Targeting Pin1 renders pancreatic cancer eradicable by synergizing with immunochemotherapy.

Pancreatic ductal adenocarcinoma (PDAC) is characterized by notorious resistance to current therapies attributed to inherent tumor heterogeneity and highly desmoplastic and immunosuppressive tumor microenvironment (TME). Unique proline isomerase Pin1 regulates multiple cancer pathways, but its role in the TME and cancer immunotherapy is unknown. Here, we find that Pin1 is overexpressed both in cancer cells and cancer-associated fibroblasts (CAFs) and correlates with poor survival in PDAC patients. Targeting Pin1 using clinically available drugs induces complete elimination or sustained remissions of aggressive PDAC by synergizing with anti-PD-1 and gemcitabine in diverse model systems. Mechanistically, Pin1 drives the desmoplastic and immunosuppressive TME by acting on CAFs and induces lysosomal degradation of the PD-1 ligand PD-L1 and the gemcitabine transporter ENT1 in cancer cells, besides activating multiple cancer pathways. Thus, Pin1 inhibition simultaneously blocks multiple cancer pathways, disrupts the desmoplastic and immunosuppressive TME, and upregulates PD-L1 and ENT1, rendering PDAC eradicable by immunochemotherapy.

Hematology and oncology clinical care during the coronavirus disease 2019 pandemic.

New York City has been at the epicenter of the coronavirus disease 2019 (COVID-19) pandemic that has already infected over a million people and resulted in more than 70,000 deaths as of early May 2020 in the United States alone. This rapid and enormous influx of patients into the health care system has had profound effects on all aspects of health care, including the care of patients with cancer. In this report, the authors highlight the transformation they underwent within the Division of Hematology and Medical Oncology as they prepared for the COVID-19 crisis in New York City. Under stressful and uncertain conditions, some of the many changes they enacted within their division included developing a regular line of communication among division leaders to ensure the development and implementation of a restructuring strategy, completely reconfiguring the inpatient and outpatient units, rapidly developing the ability to perform telemedicine video visits, and creating new COVID-rule-out and COVID-positive clinics for their patients. These changes allowed them to manage the storm while minimizing the disruption of important continuity of care to their patients with cancer. The authors hope that their experiences will be helpful to other oncology practices about to experience their own individual COVID-19 crises.

Personalized tumor vaccine for pancreatic cancer.

BACKGROUND: Pancreatic cancer is a highly lethal malignancy often presenting with advanced disease and characterized by resistance to standard chemotherapy. Immune-based therapies such checkpoint inhibition have been largely ineffective such that pancreatic cancer is categorized as an immunologically "cold tumor". In the present study, we examine the therapeutic efficacy of a personalized cancer vaccine in which tumor cells are fused with dendritic cells (DC) resulting in the broad induction of antitumor immunity. RESULTS: In the KPC spontaneous pancreatic cancer murine model, we demonstrated that vaccination with DC/KPC fusions led to expansion of pancreatic cancer specific lymphocytes with an activated phenotype. Remarkably, vaccination led to a reduction in tumor bulk and near doubling of median survival in this highly aggressive model. In a second murine pancreatic model (Panc02), vaccination with DC/tumor fusions similarly led to expansion of tumor antigen specific lymphocytes and their infiltration to the tumor site. Having shown efficacy in immunocompetent murine models, we subsequently demonstrated that DC/tumor fusions generated from primary human pancreatic cancer and autologous DCs potently stimulate tumor specific cytotoxic lymphocyte responses. CONCLUSIONS: DC/tumor fusions induce the activation and expansion of tumor reactive lymphocytes with the capacity to infiltrate into the pancreatic cancer tumor bed.

Resilience dynamics and productivity-driven shifts in the marine communities of the Western Mediterranean Sea.

Ecological resilience has become a conceptual cornerstone bridging ecological processes to conservation needs. Global change is increasingly associated with local changes in environmental conditions that can cause abrupt ecosystem reorganizations attending to system-specific resilience fluctuations with time (i.e. resilience dynamics). Here we assess resilience dynamics associated with climate-driven ecosystems transitions, expressed as changes in the relevant contribution of species with different life-history strategies, in two benthopelagic systems. We analysed data from 1994 to 2019 coming from a scientific bottom trawl survey in two environmentally contrasting ecosystems in the Western Mediterranean Sea-Northern Spain and Alboran Sea. Benthopelagic species were categorized according to their life-history strategies (opportunistic, periodic and equilibrium), ecosystem functions and habitats. We implemented an Integrated Resilience Assessment (IRA) to elucidate the response mechanism of the studied ecosystems to several candidate environmental stressors and quantify the ecosystems' resilience. We demonstrate that both ecosystems responded discontinuously to changes in chlorophyll-a concentration more than any other stressor. The response in Northern Spain indicated a more overarching regime shift than in the Alboran Sea. Opportunistic fish were unfavoured in both ecosystems in the recent periods, while invertebrate species of short life cycle were generally favoured, particularly benthic species in the Alboran Sea. The study illustrates that the resilience dynamics of the two ecosystems were mostly associated with fluctuating productivity, but subtle and long-term effects from sea warming and fishing reduction were also discernible. Such dynamics are typical of systems with wide environmental gradient such as the Northern Spain, as well as systems with highly hydrodynamic and of biogeographical complexity such as the Alboran Sea. We stress that management should become more adaptive by utilizing the knowledge on the systems' productivity thresholds and underlying shifts to help anticipate both short-term/less predictable events and long-term/expected effects of climate change.

Transcending capitalism growth strategies for biodiversity conservation.

The unlimited economic growth that fuels capitalism's metabolism has profoundly transformed a large portion of Earth. The resulting environmental destruction has led to an unprecedented rate of biodiversity loss. Following large-scale losses of habitats and species, it was recognized that biodiversity is crucial to maintaining functional ecosystems. We sought to continue the debate on the contradictions between economic growth and biodiversity in the conservation science literature and thus invite scholars to engage in reversing the biodiversity crisis through acknowledging the impacts of economic growth. In the 1970s, a global agenda was set to develop different milestones related to sustainable development, including green-blue economic growth, which despite not specifically addressing biodiversity reinforced the idea that economic development based on profit is compatible with the planet's ecology. Only after biodiversity loss captured the attention of environmental sciences researchers in the early 2000s was a global biodiversity agenda implemented. The agenda highlights biodiversity conservation as a major international challenge and recognizes that the main drivers of biodiversity loss derive from economic activities. The post-2000 biodiversity agendas, including the 2030 Agenda for Sustainable Development and the post-2020 Convention on Biological Diversity Global Strategy Framework, do not consider the negative impacts of growth-oriented strategies on biodiversity. As a result, global biodiversity conservation priorities are governed by the economic value of biodiversity and its assumed contribution to people's welfare. A large body of empirical evidence shows that unlimited economic growth is the main driver of biodiversity loss in the Anthropocene; thus, we strongly argue for sustainable degrowth and a fundamental shift in societal values. An equitable downscaling of the physical economy can improve ecological conditions, thus reducing biodiversity loss and consequently enhancing human well-being.

Trascendiendo las Estrategias de Crecimiento Capitalista para la Conservación de la Biodiversidad Resumen El crecimiento económico ilimitado que alimenta el metabolismo del capitalismo ha transformado profundamente una gran parte del planeta Tierra. La destrucción ambiental resultante ha traído como consecuencia una tasa sin precedentes de pérdida de diversidad biológica. Después de la pérdida a gran escala de hábitats y especies, se reconoció que la biodiversidad es crucial para mantener el funcionamiento de los ecosistemas. En este articulo buscamos seguir con el debate sobre las contradicciones entre el crecimiento económico y la biodiversidad en la literatura de las ciencias de la conservación y así invitar a los académicos a participar en la reducción de la crisis de biodiversidad dando a conocer los impactos del crecimiento económico. En la década de 1970, se estableció una agenda global para desarrollar diferentes metas relacionadas con el desarrollo sustentable, incluyendo el crecimiento económico verde y azul, la cual a pesar de no mencionar específicamente la biodiversidad reforzó la idea de que el desarrollo económico basado en ganancias es compatible con la ecología del planeta. Fue solamente después de que la pérdida de biodiversidad captó la atención de los investigadores de las ciencias ambientales a principios de la década de los 2000 que se implementó una agenda para la diversidad biológica. La agenda resalta que la conservación de la biodiversidad es un gran reto internacional y reconoce que las pincipales causas de la pérdida de la diversidad biológica derivan de las actividades económicas. Las agendas para la biodiversidad creadas después del 2000, incluyendo la Agenda 2030 para el Desarrollo Sustentable y el Marco de Trabajo de la Estrategia Mundial de la Convención sobre la Diversidad Biológica posterior a 2020, no consideran los impactos negativos de las estrategias para la biodiversidad orientadas por el crecimiento. Como resultado, las prioridades de la conservación mundial de la biodiversidad están gobernadas por el valor económico de la biodiversidad y la supuesta contribución que tiene para el bienestar de las personas. Una gran cantidad de evidencia empírica muestra que el crecimiento económico ilimitado es el principal conductor de la pérdida de diversidad biológica en el Antropoceno; por lo tanto, abogamos fuertemente por un decrecimiento sustentable y un cambio fundamental en los valores sociales. Una reducción equitativa de la economía física puede mejorar las condiciones ecológicas, reduciendo así la pérdida de biodiversidad y mejorando como consecuencia el bienestar humano.

Machine Learning-Based Prediction Models for Different Clinical Risks in Different Hospitals: Evaluation of Live Performance.

BACKGROUND: Machine learning algorithms are currently used in a wide array of clinical domains to produce models that can predict clinical risk events. Most models are developed and evaluated with retrospective data, very few are evaluated in a clinical workflow, and even fewer report performances in different hospitals. In this study, we provide detailed evaluations of clinical risk prediction models in live clinical workflows for three different use cases in three different hospitals. OBJECTIVE: The main objective of this study was to evaluate clinical risk prediction models in live clinical workflows and compare their performance in these setting with their performance when using retrospective data. We also aimed at generalizing the results by applying our investigation to three different use cases in three different hospitals. METHODS: We trained clinical risk prediction models for three use cases (ie, delirium, sepsis, and acute kidney injury) in three different hospitals with retrospective data. We used machine learning and, specifically, deep learning to train models that were based on the Transformer model. The models were trained using a calibration tool that is common for all hospitals and use cases. The models had a common design but were calibrated using each hospital's specific data. The models were deployed in these three hospitals and used in daily clinical practice. The predictions made by these models were logged and correlated with the diagnosis at discharge. We compared their performance with evaluations on retrospective data and conducted cross-hospital evaluations. RESULTS: The performance of the prediction models with data from live clinical workflows was similar to the performance with retrospective data. The average value of the area under the receiver operating characteristic curve (AUROC) decreased slightly by 0.6 percentage points (from 94.8% to 94.2% at discharge). The cross-hospital evaluations exhibited severely reduced performance: the average AUROC decreased by 8 percentage points (from 94.2% to 86.3% at discharge), which indicates the importance of model calibration with data from the deployment hospital. CONCLUSIONS: Calibrating the prediction model with data from different deployment hospitals led to good performance in live settings. The performance degradation in the cross-hospital evaluation identified limitations in developing a generic model for different hospitals. Designing a generic process for model development to generate specialized prediction models for each hospital guarantees model performance in different hospitals.

Vitrification of donkey sperm using straws as an alternative to conventional slow freezing.

Cryoprotectant-free vitrification of donkey sperm using 0.25 ml straws has been recently developed, but the obtained results have not been directly compared to conventional slow freezing yet. The aim of this study was to compare sperm quality parameters after cryopreservation using both methods. Semen samples were collected from three Andalusian Donkeys. Semen was centrifuged and pellets resuspended with an extender with glycerol for conventional freezing or the same extender without glycerol, but with sucrose 0.1 mol/L for vitrification. Conventional freezing was performed in nitrogen vapours and thawed in a water bath (30s/37°C). Vitrification was performed in covered 0.25 ml straws plunged directly into liquid nitrogen and warmed in 3 ml of a milk-based extender at 43°C. Total (TM, %) and progressive motility (PM, %) were evaluated by computer-assisted sperm analysis, and plasma membrane (PMI, %) and acrosome (AIS, %) integrities by epifluorescence microscopy. No differences (p > .05) were found between slow freezing and vitrification methods for any of the parameters assessed: TM (58.2 ± 16.1% vs. 52.7 ± 15.6%), PM (44.7 ± 18.2% vs. 44.3 ± 15.0%), PMI (55.4 ± 9.0% vs. 49.2 ± 11.2%) and AIS (38.4 ± 19.6% vs. 45.0 ± 11.0%), respectively. In conclusion, donkey sperm vitrification in straws presented similar sperm quality after thawing in comparison to conventional freezing. Therefore, it could be considered as an alternative to slow freezing regarding the sperm parameters assessed.

DNA fragmentation of equine cumulus cells from Cumulus-Oocyte complexes submitted to vitrification and its relationship to the developmental competence of the oocyte.

The objectives of this study were to evaluate the effect of vitrification on the DNA fragmentation rate of equine cumulus cells and to assess its relationship to oocyte in vitro maturation (IVM) after vitrification. Cumulus cells (CC) from 14 mares were recovered from COCs, previously submitted to vitrification (VIT) and IVM. The DNA fragmentation rate of the cumulus cells (CC-DF) was assessed using a chromatin dispersion test. CC-DF rates between vitrified and control COCs were statistically compared by Student's t-test. The rates of CC-DF from control COCs were lower than in vitrified COCs. The percentage of CC-DF was not significantly different (p > .05) between groups of COCs able to reach metaphase II (MII > 0) and those in which oocyte maturation was not achieved (MII = 0). In conclusion, vitrification has a deleterious effect on the DNA fragmentation of equine cumulus cells; however, this parameter cannot be used as a predictor for IVM success after COCs vitrification.

Cryo-banking of human spermatozoa by aseptic cryoprotectants-free vitrification in liquid air: Positive effect of elevated warming temperature.

Cryoprotectant-free vitrification is a common method for spermatozoa cryopreservation by direct plunging into liquid nitrogen. However, the commercial liquid nitrogen could be potentially contaminated by microorganisms. Warming temperature plays an essential role for quality of human spermatozoa after vitrification. This study aimed to evaluate comparatively a quality spermatozoa after vitrification in liquid nitrogen and clean liquid air as well as with two warming rates: at 42 °C and 45 °C. After performing of routine swim-up of normozoospermia samples, spermatozoa from the same ejaculate were divided into two groups: vitrified in liquid nitrogen (LN) and sterile liquid air (LA). Spermatozoa of LN group were warmed at 42 °C, and spermatozoa of LA groups were divided and warmed at 42 °C (LA42) and 45 °C (LA45). Then spermatozoa motility, reactive oxygen species (ROS), mitochondrial membrane potential (MMP), reactive nitrogen species (RNS), and viability were assessed. It was no found significant differences in quality of spermatozoa from LN and LA groups in the motility, ROS, MMP, RNS rates after warming at 42 °C. A tendency to obtain better spermatozoa quality was found with using of warming by 42 °C in comparison with 45 °C. It was concluded that cryoprotectant-free vitrification by direct dropping of human spermatozoa into clean liquid air can be used as an alternative to cooling in liquid nitrogen. Warming of spermatozoa at 42 °C allows to preserve the spermatozoa physiological parameters.

Deciphering the complex interplay between pancreatic cancer, diabetes mellitus subtypes and obesity/BMI through causal inference and mediation analyses.

OBJECTIVES: To characterise the association between type 2 diabetes mellitus (T2DM) subtypes (new-onset T2DM (NODM) or long-standing T2DM (LSDM)) and pancreatic cancer (PC) risk, to explore the direction of causation through Mendelian randomisation (MR) analysis and to assess the mediation role of body mass index (BMI). DESIGN: Information about T2DM and related factors was collected from 2018 PC cases and 1540 controls from the PanGenEU (European Study into Digestive Illnesses and Genetics) study. A subset of PC cases and controls had glycated haemoglobin, C-peptide and genotype data. Multivariate logistic regression models were applied to derive ORs and 95% CIs. T2DM and PC-related single nucleotide polymorphism (SNP) were used as instrumental variables (IVs) in bidirectional MR analysis to test for two-way causal associations between PC, NODM and LSDM. Indirect and direct effects of the BMI-T2DM-PC association were further explored using mediation analysis. RESULTS: T2DM was associated with an increased PC risk when compared with non-T2DM (OR=2.50; 95% CI: 2.05 to 3.05), the risk being greater for NODM (OR=6.39; 95% CI: 4.18 to 9.78) and insulin users (OR=3.69; 95% CI: 2.80 to 4.86). The causal association between T2DM (57-SNP IV) and PC was not statistically significant (ORLSDM=1.08, 95% CI: 0.86 to 1.29, ORNODM=1.06, 95% CI: 0.95 to 1.17). In contrast, there was a causal association between PC (40-SNP IV) and NODM (OR=2.85; 95% CI: 2.04 to 3.98), although genetic pleiotropy was present (MR-Egger: p value=0.03). Potential mediating effects of BMI (125-SNPs as IV), particularly in terms of weight loss, were evidenced on the NODM-PC association (indirect effect for BMI in previous years=0.55). CONCLUSION: Findings of this study do not support a causal effect of LSDM on PC, but suggest that PC causes NODM. The interplay between obesity, PC and T2DM is complex.

Are we ready to track climate-driven shifts in marine species across international boundaries? - A global survey of scientific bottom trawl data.

Marine biota are redistributing at a rapid pace in response to climate change and shifting seascapes. While changes in fish populations and community structure threaten the sustainability of fisheries, our capacity to adapt by tracking and projecting marine species remains a challenge due to data discontinuities in biological observations, lack of data availability, and mismatch between data and real species distributions. To assess the extent of this challenge, we review the global status and accessibility of ongoing scientific bottom trawl surveys. In total, we gathered metadata for 283,925 samples from 95 surveys conducted regularly from 2001 to 2019. We identified that 59% of the metadata collected are not publicly available, highlighting that the availability of data is the most important challenge to assess species redistributions under global climate change. Given that the primary purpose of surveys is to provide independent data to inform stock assessment of commercially important populations, we further highlight that single surveys do not cover the full range of the main commercial demersal fish species. An average of 18 surveys is needed to cover at least 50% of species ranges, demonstrating the importance of combining multiple surveys to evaluate species range shifts. We assess the potential for combining surveys to track transboundary species redistributions and show that differences in sampling schemes and inconsistency in sampling can be overcome with spatio-temporal modeling to follow species density redistributions. In light of our global assessment, we establish a framework for improving the management and conservation of transboundary and migrating marine demersal species. We provide directions to improve data availability and encourage countries to share survey data, to assess species vulnerabilities, and to support management adaptation in a time of climate-driven ocean changes.

Sperm morphometry is affected by increased inbreeding in the Retinta cattle breed: A molecular approach.

The effect of inbreeding depression on sperm motility is well documented, but its influence on sperm morphometry has been scarcely examined to date. Here, we combined the use of computer-assisted sperm morphometry analysis (CASMA) with a SNP-based genomic approach to determine and characterize the effect of inbreeding on the sperm shape of a highly inbred cattle population. We determined seven morphometric parameters on frozen-thawed sperm samples of 57 Retinta bulls: length (L, µm), width (W, µm), area (A, µm2 ), perimeter (P, µm), ellipticity (ELI; L/W), elongation (L-W)/(L + W) and perimeter-to-area shape factor (p2a; P2 /4 × π × A). The comparison of highly inbred (HI) and lowly inbreed (LI) individuals based on runs of homozygosity (ROH) inbreeding values (F ROH ) showed no differences between groups. An additional two-step unsupervised sperm subpopulation analysis based on morphometric parameters showed significant differences in the abundance of different sperm subpopulations between groups (p < 0.05). This analysis revealed that HI bulls harbored a higher percentage of narrow-head sperm as opposed to the higher percentage of large- and round-headed sperm detected in LI. A further genomic characterization revealed 23 regions differentially affected by inbreeding in both groups, detecting six genes (SPAG6, ARMC3, PARK7, VAMP3, DYNLRB2, and PHF7) previously related to different spermatogenesis-associated processes.

Exploring wealth-related inequalities in maternal and child health coverage in Latin America and the Caribbean.

BACKGROUND: Maternal and child health have shown important advances in the world in recent years. However, national averages indicators hide large inequalities in access and quality of care in population subgroups. We explore wealth-related inequalities affecting health coverage and interventions in reproductive, maternal, newborn, and child health in Latin America and the Caribbean. METHODS: We analyzed representative national surveys from 15 countries conducted between 2001 and 2016. We estimated maternal-child health coverage gaps using the Composite Coverage Index - a weighted average of interventions that include family planning, maternal and newborn care, immunizations, and treatment of sick children. We measured absolute and relative inequality to assess gaps by wealth quintile. Pearson's correlation coefficient was used to test the association between the coverage gap and population attributable risk. RESULTS: The Composite Coverage Index showed patterns of inequality favoring the wealthiest subgroups. In eight countries the national coverage was higher than the global median (78.4%; 95% CI: 73.1-83.6) and increased significantly as inequality decreased (Pearson r = 0.9; p < 0.01). CONCLUSIONS: There are substantial inequalities between socioeconomic groups. Reducing inequalities will improve coverage indicators for women and children. Additional health policies, programs, and practices are required to promote equity.

Recent advances in donkey sperm vitrification.

Artificial insemination (AI) with cryopreserved semen is an important tool to preserve endangered species, including European donkey breeds. Sperm vitrification is an alternative method to conventional freezing using high cooling rates and non-permeable cryoprotectant agents (CPAs). In donkeys, sperm vitrification was firstly developed in spheres by directly dropping the sperm (30 µl) into the liquid nitrogen. The vitrification media contained a combination of sucrose and bovine serum albumin as non-permeable CPAs and resulted in better sperm parameters after warming than extenders containing glycerol. Thereafter, sperm vitrification was optimized using an aseptic protocol, which consists of volumes up to 160 µl vitrified at 300 million sperm/ml using 0.25-ml straws with outer covers, obtaining similar sperm parameters as conventional freezing for total motility (52.7 ± 15.6% versus. 58.2 ± 16.1%), progressive motility (44.3 ± 15.0% versus. 44.7 ± 18.2%) and plasma membrane integrity (49.2 ± 11.2% versus. 55.4 ± 9.0%), respectively. In order to vitrify larger volumes of sperm, a procedure using 0.5-ml straws was evaluated; however, this methodology failed when compared to conventional freezing or other vitrification protocols, obtaining poor sperm quality after warming. Recently, a new methodology was developed for warming 0.25-ml straws in a water bath and after AI using the vitrified sperm, the uterine inflammatory response solved faster, and pregnancy rates were greater (22%) than frozen semen (10%) but not statistically different. In conclusion, all these findings confirm that sperm vitrification can be performed in donkeys as an alternative to conventional freezing for AI in jennies.

Comparison of different mathematical models to assess seasonal variations in the longevity of DNA integrity of cooled-stored stallion sperm.

Dynamic assessment of sperm DNA fragmentation (SDF) has shown to give fuller understanding of stallion semen quality; however, there have been limited attempts to use this parameter to investigate seasonal changes in productive functions. The aims of this study were to: (a) establish a reliable mathematical model to describe the longevity of cooled-stored sperm DNA integrity; (b) to examine the effect of seasonal variations on SDF. Ejaculates were cooled to 5°C, and SDF was analysed after 0, 6 and 24 hr of storage. The coefficient of determination (R2 ) was calculated after fine-tuning linear (LIN), exponential (EXP) and second order polynomial (POL) models. R2 was significantly higher (p < .001) for POL than for LIN and EXP. The rate of DNA degradation was calculated using the slopes of POL equations. After assessing the rate of change of the POL functions, significant differences between the acceleration of DNA fragmentation were found (p < .01) among seasons, being higher for winter and summer than spring and autumn. In conclusion, DNA analysis of stallion sperm fits better to a second order polynomial mathematical model, being spring the best season to collect and process cooled stallion semen in order to maintain the DNA integrity of the stallion sperm.

Monitoring inequality changes in full immunization coverage in infants in Latin America and the Caribbean.

OBJECTIVE: To compare inequalities in full infant vaccination coverage at two different time points between 1992 and 2016 in Latin American and Caribbean countries. METHODS: Analysis is based on recent available data from Demographic and Health Surveys, Multiple Indicator Cluster Surveys, and Reproductive Health Surveys conducted in 18 countries between 1992 and 2016. Full immunization data from children 12-23 months of age were disaggregated by wealth quintile. Absolute and relative inequalities between the richest and the poorest quintile were measured. Differences were measured for 14 countries with data available for two time points. Significance was determined using 95% confidence intervals. RESULTS: The overall median full immunization coverage was 69.9%. Approximately one-third of the countries have a high-income inequality gap, with a median difference of 5.6 percentage points in 8 of 18 countries. Bolivia, Colombia, El Salvador, and Peru have achieved the greatest progress in improving coverage among the poorest quintiles of their population in recent years. CONCLUSION: Full immunization coverage in the countries in the study shows higher-income inequality gaps that are not seen by observing national coverage only, but these differences appear to be reduced over time. Actions monitoring immunization coverage based on income inequalities should be considered for inclusion in the assessment of public health policies to appropriately reduce the gaps in immunization for infants in the lowest-income quintile.

Pancreatic cancer and autoimmune diseases: An association sustained by computational and epidemiological case-control approaches.

Deciphering the underlying genetic basis behind pancreatic cancer (PC) and its associated multimorbidities will enhance our knowledge toward PC control. The study investigated the common genetic background of PC and different morbidities through a computational approach and further evaluated the less explored association between PC and autoimmune diseases (AIDs) through an epidemiological analysis. Gene-disease associations (GDAs) of 26 morbidities of interest and PC were obtained using the DisGeNET public discovery platform. The association between AIDs and PC pointed by the computational analysis was confirmed through multivariable logistic regression models in the PanGen European case-control study population of 1,705 PC cases and 1,084 controls. Fifteen morbidities shared at least one gene with PC in the DisGeNET database. Based on common genes, several AIDs were genetically associated with PC pointing to a potential link between them. An epidemiologic analysis confirmed that having any of the nine AIDs studied was significantly associated with a reduced risk of PC (Odds Ratio (OR) = 0.74, 95% confidence interval (CI) 0.58-0.93) which decreased in subjects having ≥2 AIDs (OR = 0.39, 95%CI 0.21-0.73). In independent analyses, polymyalgia rheumatica, and rheumatoid arthritis were significantly associated with low PC risk (OR = 0.40, 95%CI 0.19-0.89, and OR = 0.73, 95%CI 0.53-1.00, respectively). Several inflammatory-related morbidities shared a common genetic component with PC based on public databases. These molecular links could shed light into the molecular mechanisms underlying PC development and simultaneously generate novel hypotheses. In our study, we report sound findings pointing to an association between AIDs and a reduced risk of PC.

Accounting for ocean connectivity and hydroclimate in fish recruitment fluctuations within transboundary metapopulations.

Marine resources stewardships are progressively becoming more receptive to an effective incorporation of both ecosystem and environmental complexities into the analytical frameworks of fisheries assessment. Understanding and predicting marine fish production for spatially and demographically complex populations in changing environmental conditions is however still a difficult task. Indeed, fisheries assessment is mostly based on deterministic models that lack realistic parameterizations of the intricate biological and physical processes shaping recruitment, a cornerstone in population dynamics. We use here a large metapopulation of a harvested fish, the European hake (Merluccius merluccius), managed across transnational boundaries in the northwestern Mediterranean, to model fish recruitment dynamics in terms of physics-dependent drivers related to dispersal and survival. The connectivity among nearby subpopulations is evaluated by simulating multi-annual Lagrangian indices of larval retention, imports, and self-recruitment. Along with a proxy of the regional hydroclimate influencing early life stages survival, we then statistically determine the relative contribution of dispersal and hydroclimate for recruitment across contiguous management units. We show that inter-annual variability of recruitment is well reproduced by hydroclimatic influences and synthetic connectivity estimates. Self-recruitment (i.e., the ratio of retained locally produced larvae to the total number of incoming larvae) is the most powerful metric as it integrates the roles of retained local recruits and immigrants from surrounding subpopulations and is able to capture circulation patterns affecting recruitment at the scale of management units. We also reveal that the climatic impact on recruitment is spatially structured at regional scale due to contrasting biophysical processes not related to dispersal. Self-recruitment calculated for each management unit explains between 19% and 32.9% of the variance of recruitment variability, that is much larger than the one explained by spawning stock biomass alone, supporting an increase of consideration of connectivity processes into stocks assessment. By acknowledging the structural and ecological complexity of marine populations, this study provides the scientific basis to link spatial management and temporal assessment within large marine metapopulations. Our results suggest that fisheries management could be improved by combining information of physical oceanography (from observing systems and operational models), opening new opportunities such as the development of short-term projections and dynamic spatial management.

Relationship between DNA fragmentation of equine granulosa cells and oocyte meiotic competence after in vitro maturation.

The acquisition of equine oocyte developmental capacity is ensured by the follicular environment, such as granulosa cells, which could reflect the meiotic development potential of immature oocytes. This study evaluated the relationship between DNA fragmentation of granulosa cells, using the chromatin dispersion test, and equine oocyte meiotic development after in vitro maturation. Granulosa cells and cumulus-oocytes complexes (n = 50) were recovered from slaughterhouse-derived ovaries. Oocytes were in vitro matured, stained and evaluated under fluorescence microscopy. Maturation rates were classified into outstanding, medium and poor levels of maturation using 25th and 75th percentiles as thresholds. For DNA assessment, each sample was processed with the Ovoselect® kit (Halotech DNA). High, low and total DNA fragmentation percentages were compared among levels of maturation rates by ANOVA, followed by Duncan test. Results were expressed as mean ± SE. Total and high DNA fragmentation rates of granulosa cells were significantly higher (p < 0.05) in follicles whose oocytes had reached outstanding maturation level than those originating from follicles whose oocytes had reached poor maturation level. In conclusion, the DNA fragmentation analysis of equine granulosa cells can be a valuable test to identify equine oocytes showing the best meiotic competence after in vitro maturation.

Low-density lipoproteins and milk serum proteins improve the quality of stallion sperm after vitrification in straws.

Lipids and proteins can be used for sperm vitrification to preserve the integrity of sperm membranes or to increase the viscosity of the medium. This study evaluated the effect of low-density lipoproteins (LDL) and milk serum proteins (Pronexcell) for stallion sperm vitrification. Hippex extender (Barex Biochemical Products, The Netherlands), plus 1% of bovine serum albumin and 100 mM of trehalose, was used as control for sperm vitrification. In experiment 1, different concentrations of LDL (L1 = 0.25, L2 = 0.5, L3 = 1%) and in experiment 2 of Pronexcell (P1 = 1, P2 = 5, P3 = 10%) were added to control extender. Vitrification was performed in 0.25-ml straws directly plunged into liquid nitrogen. Total motility (TM, %) and progressive motility (PM, %) were analysed by CASA, and plasma membrane (IMS, %) and acrosome membrane integrity (AIS, %) were assessed under epifluorescence microscopy. Post-warmed sperm parameters were compared between treatments by ANOVA. Results were expressed as mean ± SEM. In both experiments, the minimum concentration of LDL and Pronexcell obtained significantly higher values (p < 0.01) than the control extender for TM (L1 = 52.95 ± 4.4; P1 = 58.99 ± 4.6; C = 30.88 ± 3.0), PM (L1 = 36.79 ± 5.5; P1 = 47.25 ± 4.3; C = 19.20 ± 2.4), IMS (L1 = 68.88 ± 3.6; P1 = 47.25 ± 4.3; C = 52.81 ± 2.6) and AIS (L1 = 45.88 ± 3.6; P1 = 47.25 ± 4.3; C = 26.00 ± 2.1). No differences in sperm parameters were found among different concentrations of LDL or Pronexcell. In conclusion, the addition of 0.25% LDL and 1% Pronexcell to the vitrification extender is recommended to improve the quality of stallion sperm after vitrification.