were subjected to physicochemical assessment, using pharmacopeial and regulatory standards. Microbial quality analysis was also performed on the selected products. A validated HPLC method for simultaneous analysis of sildenafil citrate and tadalafil was used to detect and quantify the possible presence of phosphodiesterase inhibitors in the selected products. Results Out of a total of 57 herbal capsules, 19 were indicated for male sexual related illnesses of which only 8 fulfilled the inclusion criteria of being used exclusively for male vitality. The majority (62.5%) of the herbal products failed the weight uniformity test but all of them disintegrated within the acceptable limit of 30 min. The moisture and heavy metal contents were within limits of acceptability. Majority (87.5%) of the herbal products failed the test for the aerobic bacteria count; however, none of the isolated bacteria was pathogenic. Sildenafil citrate was detected in the majority (87.5%) of the herbal products in concentrations of 0.98–33.95 mg/g. Two products contained both sildenafil and tadalafil. High batch-to-batch variability was recorded in some physicochemical parameters and pharmaceutical adulterants. Conclusion High incidence of quality fails and adulteration of herbal capsules for sexual disorders observed means there is a real risk of unintended dosing with phosphodiesterase inhibitors. This represents a public health issue and necessitates tighter monitoring of production standards by the regulator.

Abstract Background Antidiabetic therapies are effective, but could indirectly modify the inflammatory response in the ocular microenvironment; therefore, a study was developed to evaluate the inflammatory cytokine profile in the vitreous humor of diabetic patients with retinopathy under treatment with antidiabetic drugs. Methods Observational, comparative, retrospective, cross-sectional study. Interleukins 1β, 6, 8, 10, and tumor necrosis factor-alpha (TNFα) were evaluated in the vitreous humor obtained from patients with type 2 diabetes mellitus, proliferative diabetic retinopathy, and concomitant retinal detachment or vitreous hemorrhage, and who were already on antidiabetic treatment with insulin or metformin + glibenclamide. The quantification analysis of each cytokine was performed by the cytometric bead array (CBA) technique; medians and interquartile ranges were obtained, and the results were compared between groups using the Mann-Whitney U test, where a p-value

Abstract This paper presents the exponentiated alpha-power log-logistic (EAPLL) distribution, which extends the log-logistic distribution. The EAPLL distribution emphasizes its suitability for survival data modeling by providing analytical simplicity and accommodating both monotone and non-monotone failure rates. We derive some of its mathematical properties and test eight estimation methods using an extensive simulation study. To determine the best estimation approach, we rank mean estimates, mean square errors, and average absolute biases on a partial and overall ranking. Furthermore, we use the EAPLL distribution to examine three real-life survival data sets, demonstrating its superior performance over competing log-logistic distributions. This study adds vital insights to survival analysis methodology and provides a solid framework for modeling various survival data scenarios.

Abstract Even during the third wave of the COVID-19 pandemic health professionals were facing mental health challenges. The aim of this study was to examine the mental health of doctors, nurses and other professional groups in Europe and to identify differences between the professional groups. We conducted a cross-sectional online survey in 8 European countries. We asked for demographic data, whether the participants were exposed to COVID-19 at work, for main information sources about the pandemic, the Depression Anxiety Stress Scales (DASS-21), and major stressors. A MANCOVA was carried out to find predictors of mental health among health care professionals. The sample (N = 1398) consisted of 237 physicians, 459 nurses, and 351 other healthcare professionals and 351 non-medical professionals with no direct involvement in patient care. The mean mental health of all groups was affected to a mild degree. Major predictors for depression and anxiety were the profession group with higher scores especially in the group of the nurses and working directly with COVID-patients. In the third wave of the COVID-19 pandemic, the psychological burden on health professionals has remained high, with being nurse and working directly with COVID19 patients being particular risk factors for mental distress. We found as a main result that nurses scored significantly higher on depression and anxiety than practitioners.

Abstract Smartphone applications are one of the main delivery modalities in digital health. Many of these mHealth apps use gamification to engage users, improve user experience, and achieve better health outcomes. Yet, it remains unclear whether gamified approaches help to deliver effective, safe, and clinically beneficial products to users. This study examines the compliance of 69 gamified mHealth apps with the EU Medical Device Regulation and assesses the specific risks arising from the gamified nature of these apps. Of the identified apps, 32 (46.4%) were considered non-medical devices; seven (10.1%) were already cleared/approved by the regulatory authorities, and 31 (44.9%) apps were assessed as likely non-compliant or potentially non-compliant with regulatory requirements. These applications and one approved application were assessed as on the market without the required regulatory approvals. According to our analysis, a higher proportion of these apps would be classified as medical devices in the US. The level of risk posed by gamification remains ambiguous. While most apps showed only a weak link between the degree of gamification and potential risks, this link was stronger for those apps with a high degree of gamification or an immersive game experience.

Abstract Background Metagenomics is a powerful approach for the detection of unknown and novel pathogens. Workflows based on Illumina short-read sequencing are becoming established in diagnostic laboratories. However, high sequencing depth requirements, long turnaround times, and limited sensitivity hinder broader adoption. We investigated whether we could overcome these limitations using protocols based on untargeted sequencing with Oxford Nanopore Technologies (ONT), which offers real-time data acquisition and analysis, or a targeted panel approach, which allows the selective sequencing of known pathogens and could improve sensitivity. Methods We evaluated detection of viruses with readily available untargeted metagenomic workflows using Illumina and ONT, and an Illumina-based enrichment approach using the Twist Bioscience Comprehensive Viral Research Panel (CVRP), which targets 3153 viruses. We tested samples consisting of a dilution series of a six-virus mock community in a human DNA/RNA background, designed to resemble clinical specimens with low microbial abundance and high host content. Protocols were designed to retain the host transcriptome, since this could help confirm the absence of infectious agents. We further compared the performance of commonly used taxonomic classifiers. Results Capture with the Twist CVRP increased sensitivity by at least 10–100-fold over untargeted sequencing, making it suitable for the detection of low viral loads (60 genome copies per ml (gc/ml)), but additional methods may be needed in a diagnostic setting to detect untargeted organisms. While untargeted ONT had good sensitivity at high viral loads (60,000 gc/ml), at lower viral loads (600–6000 gc/ml), longer and more costly sequencing runs would be required to achieve sensitivities comparable to the untargeted Illumina protocol. Untargeted ONT provided better specificity than untargeted Illumina sequencing. However, the application of robust thresholds standardized results between taxonomic classifiers. Host gene expression analysis is optimal with untargeted Illumina sequencing but possible with both the CVRP and ONT. Conclusions Metagenomics has the potential to become standard-of-care in diagnostics and is a powerful tool for the discovery of emerging pathogens. Untargeted Illumina and ONT metagenomics and capture with the Twist CVRP have different advantages with respect to sensitivity, specificity, turnaround time and cost, and the optimal method will depend on the clinical context.

Abstract Background Out-of-hospital cardiac arrest (OHCA) survival in the UK remains overall poor with fewer than 10% of patients surviving to hospital discharge. Extracorporeal cardiopulmonary resuscitation (ECPR) is a developing therapy option that can improve survival in select patients if treatment begins within an hour. Clinicians' perspectives are a pivotal consideration to the development of effective systems for OHCA ECPR, but they have been infrequently explored. This study investigates clinicians' views on the barriers and facilitators to establishing effective systems to facilitate transport of OHCA patients for in-hospital ECPR. Methods In January 2023, Thames Valley Air Ambulance (TVAA) and Harefield Hospital developed an ECPR partnership pathway for conveyance of OHCA patients for in-hospital ECPR. The authors of this study conducted a survey of clinicians across both services looking to identify clear barriers and positive contributors to the effective implementation of the programme. The survey included questions about technical and non-technical barriers and facilitators, with free-text responses analysed thematically. Results Responses were received from 14 pre-hospital TVAA critical care and 9 in-hospital clinicians’ representative of various roles and experiences. Data analysis revealed 10 key themes and 19 subthemes. The interconnected themes, identified by pre-hospital TVAA critical care clinicians as important barriers or facilitators in this ECPR system included educational programmes; collectiveness in effort and culture; teamwork; inter-service communication; concurrent activity; and clarity of procedures. Themes from in-hospital clinicians’ responses were distilled into key considerations focusing on learning and marginal gains, standardising and simplifying protocols, training and simulation; and nurturing effective teams. Conclusion This study identified several clear themes and subthemes from clinical experience that should be considered when developing and modelling an ECPR system for OHCA. These insights may inform future development of ECPR programmes for OHCA in other centres. Key recommendations identified include prioritising education and training (including regular simulations), standardising a ‘pitstop style’ handover process, establishing clear roles during the cannulation process and developing standardised protocols and selection criteria. This study also provides insight into the feasibility of using pre-hospital critical care teams for intra-arrest patient retrieval in the pre-hospital arena.

Abstract Background CD155 is a transmembrane protein that inhibits antitumor immune response and represents a predictor of worse prognosis in non-small-cell lung cancer (NSCLC). However, it remains unexplored its association with clinical characteristics and genomic status of Latin American patients. This study characterizes the CD155 expression and its clinical implications in this population. Methods Tissue biopsies from 86 patients with locally-advanced or metastatic NSCLC were assessed for CD155 protein expression, ALK rearrangements and EGFR mutations. Cutoff values for high CD155 expression (CD155high) were determined from receiver operating characteristic (ROC) curves according to 2-year survival. It was evaluated its association with clinicopathological features, median progression-free survival (mPFS) and overall survival (mOS). Results the cutoff score for CD155high was 155 in the entire cohort and in patients without oncogenic alterations, and it was 110 in patients with oncogenic alterations. Eighty-four patients (97.7%) were CD155 positive, of which fifty-six (65.0%) had CD155high. EGFR L858R mutation related to lower CD155 IHC score than exon 19 deletion. Individuals with CD155high showed a shorter mOS (13.0 vs. 30.8 months; HR: 1.96 [95% CI, 1.15–3.35]; p = 0.014). Patients without oncogenic alterations having a CD155high displayed shorter mPFS (1.6 vs. 6.4 months, HR: 2.09 [95% CI, 1.06–4.20]; p = 0.034) and mOS (2.9 vs. 23.1 months; HR: 1.27 [95% CI, 1.07– 4.42]; p = 0.032). Patients with oncogenic alterations having CD155high only showed a trend to shorter mOS (26.3 vs. 52.0 months; HR: 2.39 [95% CI, 0.98–5.83]; p = 0.058). Conclusion CD155high is a predictor of worse outcomes in patients with advanced NSCLC, predominantly among those without oncogenic alterations. CD155 could be a potential biomarker and a molecular target in patients with poor responses to current therapies.

Abstract We analysed a large dataset consisting of 457 soil profiles of Andisols and Ultisols of volcanic origin compared to 60 non-volcanic soils. We hypothesised that soil pH has a greater impact on the development of Al-organomineral complexes in volcanic soils compared to non-volcanic soils, in the latter, the silt and clay fractions play a crucial role. Soil pH >4.5 strongly influenced the formation of Al-organomineral complexes in volcanic soils, while an increase in allophane content led to a decrease in SOC. Ultisols with more crystalline clays, such as halloysite and disordered kaolinite, the pH had a weaker impact and there was no effect on non-volcanic soils. Instead, a positive correlation (R2 = 0.63, p

La Región de las Américas ha experimentado históricamente desigualdades sociales enraizadas en el colonialismo, las cuales se reflejan y reproducen en el ámbito de la salud. La incursión de la pandemia de COVID-19 afectó a toda la Región, pero golpeó con mayor fuerza a los grupos socialmente más desaventajados, y agravó las inequidades en salud. Bajo la premisa que las pandemias no son fenómenos socialmente neutrales, en este informe especial se analizan los impactos desiguales de la pandemia desde distintas perspectivas –histórica, epidemiológica, política, social, económica, ambiental y poblacional. Se ofrecen aquí reflexiones críticas sobre las implicaciones negativas de las desigualdades para el bienestar, no solo de las poblaciones más afectadas, sino de la sociedad en su conjunto. Se concluye con recomendaciones estratégicas para progresar hacia la equidad en salud en el escenario pospandémico. Se destaca la importancia de avanzar en la madurez de los sistemas de información para el monitoreo de la equidad en salud, la resiliencia de los sistemas de salud, y la implementación de políticas y prácticas explícitas dirigidas a eliminar las inequidades en salud. Se espera que todo lo anterior allane el camino hacia la prosperidad y el desarrollo sostenible en la Región.

Abstract Maintaining patients’ temperature during surgery is beneficial since hypothermia has been linked with perioperative complications. Laparoscopic surgery involves the insufflation of carbon dioxide (CO2) into the peritoneal cavity and has become the standard in many surgical indications since it is associated with better and faster recovery. However, the use of cold and dry CO2 insufflation can lead to perioperative hypothermia. We aimed to assess the difference between intraperitoneal and core temperatures during laparoscopic surgery and evaluate the influence of duration and CO2 insufflation volume by fitting a mixed generalized additive model. In this prospective observational single-center cohort trial, we included patients aged over 17 with American Society of Anesthesiology risk scores I to III undergoing laparoscopic surgery. Anesthesia, ventilation, and analgesia followed standard protocols, while patients received active warming using blankets and warmed fluids. Temperature data, CO2 ventilation parameters, and intraabdominal pressure were collected. We recruited 51 patients. The core temperature was maintained above 36 °C and progressively raised toward 37 °C as pneumoperitoneum time passed. In contrast, the intraperitoneal temperature decreased, thus creating a widening difference from 0.4 [25th–75th percentile: 0.2–0.8] °C at the beginning to 2.3 [2.1–2.3] °C after 240 min. Pneumoperitoneum duration and CO2 insufflation volume significantly increased this temperature difference (P

Abstract The challenge of transforming organized DNA structures into their metallized counterparts persists in the scientific field. In this context, utilizing DNA molecules modified with 7-deazapurine, provides a transformative solution. In this study, we present the solution structure of a DNA duplex that can be transformed into its metallized equivalent while retaining the natural base pairing arrangement through the creation of silver-modified Watson-Crick base pairs. Unlike previously documented X-ray structures, our research demonstrates the feasibility of preserving the intrinsic DNA self-assembly while incorporating AgI into the double helix, illustrating that the binding of silver does not disrupt the canonical base-pairing organization. Moreover, in our case, the uninterrupted AgI chain deviates from forming conventional straight linear chains; instead, it adheres to a helical arrangement dictated by the underlying DNA structure. This research challenges conventional assumptions and opens the door to precisely design structures based on the organization of highly stable Ag-DNA assemblies.

El estudio de costos catastróficos que experimentan las personas afectadas por tuberculosis realizado en Colombia durante la pandemia de COVID-19 trajo consigo la oportunidad de implementar encuestas telefónicas como medio para la recopilación de información. Lo anterior se constituye como una innovación metodológica en los estándares establecidos por la Organización Mundial de la Salud (OMS) que, para este tipo de estudios, suelen tener base en el empleo de encuestas cara a cara con los pacientes que acuden a las instalaciones de salud. El diseño del estudio, sus objetivos y metodología fueron adaptados del manual práctico para la realización de encuestas de costos de la tuberculosis de la OMS. Se seleccionaron 1 065 personas afectadas por tuberculosis como participantes del estudio, a quienes se les administró de manera telefónica el cuestionario estándar adaptado al contexto colombiano. Fue posible obtener datos estructurados sobre los costos directos e indirectos que enfrentan los pacientes con tuberculosis y sus familias; de manera general, se observó que todas las variables de recopilación alcanzaron una completitud mayor a 80%, con un tiempo promedio de encuesta de 40 minutos y una tasa de rechazo de 8%. La metodología de encuestas telefónicas desarrollada para determinar la línea base del estudio de costos catastróficos en Colombia resultó innovadora por el formato telefónico, que mantiene los estándares de información requerida para permitir estimaciones comparables a nivel internacional, y es un medio útil en la generación de resultados estandarizados en eventos en los cuales existe limitación para la realización de encuestas cara a cara.

Phragmipedium kovachii is a species of orchid endemic to the Amazonas and San Martín regions. Unfortunately, its excessive extraction has made it a critically endangered species. In this study, we performed next-generation sequencing of P. kovachii (GenBank accession number OR348669) and assembled its complete chloroplast genome. The complete chloroplast genome of P. kovachii is A + T-rich (64.3%), measuring 152,918 bp in length. This plastid genome contains a total of 124 genes (77 protein-coding genes, 39 tRNAs, and eight rRNAs) and five pseudogenes, including a pair of inverted repeats (IRs) 25,116 bp in size and separated by a large single-copy (LSC) region of 89,216 bp and a small single-copy (SSC) region of 13,470 bp. This genome has a typical quadripartite organization following the structure of other Orchidaceae plastomes. Phylogenetic analyses revealed the close relationship between P. kovachii and P. besseae. This study contributes to the understanding of the phylogenetic relationships of the monophyletic group Cypripedioideae.

Introduction: Emergency departments are the primary entry point for emergencies in the public healthcare system. Resource constraints burden a large proportion of the public hospital emergency departments, which includes limited access to radiological services. Emergency point-of-care ultrasound provides a tool capable of bridging this gap. The Eastern Cape is yet to describe the utilisation of emergency point-of-care ultrasound in any of its emergency departments. Methods: Frere Hospital initiated a clinical audit to assess the utilisation of emergency point-of-care ultrasound in its emergency department in 2022. This study was a retrospective review of the audit between 01 November 2022 until 28 February 2023. Data from the handwritten register regarding patient's presenting complaints and provisional diagnoses was also captured during the study period to draw comparisons between burden of disease and use of emergency point-of-care ultrasound. Results: A total of 9501 patients attended Frere Hospital's emergency department over the study period with 492 emergency point-of-care ultrasounds performed (overall utilisation rate 5.2 %). The five credentialed emergency point-of-care ultrasound providers performed the majority (n = 360, 73.2 %) of the applications, compared to 132 (26.8 %) performed by the seven non-credentialed providers. The extended focused abdominal sonography in trauma (eFAST) was the most frequently performed application (n = 140, 28.5 %). Conclusion: Emergency point-of-care ultrasound is underutilised in Frere Hospital's emergency department. The varied casemix requires upskilling of clinicians in emergency point-of-care ultrasound to suit the burden of disease experienced in the department. Ongoing emergency point-of-care ultrasound training, credentialing and research is important to ensure appropriate and quality emergency point-of-care ultrasound utilisation.

AIM: To investigate the effect of adding autologous serum eye drops to the postoperative regime after amniotic membrane transplantation for severe persistent corneal ulcers. METHODS: Forty eyes of 40 patients with persistent corneal ulcers were randomly assigned to artificial tears (sodium hyaluronate 0.2%, ATs group, n=20) or autologous serum eye drops (ASEDs, n=20) following treatment with amniotic membrane transplantation. Digital slit lamp images were acquired from all patients before and 30d post treatment. The area with fibrovascular tissue was calculated using Image J. Central corneal sensitivity was assessed by Cochet-Bonnet aesthesiometry before and one month after treatment. Scar tissue transparency was assessed with a novel optical densitometry. RESULTS: Mean age of patients was 61.65±16.47y and 57.3±19.11y in the ATs group and ASEDs group, respectively. Twenty-two male and 18 female patients were included in the study. The improvement in visual acuity was significantly greater in the ASEDs group (0.14±0.04) than the ATs (0.08±0.04; P=0.00046). Cochet-Bonnet aesthesiometry improved significantly after treatment with a similar rate between groups. There were no statistically significant differences in the area of postoperative fibrovascular tissue between the two groups (P=0.082). The success rate in the two groups was similar. The difference in densitometry between the ATs and ASEDs group was statistically significant (P=0.042) with greater reduction from baseline in the ASEDS group. CONCLUSION: Autologous serum eye drops can lead to better visual acuity, more stable results and improved densitometry and should be considered in the postoperative care following amniotic membrane transplantation.

Osteoarthritis (OA) is a major clinical challenge, and effective disease-modifying drugs for OA are still lacking due to the complicated pathology and scattered treatment targets. Effective early treatments are urgently needed to prevent OA progression. The excessive amount of transforming growth factor β (TGFβ) is one of the major causes of synovial fibrosis and subchondral bone sclerosis, and such pathogenic changes in early OA precede cartilage damage. Herein we report a novel strategy of intra-articular sustained-release of pirfenidone (PFD), a clinically-approved TGFβ inhibitor, to achieve disease-modifying effects on early OA joints. We found that PFD effectively restored the mineralization in the presence of excessive amount of TGFβ1 (as those levels found in patients’ synovial fluid). A monthly injection strategy was then designed of using poly lactic-co-glycolic acid (PLGA) microparticles and hyaluronic acid (HA) solution to enable a sustained release of PFD (the “PLGA-PFD + HA” strategy). This strategy effectively regulated OA progression in destabilization of the medial meniscus (DMM)- induced OA mice model, including preventing subchondral bone loss in early OA and subchondral bone sclerosis in late OA, and reduced synovitis and pain with cartilage preservation effects. This finding suggests the promising clinical application of PFD as a novel disease-modifying OA drug.

Both the mineralogy and geochemistry of coal mine waste presents environmental and social challenges while simultaneously offering the potential source for recovery of metals, including critical raw materials (CRMs). Assessing these challenges and opportunities requires effective waste management strategies and comprehensive material characterization. This study deals with the integration of analytical data obtained from various portable sensor technologies. Infrared reflection spectroscopy (covering a wide wavelength range of 0.4 to 15 µm), and geochemical x-ray fluorescence (XRF) were utilized to differentiate between samples belonging to various geological lithologies and quantify elements of interest. Therefore, we developed a methodological framework that encompasses data integration and machine learning techniques. The model developed using the infrared data predicts the Sr concentration with a model accuracy of R2 = 0.77 for the testing dataset; however, the model performances decreased for predicting other elements such as Pb, Zn, Y, and Th. Despite these limitations, the approach demonstrates better performance in discriminating materials based on both mineralogical and geochemical compositions. Overall, the developed methodology, enables rapid and in-situ determination of coal mine waste composition, providing insights into waste composition that are directly linked to potential environmental impact, and the possible recovery of economically valuable metals.

Introduction. Pension systems are a key element of social protection for the elderly. They are designed to provide senior citizens with stable income not from work. However, pension systems currently being developed in Europe are increasingly exposing the working-age population to the risk of poverty in old age. The European pension paradigm strives for an adequate level of pension payments and builds financial protection against poverty, while the future evolution of wages and prices remains unknown for Europe as a whole. Methods. Scientific research is based on general and special methods of scientific cognition. In the process of forming the concept of the scientific article, modern scientific methods of studying economic and social phenomena were used, including methods of system-structural, functional, factorial and comparative analysis, as well as categorical, logical and structural analysis and synthesis, detailing and generalization, grouping and comparison, identification of cause-and-effect relationships. The authors proceed from an understanding of the scientific hypothesis of reforming the pension system, which ensures long-term investment by the working-age population with income in the future. The empirical base of the study was made up of current data from cross-country comparative studies of Europe in terms of typology of state pension systems. Results. Based on the functional method of cognition, the authors of the scientific article systematize the main types of state pension systems of the European Union, representing the complex content of the indicator value of pension payments. It is noted that in the context of reforming the pension systems of the European Union countries, the reorganization of the functional and ideological components of pension provision, aimed at protecting consumers of pension savings, makes it possible to increase the socio-economic standard of living. Although EU pension systems differ in many respects, they all have one common problem - finding ways to maintain the financial sustainability of the budgetary system while paying pensions in the long term against the backdrop of an aging population and the problem of increasing the ratio of pensioners to the working-age population.

Echocardiography is recommended as a first-line diagnostic tool in patients with premature ventricular contractions (PVCs). However, standard echocardiography is not always able to identify early signs of myocardial dysfunction and cardiac magnetic resonance (CMR) may offer additional information. Since CMR has lower accessibility and higher cost compared to echocardiography, we wanted to evaluate how additional echocardiographic parameters, not included in routine examinations, perform compared to CMR in detecting signs of cardiomyopathy in PVC patients with normal findings at a standard echocardiogram. We compared CMR findings and results from an extended echocardiographic examination in thirty-nine patients who had a high PVC burden. The additional echocardiographic parameters were global longitudinal strain, mechanical dispersion, ventricular–arterial coupling, integrated backscatter and left atrial activation time. Eleven patients had pathological findings at CMR. The additional echocardiographic parameters did not significantly differ between patients with or without CMR findings. However, several patients with normal CMR findings showed signs of ventricular dysfunction when evaluated with the additional echocardiographic parameters, which suggests that these could possibly offer supplementary information in the assessment of PVC patients.

Based on several alternative approaches there is by now some evidence suggesting that there is a negative relationship between exports and domestic sales. But in the majority of cases this regularity has focused on industrialized countries. While the external trade of African countries faces numerous challenges, with the low level of intra regional trade and the concentration of exports in some raw materials. Thus the aim of this paper to assess this new export channel for African countries. We then estimate a dynamic panel model with an error correction mechanism of the export market share (the difference between exports and foreign demand) for the six economies of the CEMAC zone between 1974 and 2021. Through the use of instrumental variables (2SLS) we address the role of endogeneity. According to the results, such link is prominent for African countries such the CEMAC countries where domestic demand impacts effectively negatively exports in CEMAC with a negative elasticity of around 53 %. When allowing for an asymmetric relationship between domestic sales and exports the results remain unchanged suggesting that a significant relationship between domestic demand and exports performance still holds.

RESUMO Como ferramenta de prova e ferramenta de governo, a Estatística desempenhou papéis fundamentais no desenvolvimento da ciência, nos modos de ação do Estado, e em vários ramos da economia. O desenvolvimento das tecnologias digitais no século XXI conduziu a uma produção crescente de dados e ao surgimento de um novo campo algorítmico de conhecimento e ação. Por meio de pesquisa empírica fundamentada em contribuições teóricas da sociologia da quantificação e dos Estudos de Ciência e Tecnologia, este artigo analisa algumas transformações nas estatísticas públicas produzidas pelos Institutos Nacionais de Estatística. Isso se baseia em uma investigação da recente promoção de Big Data e Inteligência Artificial para estatísticas oficiais no contexto das Nações Unidas.

Este artículo indaga la intervención social del Estado entrerriano durante el gobierno del radical del pueblo Carlos R. Contín a través de una agencia estatal primordial en su gestión de gobierno, el Ministerio de Acción Social. Para el equipo de gobierno, el Estado provincial debía privilegiar su intervención social en la sociedad entrerriana para mejorar los servicios sociales y asistenciales para que una mayor proporción de la población estuviera mejor protegida de los males de la desigualdad. En definitiva, el gobernador decía perseguir como finalidad de su política de gobierno la igualación de oportunidades sociales, económicas y políticas, razón por la que se produjo una reorganización del esquema ministerial y un ajuste en la organización administrativa en función de una nueva estrategia de intervención estatal en los asuntos públicos considerados trascendentes y prioritarios. Sin duda, el Ministerio de Acción Social fue el mecanismo institucional privilegiado para tal fin.

Abstract Objectives Cryptococcosis remains a severe global health concern, underscoring the urgent need for rapid and reliable diagnostic solutions. Point-of-care tests (POCTs), such as the cryptococcal antigen semi-quantitative (CrAgSQ) lateral flow assay (LFA), offer promise in addressing this challenge. However, their subjective interpretation poses a limitation. Our objectives encompass the development and validation of a digital platform based on Artificial Intelligence (AI), assessing its semi-quantitative LFA interpretation performance, and exploring its potential to quantify CrAg concentrations directly from LFA images. Methods We tested 53 cryptococcal antigen (CrAg) concentrations spanning from 0 to 5000 ng/ml. A total of 318 CrAgSQ LFAs were inoculated and systematically photographed twice, employing two distinct smartphones, resulting in a dataset of 1272 images. We developed an AI algorithm designed for the automated interpretation of CrAgSQ LFAs. Concurrently, we explored the relationship between quantified test line intensities and CrAg concentrations. Results Our algorithm surpasses visual reading in sensitivity, and shows fewer discrepancies (p

A partir del primer trimestre del 2020 las economías de todo el mundo iniciaron una desaceleración en su actividad debido al confinamiento generado por la pandemia del COVID-19. En varias economías, se implementaron políticas monetarias y fiscales expansivas para tratar de evitar una caída drástica del desempleo y la producción. El objetivo de este trabajo es analizar la relación entre los niveles de inflación y desempleo al inicio de la pandemia, tanto de México, como de Estados Unidos de Norteamérica y, evaluar si existe una diferencia de dicha relación entre ambos países. Se utilizaron datos mensuales de la inflación y el desempleo desde enero de 2016 a diciembre 2020, considerando un Modelo Aditivo Generalizado (MAG) para estudiar la relación entre la inflación y el desempleo en ambos países. Los resultados esperados sugerirían la existencia evidente de la curva de Phillips en el corto plazo en Estados Unidos, no así en México, por lo que no justificaría en este último una política fiscal expansiva para estimular la economía. Se concluye que políticas económicas ortodoxas para estimular a la economía y disminuir el desempleo no forzosamente tendrían los efectos esperados en el caso de México y sí en un incremento de precios.

Abstract Background Non-pharmacological interventions have proven effective at alleviating depression and anxiety symptoms in older adults. Methodological refinement and testing of these interventions in new contexts are needed on a small scale before their effectiveness and implementation can be evaluated. The purpose of this pilot study is to assess the feasibility of a future large-scale trial comparing an adapted mental health multi-component evidence-based intervention (VIDACTIVA) versus standard care for older adults experiencing depression symptoms in urban, resource-limited settings in Lima, Peru. Furthermore, this study will explore the acceptability, feasibility, and fidelity of implementing the intervention. Methods We will conduct an open-label, mixed methods pilot feasibility study with two parallel groups. A total of 64 older adults, stratified by sex, will be randomized at a 1:1 ratio to either the “intervention” or “control.” Participants will be followed for 22 weeks after enrollment. Those in the intervention group will receive eight VIDACTIVA sessions administered by community health workers (CHWs) over 14 weeks, with an additional eight weeks of follow-up. Participants in the control group will receive two psychoeducation sessions from a study fieldworker and will be directed to health care centers. Standard care does not involve CHWs. We will evaluate screening rates, recruitment strategies, retention rates, the acceptability of randomization, and assessments. Additionally, we will assess preliminary implementation outcomes—acceptability, feasibility, and fidelity—from the perspectives of CHWs (interventionists), older adults (main participants), older adults’ relatives, and healthcare professionals. Discussion If the findings from this feasibility trial are favorable, a fully powered randomized controlled trial will be conducted to evaluate `both the effectiveness and implementation of the intervention. This research will make a substantial contribution to the field of mental health in older adults, particularly by emphasizing a meticulous examination and documentation of the implementation process. By doing so, this study will offer valuable methodologies and metrics for adapting and assessing mental health interventions tailored to the unique needs of older adults in resource-constrained contexts and diverse cultural settings. Trial registration The current trial registration number is NCT06065020, which was registered on 26th September 2023.

Abstract KRAS belongs to a family of small GTPases that act as binary switches upstream of several signalling cascades, controlling proliferation and survival of cells. Mutations in KRAS drive oncogenesis, especially in pancreatic, lung, and colorectal cancers (CRC). Although historic attempts at targeting mutant KRAS with small molecule inhibitors have proven challenging, there are recent successes with the G12C, and G12D mutations. However, clinically important RAS mutations such as G12V, G13D, Q61L, and A146T, remain elusive drug targets, and insights to their structural landscape is of critical importance to develop novel, and effective therapeutic concepts. We present a fully open, P-loop exposing conformer of KRAS G13D by X-ray crystallography at 1.4–2.4 Å resolution in Mg2+-free phosphate and malonate buffers. The G13D conformer has the switch-I region displaced in an upright position leaving the catalytic core fully exposed. To prove that this state is druggable, we developed a P-loop-targeting monoclonal antibody (mAb). The mAb displayed high-affinity binding to G13D and was shown using high resolution fluorescence microscopy to be spontaneously taken up by G13D-mutated HCT 116 cells (human CRC derived) by macropinocytosis. The mAb inhibited KRAS signalling in phosphoproteomic and genomic studies. Taken together, the data propose novel druggable space of G13D that is reachable in the cellular context. It is our hope that these findings will stimulate attempts to drug this fully open state G13D conformer using mAbs or other modalities.

We report a new breeding site of Ara militaris mexicanus (Ridway, 1915), Military Macaw, in the state of Puebla in the Alto Balsas river basin, Mexico. The breeding site is in the Cañón Grande area along the Nexapa River. Observed temporality and breeding behaviors agree with the recorded breeding season of this species in Central Mexico. Notably, the region has no current designation as a protected natural area for conservation. We recommend collaboration with the local community to initiate efforts towards designate the Alto Balsas river basin as a protected natural area.

Abstract The dynamics of first-order phase transitions in strongly coupled systems are relevant in a variety of systems, from heavy ion collisions to the early universe. Holographic theories can be used to model these systems, with fluctuations usually suppressed. In this case the system can come close to a spinodal point where theory and experiments indicate that the behaviour should be similar to a critical point of a second-order phase transition. We study this question using a simple holographic model and confirm that there is critical slowing down and scaling behaviour close to the spinodal point, with precise quantitative estimates. In addition, we determine the start of the scaling regime for the breakdown of quasistatic evolution when the temperature of a thermal bath is slowly decreased across the transition. We also extend the analysis to the dynamics of second-order phase transitions and strong crossovers.

Abstract The morphometric characterization of large-scale depressions, with high-resolution contributions and in urban contexts, has been carried out in the cities of Cozumel and Playa del Carmen. For Tulum, the inputs have been insufficient in identifying depressions at a detailed level. This research aimed to analyze and characterize the negative exokarstic relief of the city of Tulum through morphometric parameters and urban elements that contribute to the knowledge of the human-nature relationship. From the DEM ALOS PALSAR, contour lines, elevation models, slopes, and shadows were extracted, which allowed the identification of depressions, topographic profiles, and the calculation of morphometric indices; subsequently, the distribution of depressions was analyzed concerning urban elements. The identified depressions were classified into uvalas, sinkholes, and poljes. The analysis of the topographic profiles allowed us to recognize units in the shape of "V" (64%), "U" (19%), and "Hoya" (17%). The highest concentration of type V depressions is observed in the city's central area, characterized by a medium and high population density, as well as the centralization of commercial and public establishments. The detailed characterization of depressions is a planning and management tool for the territory.

Abstract Tuberculosis (TB) remains a leading cause of death, but antibiotic treatments for tuberculous meningitis, the deadliest form of TB, are based on those developed for pulmonary TB and not optimized for brain penetration. Here, we perform first-in-human dynamic 18F-pretomanid positron emission tomography (PET) in eight human subjects to visualize 18F-pretomanid biodistribution as concentration-time exposures in multiple compartments (NCT05609552), demonstrating preferential brain versus lung tissue partitioning. Preferential, antibiotic-specific partitioning into brain or lung tissues of several antibiotics, active against multidrug resistant (MDR) Mycobacterium tuberculosis strains, are confirmed in experimentally-infected mice and rabbits, using dynamic PET with chemically identical antibiotic radioanalogs, and postmortem mass spectrometry measurements. PET-facilitated pharmacokinetic modeling predicts human dosing necessary to attain therapeutic brain exposures. These data are used to design optimized, pretomanid-based regimens which are evaluated at human equipotent dosing in a mouse model of TB meningitis, demonstrating excellent bactericidal activity without an increase in intracerebral inflammation or brain injury. Importantly, several antibiotic regimens demonstrate discordant activities in brain and lung tissues in the same animal, correlating with tissue antibiotic exposures. These data provide a mechanistic basis for the compartmentalized activities of antibiotic regimens, with important implications for developing treatments for meningitis and other infections in compartments with unique antibiotic penetration.

Abstract Point defect qubits in semiconductors have demonstrated their outstanding capabilities for high spatial resolution sensing generating broad multidisciplinary interest. Hexagonal boron nitride (hBN) hosting point defect qubits have recently opened up new horizons for quantum sensing by implementing sensing foils. The sensitivity of point defect sensors in hBN is currently limited by the linewidth of the magnetic resonance signal, which is broadened due to strong hyperfine couplings. Here, we report on a vacancy-related spin qubit with an inherently low symmetry configuration, the VB2 center, giving rise to a reduced magnetic resonance linewidth at zero magnetic fields. The VB2 center is also equipped with a classical memory that can be utilized for storing population information. Using scanning transmission electron microscopy imaging, we confirm the existence of the VB2 configuration in free-standing monolayer hBN.