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Abstract MicroRNAs (miRNAs) have been implicated in human disorders, from cancers to infectious diseases. Targeting miRNAs or their target genes with small molecules offers opportunities to modulate dysregulated cellular processes linked to diseases. Yet, predicting small molecules associated with miRNAs remains challenging due to the small size of small molecule-miRNA datasets. Herein, we develop a generalized deep learning framework, sChemNET, for predicting small molecules affecting miRNA bioactivity based on chemical structure and sequence information. sChemNET overcomes the limitation of sparse chemical information by an objective function that allows the neural network to learn chemical space from a large body of chemical structures yet unknown to affect miRNAs. We experimentally validated small molecules predicted to act on miR-451 or its targets and tested their role in erythrocyte maturation during zebrafish embryogenesis. We also tested small molecules targeting the miR-181 network and other miRNAs using in-vitro and in-vivo experiments. We demonstrate that our machine-learning framework can predict bioactive small molecules targeting miRNAs or their targets in humans and other mammalian organisms.

Abstract Current influenza vaccines are strain-specific and require frequent updates to combat new strains, making a broadly protective influenza vaccine (BPIV) highly desirable. A promising strategy is to induce T-cell responses against internal proteins conserved across influenza strains. In this study, pH1N1 pre-exposed pigs were immunized by aerosol using viral vectored vaccines (ChAdOx2 and MVA) expressing matrix (M1) and nucleoprotein (NP). Following H3N2 challenge, all immunizations (M1, NP or NPM1) reduced lung pathology, but M1 alone offered the greatest protection. NP or NPM1 immunization induced both T-cell and antibody responses. M1 immunization generated no detectable antibodies but elicited M1-specific T-cell responses, suggesting T cell-mediated protection. Additionally, a single aerosol immunization with the ChAdOx vaccine encoding M1, NP and neuraminidase reduced lung pathology. These findings provide insights into BPIV development using a relevant large natural host, the pig.

[Purpose] This paper seeks to develop, from the current doctrine and regulations, some guidelines for the debate that the Law will have to give shortly, about a new type of personality and its attributes those humanoid robots that are capable of questioning their initial programming and take actions on your own. [Methodology] It is a work developed through a legal-hermeneutical and documentary analysis methodology. The authors used legal doctrine as sources, especially books and book chapters, research results, as well as articles in scientific journals evaluated by peers and indexed in legal databases. To develop the objective of the paper, the authors outlined several stages, first, the search and recovery of information, second a critical analysis, and finally the interpretation of all of the above. [Findings] The authors present their results, on the one hand, with an analysis of the personality of humanoid robots, and on the other, with some reflections on their attributes. The paper presents a critical study on the legal situation of the regulation of the autonomy of the will; which must be understood as the materialized faculty of self-determination that these robots could have in making their own decisions and concerning the rights, obligations, and responsibilities that the Law decides to recognize. All of the above, from artificial intelligence systems that are not subordinated to their initial programming, or the immediate and permanent control of a natural person.

Abstract The development of computational tools for the systematic prediction of metabolic vulnerabilities of cancer cells constitutes a central question in systems biology. Here, we present gmctool, a freely accessible online tool that allows us to accomplish this task in a simple, efficient and intuitive environment. gmctool exploits the concept of genetic Minimal Cut Sets (gMCSs), a theoretical approach to synthetic lethality based on genome-scale metabolic networks, including a unique database of synthetic lethals computed from Human1, the most recent metabolic reconstruction of human cells. gmctool introduces qualitative and quantitative improvements over our previously developed algorithms to predict, visualize and analyze metabolic vulnerabilities in cancer, demonstrating a superior performance than competing algorithms. A detailed illustration of gmctool is presented for multiple myeloma (MM), an incurable hematological malignancy. We provide in vitro experimental evidence for the essentiality of CTPS1 (CTPS synthase) and UAP1 (UDP-N-Acetylglucosamine Pyrophosphorylase 1) in specific MM patient subgroups.

Abstract Background Benzodiazepines are frequently prescribed drugs; however, their prolonged use can lead to tolerance, dependence, and other adverse effects. Despite these risks, long-term use remains common, presenting a public health concern. This study aims to explore the beliefs and opinions held by the public regarding benzodiazepines, as understanding these perspectives may provide insights into their usage patterns. Methods We collected public tweets published in English between January 1, 2019, and October 31, 2020, that mentioned benzodiazepines. The content of each tweet and the characteristics of the users were analyzed using a mixed-method approach, including manual analysis and semi-supervised machine learning. Results Over half of the Twitter users highlighted the efficacy of benzodiazepines, with minimal discussion of their side effects. The most active participants in these conversations were patients and their families, with health professionals and institutions being notably absent. Additionally, the drugs most frequently mentioned corresponded with those most commonly prescribed by healthcare professionals. Conclusions Social media platforms offer valuable insights into users’ experiences and opinions regarding medications. Notably, the sentiment towards benzodiazepines is predominantly positive, with users viewing them as effective while rarely mentioning side effects. This analysis underscores the need to educate physicians, patients, and their families about the potential risks associated with benzodiazepine use and to promote clinical guidelines that support the proper management of these medications. Clinical trial number Not applicable.

ABSTRACT Introduction: Although nerves and vessels of the penis play important role in erection, there are few studies on their development in human fetus. Therefore, the objective of the present study is to analyze, quantitatively, in the corpora cavernosa and corpus spongiosum, the development of the nerves and vessels in the fetal penis at different gestational ages. Material and Methods: Fifty-six fresh, macroscopically normal human fetuses aged from 13 to 36 weeks post-conception (WPC) were used. Gestational age was determined by the foot length criterion. Penises were immediately fixed in 10% formalin, and routinely processed for paraffin embedding, after which tissue sections from the mid-shaft were obtained. We used immunohistochemical staining to analyze the nerves and vessels in the corpus cavernous and in the corpus spongiosum. These elements were identified and quantified as percentage by using the Image-J software. Results: The quantitative analysis showed that the percentage of nerves varied from 3.03% to 20.35% in the corpora cavernosa and from 1.89% to 23.88% in the corpus spongiosum. The linear regression analysis indicated that nerves growth (incidence) in the corpora cavernosa and corpus spongiosum correlated significantly and positively with fetal age (r2=0.9421, p

Abstract In the era of renewed space exploration, comprehending the effects of the space environment on human health, particularly for deep space missions, is crucial. While extensive research exists on the impacts of spaceflight, there is a gap regarding female reproductive risks. We hypothesize that space stressors could have enduring effects on female health, potentially increasing risks for future pregnancies upon return to Earth, particularly related to small-for-gestational-age (SGA) fetuses. To address this, we identify a shared microRNA (miRNA) signature between SGA and the space environment, conserved across humans and mice. These miRNAs target genes and pathways relevant to diseases and development. Employing a machine learning approach, we identify potential FDA-approved drugs to mitigate these risks, including estrogen and progesterone receptor antagonists, vitamin D receptor antagonists, and DNA polymerase inhibitors. This study underscores potential pregnancy-related health risks for female astronauts and proposes pharmaceutical interventions to counteract the impact of space travel on female health.

Abstract Background Sarcopenia and low areal bone mineral density (aBMD) are prevalent musculoskeletal complications after paediatric cancer treatment. However, their relationship has not been examined in young paediatric cancers survivors. This study aimed to evaluate aBMD differences according to sarcopenia status and the risk of low aBMD Z‐score in young paediatric cancer survivors with sarcopenia confirmed/probable. Methods This cross‐sectional study included 116 paediatric cancer survivors (12.1 ± 3.3 years old; 42.2% female). Handgrip strength was used to assessed muscle strength. Dual‐energy X‐ray absorptiometry estimated aBMD (g/cm2) and appendicular lean mass index (ALMI, kg/m2). ‘No sarcopenia’ was defined when muscle strength was >decile 2. ‘Sarcopenia probable’ was defined when muscle strength was ≤ decile 2 and ALMI Z‐score was > −1.5 standard deviation (SD). ‘Sarcopenia confirmed’ was defined when muscle strength was ≤ decile 2 and ALMI Z‐score ≤ −1.5 SD. Analysis of covariance and logistic regression, adjusted for time from treatment completion, radiotherapy exposure, calcium intake, and physical activity, was used to evaluate aBMD and estimate the odds ratios (ORs) of low aBMD (aBMD Z‐score < −1.0). Results Survivors with sarcopenia confirmed had significantly lower aBMD than those without sarcopenia at total body (−1.2 [95% CI: −1.5 to −0.8] vs. 0.2 [−0.2 to 0.6], P

Adolescence is a period of special significance for the development of personal and social values. Positive adolescent development (PYD) can be an ideal perspective from which to promote values in young people through their sports practice. The aim of the study was to adapt and analyse the measurement properties of the Values Scale for Positive Youth Development for use in the context of sport in young athletes. A total of 599 adolescents, competitors of different sports modalities, participated in the study. Confirmatory factor analysis and reliability and invariance analyses were performed. The results confirmed a good model fit, with adjustment indexes (CFI, GFI and AGFI) above 0.90 and error (RMSEA and SRMR) below 0.08. The factor loadings above 0.50 were obtained for all items. Adequate reliability of the scales was also confirmed, between 0.72 and 0.89, and gender, age and sport invariance were confirmed. In conclusion, the analysed scale is a valid and reliable instrument with adequate psychometric properties, which makes it an appropriate assessment tool to be used in sports contexts, based on the positive adolescent development approach.

Abstract Neuroligin-2 (Nlgn2) is a key synaptic adhesion protein at virtually all GABAergic synapses, which recruits GABAARs by promoting assembly of the postsynaptic gephyrin scaffold. Intriguingly, loss of Nlgn2 differentially affects subsets of GABAergic synapses, indicating that synapse-specific interactors and redundancies define its function, but the nature of these interactions remain poorly understood. Here we investigated how Nlgn2 function in hippocampal area CA1 is modulated by two proposed interaction partners, MDGA1 and MDGA2. We show that loss of MDGA1 expression, but not heterozygous deletion of MDGA2, ameliorates the abnormal cytosolic gephyrin aggregation, the reduction in inhibitory synaptic transmission and the exacerbated anxiety-related behaviour characterizing Nlgn2 knockout (KO) mice. Additionally, combined Nlgn2 and MDGA1 deletion causes an exacerbated layer-specific loss of gephyrin puncta. Given that both Nlgn2 and the MDGA1 have been correlated with many psychiatric disorders, our data support the notion that cytosolic gephyrin aggregation may represent an interesting target for novel therapeutic strategies.

Abstract Background Polymorphisms are common in nature, but they are rarely shared among closely related species. Polymorphisms could originate through convergence, ancestral polymorphism, or introgression. Although shared neutral genomic variation across species is commonplace, few examples of shared functional traits exist. The blue-orange petal color polymorphisms in two closely related species, Lysimachia monelli and L. arvensis were investigated with UV-vis reflectance spectra, flavonoid biochemistry, and transcriptome comparisons followed by climate niche analysis. Results Similar color morphs between species have nearly identical reflectance spectra, flavonoid biochemistry, and ABP gene expression patterns. Transcriptome comparisons reveal two orange-specific genes directly involved in both blue-orange color polymorphisms: DFR-2 specificity redirects flux from the malvidin to the pelargonidin while BZ1-2 stabilizes the pelargonidin with glucose, producing the orange pelargonidin 3-glucoside. Moreover, a reduction of F3’5’H expression in orange petals also favors pelargonidin production. The climate niches for each color morph are the same between the two species for three temperature characteristics but differ for four precipitation variables. Conclusions The similarities in reflectance spectra, biochemistry, and ABP genes suggest that a single shift from blue-to-orange shared by both lineages is the most plausible explanation. Our evidence suggests that this persistent flower color polymorphism may represent an ancestrally polymorphic trait that has transcended speciation, yet future analyses are necessary to confidently reject the alternative hypotheses.

Abstract Background The handstand is an essential skill in acrobatic sports. This skill requires the athlete to maintain an inverted upright stance with only the hands supported, which requires a great effort of muscular coordination and motor control. Several factors influence the ability to control the posture, including fatigue, which is a bit studied constraint of handstand performance. Research question With the aim to find out whether variability in movement control can be an indicator of fatigue, the present study was carried out. Method Fourteen male acrobatic gymnasts were required to perform handstands. The time series for analyzing variability were capturing using Force Platforms, which is a traditional laboratory instrument, and Inertial Measurement Units (IMU), which is a more recent and less widely used, but more accessible tool. For this purpose, an analysis of the amount of variability was carried out, using the standard deviation. And analysis of the structure of variability (or complexity), using Detrended Fluctuation Analysis (DFA) and Fuzzy Entropy (FuEn). Results Our results reveal that fatigue causes significant increases in the amount of variability in the medio-lateral axis on the force platform, and in the IMU located in the area of the L5 vertebra. These changes are accompanied by increased auto-correlation in the medio-lateral axis of the force platform, and more unpredictable behavior in the L5 IMU.

This research explores the efficacy of the YOLOR (You Only Learn One Representation) algorithm integrated with the Deep Sort algorithm for real-time vehicle detection, classification, and counting in Morelia, Mexico. The study aims to enhance traffic monitoring and management by leveraging advanced deep learning techniques. The methodology involves deploying the YOLOR model at six key monitoring stations, with varying confidence levels and pre-trained weights, to evaluate its performance across diverse traffic conditions. The results demonstrate that the model is effective compared to other approaches in classifying multiple vehicle types. The combination of YOLOR and Deep Sort proves effective in tracking vehicles and distinguishing between different types, providing valuable data for optimizing traffic flow and infrastructure planning. This innovative approach offers a scalable and precise solution for intelligent traffic management, setting new methodologies for urban traffic monitoring systems.

ABSTRACT Purpose: The gubernaculum seems to be the most important anatomical structure in the testicular migration process. The objective of this paper is to review current literature regarding the role of gubernaculum testis nerves in testicular migration. We conducted a comprehensive literature review about the gubernaculum testis innervation. A PubMed database search was performed in April 2024, focusing on gubernaculum testis and cryptorchidism and genitofemoral nerve (GFN) and calcitonin gene-related peptide (CGRP) gene. The gubernaculum has its own nerve supply, the GFN, descending on the anteromedial surface of the psoas muscle from L1-L2 segments. The second phase of testicular descent is regulated by androgens and CGRP, released from the sensory nucleus of the GFN. The GFN doesn't directly play a role in testicular migration but there is a theory that shows a regulatory function of this nerve in hormonal action during this process. The gubernaculum testis has important structural alterations during the testicular migration and the genitofemoral nerve and CGRP gene are of great importance in this process. The genitofemoral nerve provides motor innervation to the cremaster muscle and gubernaculum, which helps regulate the position of the testes within the scrotum.

Background/Objective: Stiff person syndrome (SPS) and type 1 diabetes (T1D) are heterogeneous disorders characterized by antibodies (Abs) against glutamic acid decarboxylase (GAD). Case Report: We describe 2 patients with T1D and autoimmune thyroid disease who presented with muscle rigidity and intermittent spasms that affected gait and with elevated circulating anti-GAD titers. Classic SPS and stiff limb syndrome were diagnosed, respectively. Muscle spasms resolved with immunotherapy and muscle relaxants in both patients, and the ability to ambulate without an assistive device was restored in 1 patient. Patients also had brittle diabetes with high glycemic variability, requiring the use of flash glucose monitoring with an insulin pump and a second-generation basal insulin analog, respectively. Discussion: GAD Ab–associated syndromes include SPS, T1D, and other endocrinopathies. The clinical heterogeneity implies variable susceptibility of γ-aminobutyric acid-ergic neurons and pancreatic beta cells to anti-GAD or other autoantibodies. Conclusion: Our case series represent the heterogeneity in natural history, clinical course, and response to therapy in patients with Abs against GAD-spectrum disorders.

Background:: Deep brain stimulation of the central thalamus (CT-DBS) has potential for modulating states of consciousness, but it can also trigger electrographic seizures, including poly-spike-wave trains (PSWT). Objectives:: To report the probability of inducing PSWTs during CT-DBS in awake, freely-moving mice. Methods:: Mice were implanted with electrodes to deliver unilateral and bilateral CT-DBS at different frequencies while recording electroencephalogram (EEG). We titrated stimulation current by gradually increasing it at each frequency until a PSWT appeared. Subsequent stimulations to test arousal modulation were performed at the current one step below the current that caused a PSWT during titration. Results:: In 2.21% of the test stimulations (10 out of 12 mice), CT-DBS caused PSWTs at currents lower than the titrated current, including currents as low as 20 μA. Conclusion:: Our study found a small but significant probability of inducing PSWTs even after titration and at relatively low currents. EEG should be closely monitored for electrographic seizures when performing CT-DBS in both research and clinical settings.

Campylobacter jejuni plays a significant role in human health, food production, and veterinary practice. Biofilm formation is a likely mechanism explaining the survival of C. jejuni in seemingly unfavourable environments, but the underlying mechanisms are poorly understood. We propose a mathematical model to unify various observations regarding C. jejuni biofilm formation. Specifically, we present a cellular automaton with stochastic dynamics that describes both the probability of biofilm initiation and its subsequent growth. Our model incorporates fundamental processes such as cell rearrangement, diffusion of chemical compounds, accumulation of extracellular material, cell growth, lysis, and deactivation due to nutrient scarcity. The model predicts an optimal nutrient concentration that enhances population survival, revealing a trade-off where higher nutrient levels may harm individual cells but benefit the overall population. Our results suggest that the lower biofilm accumulation observed experimentally in aerobic conditions compared to microaerobic conditions may be due to a reduced surface invasion probability of individual cells. However, cells that do manage to invade can generate microcolonies of a similar size under both aerobic and microaerobic conditions. These findings provide new insights into the survival probability and size of C. jejuni biofilms, suggesting potential targets for controlling its biofilm formation in various environments.

In this paper, the convergence of the spectral parameter power series method, proposed by Kravchenko, is performed for the Sturm–Liouville equation with Kurzweil–Henstock integrable coefficients. Numerical simulations of some examples are also presented to validate the performance of the method.

Abstract Background Albuminuria is considered an early and sensitive marker of kidney dysfunction, but also an independent cardiovascular risk factor. Considering the possible relationship among metabolic liver disease, cardiovascular disease and chronic kidney disease, we aimed to evaluate the risk of developing albuminuria regarding the presence of epicardial adipose tissue and the steatotic liver disease status. Methods A retrospective long-term longitudinal study including 181 patients was carried out. Epicardial adipose tissue and steatotic liver disease were assessed by computed tomography. The presence of albuminuria at follow-up was defined as the outcome. Results After a median follow up of 11.2 years, steatotic liver disease (HR 3.15; 95% CI, 1.20–8.26; p = 0.02) and excess amount of epicardial adipose tissue (HR 6.12; 95% CI, 1.69–22.19; p = 0.006) were associated with an increased risk of albuminuria after adjustment for visceral adipose tissue, sex, age, weight status, type 2 diabetes, prediabetes, hypertriglyceridemia, hypercholesterolemia, arterial hypertension, and cardiovascular prevention treatment at baseline. The presence of both conditions was associated with a higher risk of developing albuminuria compared to having steatotic liver disease alone (HR 5.91; 95% CI 1.15–30.41, p = 0.033). Compared with the first tertile of visceral adipose tissue, the proportion of subjects with liver steatosis and abnormal epicardial adipose tissue was significantly higher in the second and third tertile. We found a significant correlation between epicardial fat and steatotic liver disease (rho = 0.43 [p

Abstract Background The Point-of-Care Diabetic Retinopathy Examination Program (POCDREP) was initiated in 2015 at the University of Pittsburgh/UPMC in response to low diabetic retinopathy (DR) examination rates, a condition affecting a quarter of people with diabetes mellitus (PwDM) and leading to blindness. Early detection and treatment are critical with DR prevalence projected to triple by 2050. Approximately, half of PwDM in the U.S. undergo yearly examinations, and there are reported varying follow-up rates with eye care professionals, with limited data on the factors influencing these trends. POCDREP aimed to address screening and follow-up gap, partnering with diverse healthcare entities, including primary care sites, free clinics, and federally qualified health centers. Methods A non-concurrent retrospective cohort study spanning 2015–2018 examined data using electronic health records of patients who underwent retinal imaging. Imaging was performed using 31 cameras across various settings, with results interpreted by ophthalmologists. Follow-up recommendations were made for cases with vision-threatening DR (VTDR), incidental findings, or indeterminate results. Factors influencing follow-up were analyzed, including demographic, clinical, and imaging-related variables. We assessed the findings at follow-up of patients with indeterminate results. Results Out of 7,733 examinations (6,242 patients), 32.25% were recommended for follow-up. Among these, 5.57% were classified as having VTDR, 14.34% had other ocular findings such as suspected glaucoma and age-related macular degeneration (AMD), and 12.13% were indeterminate. Of those recommended for follow-up, only 30.87% were assessed by eye care within six months. Older age, marriage, and severe DR were associated with higher odds of following up. Almost two thirds (64.35%) of the patients with indeterminate exams were found with a vision-threatening disease at follow-up. Conclusion The six-month follow-up rate was found to be suboptimal. Influential factors for follow-up included age, marital status, and the severity of diabetic retinopathy (DR). While the program successfully identified a range of ocular conditions, screening initiatives must extend beyond mere disease detection. Ensuring patient follow-up is crucial to DR preventing programs mission. Recommended strategies to improve follow-up adherence include education, incentives, and personalized interventions. Additional research is necessary to pinpoint modifiable factors that impact adherence and to develop targeted interventions.

RESUMEN Introducción y objetivos: La mayoría de los pacientes con embolia pulmonar (EP) aguda reciben únicamente anticoagulación. La reperfusión es necesaria en los pacientes con EP de alto riesgo y en una minoría de pacientes con EP de riesgo intermedio-alto. La trombólisis sistémica (TS) es el tratamiento de reperfusión de primera línea, pero debido a las contraindicaciones y a la preocupación por las hemorragias graves, las terapias dirigidas por catéter (TDC) están surgiendo como una alternativa adecuada. El objetivo del presente estudio fue detectar predictores del uso de TDC con respecto a otras terapias en pacientes con EP aguda. Métodos: Este registro incluyó pacientes consecutivos con EP de riesgo intermedio y alto en dos centros terciarios, con un equipo de respuesta a la EP, desde 2014 hasta 2022. Los pacientes se agruparon según la terapia inicial: solo anticoagulación, TDC o TS; y se evaluaron los predictores de selección de terapia y variables de seguridad. Resultados: Se incluyó a un total de 274 pacientes. De ellos, 112 recibieron solo anticoagulación, 96 recibieron TS como tratamiento primario y 66 fueron sometidos a TDC en un primer momento. Las comorbilidades fueron mayores en el grupo TDC que en los otros dos. Los pacientes sometidos a TS o TDC presentaban mayores parámetros de gravedad de la EP al ingreso hospitalario. Tras el análisis multivariable, el índice de comorbilidad de Charlson (OR = 1,29; IC95%, 1,05-1,59), la cirugía reciente (OR = 11,07; IC95%, 3,07-39,87) y la EP central bilateral (OR = 2,42; IC95%, 1,10-5,32) siguieron siendo predictores independientes del uso de TDC. En cuanto a los resultados precoces de seguridad, sólo se produjeron hemorragias intracraneales en el grupo TS (1,8% de los pacientes). Conclusiones: Este registro contemporáneo utilizó TDC como terapia inicial en el 24% de los pacientes de riesgo intermedio y alto, principalmente en pacientes comórbidos y posquirúrgicos. La TDC fue una alternativa segura y eficaz al tratamiento médico en pacientes seleccionados.

ABSTRACT Introduction and objectives: Most patients with acute pulmonary embolism (PE) receive anticoagulation only. Reperfusion is required in high-risk and a minority of intermediate-risk PE patients. Systemic thrombolysis (ST) is the first-line reperfusion therapy, but due to contraindications and major bleeding concerns, the use of catheter-directed therapies (CDT) is increasing as a suitable alternative. The objective of the present study was to detect predictors of the use of CDT compared with other therapies in patients with acute PE. Methods: This registry included consecutive intermediate- and high-risk PE patients in 2 tertiary centers with a 24/7 PE response team from 2014 to 2022. The patients were grouped according to the primary treatment: anticoagulation only, CDT, or ST. We evaluated predictors of treatment assignment and safety endpoints. Results: A total of 274 patients were included. Of them, 112 received anticoagulation only, 96 received ST as the primary treatment, and 66 underwent CDT first. Comorbidities were higher in the CDT group than in the other 2 groups. Patients undergoing ST/CDT had higher PE severity parameters at hospital admission. On multivariable analysis, independent predictors for the use of CDT were Charlson Comorbidity Index (OR, 1.29; 95%CI, 1.05-1.59), recent surgery (OR, 11.07; 95%CI, 3.07-39.87), and bilateral central PE (OR, 2.42; 95%CI, 1.10-5.32). Analysis of early safety outcomes showed that intracranial bleeding occurred only in the ST group (1.8% of patients). Conclusions: This contemporary registry used CDT as the primary treatment in 24% of intermediate- and high-risk patients, mainly in comorbid and postsurgical patients. CDT was a safe and effective alternative to medical therapy in selected patients.

Abstract Extreme hydrological and thermal regimes characterize the Mediterranean zone and can influence the phenology of greenhouse gas (GHG) emissions in reservoirs. Our study examined the seasonal changes in GHG emissions of a shallow, eutrophic, hardwater reservoir in Spain. We observed distinctive seasonal patterns for each gas. CH4 emissions substantially increased during stratification, influenced predominantly by the increase in water temperature, net ecosystem production, and the decline in reservoir mean depth. N2O emissions mirrored CH4's seasonal trend, significantly correlating to water temperature, wind speed, and gross primary production. Conversely, CO2 emissions decreased during stratification and displayed a quadratic, rather than a linear relationship with water temperature—an unexpected deviation from CH4 and N2O emission patterns—likely associated with photosynthetic uptake of bicarbonate and formation of intracellular calcite that might be exported to sediments. This investigation highlights the imperative of integrating these idiosyncratic patterns into GHG emissions models, enhancing their predictive power.

IntroductionPatients with coronary artery disease (CAD) have a higher risk of developing cognitive impairment and mental health disorders compared to the general population. Physical exercise might improve their brain health. The overall goal of the HEART-BRAIN randomized controlled trial (RCT) is to investigate the effects of different types of exercise on brain health outcomes in patients with CAD, and the underlying mechanisms.MethodsThis three-arm, single-blinded RCT will include 90 patients with CAD (50–75 years). Participants will be randomized into: (1) control group—usual care (n = 30), (2) aerobic high-intensity interval training (HIIT) (n = 30), or (3) HIIT combined with resistance exercise training (n = 30). The 12-week intervention includes 3 supervised sessions (45-min each) per week for the exercise groups. Outcomes will be assessed at baseline and post-intervention. The primary outcome is to determine changes in cerebral blood flow assessed by magnetic resonance imaging. Secondary outcomes include changes in brain vascularization, cognitive measures (i.e., general cognition, executive function and episodic memory), and cardiorespiratory fitness. Additional health-related outcomes, and several potential mediators and moderators will be investigated (i.e., brain structure and function, cardiovascular and brain-based biomarkers, hemodynamics, physical function, body composition, mental health, and lifestyle behavior).ConclusionThe HEART-BRAIN RCT will provide novel insights on how exercise can impact brain health in patients with CAD and the potential mechanisms explaining the heart-brain connection, such as changes in cerebral blood flow. The results may have important clinical implications by increasing the evidence on the effectiveness of exercise-based strategies to delay cognitive decline in this high-risk population.Clinical trial registrationClinicalTrials.gov, identifier [NCT06214624].

Abstract Optical forces and torques offer the route towards full degree-of-freedom manipulation of matter. Exploiting structured light has led to the discovery of gradient and curl forces, and nontrivial optomechanical manifestations, such as negative and lateral optical forces. Here, we uncover the existence of two fundamental torque components, which originate from the reactive helicity gradient and momentum curl of light, and which represent the rotational analogues to the gradient and curl forces, respectively. Based on the two components, we introduce and demonstrate the concept of lateral optical torques, which act transversely to the spin of illumination. The orbital angular momentum of vortex beams is shown to couple to the curl torque, promising a path to extreme torque enhancement or achieving negative optical torques. These results highlight the intersection between the areas of structured light, Mie-tronics and rotational optomechanics, even inspiring new paths of manipulation in acoustics and hydrodynamics.

Abstract We present a flora and fauna dataset for the Mira-Mataje binational basins. This is an area shared between southwestern Colombia and northwestern Ecuador, where both the Chocó and Tropical Andes biodiversity hotspots converge. We systematized data from 120 sources in the Darwin Core Archive (DwC-A) standard and geospatial vector data format for geographic information systems (GIS) (shapefiles). Sources included natural history museums, published literature, and citizen science repositories across 13 countries. The resulting database has 33,460 records from 6,821 species, of which 540 have been recorded as endemic, and 612 as threatened. The diversity represented in the dataset is equivalent to 10% of the total plant species and 26% of the total terrestrial vertebrate species in both hotspots. The dataset can be used to estimate and compare biodiversity patterns with environmental parameters and provide value to ecosystems, ecoregions, and protected areas. The dataset is a baseline for future assessments of biodiversity in the face of environmental degradation, climate change, and accelerated extinction processes.

Abstract Light carries intrinsic spin angular momentum (SAM) when the electric or magnetic field vector rotates over time. A familiar vector equation calculates the direction of light’s SAM density using the right-hand rule with reference to the electric and magnetic polarisation ellipses. Using Maxwell’s equations, this vector equation can be decomposed into a sum of two distinct terms, akin to the well-known Poynting vector decomposition into orbital and spin currents. We present the first general study of this spin decomposition, showing that the two terms, which we call canonical and Poynting spin, are chiral analogies to the canonical and spin momenta of light in its interaction with matter. Like canonical momentum, canonical spin is directly measurable. Both canonical and Poynting spin incorporate spatial variation of the electric and magnetic fields and are influenced by optical vortices. The decomposition allows us to show that a linearly polarised vortex beam, which has no total SAM, can nevertheless exert longitudinal chiral pressure due to equal and opposite canonical and Poynting spins.

This research focuses on analyzing the effect of high employment temporality on technical efficiency and productivity. Previous literature points out a set of benefits and drawbacks related to fixed-term contracts. To ascertain the influence of temporality on efficiency, the critical case of the hotel sector in the Canary Islands is studied where the temporary employment rate (40%). So this paper explores the effect of temporary employment on technical efficiency in the hotel sector of the Canary Islands (a Spanish region). The magnitude of this case study can be clearly checked, given that the Canary Islands is the most popular region in the European Union visited by residents. A production stochastic frontier is estimated by distinguishing between two types of employment: permanent and temporary. Results suggest that high levels of temporality tend to reduce technical efficiency and productivity. A high conversion rate from temporary to permanent jobs seems to increase efficiency. The contribution of this paper is threefold: (i) filling the gap in the literature on the influence of temporary employment on technical efficiency, evaluating its effect for a case study where job temporality is dramatically high, (ii) partial factor productivities for permanent and fixed-term workers are estimated, and (iii) exploring the influence of less studied variables like the level of conversion from fixed-term to permanent employment on efficiency. The findings can be relevant for human resources management for firms where temporary rates are high. Human resource management should consider the type of labor contracts used, as well as the perspectives of conversion into permanent ones for their temporary workers, given their potential influence in technical efficiency, labour productivity, and firm performance.

Tuberculosis is a highly lethal bacterial disease worldwide caused by Mycobacterium tuberculosis (Mtb). Caespitate is a phytochemical isolated from Helichrysum caespititium, a plant used in African traditional medicine that shows anti-tubercular activity, but its mode of action remains unknown. It is suggested that there are four potential targets in Mtb, specifically in the H37Rv strain: InhA, MabA, and UGM, enzymes involved in the formation of Mtb’s cell wall, and PanK, which plays a role in cell growth. Two caespitate conformational structures from DFT conformational analysis in the gas phase (GC) and in solution with DMSO (CS) were selected. Molecular docking calculations, MM/GBSA analysis, and ADME parameter evaluations were performed. The docking results suggest that CS is the preferred caespitate conformation when interacting with PanK and UGM. In both cases, the two intramolecular hydrogen bonds characteristic of caespitate’s molecular structure were maintained to achieve the most stable complexes. The MM/GBSA study confirmed that PanK/caespitate and UGM/caespitate were the most stable complexes. Caespitate showed favorable pharmacokinetic characteristics, suggesting rapid absorption, permeability, and high bioavailability. Additionally, it is proposed that caespitate may exhibit antibacterial and antimonial activity. This research lays the foundation for the design of anti-tuberculosis drugs from natural sources, especially by identifying potential drug targets in Mtb.

This article employed pupillometry as a non-invasive technique to analyze pupillary light reflex (PLR) using LED flash stimuli. Particularly, for the experiments, only the red LED with a wavelength of 600 nm served as the light stimulation source. To stabilize the initial pupil size, a pre-stimulus (PRE) period of 3 s was implemented, followed by a 1 s stimulation period (ON) and a 4 s post-stimulus period (POST). Moreover, an experimental, low-cost pupillometer prototype was designed to capture pupillary images of 13 participants. The prototype consists of a 2-megapixel web camera and a lighting system comprising infrared and RGB LEDs for image capture in low-light conditions and stimulus induction, respectively. The study reveals several characteristic features for classifying the phenomenon, notably the mobility of Hjórth parameters, achieving classification percentages ranging from 97% to 99%, and offering novel insights into pattern recognition in pupillary activity. Moreover, the proposed device successfully captured the PLR from all the participants with zero reported incidents or health affectations.

COVID-19 is no longer a public health emergency of international concern, but long COVID’s effects are yet to be fully understood. Hence, globally, SARS-CoV-2 is still a profound threat to public health and of perilous nature as a zoonotic disease. Timely vaccination provided to individuals worldwide during the pandemic phase was under a certain degree of control; however, few studies have reported the effectiveness of vaccines administered in Mexico, and its surveillance is paramount. Furthermore, an unknown proportion of Mexican individuals have not yet received any vaccine, and the circulation of the Omicron, Pirola, and FLiRT variants is ongoing. A cross-sectional serology survey study design was employed, involving 150 individuals from Southern Mexico (Oaxaca) whose humoral immune responses after vaccination were tested by an ELISA; the receptor-binding domain of the SARS-CoV-2 spike protein served as a recombinant antigen in the ELISA. One hundred thirty-nine out of 150 individuals (92.6%; 95%-CI = 87–95%) examined were positive for the ELISA, but in 11 individuals, the vaccines did not induce any immune response. Interestingly, the immune responses (antibody prevalence and levels) of females (58%) were higher (T= −2.21; p-value = 0.02) than those of males (41%). However, in this sample population of Southern Mexico, age, vaccine type, comorbidity, and body mass index did not have any effect (p > 0.05) after COVID-19 vaccination. Taking all results together, here, we present factors that affected immune responses of individuals during the first vaccination campaign in Oaxaca, Mexico; however, vaccine surveillance during the post-pandemic phase needs further investigation.

Timely acquisition of ash cloud heights is crucial for aviation safety and forecasting volcanic ash dispersion and fallout. Since visual observations are not always available, we assess the suitability of retrieving ash cloud heights from brightness temperature and plume direction observed in GOES-16 satellite imagery, VOLCAT solutions, and Washington-VAAC advisories during the 2022–2023 eruption of Cotopaxi volcano, Ecuador. We find that these satellite-derived height estimates consistently yield lower values than visual cameras. While the plume direction method and Washington-VAAC advisories produce the closest approximations, they also exhibit significant deviations. Remarkably, the brightness temperature method, despite producing the lowest height values, shows the best linear regression with visual observations. Near-real-time retrieval of ash cloud height from GOES-16 imagery is a promising alternative to direct visual observation, particularly at night, in adverse weather, or for remote volcanoes, especially if improvements, such as incorporating high-resolution local meteorological models, are introduced.

Abstract Our previous research revealed a key microRNA signature that is associated with spaceflight that can be used as a biomarker and to develop countermeasure treatments to mitigate the damage caused by space radiation. Here, we expand on this work to determine the biological factors rescued by the countermeasure treatment. We performed RNA-sequencing and transcriptomic analysis on 3D microvessel cell cultures exposed to simulated deep space radiation (0.5 Gy of Galactic Cosmic Radiation) with and without the antagonists to three microRNAs: miR-16-5p, miR-125b-5p, and let-7a-5p (i.e., antagomirs). Significant reduction of inflammation and DNA double strand breaks (DSBs) activity and rescue of mitochondria functions are observed after antagomir treatment. Using data from astronaut participants in the NASA Twin Study, Inspiration4, and JAXA missions, we reveal the genes and pathways implicated in the action of these antagomirs are altered in humans. Our findings indicate a countermeasure strategy that can potentially be utilized by astronauts in spaceflight missions to mitigate space radiation damage.

Objective: The objective of this study was to analyze the evolution in the diagnosis and management of indeterminate thyroid nodules over three time periods. Methods: In total, 3020 patients with thyroid nodules underwent cytological evaluation during three periods (2006– 2008, 2012–2014, 2017–2019). The distribution of diagnostic cytology, risk of malignancy, diagnostic performance indices of fine needle aspiration (FNA), and cytologic–histologic correlation in indeterminate cytology were analyzed. Results: Only 2.2% of cytology tests were insufficient for a diagnosis. About 86.9% cytology was benign, 1.7% malignant, and 11.4% indeterminate. Indeterminate cytology rates were 15.9% (2006–2008), 10.1% (2012–2014), and 10% (2017–2019). Surgery was performed in 13% of benign cytology, resulting in malignant histology in 2.7%. All malignant and suspicious cytology underwent surgery, with malignancy confirmed in 98% and 77% of cases, respectively. All ‘indeterminate with atypia’ cytology (2006–2008) and Bethesda IV (2012–2014; 2017–2019) underwent surgery, with malignancy confirmed in 19.6%, 43.8%, and 25.7%, respectively. In the ‘indeterminate without atypia’ category (2006–2008) and Bethesda III (2012–2014; 2017–2019), diagnostic surgery was performed in 57.7%, 78.6%, and 59.4%, respectively, with malignancy confirmed in 3.3%, 20.5%, and 31.6%. The FNA sensitivity was 91.6%, with a negative predictive value greater than 96% in all periods. The specificity exceeded 75% in the last two periods. Conclusion: The Bethesda system reduces indeterminate cytology and improves the accuracy of FNA diagnosis. We reported a higher proportion of malignancy than expected in Bethesda III, underscoring the importance of having institution-specific data to guide decision-making. However, there is a need for risk stratification tools that allow for conservative management in low-risk cases.

Dairy products provide essential nutrients when consumed and they also create rural employment. A small dairy can help a family maintain their livelihood. The objective of this study was to evaluate the microbiological quality of raw goat milk obtained during the milking-storage process using Good Hygiene Practices. The study was carried in northern Mexico, which is characterized by a desert climate. The experiment was carried in four herds, six samplings per herd with a total of 302 goats. Samples of milk extracted directly from the udder, milk extracted from the milking bucket and milk extracted from the storage bucket were analyzed. In addition, samples were taken from the milker’s hands. The data were analyzed using ANOVA and the statistical difference with the Tuky test (p

Abstract Reservoirs act as carbon sinks when sedimentation of particulate organic carbon (POC) exceeds CO2 and CH4 emissions. Here, we study the poorly explored process where phytoplankton‐derived acidic polysaccharides (APs) aggregate into particulate organic matter, promoting carbon export to sediments. This source of POC in sediments can mineralize to CO2 and CH4 over various timescales. Our research, centered on a Mediterranean reservoir, elucidates phenological trends of APs and POC sedimentation and identifies their predominant drivers. Our findings present synchronic sedimentation patterns of POC and APs but identify a 2‐week delay between POC sedimentation and CH4 emissions. Despite its eutrophic status, our data demonstrate this reservoir's role as a carbon sink, sequestering 4.33 g C m−2 yr−1. This highlights the need to consider various time scales when quantifying carbon budgets in reservoirs.

Over the last two decades, a considerable amount of equipment has been acquired (spreaders, seeders, sprayers, among others) to respond to the challenges of the precision agriculture (PA) concept. Most of this equipment has been purchased at a high cost. However, many of them, despite still being functional and equipped with sensors, actuators, and electronic processing units capable of adjusting to variations in speed, have become obsolete in terms of communication and incompatible with new monitoring and control systems based on the “Isobus” protocol. This work aims to present a solution for updating the control system (“Ferticontrol”) of a “Vicon RS-EDW” spreader with variable rate application (VRA), making it compatible with the “InCommand” system from “Ag Leader”. The solution includes serial protocol mediation using low-cost tools such as “Arduino” and “Raspberry Pi” microcontrollers and open-source software. The development shows that it is possible to implement a solution that is accessible to farmers in general. It also provides a niche business opportunity for young researchers to set up small technology-based enterprises associated with universities and research centers. These partnerships guarantee permanent innovation and represent a decisive step towards modern, technological, competitive, and sustainable agriculture.

Abstract The aim of this study was to evaluate the mediation role of muscle quantity in the relationship between physical fitness and cardiometabolic risk factors (CMRF) in adolescents. This cross-sectional study conducted with 120 adolescents of both sexes, aged between 10 and 17 years. Body mass, height, fat mass (FM), lean mass, blood pressure, high-density lipoprotein, low-density lipoprotein, triglycerides, glucose, insulin, cardiorespiratory fitness (CRF) and 1 repetition maximum strength (1-RM) with evaluation of the leg press 45° (RM-leg), bench press (RM-bench) and arm curl (RM-arm). Body mass index z-score, appendicular skeletal muscle mass, appendicular skeletal muscle mass index, lean mass index (LMI), muscle-to-fat ratio (MFR), age at peak height velocity, and CMRF z-score were calculated. The direct relation between FM and CMRF was mediated by the LMI (26%) and inverse relation between CRF and CMRF was mediated by the LMI (26%). For girls, the direct relation between FM and CMRF was mediated by the LMI (32%); the inverse relation between CRF, RM-leg, RM-arm and CMRF was mediated by the LMI (32%, 33%, and 32%, respective). For boys, the indirect effect was not significant, indicating that LMI is not a mediator in the relation between FM, CRF, 1-RM with CMRF. The direct relation between RM-leg and CMRF was mediated by the MRF (16%). This finding evidenced the importance of promoting a healthy lifestyle to improve physical fitness levels and the quantity of muscle mass in adolescents.

Abstract Despite significant advances in reconstructing genome-scale metabolic networks, the understanding of cellular metabolism remains incomplete for many organisms. A promising approach for elucidating cellular metabolism is analysing the full scope of enzyme promiscuity, which exploits the capacity of enzymes to bind to non-annotated substrates and generate novel reactions. To guide time-consuming costly experimentation, different computational methods have been proposed for exploring enzyme promiscuity. One relevant algorithm is PROXIMAL, which strongly relies on KEGG to define generic reaction rules and link specific molecular substructures with associated chemical transformations. Here, we present a completely new pipeline, PROXIMAL2, which overcomes the dependency on KEGG data. In addition, PROXIMAL2 introduces two relevant improvements with respect to the former version: i) correct treatment of multi-step reactions and ii) tracking of electric charges in the transformations. We compare PROXIMAL and PROXIMAL2 in recovering annotated products from substrates in KEGG reactions, finding a highly significant improvement in the level of accuracy. We then applied PROXIMAL2 to predict degradation reactions of phenolic compounds in the human gut microbiota. The results were compared to RetroPath RL, a different and relevant enzyme promiscuity method. We found a significant overlap between these two methods but also complementary results, which open new research directions into this relevant question in nutrition.

Abstract It has been well documented that the usage of a textured cover layer reduces reflection from the air‐solar cell interface, which ultimately enhances the power conversion efficiency (PCE) of a solar cell. The most commonly used patterns, such as pyramids, micropillars, nanowires (NW), and nanoholes have been widely studied and optimized. Besides using such NWs to enhance light absorption, this work also additionally considers the concept of mimicking the antireflection coating of single or multiple layers in minimizing the reflectance and thus enhancing the total absorptance further. It is shown here that at least one order of magnitude shorter multilayer NW pattern of 268 nm total height can outperform a standard NW of 4270 nm height, which needs less material and can also be fabricated at a reduced cost. Furthermore, the proposed design with reduced height has a significantly lower surface‐to‐volume ratio, which also reduces surface recombination loss than the other textured surface patterns. The results presented in this work have been comprehensively analyzed by initially optimizing optical absorption and then completing the electrical simulations. The optimized design in conjunction with a back reflector offers an efficiency as high as 16.434%.

Abstract Background The immature platelet fraction (IPF), a parameter obtained by the Sysmex XN‐1000V analyzer, is used in humans to differentiate between central (CEN) and peripheral (PER) thrombocytopenia (TP) but has not been evaluated in small animals. Objectives Compare IPF between healthy, clinical non‐TP and TP dogs and cats, study IPF in different causes of TP in dogs and cats and, establish IPF reference intervals (RIs), and study the effect of age and sex on IPF in healthy dogs and cats. Animals A total of 3281 dogs and 726 cats. Methods Retrospective review of medical records. Animals were classified as nonthrombocytopenic (healthy group and group of clinical patients without TP [NTP]) or TP. These latter animals were subclassified as pseudothrombocytopenia (PSE), CEN and PER, based on evaluation of platelet clumps, estimated platelet count in blood smears and final diagnosis. Blood samples were evaluated using a Sysmex XN‐1000V with a specific platelet channel (PLT‐F). Results The IPF was significantly different between each subtype of TP in both species. Immature platelet fractions

Abstract Background European Union (EU) research on cybersecurity is actively developing more efficient digital steganalysis techniques aimed at uncovering hidden online illegal content in apparently legitimate multimedia files. Beyond issues such as the design, effectiveness and functionality of the technology, this paper addresses the recently raised concern of societal impact, which refers to the influence, consequences, or effects, whether expected or not, that a particular action, policy, or technological advance has on society as a whole or on different segments of society. These impacts can be broad and multifaceted, encompassing economic, social, cultural, environmental and ethical dimensions, amongst others. Aim The aim of this article is to take an exploratory look at the societal challenges and benefits associated with the use of digital steganalysis tools in cybercrime investigations in EU member states, adopting a dual mixed-methods perspective. Methods First, a systematic review of the scientific literature published within 2017–2023, focusing on the societal dimension of steganalysis tools, including peer reviewed journal and conference papers on steganalysis and crime (N = 55) was carried out. For the second part of the paper, two nominal group discussions were conducted with experts from Law Enforcement Agencies (LEAs): the first on societal benefits (N = 7), the second on societal challenges (N = 6). These consensus-building discussions aimed to identify, quantitatively assess and rank the various challenges and potential social benefits associated with the use of digital steganalysis tools in police investigations. Results Findings reveal a widespread oversight in addressing the social impact dimension by tool designers on academic papers, especially regarding societal acceptance issues. The expert-citizens argued for stakeholders and public awareness of both risks and benefits of steganalysis tools. Conclusions This study highlights the current need to consider not only the technological aspects, but also the profound social dimension arising from the use of these tools, such as public awareness of cybercrime and the ethical design and use of digital crime investigation tools. Understanding and evaluating societal impacts is essential for making informed decisions, shaping policies, and addressing the needs and concerns of diverse stakeholders in various domains. This multidisciplinary approach is crucial to achieving a more balanced and comprehensive understanding of the impact of digital steganalysis tools in the field of digital criminal investigation.

Abstract Mammalian sex determination is controlled by antagonistic gene cascades operating in embryonic undifferentiated gonads. The expression of the Y-linked gene SRY is sufficient to trigger the testicular pathway, whereas its absence in XX embryos leads to ovarian differentiation. Yet, the potential involvement of non-coding regulation in this process remains unclear. Here we show that the deletion of a single microRNA cluster, miR-17~92, induces complete primary male-to-female sex reversal in XY mice. Sry expression is delayed in XY knockout gonads, which develop as ovaries. Sertoli cell differentiation is reduced, delayed and unable to sustain testicular development. Pre-supporting cells in mutant gonads undergo a transient state of sex ambiguity which is subsequently resolved towards the ovarian fate. The miR-17~92 predicted target genes are upregulated, affecting the fine regulation of gene networks controlling gonad development. Thus, microRNAs emerge as key components for mammalian sex determination, controlling Sry expression timing and Sertoli cell differentiation.

Abstract MYC plays various roles in pluripotent stem cells, including the promotion of somatic cell reprogramming to pluripotency, the regulation of cell competition and the control of embryonic diapause. However, how Myc expression is regulated in this context remains unknown. The Myc gene lies within a ~ 3-megabase gene desert with multiple cis-regulatory elements. Here we use genomic rearrangements, transgenesis and targeted mutation to analyse Myc regulation in early mouse embryos and pluripotent stem cells. We identify a topologically-associated region that homes enhancers dedicated to Myc transcriptional regulation in stem cells of the pre-implantation and early post-implantation embryo. Within this region, we identify elements exclusively dedicated to Myc regulation in pluripotent cells, with distinct enhancers that sequentially activate during naive and formative pluripotency. Deletion of pluripotency-specific enhancers dampens embryonic stem cell competitive ability. These results identify a topologically defined enhancer cluster dedicated to early embryonic expression and uncover a modular mechanism for the regulation of Myc expression in different states of pluripotency.

Abstract Magnetic order typically emerges due to the short-range exchange interaction between the constituent electronic spins. Recent discoveries have found a crucial role for spin-phonon coupling in various phenomena from optical ultrafast magnetization switching to dynamical control of the magnetic state. Here, we demonstrate theoretically the emergence of a biquadratic long-range interaction between spins mediated by their coupling to phonons hybridized with vacuum photons into polaritons. The resulting ordered state enabled by the exchange of virtual polaritons between spins is reminiscent of superconductivity mediated by the exchange of virtual phonons. The biquadratic nature of the spin-spin interaction promotes ordering without favoring ferro- or antiferromagnetism. It further makes the phase transition to magnetic order a first-order transition, unlike in conventional magnets. Consequently, a large magnetization develops abruptly on lowering the temperature which could enable magnetic memories admitting ultralow-power thermally-assisted writing while maintaining a high data stability. The role of photons in the phenomenon further enables an in-situ static control over the magnetism. These unique features make our predicted spin-spin interaction and magnetism highly unconventional paving the way for novel scientific and technological opportunities.

Background: Pediatric cancer survivors are at increased risk of muscle weakness and low areal bone mineral density (aBMD). However, the prevalence of muscle strength deficits is not well documented, and the associations of muscle strength with aBMD are unknown in this population. Therefore, this study aimed to investigate the prevalence of upper- and lower-body muscle strength deficits and to examine the associations of upper- and lower-body muscle strength with age-, sex, and race-specific aBMD Z-scores at the total body, total hip, femoral neck, and lumbar spine. Methods: This cross-sectional study included 116 pediatric cancer survivors (12.1 ± 3.3 years old, mean ± SD; 42.2% female). Upper- and lower-body muscle strength were assessed by handgrip and standing long jump test, respectively. Dual‑energy X‑ray absorptiometry was used to measure aBMD (g/cm2). Associations between muscle strength and aBMD were evaluated in multivariable linear regression models. Logistic regression was used to evaluate the contribution of muscle strength (1-decile lower) to the odds of having low aBMD (Z-score ≤ 1.0). All analyses were adjusted for time from treatment completion, radiotherapy exposure, and body mass index. Results: More than one-half of survivors were within the 2 lowest deciles for upper- (56.9%) and lower- body muscle strength (60.0%) in comparison to age- and sex-specific reference values. Muscle strength deficits were associated with lower aBMD Z-scores at all sites (B = 0.133–0.258, p = 0.001–0.032). Each 1-decile lower in upper-body muscle strength was associated with 30%–95% higher odds of having low aBMD Z-scores at all sites. Each 1-decile lower in lower-body muscle strength was associated with 35%–70% higher odds of having low aBMD Z-scores at total body, total hip, and femoral neck. Conclusion: Muscle strength deficits are prevalent in young pediatric cancer survivors, and such deficits are associated with lower aBMD Z-scores at all sites. These results suggest that interventions designed to improve muscle strength in this vulnerable population may have the added benefit of improving aBMD.

Acute transient contrast-induced neurologic deficit is an uncommon condition triggered by the administration of intra-arterial contrast during angiography. It can present with encephalopathy, cortical blindness, seizures, or focal deficits. This report describes a patient who presented with severe neurologic deficits after percutaneous coronary intervention, with complete symptom resolution within 72 hours.

Store‐operated Ca2+ entry (SOCE) is a major mechanism for Ca2+ influx in colorectal cancer (CRC) cells. This mechanism, regulated by the filling state of the intracellular Ca2+ stores, is mediated by the endoplasmic reticulum Ca2+ sensors of the stromal interaction molecules (STIM) family [stromal interaction molecule 1 (STIM1) and STIM2] and the Ca2+‐release‐activated Ca2+ channels constituted by Orai family members, with predominance of calcium release‐activated calcium channel protein 1 (Orai1). CRC cells exhibit enhanced SOCE due to remodeling of the expression of the key SOCE molecular components. The enhanced SOCE supports a variety of cancer hallmarks. Here, we show that treatment of the colorectal adenocarcinoma cell lines HT‐29 and Caco‐2 with inanimate Lacticaseibacillus paracasei (CECT9610) and Lactiplantibacillus plantarum (CECT9608) attenuates SOCE, although no detectable effect is seen on SOCE in normal colon mucosa cells. The effect of Lacticaseibacillus paracasei and Lactiplantibacillus plantarum postbiotics was mediated by downregulation of Orai1 and STIM1, while the expression levels of Orai3 and STIM2 remained unaltered. Treatment of HT‐29 and Caco‐2 cells with inanimate Lacticaseibacillus paracasei and Lactiplantibacillus plantarum impairs in vitro migration by a mechanism likely involving attenuation of focal adhesion kinase (FAK) tyrosine phosphorylation. Cell treatment with the Orai1 inhibitor synta‐66 attenuates SOCE and prevents any further effect of Lacticaseibacillus paracasei and Lactiplantibacillus plantarum postbiotics. Together, our results indicate for the first time that Lacticaseibacillus paracasei and Lactiplantibacillus plantarum postbiotics selectively exert negative effects on Ca2+ influx through SOCE in colorectal adenocarcinoma cell lines, providing evidence for an attractive strategy against CRC.

Abstract Over the last quarter century, increasing honey bee colony losses motivated standardized large-scale surveys of managed honey bees (Apis mellifera), particularly in Europe and the United States. Here we present the first large-scale standardized survey of colony losses of managed honey bees and stingless bees across Latin America. Overall, 1736 beekeepers and 165 meliponiculturists participated in the 2-year survey (2016–2017 and 2017–2018). On average, 30.4% of honey bee colonies and 39.6% of stingless bee colonies were lost per year across the region. Summer losses were higher than winter losses in stingless bees (30.9% and 22.2%, respectively) but not in honey bees (18.8% and 20.6%, respectively). Colony loss increased with operation size during the summer in both honey bees and stingless bees and decreased with operation size during the winter in stingless bees. Furthermore, losses differed significantly between countries and across years for both beekeepers and meliponiculturists. Overall, winter losses of honey bee colonies in Latin America (20.6%) position this region between Europe (12.5%) and the United States (40.4%). These results highlight the magnitude of bee colony losses occurring in the region and suggest difficulties in maintaining overall colony health and economic survival for beekeepers and meliponiculturists.

Dendritic cells (DCs) play critical roles in HIV pathogenesis and require further investigation in the female genital tract, a main portal of entry for HIV infection. Here we characterized genital DC populations at the single cell level and how DC subsets respond to HIV immediately following exposure. We found that the genital CD11c+HLA-DR+ myeloid population contains three DC subsets (CD1c+ DC2s, CD14+ monocyte-derived DCs and CD14+CD1c+ DC3s) and two monocyte/macrophage populations with distinct functional and phenotypic properties during homeostasis. Following HIV exposure, the antiviral response was dominated by DCs’ rapid secretory response, activation of non-classical inflammatory pathways and host restriction factors. Further, we uncovered subset-specific differences in anti-HIV responses. CD14+ DCs were the main population activated by HIV and mediated the secretory antimicrobial response, while CD1c+ DC2s activated inflammasome pathways and IFN responses. Identification of subset-specific responses to HIV immediately after exposure could aid targeted strategies to prevent HIV infection.