Understanding the response of the Western Mediterranean cephalopods to environment and fishing in a context of alleged winners of change.

Increasing impacts of both fisheries and climate change have resulted in shifts in the structure and functioning of marine communities. One recurrent observation is the rise of cephalopods as fish recede. This is generally attributed to the removal of main predators and competitors by fishing, while mechanistic evidence is still lacking. In addition, climate change may influence cephalopods due to their high environmental sensitivity. We aim to unveil the effects of different anthropogenic and environmental drivers at different scales focusing on the cephalopod community of the Western Mediterranean Sea. We investigate several ecological indicators offering a wide range of information about their ecology, and statistically relating them with environmental, biotic and fisheries drivers. Our results highlight non-linear changes of indicators along with spatial differences in their responses. Overall, the environment drivers have greater effects than biotic and local human impacts with contrasting effects of temperature across the geographic gradient. We conclude that cephalopods may be impacted by climate change in the future while not necessary through positive warming influence, which should make us cautious when referring to them as generalized winners of current changes.

Spatial structuring of Mediterranean fisheries landings in relation to their seasonal and long-term fluctuations.

The Western Mediterranean fisheries significantly contribute to the regional blue economy, despite evidence of ongoing, widespread overexploitation of stocks. Understanding the spatial distribution and population dynamics of species is crucial for comprehending fisheries dynamics combining local and regional scales, although the underlying processes are often neglected. In this study, we aimed to (i) evaluate the seasonal and long-term spatio-temporal fluctuations of crustacean, cephalopod, and fish populations in the Western Mediterranean, (ii) determine whether these fluctuations are driven by the spatial structure of the fisheries or synchronic species fluctuations, and (iii) compare groupings according to the individual species and life history-based groups. We used dynamic factor analysis to detect underlying patterns in a Landing Per Unit Effort (LPUE) time series (2009-2020) for 23 commercially important species and 33 ports in the Western Mediterranean. To verify the spatial structure of ports and species groupings we investigated the seasonal and long-term spatio-temporal fluctuations and common LPUE trends that exhibit non-homogeneous and species-specific trends, highlighting the importance of life history, environmental and demographic preferences. Long-term trends revealed spatial segregation with a north-south gradient, demonstrating complex population structures of Western Mediterranean resources. Seasonal patterns exhibited a varying spatial aggregation based on species-port combinations. These findings can inform the Common Fishery Policy on gaps challenging their regionalisation objectives in the Mediterranean Sea. We highlight the need for a nuanced and flexible approach and a better understanding of sub-regional processes for effective management and conservation - a current challenge for global fisheries. Our LPUE approach provides insight into population dynamics and changes in regional fisheries, relevant beyond the Mediterranean Sea.

Cross-basin and cross-taxa patterns of marine community tropicalization and deborealization in warming European seas.

Ocean warming and acidification, decreases in dissolved oxygen concentrations, and changes in primary production are causing an unprecedented global redistribution of marine life. The identification of underlying ecological processes underpinning marine species turnover, particularly the prevalence of increases of warm-water species or declines of cold-water species, has been recently debated in the context of ocean warming. Here, we track changes in the mean thermal affinity of marine communities across European seas by calculating the Community Temperature Index for 65 biodiversity time series collected over four decades and containing 1,817 species from different communities (zooplankton, coastal benthos, pelagic and demersal invertebrates and fish). We show that most communities and sites have clearly responded to ongoing ocean warming via abundance increases of warm-water species (tropicalization, 54%) and decreases of cold-water species (deborealization, 18%). Tropicalization dominated Atlantic sites compared to semi-enclosed basins such as the Mediterranean and Baltic Seas, probably due to physical barrier constraints to connectivity and species colonization. Semi-enclosed basins appeared to be particularly vulnerable to ocean warming, experiencing the fastest rates of warming and biodiversity loss through deborealization.

Evaluation of Improvest effects on production parameters of gilts from two different genetic sire lines.

The objective was to evaluate the effects of Improvest on the performance and carcass characteristics of gilts from two different genetic sire lines and the performance of Improvest gilts with castrated male pigs. It was hypothesized that performance parameters observed for Improvest gilts would be similar to barrows, thus narrowing the performance gaps between traditionally managed gilts and barrows. Pigs were from Large White/Landrace dams and either Duroc-Pietrain (DP) or Duroc (D) sires. Females within each genetic sire line were randomized by weight to receive the first dose of Improvest (IMP) on day 25 of the study or to serve as a nontreated control (DP IMP gilt (n = 6 pens; 19 pigs/pen), D IMP gilt (n = 6 pens; 19 pigs/pen), DP CON gilt (n = 6 pens; 19 pigs/pen), D CON gilt (n = 6 pens; 19 pigs/pen). The second dose of Improvest was administered 6 wk later (i.e., day 67). Barrows did not receive Improvest (DP barrow [n = 10 pens; 19 to 20 pigs/pen], D barrow [n = 10 pens; 19 to 20 pigs/pen]). Average daily gain (ADG), average daily feed intake (ADFI), and gain-to-feed ratio (G:F) were measured at 21 d intervals throughout the duration of the study. The targeted weight for pigs to be marketed was 133 ±â€…2.5 kg. Carcass characteristics and loin quality parameters were evaluated on a subset of pigs (n = 283). Improvest-treated gilts of both genetic lines had increased (P ≤ 0.05) ADG and ADFI compared to untreated gilts during the post-second dose intervals with values exceeding that of barrows from day 84 to marketing. Overall, DP IMP gilts had increased (P ≤ 0.05) G:F post-second dose compared to DP CON gilts and DP barrows, yet all other treatments were similar. As pigs were marketed at a similar weight, there was no difference in the final weight, however, DP IMP gilts and DP barrows reached market weight sooner (P ≤ 0.05) than DP CON gilts (109.9 and 111.8 vs. 114.3 ±â€…0.8 d). Backfat and loin weight were greater (P < 0.01) in IMP gilts versus CON gilts, while IMP gilts and barrows had similar values within each respective genetic sire line. There were no differences between treatments (P ≥ 0.08) for pH and instrumental color of the loins. When the pass rate of loins (Japanese color score ≥ 3.0 and marbling ≥ 2.0) was evaluated, IMP gilts were at intermediate values between CON gilts and barrows for each respective genetic sire line. Overall, Improvest within a genetic line improved gilt carcass measurements so that they were more similar to barrows.

Spatial patterns of ß-diversity under cumulative pressures in the Western Mediterranean Sea.

Understanding the spatial dynamics of biodiversity is an essential issue in marine ecology and requires combining information at local and regional scales. ß-diversity is an important measure of biodiversity that informs on the differences in community composition between sites and, thus, in the species turnover in the community structure. In this study, we analysed and predicted the spatial patterns of ß-diversity for fishes, invertebrates and the demersal assemblage along the Iberian Mediterranean coast. We used Bayesian Bootstrap Generalized Dissimilarity Models (BBGDMs) to study the effects of environment and human pressures on the ß-diversity of invertebrate, fishes and the entire demersal assemblage from 1994 to 2015 using different time windows to account for temporal variability. Then, we used these relationships to predict the spatial patterns of ß-diversity in the whole Iberian Mediterranean coast. Our results highlighted that the regional spatial patterns of ß-diversity were best described by bathymetry and a cumulative index of coastal impacts. We identified specific regions with the highest ß-diversity in the study area, which were complementary to hotspots of species richness and presented different degree of overlapping with existent marine protected areas. Overall, our study illustrates that by modelling spatial turnover using ß-diversity we can better understand and predict spatial variation of biodiversity and the effects of particular variables, providing relevant information to end-users and policy makers for designing specific spatial conservation and management strategies.

Determinantes del estado de vacunación infantil: abordando la brecha de equidad en República Dominicana-2019 / Determinants of childhood immunization status: addressing the equity gap in the Dominican Republic­2019

Introducción: Las desigualdades amenazan el progreso del país hacia la equidad y la cobertura de vacunación infantil. Siendo la cobertura inferior a la meta del 90% de la Organización Mundial de la Salud. Objetivo: Identificar los determinantes sociales y las desigualdades en el estado de vacunación infantil en República Dominicana, 2019. Métodos: Se realiza un análisis basado en la Encuesta de Indicadores Múltiples por Conglomerados. Incluyendo una muestra ponderada de 1674 niños de 12-23 meses. Se calcula la regresión logística multinomial para identificar factores asociados a la vacunación. Adoptando p<0,05 para significación estadística. Utilizando una razón de probabilidades ajustada con intervalo de confianza del 95%. Empleando HEAT 4.0 para medir desigualdades y SPSS.23 para gestión y análisis de datos. Resultados: La edad media de los niños fue 17,4±3,5 meses. El 33% de ellos estaban completamente vacunados. La cobertura fue significativamente menor entre hijos de madre sin educación [AOR= 7,27; IC95%= 2,98­17,74]. La mayor cobertura se concentra en niños con altos niveles de educación y riqueza. Conclusión: Para lograr una cobertura de vacunación completa y equitativa, las intervenciones de salud pública deben diseñarse para satisfacer las necesidades de grupos de alto riesgo.

Introduction: In the Dominican Republic, inequalities threaten progress towards childhood vaccination equity and coverage, the latter being inferior to the World Health Organization's 90% goal. Objective: Identify the social determinants and inequalities in the state of childhood vaccination in the Dominican Republic, 2019. Methods: An analysis based on the Multiple Indicator Cluster Surveys is conducted. Including a weighted sample of 1674 children aged 12-23 months. The multinomial logistic regression is calculated to identify factors associated with vaccination. Using p<0,05 for statistical significance and an adjusted probability ratio with a 95% confidence interval. Employing HEAT 4.0 to measure inequalities and SPSS.23 for data management and analysis. Results: The children's mean age was 17,4±3,5 months. 33% of them were completely vaccinated. Coverage was significantly lower in children of mothers without education [AOR= 7,27; CI95%= 2,98­17,74]. Coverage was the highest in kids with high levels of education and wealth. Conclusion: To achieve complete and equitable vaccine coverage, public health interventions should be designed to satisfy the needs of high-risk groups.

Inhibiting NR5A2 targets stemness in pancreatic cancer by disrupting SOX2/MYC signaling and restoring chemosensitivity.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a profoundly aggressive and fatal cancer. One of the key factors defining its aggressiveness and resilience against chemotherapy is the existence of cancer stem cells (CSCs). The important task of discovering upstream regulators of stemness that are amenable for targeting in PDAC is essential for the advancement of more potent therapeutic approaches. In this study, we sought to elucidate the function of the nuclear receptor subfamily 5, group A, member 2 (NR5A2) in the context of pancreatic CSCs. METHODS: We modeled human PDAC using primary PDAC cells and CSC-enriched sphere cultures. NR5A2 was genetically silenced or inhibited with Cpd3. Assays included RNA-seq, sphere/colony formation, cell viability/toxicity, real-time PCR, western blot, immunofluorescence, ChIP, CUT&Tag, XF Analysis, lactate production, and in vivo tumorigenicity assays. PDAC models from 18 patients were treated with Cpd3-loaded nanocarriers. RESULTS: Our findings demonstrate that NR5A2 plays a dual role in PDAC. In differentiated cancer cells, NR5A2 promotes cell proliferation by inhibiting CDKN1A. On the other hand, in the CSC population, NR5A2 enhances stemness by upregulating SOX2 through direct binding to its promotor/enhancer region. Additionally, NR5A2 suppresses MYC, leading to the activation of the mitochondrial biogenesis factor PPARGC1A and a shift in metabolism towards oxidative phosphorylation, which is a crucial feature of stemness in PDAC. Importantly, our study shows that the specific NR5A2 inhibitor, Cpd3, sensitizes a significant fraction of PDAC models derived from 18 patients to standard chemotherapy. This treatment approach results in durable remissions and long-term survival. Furthermore, we demonstrate that the expression levels of NR5A2/SOX2 can predict the response to treatment. CONCLUSIONS: The findings of our study highlight the cell context-dependent effects of NR5A2 in PDAC. We have identified a novel pharmacological strategy to modulate SOX2 and MYC levels, which disrupts stemness and prevents relapse in this deadly disease. These insights provide valuable information for the development of targeted therapies for PDAC, offering new hope for improved patient outcomes. A Schematic illustration of the role of NR5A2 in cancer stem cells versus differentiated cancer cells, along with the action of the NR5A2 inhibitor Cpd3. B Overall survival of tumor-bearing mice following allocated treatment. A total of 18 PDX models were treated using a 2 x 1 x 1 approach (two animals per model per treatment); n=36 per group (illustration created with biorender.com ).

Timing of maternal nutrient restriction during mid- to late-gestation influences net umbilical uptake of glucose and amino acids in adolescent sheep.

Previous research demonstrated that maternal nutrient restriction during mid- to late-gestation influenced net umbilical uptakes of glucose and amino acids in sheep. However, it is unclear how the timing and duration of nutrient restriction during mid- to late-gestation influences net uterine, uteroplacental, and fetal flux of glucose and amino acids. On day 50 of gestation, 41 adolescent ewe lambs carrying singletons were randomly assigned to one of six dietary treatments: 1) 100% of nutrient requirements from days 50 to 90 of gestation (CON; n = 7); 2) 60% of nutrient requirements (RES; n = 7) from days 50 to 90 of gestation; 3) 100% of nutrient requirements from days 50 to 130 of gestation (CON-CON; n = 6); 4) 100% of nutrient requirements from days 50 to 90 of gestation and 60% of nutrient requirements from days 90 to 130 of gestation (CON-RES; n = 7); 5) 60% of nutrient requirements from days 50 to 90 of gestation and 100% of nutrient requirements from days 90 to 130 of gestation (RES-CON; n = 7); or 6) 60% of nutrient requirements from days 50 to 130 of gestation (RES-RES; n = 7). On day 90 (n = 14) and day 130 (n = 27), intraoperative procedures were performed to evaluate uteroplacental blood flows, collect blood samples, and then ewes were euthanized. Net uterine, uteroplacental, and umbilical fluxes of glucose and amino acids were calculated by multiplying blood flow by the arterial-venous concentration difference. Data from days 90 and 130 were analyzed separately using ANOVA in SAS. Maternal nutrient restriction during mid-gestation increased (P = 0.04) net umbilical glucose uptake but, maternal nutrient restriction during late-gestation decreased (P = 0.02) net umbilical glucose uptake. Net umbilical essential amino acid uptake decreased (P = 0.03) with nutrient restriction during mid-gestation; however, net umbilical uptakes of Phe (P = 0.02), Thr (P = 0.05), Met (P = 0.09), and His (P = 0.08) increased or tended to increase after nutrient restriction during late-gestation. These data demonstrate that net umbilical glucose and amino acid uptakes were influenced by the timing of nutrient restriction during mid- to late-gestation. Elevated net umbilical glucose uptake after mid-gestational nutrient restriction was sustained throughout late-gestation, independent of late-gestational feeding level. Long-term adaptations in umbilical glucose uptake may have implications for prenatal and postnatal growth and development of the offspring.

Maternal undernutrition during gestation can lead to decreased fetal growth, decreased uteroplacental blood flow, and changes in nutrient supply to the fetus. However, it is unclear how the timing (mid-gestation vs. late-gestation) and duration (40 d vs. 80 d) of nutrient restriction influence nutrient supply to the fetus during mid- to late-gestation. Pregnant ewe lambs fed a pelleted diet to meet 100% of nutritional requirements or 60% of nutritional requirements during mid-gestation alone (days 50 to 90) or during mid- and late-gestation (days 50 to 130). At the end of mid-gestation and late-gestation, the net nutrient supply between the maternal, placental, and fetal compartments was measured. The results indicated that the timing of nutrient restriction influenced the net nutrient supply to the fetus but, the duration of nutrient restriction did not. Nutrient restriction during mid-gestation increased glucose to the fetus but nutrient restriction during late-gestation decreased glucose to the fetus. The opposite response occurred for fetal essential amino acid supply where nutrient restriction during mid-gestation decreased essential amino acid supply to the fetus but increased for several essential amino acids during late-gestational nutrient restriction. The timing of maternal undernutrition during mid- to late-gestation can affect the amount of nutrients delivered to the fetus and thus, could potentially impact postnatal growth and development.

The effect of timing of Improvest administration on growth performance and carcass characteristics in gilts.

Improvest (IMP; Zoetis Inc., Parsippany, NJ) has been approved by the U.S. Food and Drug Administration for use in gilts. Improvest is administered twice: the first dose should be administered no earlier than 9 wk of age and the second dose (D2) at least 4 wk after the first dose. The aim of this study was to determine how the timing of IMP before harvest affects growth performance and carcass characteristics in gilts. A total of 1,632 gilts were allocated to four groups (12 pens/treatment; 34 gilts/pen): 1) a control group did not receive IMP; 2) T-early gilts received IMP on day 7 (day 0 = 10 wk postweaning), and D2 on day 40 (i.e., 35 d prior to first removal for harvest); 3) T-medium gilts received IMP on day 21 and D2 on day 56 (i.e., 19 d prior to first removal for harvest); 4) T-late gilts received IMP on day 35 and D2 on day 70 (i.e., 5 d before first removal for harvest). Pigs were selected for harvest by visual observation on days 75, 89, 103, and 117: 1) the heaviest 7 gilts/pen for each treatment on day 75; 2) the heaviest 10 gilts/pen of each treatment at day 89; 3) the heaviest 10 gilts/pen of each treatment on day 103; and 4) the remaining 7 gilts/pen on day 117. Weights and feed disappearance were recorded every 2 wk and during harvest dates to calculate average daily gain (ADG), average daily feed intake (ADFI), and feed efficiency (Gain:Feed; G:F). Generalized linear mixed models of SAS were used to analyze all variables. The increase in ADFI over Control gilts was observed 15 d post D2 and continued through 77 d post D2, with advantages in ADG occurring between 15 and 35 d post D2. Control and IMP treated gilts had similar G:F 15 to 33 d post D2. The overall ADG and ADFI from day 0 to market, final live weights, and hot carcass weights were significantly greater (P ≤ 0.05) in IMP gilts compared to Control. When G:F based on live weight was averaged across all groups (i.e., from day 0 to market), T-early had the lowest (P ≤ 0.05) G:F compared to Control, T-medium, and T-late gilts, which did not differ. Carcasses from IMP gilts had increased (P < 0.01) backfat, but similar (P = 0.5) Longissimus muscle depth, compared to Control. Within a cohort of similar aged gilts finishing during the summer, this study indicates that the trajectory of growth is enhanced within a similar window post D2 of IMP. Gilts treated with IMP had heavier carcasses with increased backfat and similar Longissimus muscle depth.

Analysis of lncRNAs in Lupinus mutabilis (Tarwi) and Their Potential Role in Drought Response.

Lupinus mutabilis is a legume with high agronomic potential and available transcriptomic data for which lncRNAs have not been studied. Therefore, our objective was to identify, characterize, and validate the drought-responsive lncRNAs in L. mutabilis. To achieve this, we used a multilevel approach based on lncRNA prediction, annotation, subcellular location, thermodynamic characterization, structural conservation, and validation. Thus, 590 lncRNAs were identified by at least two algorithms of lncRNA identification. Annotation with the PLncDB database showed 571 lncRNAs unique to tarwi and 19 lncRNAs with homology in 28 botanical families including Solanaceae (19), Fabaceae (17), Brassicaceae (17), Rutaceae (17), Rosaceae (16), and Malvaceae (16), among others. In total, 12 lncRNAs had homology in more than 40 species. A total of 67% of lncRNAs were located in the cytoplasm and 33% in exosomes. Thermodynamic characterization of S03 showed a stable secondary structure with -105.67 kcal/mol. This structure included three regions, with a multibranch loop containing a hairpin with a SECIS-like element. Evaluation of the structural conservation by CROSSalign revealed partial similarities between L. mutabilis (S03) and S. lycopersicum (Solyc04r022210.1). RT-PCR validation demonstrated that S03 was upregulated in a drought-tolerant accession of L. mutabilis. Finally, these results highlighted the importance of lncRNAs in tarwi improvement under drought conditions.

Matching an Old Marine Paradigm: Limitless Connectivity in a Deep-Water Fish over a Large Distance.

Investigations of population structuring in wild species are fundamental to complete the bigger picture defining their ecological and biological roles in the marine realm, to estimate their recovery capacity triggered by human disturbance and implement more efficient management strategies for fishery resources. The Blackspot Seabream (Pagellus bogaraveo, Brünnich 1768) is a commercially valuable deep-water fish highly exploited over past decades. Considering its exploitation status, deepening the knowledge of intraspecific variability, genetic diversity, and differentiation using high-performing molecular markers is considered an important step for a more effective stock assessment and fishery management. With one of the largest efforts conceived of and completed by countries overlooking the Atlantic and Mediterranean coasts in recent years, a total of 320 individuals were collected from different fishing grounds in the Mediterranean Sea and Atlantic Ocean and analysed using 29 microsatellite loci. We applied multiple statistical approaches to investigate the species' connectivity and population structure across most of its described distribution area. Considering the incomplete knowledge regarding the migratory behaviour of adults, here we suggest the importance of egg and larval dispersal in sustaining the observed genetic connectivity on such a large geographical scale.

Selection and Conservation of Gametes and Embryos for Improving Assisted Reproductive Technologies.

We are delighted to present this Special Issue, which is dedicated to the paramount subject of gametes and embryo selection and conservation for improving Assisted Reproductive Technologies (ARTs) [...].

Neoadjuvant botensilimab plus balstilimab response pattern in locally advanced mismatch repair proficient colorectal cancer.

In patients with locally advanced cancer without distant metastases, the neoadjuvant setting presents a platform to evaluate new drugs. For mismatch repair proficient/microsatellite stable (pMMR/MSS) colon and rectal cancer, immunotherapy has shown limited efficacy. Herein, we report exceptional responses observed with neoadjuvant botensilimab (BOT), an Fc-enhanced next-generation anti-CTLA-4 antibody, alongside balstilimab (BAL; an anti-PD-1 antibody) in two patients with pMMR/MSS colon and rectal cancer. The histological pattern of rapid immune response observed ("inside-out" (serosa-to-mucosa) tumor regression) has not been described previously in this setting. Spatial biology analyses (RareCyte Inc.) reveal mechanisms of actions of BOT, a novel innate-adaptive immune activator. These observations have downstream implications for clinical trial designs using neoadjuvant immunotherapy and potentially sparing patients chemotherapy.

Spatiotemporal and meteorological relationships in dengue transmission in the Dominican Republic, 2015-2019.

Dengue has broadened its global distribution substantially in the past two decades, and many endemic areas are experiencing increases in incidence. The Dominican Republic recently experienced its two largest outbreaks to date with 16,836 reported cases in 2015 and 20,123 reported cases in 2019. With continued increases in dengue transmission, developing tools to better prepare healthcare systems and mosquito control agencies is of critical importance. Before such tools can be developed, however, we must first better understand potential drivers of dengue transmission. To that end, we focus in this paper on determining relationships between climate variables and dengue transmission with an emphasis on eight provinces and the capital city of the Dominican Republic in the period 2015-2019. We present summary statistics for dengue cases, temperature, precipitation, and relative humidity in this period, and we conduct an analysis of correlated lags between climate variables and dengue cases as well as correlated lags among dengue cases in each of the nine locations. We find that the southwestern province of Barahona had the largest dengue incidence in both 2015 and 2019. Among all climate variables considered, lags between relative humidity variables and dengue cases were the most frequently correlated. We found that most locations had significant correlations with cases in other locations at lags of zero weeks. These results can be used to improve predictive models of dengue transmission in the country.

Theoretical FRET Efficiency of an Antenna Material Containing Natural Dyes and Zeolite L.

We calculated the Förster resonance energy-transfer (FRET) efficiency of a theoretical host-guest composite formed by all-trans ß-cryptoxanthin (BCRY), all-trans zeaxanthin (ZEA), and a zeolite-LTL (Linde Type L) nanochannel with the help of computational chemistry tools. Climate change demands urgently the development of novel renewable energies, and in such a context, artificial photosynthesis arises as a promising technology capable of contributing to satisfying humankind's energy needs. All artificial photosynthetic devices need antennas to harvest and transfer energy to a reaction center efficiently. Antenna materials integrated by highly fluorescent synthetic pigments embedded onto the nanochannels of a zeolite-LTL have already been shown experimentally to be very efficient supramolecular assemblies. However, research work computing the efficiency of an antenna made of nonfluorescent natural pigments and a zeolite-LTL nanochannel has not been undertaken yet, at least to our knowledge. Fortunately, natural dyes possess outstanding features to study them dynamically; they are environmentally friendly, inexpensive, ubiquitous, and abundant. Density functional theory (DFT) methods were chiefly employed along with the CAM-B3LYP functional and the 3-21G*/6-311+G(d,p) basis sets. The ONIOM method enabled geometry and energy calculations of dyes inside the zeolite-LTL (ZL) nanochannel. The Förster resonance energy-transfer (FRET) efficiency and the Förster radius of the composite were 40.9% and 24.9 Å, respectively. Theoretical findings suggested that this composite might contribute to diminishing costs and improving the environmental friendliness of an antenna system.

ACT-Discover: identifying karyotype heterogeneity in pancreatic cancer evolution using ctDNA.

BACKGROUND: Liquid biopsies and the dynamic tracking of somatic mutations within circulating tumour DNA (ctDNA) can provide insight into the dynamics of cancer evolution and the intra-tumour heterogeneity that fuels treatment resistance. However, identifying and tracking dynamic changes in somatic copy number alterations (SCNAs), which have been associated with poor outcome and metastasis, using ctDNA is challenging. Pancreatic adenocarcinoma is a disease which has been considered to harbour early punctuated events in its evolution, leading to an early fitness peak, with minimal further subclonal evolution. METHODS: To interrogate the role of SCNAs in pancreatic adenocarcinoma cancer evolution, we applied whole-exome sequencing of 55 longitudinal cell-free DNA (cfDNA) samples taken from 24 patients (including 8 from whom a patient-derived xenograft (PDX) was derived) with metastatic disease prospectively recruited into a clinical trial. We developed a method, Aneuploidy in Circulating Tumour DNA (ACT-Discover), that leverages haplotype phasing of paired tumour biopsies or PDXs to identify SCNAs in cfDNA with greater sensitivity. RESULTS: SCNAs were observed within 28 of 47 evaluable cfDNA samples. Of these events, 30% could only be identified by harnessing the haplotype-aware approach leveraged in ACT-Discover. The exceptional purity of PDX tumours enabled near-complete phasing of genomic regions in allelic imbalance, highlighting an important auxiliary function of PDXs. Finally, although the classical model of pancreatic cancer evolution emphasises the importance of early, homogenous somatic events as a key requirement for cancer development, ACT-Discover identified substantial heterogeneity of SCNAs, including parallel focal and arm-level events, affecting different parental alleles within individual tumours. Indeed, ongoing acquisition of SCNAs was identified within tumours throughout the disease course, including within an untreated metastatic tumour. CONCLUSIONS: This work demonstrates the power of haplotype phasing to study genomic variation in cfDNA samples and reveals undiscovered intra-tumour heterogeneity with important scientific and clinical implications. Implementation of ACT-Discover could lead to important insights from existing cohorts or underpin future prospective studies seeking to characterise the landscape of tumour evolution through liquid biopsy.

Long COVID in Cancer: A Matched Cohort Study of 1-year Mortality and Long COVID Prevalence Among Patients With Cancer Who Survived an Initial Severe SARS-CoV-2 Infection.

OBJECTIVES: The long-term effects of severe acute respiratory syndrome coronavirus 2 (coronavirus disease 2019 [COVID-19]) infection in patients with cancer are unknown. We examined 1-year mortality and prevalence of long COVID in patients with and without cancer after initial hospitalization for acute COVID-19 infection. METHODS: We previously studied 585 patients hospitalized from March to May 2020 with acute COVID-19 infection at Weill Cornell Medicine (117 patients with cancer and 468 age, sex, and comorbidity-matched non-cancer controls). Of the 456 patients who were discharged, we followed 359 patients (75 cancer and 284 non-cancer controls) for COVID-related symptoms and death, at 3, 6, and 12 months after initial symptom onset. Pearson χ 2 and Fisher exact tests were used to determine associations between cancer, postdischarge mortality, and long COVID symptoms. Multivariable Cox proportional hazards models adjusting for potential confounders were used to quantify the risk of death between patients with and without cancer. RESULTS: The cancer cohort had higher mortality after hospitalization (23% vs 5%, P < 0.001), a hazard ratio of 4.7 (95% CI: 2.34-9.46) for all-cause mortality, after adjusting for smoking and oxygen requirement. Long COVID symptoms were observed in 33% of patients regardless of cancer status. Constitutional, respiratory, and cardiac complaints were the most prevalent symptoms in the first 6 months, whereas respiratory and neurological complaints (eg, "brain fog" and memory deficits) were most prevalent at 12 months. CONCLUSIONS: Patients with cancer have higher mortality after hospitalization for acute severe acute respiratory syndrome coronavirus 2 infections. The risk of death was highest in the first 3 months after discharge. About one-third of all patients experienced long COVID.

A Large-Scale Proteomics Resource of Circulating Extracellular Vesicles for Biomarker Discovery in Pancreatic Cancer.

Pancreatic cancer has the worst prognosis of all common tumors. Earlier cancer diagnosis could increase survival rates and better assessment of metastatic disease could improve patient care. As such, there is an urgent need to develop biomarkers to diagnose this deadly malignancy earlier. Analyzing circulating extracellular vesicles (cEVs) using 'liquid biopsies' offers an attractive approach to diagnose and monitor disease status. However, it is important to differentiate EV-associated proteins enriched in patients with pancreatic ductal adenocarcinoma (PDAC) from those with benign pancreatic diseases such as chronic pancreatitis and intraductal papillary mucinous neoplasm (IPMN). To meet this need, we combined the novel EVtrap method for highly efficient isolation of EVs from plasma and conducted proteomics analysis of samples from 124 individuals, including patients with PDAC, benign pancreatic diseases and controls. On average, 912 EV proteins were identified per 100µL of plasma. EVs containing high levels of PDCD6IP, SERPINA12 and RUVBL2 were associated with PDAC compared to the benign diseases in both discovery and validation cohorts. EVs with PSMB4, RUVBL2 and ANKAR were associated with metastasis, and those with CRP, RALB and CD55 correlated with poor clinical prognosis. Finally, we validated a 7-EV protein PDAC signature against a background of benign pancreatic diseases that yielded an 89% prediction accuracy for the diagnosis of PDAC. To our knowledge, our study represents the largest proteomics profiling of circulating EVs ever conducted in pancreatic cancer and provides a valuable open-source atlas to the scientific community with a comprehensive catalogue of novel cEVs that may assist in the development of biomarkers and improve the outcomes of patients with PDAC.

Development of a 3D Printed Brain Model with Vasculature for Neurosurgical Procedure Visualisation and Training.

BACKGROUND: Simulation-based techniques using three-dimensional models are gaining popularity in neurosurgical training. Most pre-existing models are expensive, so we felt a need to develop a real-life model using 3D printing technology to train in endoscopic third ventriculostomy. METHODS: The brain model was made using a 3D-printed resin mold from patient-specific MRI data. The mold was filled with silicone Ecoflex™ 00-10 and mixed with Silc Pig® pigment additives to replicate the color and consistency of brain tissue. The dura mater was made from quick-drying silicone paste admixed with gray dye. The blood vessels were made from a silicone 3D-printed mold based on magnetic resonance imaging. Liquid containing paprika oleoresin dye was used to simulate blood and was pumped through the vessels to simulate pulsatile motion. RESULTS: Seven residents and eight senior neurosurgeons were recruited to test our model. The participants reported that the size and anatomy of the elements were very similar to real structures. The model was helpful for training neuroendoscopic 3D perception and navigation. CONCLUSIONS: We developed an endoscopic third ventriculostomy training model using 3D printing technology that provides anatomical precision and a realistic simulation. We hope our model can provide an indispensable tool for young neurosurgeons to gain operative experience without exposing patients to risk.

The trade-off between condition and growth shapes juveniles' survival of harvested demersal fish of the Mediterranean sea.

Fish body condition and growth are two interrelated traits closely associated with species life history and fitness, whose trade-off can ultimately impact population dynamics albeit seldom empirically demonstrated. They can intricately affect survival rates, which are particularly relevant for species under exploitation. Using individual spatiotemporal information in Northwestern Mediterranean, we document for the first time the existence of a trade-off between condition and growth in regulating survival dynamics in two important fish species for the Mediterranean fisheries that are characterized by contrasting life histories. For the European hake (Merluccius merluccius), a benthopelagic species, juveniles' body condition was detected to be positively linked to survival and negatively associated with the growth of this age group. For the red mullet (Mullus barbatus), the same pattern was observed for young adults. We also show that the observed patterns on a regional level have a clear spatial dependence as we found that observed body condition over a local scale had a broad effect on the population dynamics of the whole region, with the Ebro delta area emerging as the demographic engine of the two species. We discuss our results in the context of fisheries management and underline the importance of improving current stock assessment models and spatially based fishery management towards incorporating body condition and growth due to their influence on important parameters such as survival.