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Background Radiological complete response (CR-MRI) to neoadjuvant chemotherapy (NAC) by MRI predicts pathologic complete response (pCR) rates in pts with TNBC treated preoperatively with A/TX-based regimens and in some studies, it correlates with disease-free survival (DFS). The main aim of this study was to assess the relevance of the MRI response to primary chemotherapy associated with clinical stage and HER2 expression (Zero vs Low), in a cohort of 143 TNBC pts treated with A and TX +/- carboplatin (CP) in the NAC setting. Methods Retrospective study of pts treated with NAC for TNBC between January 2002 and June 2021, who underwent MRI to assess tumour response before NAC, after 4 cycles of anthracycline and cyclophosphamide (AC) and after TX. Survival analysis was based on the Kaplan-Meier and survival curves were compared using the log-rank test. A p value of less than 0.05 was considered as statistically significant. Results A total of 143 TNBC pts with a median age of 52 years; 7, 63 and 73 pts had stage I, II and III disease, respectively. The NAC regimen consisted in 117 pts 4 cycles of AC followed by TX and in 24 pts the same adding CP (in 21 pts with non-CR-MRI, 2 with CR-MRI and 1 without MRI after AC). PCR was observed in 41%. Of 30 pts with CR-MRI after AC, 83% obtain a pCR (p< 0.001), and of 52 pts with CR-MRI at the end of NAC, 70.7% obtain a pCR (p< 0,001) of which 90% had a CR-MRI after AC. Adding CP increased pCR by 6% (p=0.564). According HER2-zero vs low expression, the pCR was 38% and 47% respectively, with no significant differences. With a median follow-up of 60 months, 34% recurred and 16% died of TNBC. In pts with pCR, the DFS at 5 years (y) was 96% and 47% for pts without pCR (p< 0.001), with a DFS of 91% if CR-MRI at the end of NAC and 48% if non-CR-MRI (p< 0.001). In HER2-Zero tumours the DFS at 5 y was 64% vs 66% in HER-2 low. Interestingly, overall survival (OS) at 5 y was 72% in HER2-Zero and 84% in HER2-low (p=0.080). Conclusions Performing serial MRI in the course of NAC in TNBC may be a reliable indicator of pCR, adding platinum to TX in pts with CR-MRI may increase pCR rate. HER2-Zero expression in TNBC, seems to confer worse OS rates. Citation Format: Marina Sierra Boada, Luis Antonio Fernandez, Elsa Dalmau, Gemma Llort, Maria Marin, Pablo Andreu, Natalia Lopez, Carla Climent, Marta Rodriguez, Sandra Soriano, Miquel Angel Segui. Magnetic resonance imaging (MRI) and clinicopathological analysis of triple-negative breast cancer (TNBC) patients (pts) treated with primary anthracyclines(A)/taxanes(TX)-based chemotherapy. [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-07-40.

Adjuvant therapy; Breast cancer; Olaparib Terapia adyuvante; Cáncer de mama; Olaparib Teràpia adjuvant; Càncer de mama; Olaparib Background The randomized, double-blind OlympiA trial compared 1 year of the oral poly(adenosine diphosphate-ribose) polymerase inhibitor, olaparib, to matching placebo as adjuvant therapy for patients with pathogenic or likely pathogenic variants in germline BRCA1 or BRCA2 (gBRCA1/2pv) and high-risk, human epidermal growth factor receptor 2-negative, early breast cancer (EBC). The first pre-specified interim analysis (IA) previously demonstrated statistically significant improvement in invasive disease-free survival (IDFS) and distant disease-free survival (DDFS). The olaparib group had fewer deaths than the placebo group, but the difference did not reach statistical significance for overall survival (OS). We now report the pre-specified second IA of OS with updates of IDFS, DDFS, and safety. Patients and methods One thousand eight hundred and thirty-six patients were randomly assigned to olaparib or placebo following (neo)adjuvant chemotherapy, surgery, and radiation therapy if indicated. Endocrine therapy was given concurrently with study medication for hormone receptor-positive cancers. Statistical significance for OS at this IA required P < 0.015. Results With a median follow-up of 3.5 years, the second IA of OS demonstrated significant improvement in the olaparib group relative to the placebo group [hazard ratio 0.68; 98.5% confidence interval (CI) 0.47-0.97; P = 0.009]. Four-year OS was 89.8% in the olaparib group and 86.4% in the placebo group (Δ 3.4%, 95% CI −0.1% to 6.8%). Four-year IDFS for the olaparib group versus placebo group was 82.7% versus 75.4% (Δ 7.3%, 95% CI 3.0% to 11.5%) and 4-year DDFS was 86.5% versus 79.1% (Δ 7.4%, 95% CI 3.6% to 11.3%), respectively. Subset analyses for OS, IDFS, and DDFS demonstrated benefit across major subgroups. No new safety signals were identified including no new cases of acute myeloid leukemia or myelodysplastic syndrome. Conclusion With 3.5 years of median follow-up, OlympiA demonstrates statistically significant improvement in OS with adjuvant olaparib compared with placebo for gBRCA1/2pv-associated EBC and maintained improvements in the previously reported, statistically significant endpoints of IDFS and DDFS with no new safety signals. Funding for this work, which was conducted as a collaborative partnership among the Breast International Group, NRG Oncology, Frontier Science, AstraZeneca, and Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, U.S.A. (MSD), was provided by the National Institutes of Health (grant numbers: U10CA 180868, UG1CA 189867, and U10CA 180822) and by AstraZeneca as part of an alliance between AstraZeneca and MSD. Provision of olaparib and placebo was from AstraZeneca.

The perception of body and social odours (SOP) is crucial for interpersonal chemosensory signalling and mate choice, yet little is known about the role of the SOP on the quality of partnerships and the attachment style. The aim of this study was to investigate the role of the SOP in women’s stress responses by considering the role of biopsychosocial variables in the quality of interpersonal relationships (also considering intimate partner violence). In total, 253 women filled out an online survey that included a series of questionnaires to investigate self-perceived stress (PSS), emotional regulation (ERQ), olfactory social assessment (SOS), quality of partnership (RRQ), attachment style (RQ), and the Conflict Tactile Scale 2 (CTS-2). The main results highlight that a high awareness of social odours correlates with a good quality of relationship and with an emotional regulation capacity; the PSS correlates negatively with the ERQ (i.e., as the PSS increases, the ERQ decreases). The level of IPV predicts an interpersonal style characterized by a low desire to develop meaningful relationships but with a tendency to depend on and trust another. The idea of being hurt by the other is not central in women who experience this type of relationship. The study’s main conclusion is that social odour perception is important for emotional regulation and in partner relationships.

The COVID-19 pandemic is one of the past century's deadliest and most widespread viral outbreaks, with higher mortality rates in men than women. Disruptions in funeral rituals and customs, no social recognition of the loss, and limited social support intricate the grieving process and are linked with disenfranchised (not openly acknowledged, socially recognized, or publicly mourned) grief. Depression is also highly comorbid with complicated grief. Losing a spouse can be devastating, but more severe for women with limited or no resources, vulnerable to the patriarchal society. In the current COVID-19 era, increased uncertainty and disenfranchised grief can worsen the clinical scenario and intervention, as highlighted by the present case report of disenfranchised grief with depressive symptoms in a 30 years old woman from rural India who, after a year of her marriage, lost her husband due to COVID-19. This case study emphasizes the impact of multiple axes of disadvantages due to sociodemographic and cultural determinants that can complicate the grieving process in the current context. The bioecological model of grief recovery considered the individual features and the societal/environmental factors to postulate the appropriate intervention. Finding meaning and purpose in life, and restoration-oriented coping were successful for clinical management.

Supplementary Table 1 from Caveolin-1 (CAV1) Is a Target of EWS/FLI-1 and a Key Determinant of the Oncogenic Phenotype and Tumorigenicity of Ewing's Sarcoma Cells

Tumors of the Ewing's sarcoma family (ESFT), such as Ewing's sarcoma (EWS) and primitive neuroectodermal tumors (PNET), are highly aggressive malignancies predominantly affecting children and young adults. ESFT express chimeric transcription factors encoded by hybrid genes fusing the EWS gene with several ETS genes, most commonly FLI-1. EWS/FLI-1 proteins are responsible for the malignant phenotype of ESFT, but only few of their transcriptional targets are known. Using antisense and short hairpin RNA–mediated gene expression knockdown, array analyses, chromatin immunoprecipitation methods, and reexpression studies, we show that caveolin-1 (CAV1) is a new direct target of EWS/FLI-1 that is overexpressed in ESFT cell lines and tumor specimens and is necessary for ESFT tumorigenesis. CAV1 knockdown led to up-regulation of Snail and the concomitant loss of E-cadherin expression. Consistently, loss of CAV1 expression inhibited the anchorage-independent growth of EWS cells and markedly reduced the growth of EWS cell–derived tumors in nude mice xenografts, indicating that CAV1 promotes the malignant phenotype in EWS carcinogenesis. Reexpression of CAV1 or E-cadherin in CAV1 knockdown EWS cells rescued the oncogenic phenotype of the original EWS cells, showing that the CAV1/Snail/E-cadherin pathway plays a central role in the expression of the oncogenic transformation functions of EWS/FLI-1. Overall, these data identify CAV1 as a key determinant of the tumorigenicity of ESFT and imply that targeting CAV1 may allow the development of new molecular therapeutic strategies for ESFT patients. (Cancer Res 2006; 66(20): 9937-47)

Supplementary Figures 1-4 from Caveolin-1 (CAV1) Is a Target of EWS/FLI-1 and a Key Determinant of the Oncogenic Phenotype and Tumorigenicity of Ewing's Sarcoma Cells

Supplementary Table 2 from Caveolin-1 (CAV1) Is a Target of EWS/FLI-1 and a Key Determinant of the Oncogenic Phenotype and Tumorigenicity of Ewing's Sarcoma Cells

Supplementary Methods, Figure and Table Legends from Caveolin-1 (CAV1) Is a Target of EWS/FLI-1 and a Key Determinant of the Oncogenic Phenotype and Tumorigenicity of Ewing's Sarcoma Cells

At high latitudes, the biological carbon pump, which exports organic matter from the surface ocean to the interior, has been attributed to the gravitational sinking of particulate organic carbon. Conspicuous deficits in ocean carbon budgets challenge this as a sole particle export pathway. Recent model estimates revealed that particle injection pumps have a comparable downward flux of particulate organic carbon to the biological gravitational pump, but with different seasonality. To date, logistical constraints have prevented concomitant and extensive observations of these mechanisms. Here, using year-round robotic observations and recent advances in bio-optical signal analysis, we concurrently investigated the functioning of two particle injection pumps, the mixed layer and eddy subduction pumps, and the gravitational pump in Southern Ocean waters. By comparing three annual cycles in contrasting physical and biogeochemical environments, we show how physical forcing, phytoplankton phenology and particle characteristics influence the magnitude and seasonality of these export pathways, with implications for carbon sequestration efficiency over the annual cycle. L.L. was supported by a European Union’s Horizon 2020 Marie Sklodowska-Curie grant (no. 892653). Visits by L.L. to IMAS/UTas were supported by the Australian Research Council Special Research Initiative for Antarctic Gateway Partnership (Project ID SR140300001), the Australian Research Council Centre of Excellence for Climate System Science (Project ID B0018492), and the UTas visiting scholar program. J.L. was supported by the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No. 754433. N.B. was supported by a European Research Council Consolidator Grant (GOCART, agreement number 724416). P.S. was supported by the Australian Research Council Centre of Excellence for Climate Extremes (Project ID CE170100023). P.W.B. was funded by the Australian Research Council by Laureate Fellowship FL160100131. We thank the Argo Data Management team (ADMT) and the BGC-Argo Data Management team (BGC ADMT). The specific float used in this study was funded by the ARC SRI for Antarctic Gateway Partnership (Project ID SR140300001). We thank the captain and crew of RV Investigator voyage IN2016_V03 and chief scientists Bernadette Sloyan and Susan Wijffels for deploying the float.

Despite its robust proteopathic nature, the spatiotemporal signature of disrupted protein modules in sporadic Alzheimer's disease (AD) brains remains poorly understood. This considered oxidative stress contributes to AD progression and early intervention with coenzyme Q10 or its reduced form, ubiquinol, delays the progression of the disease. Using MALDI-MSI and functional bioinformatic analysis, we have developed a protocol to express how deregulated protein modules arise from hippocampus and cortex in the AD mice model 3xTG-AD in an age-dependent manner. This strategy allowed us to identify which modules can be efficiently restored to a non-pathological condition by early intervention with ubiquinol. Indeed, an early deregulation of proteostasis-related protein modules, oxidative stress and metabolism has been observed in the hippocampus of 6-month mice (early AD) and the mirrored in cortical regions of 12-month mice (middle/late AD). This observation has been validated by IHC using mouse and human brain sections, suggesting that these protein modules are also affected in humans. The emergence of disrupted protein modules with AD signature can be prevented by early dietary intervention with ubiquinol in the 3xTG-AD mice model., A pesar de su robusta naturaleza proteopática, la firma espaciotemporal de los módulos de proteínas interrumpidos en los cerebros de la enfermedad de Alzheimer (EA) esporádica sigue siendo poco conocida. Este considerado estrés oxidativo contribuye a la progresión de la EA y la intervención precoz con coenzima Q10 o su forma reducida, el ubiquinol, retrasa la progresión de la enfermedad. Usando MALDI-MSI y análisis bioinformático funcional, hemos desarrollado un protocolo para expresar cómo surgen módulos de proteína desregulados del hipocampo y la corteza en el modelo de ratones AD 3xTG-AD de una manera dependiente de la edad. Esta estrategia nos permitió identificar qué módulos se pueden restaurar de manera eficiente a una condición no patológica mediante una intervención temprana con ubiquinol. De hecho, una desregulación temprana de los módulos proteicos relacionados con la proteostasis, Se ha observado estrés oxidativo y metabolismo en el hipocampo de ratones de 6 meses (EA temprana) y se refleja en regiones corticales de ratones de 12 meses (EA media/tardía). Esta observación ha sido validada por IHC utilizando secciones de cerebro humano y de ratón, lo que sugiere que estos módulos de proteína también se ven afectados en humanos. La aparición de módulos de proteínas interrumpidos con la firma AD puede prevenirse mediante una intervención dietética temprana con ubiquinol en el modelo de ratones 3xTG-AD.

In the next few years, the prevalence of diabetes mellitus (DM) is projected to dramatically increase globally, but most of the cases will occur in low-to-middle-income countries. Some of the major risk factors for diabetes accelerate the development of dementia in African-Americans, thus leading to a higher prevalence of dementia than Caucasians. Sub-Saharan Africa women have a disproportionately two-to-eight fold increased prevalence of dementia. In the eye of this storm, Nigeria holds the highest number of diabetics on the African continent, and its prevalence is rising in parallel to obesity, hypertension, and the population’s aging. The socio-economic impact of the rising prevalence of DM and dementia will be huge and unsustainable for the healthcare system in Nigeria, as has been recognized in developed economies. Here, we analyze the current situation of women's health in Nigeria and explore future perspectives and directions. The complex interplay of factors involved in diabetes and dementia in Nigerian women include key biological agents (metabolic syndrome, vascular damage, inflammation, oxidative stress, insulin resistance), nutritional habits, lifestyle, and anemia, that worsen with comorbidities. In addition, restricted resources, lack of visibility, and poor management result in a painful chain that increases the risk and burden of disease in Nigerian women from youth to elderly ages. Heath policies to increase the ra- tio of mental health professionals per number of patients, mostly in rural areas, foment of proactive primary care centers, and interventions targeting adolescents and adult women and other specific mothers-children pairs are strongly required for a sustainable development goal.

Complete blood count inflammatory markers (CBC-IMs) have been associated with cardiovascular diseases and mortality. We aimed to evaluate the relationship between preoperative CBC-IMs and 5-year survival after carotid endarterectomy (CEA). Retrospective analysis of 411 consecutive patients who underwent CEA between 2004 and 2018 was done. CBC-IM included the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte (LMR) ratio, and systemic immune-inflammation index (SII). Survival rate at 5 years was 79.8%. Age (hazard ratio (HR) = 1.05, P = .003), hemoglobin (HR = 0.78, P < .001), heart failure (HR = 2.91, P = .005), American Society of Anesthesiologists (ASA)-IV score (HR = 2.41, P = .043), and active neoplastic disease (HR = 2.61, P = .028) were independently related to survival. The discrimination of this model (C-statistic) was 0.698. Spline analysis showed a linear relationship between survival and NLR ( P < .001), PLR ( P < .001), and SII ( P < .001). After adjusting for the baseline predictive score, there was a significant relationship between survival and NLR (HR = 1.191, P = .001), PLR (HR = 1.004, P = .017), and SII (HR = 1.001, P < .001). The addition of NLR, PLR, and SII to the survival model improved the continuous net reclassification index (c-NRI) by 0.29 ( P = .028), 0.347 ( P = .008), and 0.481 ( P < .001), respectively, but not the C-statistic. CBC-IMs show a linear and independent relationship with 5-year survival after CEA and may moderately contribute to patient selection for this preventive intervention.

Gemfibrozil (GFZ) is a lipid-lowering drug with several other effects, such as antioxidant and anti-inflammatory activities. In the current study, chronic d-galactose treatment (d-gal, 150 mg/kg/day; i.p., 6 weeks) induced a model of accelerated aging in male mice and was used to study the behavioral, anti-oxidative, and neuroprotective effects of GFZ (100 mg/kg/day; p.o.). Anxiety-like behaviors were assessed using the elevated plus-maze while working memory was measured by spontaneous alternation in a Y-maze. Brain oxidative stress was determined by measuring malondialdehyde (MDA) levels, superoxide dismutase (SOD), and glutathione peroxidase (GPx) activities. Neuropathological evaluation of the brain with hematoxylin-eosin and Masson's trichrome staining was also performed. The results demonstrated that the anxious-like phenotype and the cognitive impairments observed in d-gal-treated mice could be prevented in those animals coadministered with GFZ. Besides, the decrease in SOD and GPx antioxidant enzymatic activities and increase of MDA levels were also prevented in the brains of d-gal plus GFZ treated mice. Preliminary hematoxylin-eosin staining also suggested neuroprotective effects of GFZ. The results of Masson's trichrome staining showed no evidence of fibrosis in brain sections of different experimental groups. The current data provide novel insights into GFZ in the d-galactose-induced aging mouse model that open promising future research lines to determine inflammatory mediators and cell signaling underlying these effects.

The ocean plays a key role in climate change mitigation by absorbing heat and CO2 accumulating in the atmosphere due to anthropogenic greenhouse gases emissions. While it is commonly accepted that anthropogenic CO2 is absorbed by the ocean primarily through physical and chemical mechanisms, biological cycling of carbon is mainly responsible for maintaining the vertical gradient of dissolved inorganic carbon in the ocean. Thanks to a series of processes known as the biological carbon pump, oceanic phytoplankton uptakes carbon and promotes sinking of particulate organic matter to the deeper ocean. Uncertainty about the strength of these processes and about their response to ongoing and projected climate change is large enough to confound predictions of future ocean carbon uptake. One of the most important limiting factors for phytoplankton growth over large oceanic areas is the availability of iron. While there is no doubt regarding the importance of dust transport and deposition over open oceans as the most important iron source, questions remain still open regarding closing the relationship between dust sources, long-range transport, iron solubilisation during transport and deposition processes. Overall, better understanding the mechanisms behind the spatial and temporal variability of atmospheric dust-ocean interactions is key to interpret the response of ocean biogeochemistry and to increase confidence in future climate projections. In this work, we present a reconstruction of global ocean biogeochemistry for the last 30 years, where we evaluate the impact on ocean biogeochemical cycles of newly produced iron deposition fields. These were derived with EC-Earth3-Iron, a version of the Earth System Model EC-Earth3 with a state-of-the-art description of the atmospheric iron cycle. EC-Earth3-Iron estimates iron emissions considering explicitly the mineralogy of dust sources, and accounts for the contribution of anthropogenic combustion and biomass burning sources. The model includes an advanced representation of the iron solubilization in the atmosphere, which occurs through acidic attack, organic-ligand mediated dissolution and photo-reductive processes. Furthermore, it allows distinguishing the contribution to the soluble (and total) iron deposition in the ocean of the natural and anthropogenic dust sources, fossil fuels combustion and biomass burning, and characterizing thus separately their impact on ocean biogeochemistry. We compare the ocean biogeochemistry reconstruction against a control where commonly used climatologies for iron deposition fields are prescribed.

Denne rapporten er utarbeidet av en intern arbeidsgruppe ved USN etter utnevning og mandat fra direktør for Avdeling for Studie og Utdanningskvalitet (AUS) Vibeke Bredahl. Formålet med rapporten er å foreslå konkrete tiltak som kan utvikles og videreutvikles ved USN for å ivareta studiekvaliteten for studenter med norsk som andrespråk. Disse tiltakene bygger på eksisterende tilbud både ved USN og andre utdanningsinstitusjoner, og på forskning på nasjonalt og internasjonalt nivå. Arbeidsgruppen vil takke Vibeke Bredahl for tilliten til å utarbeide rapporten, vi håper at den kan bidra til en styrking av nåværende tiltak og aktiviteter rettet mot denne gruppe studenter. Arbeidsgruppen vil også takke Knut Gunnar Aspesen for støtte til å beregne kostnader tilknyttet tiltakene. Sist, men ikke minst, koordinatoren i gruppen vil takke hele arbeidsgruppa for en fantastisk faglig innsats med stort engasjement og profesjonalitet til å samarbeide. Dere har fått frem viktigheten av å støtte oss på evidensbaserte tiltak for å støtte våre studenter med norsk som andrespråk. Det er deres interesse og oppriktig involvering for våre studenter som har fått arbeidet i gruppen frem gjennom hele prosessen.

Publisher Copyright: © 2023 by the authors. A sample of 351 adults (women/men 4:1) aged 18 to 60 participated in an online survey administered during the first two waves (15 March-25 April and 10 October-25 November 2020) of the COVID-19 pandemic in Ukraine. The user ethnography profile was Generation Z (born in the 1990s), female (81.2%), Instagrammer (60.3%), unmarried (56.9%) and student (42.9%). An increased time spent on social media (3.18 h/day), searching for COVID-19-related information (1.01 h/day) after the first COVID-19 case and the observation of fake news that went viral (58.8%) decreased in the second wave. Alterations (increase or reduction) in sleep patterns (46.7%) and changes (increase or loss) in appetite (32.7%) affected participants' well-being, but only sleep ameliorated in the second wave. Mental health reports unveiled moderate perceived stress (PSS-10: 20.61 ± 1.13) and mild anxiety (GAD-7: 14.17 ± 0.22), which improved in the second wave. A higher prevalence of severe anxiety (8.5%) was found among individuals in the first survey (8.5%) than those in the second (3.3%). Social media counteracted physical distance policies and played as an immediate source of (mis)information for users, but also anticipated the impact of the most uncertain times of this COVID-19 physical health crisis on well-being and mental health.

This work is a contribution to the Ocean Colour Radiometry Virtual Constellation (OCR-VC) of the Committee on Earth Observation Satellites (CEOS), through the International Ocean Colour Coordinating Group. This paper is also a contribution towards the preparation of the Aquatic Carbon Roadmap of CEOS over the next couple of years.-- 41 pages, 3 figures, 10 tables.-- Data availability: Data for Fig. 1a were generated from a free Scopus (https://www.scopus.com/) search of the terms "Ocean carbon satellite" (using All fields) in March 2022. Data from Fig. 1b and 1c were generated from the workshop registration and are available within the figure (participation number, geographical representation and gender split), The ocean plays a central role in modulating the Earth’s carbon cycle. Monitoring how the ocean carbon cycle is changing is fundamental to managing climate change. Satellite remote sensing is currently our best tool for viewing the ocean surface globally and systematically, at high spatial and temporal resolutions, and the past few decades have seen an exponential growth in studies utilising satellite data for ocean carbon research. Satellite-based observations must be combined with in-situ observations and models, to obtain a comprehensive view of ocean carbon pools and fluxes. To help prioritise future research in this area, a workshop was organised that assembled leading experts working on the topic, from around the world, including remote-sensing scientists, field scientists and modellers, with the goal to articulate a collective view of the current status of ocean carbon research, identify gaps in knowledge, and formulate a scientific roadmap for the next decade, with an emphasis on evaluating where satellite remote sensing may contribute. A total of 449 scientists and stakeholders participated (with balanced gender representation), from North and South America, Europe, Asia, Africa, and Oceania. Sessions targeted both inorganic and organic pools of carbon in the ocean, in both dissolved and particulate form, as well as major fluxes of carbon between reservoirs (e.g., primary production) and at interfaces (e.g., air-sea and land–ocean). Extreme events, blue carbon and carbon budgeting were also key topics discussed. Emerging priorities identified include: expanding the networks and quality of in-situ observations; improved satellite retrievals; improved uncertainty quantification; improved understanding of vertical distributions; integration with models; improved techniques to bridge spatial and temporal scales of the different data sources; and improved fundamental understanding of the ocean carbon cycle, and of the interactions among pools of carbon and light. We also report on priorities for the specific pools and fluxes studied, and highlight issues and concerns that arose during discussions, such as the need to consider the environmental impact of satellites or space activities; the role satellites can play in monitoring ocean carbon dioxide removal approaches; economic valuation of the satellite based information; to consider how satellites can contribute to monitoring cycles of other important climatically-relevant compounds and elements; to promote diversity and inclusivity in ocean carbon research; to bring together communities working on different aspects of planetary carbon; maximising use of international bodies; to follow an open science approach; to explore new and innovative ways to remotely monitor ocean carbon; and to harness quantum computing. Overall, this paper provides a comprehensive scientific roadmap for the next decade on how satellite remote sensing could help monitor the ocean carbon cycle, and its links to the other domains, such as terrestrial and atmosphere, This work was funded through a European Space Agency (ESA) project “Biological Pump and Carbon Exchange Processes (BICEP)” and by the Simons Foundation Project “Collaboration on Computational Biogeochemical Modeling of Marine Ecosystems (CBIOMES)” (549947, SS). It was also supported by the UK National Centre for Earth Observation (NCEO). Additional support from the Ocean Colour Component of the Climate Change Initiative of the European Space Agency (ESA) is gratefully acknowledged. Robert J. W. Brewin is supported by a UKRI Future Leader Fellowship (MR/V022792/1). Robert J. W. Brewin, Giorgio Dall'Olmo and Gavin H. Tilstone were supported by the Atlantic Meridional Transect Programme. Thomas Frölicher was supported by the Swiss National Science Foundation (Grant No. PP00P2_198897). Astrid Bracher’s contribution is funded by the ESA 656 708 S5P + Innovation Theme 7 Ocean Colour (S5POC) project (No 4000127533/19/I-NS). Jamie Shutler acknowledges support from the ESA Ocean Health Ocean Acidification project (No. AO/1-10757/21/I-DT), With the institutional support of the ‘Severo Ochoa Centre of Excellence’ accreditation (CEX2019-000928-S)

The issue of monitoring the structural condition of bridges is becoming a top priority worldwide. As is well known, any infrastructure undergoes a progressive deterioration of its structural conditions due to aging by normal service loads and environmental conditions. At the same time, it may suffer serious damages or collapse due to natural phenomena such as earthquakes or strong winds. For this reason, it is essential to rely on efficient and widespread monitoring techniques applied throughout the entire road network. This paper aims to introduce an integrated procedure for structural and material monitoring. With regard to structural monitoring, an innovative approach for monitoring based on Vehicle by Bridge Interaction (VBI) will be proposed. Furthermore, with regard to material monitoring, to evaluate concrete degradation, a non-invasive method based on the continuous monitoring of the pH, as well as chloride and sulfate ions concentration in the concrete, is presented.

Familial adenomatous polyposis (FAP) is an autosomal dominant syndrome responsible for 1% of colorectal cancers (CRCs). Up to 90% of classic FAPs are caused by inactivating mutations in APC, and mosaicism has been previously reported in 20% of de novo cases, usually linked to milder phenotypic manifestations. This study aimed to explore the prevalence of mosaicism in 11 unsolved cases of classic FAP and to evaluate the diagnostic yield of somatic testing. Paired samples of colorectal polyps, tumors, and/or mucosa were analyzed using a custom next-generation sequencing panel targeting 15 polyposis and CRC-predisposing genes. Whenever possible, the extension of mosaicism to blood or sperm was also examined. Of 11 patients with classic adenomatous polyposis, a mosaic pathogenic variant in APC was identified in 7 (64%). No other altered genes were identified. In two of seven patients (29%), mosaicism was found restricted to colonic tissues, whereas in five of seven patients (71%), it was extended to the blood. Germline affectation was confirmed in one patient. We report the first analysis at a somatic level of 15 genes associated with CRC susceptibility, which highlights the role of APC mosaicism in classic FAP etiology. The results further reinforce the importance of testing target tissues when blood test results are negative.

Gemfibrozil (GFZ) is a medication of the fibrate category with agonistic effects on PPAR-α and is effective for hypertriglyceridemia and mixed dyslipidemia. This agent also has anti-inflammatory and antioxidant properties. The current study investigated the effects of GFZ on hepatorenal damages in a D-galactose (D-gal)-induced aging model. We used twenty-eight male mice, which were equally and randomly divided into four groups as follows: Normal, D-gal (150 mg/kg/day; i.p., for 6 weeks), GFZ (100 mg/kg/day GFZ, p.o. for 6 weeks) and the combined D-gal + GFZ. Liver and kidney function indices were measured as serum creatinine, blood urine nitrogen, alanine aminotransferase, and aspartate aminotransferase. Oxidative stress in hepatic and renal tissue was evaluated through malondialdehyde, superoxide dismutase, and glutathione peroxidase levels. Finally, the liver and kidney tissues were assessed for histopathological lesions. The results showed that D-gal induced aging leads to abnormalities in liver and kidney function indices. D-gal also induced significant oxidative stress and histopathological lesions in these organs. GFZ improved function indices and oxidative stress compared to the D-gal -treated animals. Histological evaluations of the liver and kidney also confirmed these results. These data provide evidence for the potential therapeutic of GFZ in clinical practice for mitigating the hepatorenal damages of aging.

Burying and burrowing are promising rodent-typical behaviors to model neuropsychiatric symptoms (NPS). However, the original tests could be insufficient to conclude which NPS are modeled. Here, we propose methodological modifications such as the two-zone configuration and dual analysis in the Marble Burying Test (MB). Also, a new Brief Burrowing Test (BB), a 20 min brief version of the Deacon’s Burrowing Test (DB). We comprehensively studied these behaviors in 12-month-old male and female mice with normal and Alzheimer’s disease (AD)-pathological aging. The results: 1) confirm our precedent report of sexual dimorphism, with enhanced burying in male 3xTg-AD mice; 2) describe for the first time burrowing behavior in 3xTg-AD mice and its sex dependence; 3) regardless of the pattern, MB and BB reflected a goal-directed rather than an indiscriminate digging; 4) using the MB and BB to model anxiety-like behavior it’s not recommended; 5) burying and burrowing represent a repetitive rather than a stereotyped-like or perseverative behavior. In addition: 1) burying and burrowing behavioral patterns are alike, connected by several correlations; 2) the two-zones configuration is a useful tool to assess the intentionality of the burying and burrowing behaviors and to perform a more accurate screening of the NPS modeled by them.

Southern Ocean eddies shape the foraging ecology of marine apex predators such as marine mammals and seabirds. A growing number of animal tracking studies show that predators alter their swimming, ...

Alzheimer’s disease (AD) patients suffer from circadian rhythm alterations affecting their daily physical activity patterns with less willingness to perform a voluntary exercise. In preclinical studies, there is no clarity on whether animal models of AD can replicate these impairments. Here, we provide a proof of concept of the performance and behavioral effects of four weeks of voluntary wheel running (VWR) in a group of 14-month-old male and female 3xTg-AD mice at advanced stages of AD and the daily variance (behavioral circadian rhythmicity) of VWR associated with sex and their neuropsychiatric-like phenotype. Higher levels of horizontal exploration in the open field (OF) test were found in mice submitted to exercise. A linear mixed effect model showed significant sex-dependent differences in the VWR activity performed on the first night of follow-up, with high-NIBI males running less than high-NIBI females. Thus, an influence of NPS-like symptoms on the circadian patterns of VWR may account for such differences. In addition, males remained more active than females during diurnal periods. We hypothesize that this increment in energy expenditure during resting periods may be related to hyperactive behavior, similar to that observed in humans’ exacerbated agitation or sundowning behavior. These findings support the usage of the 3xTg-AD mouse as a reliable model for studying circadian rhythm alterations in AD and, at the translational level, the importance of tailored and individualized physical activity programs in clinical settings.

Coping with emotional stressors strongly impacts older people due to their age-related impaired neuroendocrine and immune systems. Elevated cortisol levels seem to be associated with an increased risk of cognitive decline and dementia. In Alzheimer’s disease (AD), alterations in the innate immune system result in crosstalk between immune mediators and neuronal and endocrine functions. Besides, neuropsychiatric symptoms such as depression, anxiety, or agitation are observed in most patients. Here, we studied the psychophysiological response to intrinsic (AD-phenotype) and extrinsic (anxiogenic tests) stress factors and their relation to liver, kidneys, heart, and spleen oxidative status in 18-months-old female gold-standard C57BL/6 mice and 3xTg-AD mice model for AD. The emotional, cognitive, and motor phenotypes were assessed under three different anxiogenic conditions. Survival, frailty index, and immunoendocrine status (corticosterone levels and oxidative stress of peripheral organs) were evaluated. Genotype differences in neuropsychiatric-like profiles and cognitive disfunction in 3xTg-AD females that survived beyond advanced stages of the disease persisted despite losing other behavioral and hypothalamic–pituitary–adrenal (HPA) physiological differences. A secondary analysis studied the impact of social isolation, naturally occurring in 3xTg-AD mice due to the death of cage mates. One month of isolation modified hyperactivity and neophobia patterns and disrupt the obsessive-compulsive disorder-like digging ethogram. Frailty index correlated with spleen organometrics in all groups, whereas two AD-specific salient functional correlations were identified: (1) Levels of corticosterone with worse performance in the T-maze, (2) and with a lower splenic GPx antioxidant enzymatic activity, which may suppose a potent risk of morbidity and mortality in AD.

Misophonia is a poorly understood and underdiagnosed disorder. People who suffer from this condition without knowing it has a notable deterioration in their quality of life, affecting their personal and social relationships. The present study characterized the self-concept of 82 people (women:men, 3:2) attending a medical psychology center in Barcelona before and after their diagnosis of misophonia and intervention to raise awareness. The social representation of misophonia was also studied in their close relatives. A lexicometric analysis using IRaMuTeQ software qualified and quantified the 164 participants' words to describe the patient's behavior (associative cards method) in a list of situations reported but not yet identified as triggers of misophonic responses. The corpus of text, branching, and the word clouds of the most used words showed a high frequency of negative qualifiers (attributed to personality) from relatives [ranking:“irritable” (n=30), “narrow-minded” (n=24) and “anxious” (n=15)] and in the self-concept of patients [ranking: “irritable” (n=34) and “anxious” (n=26), tolerant (n=24) and frank (n=18)], with higher diversification in patients than relatives (14:8 qualifiers n>10), and an increased post-intervention (17:10 qualifiers >10). The intervention strongly modified the corpus since “misophonic” and “disorder” appeared in the self-concept post-intervention, but not the concept, suggesting relatives need substantial efforts to be aware of the nature/impact of the disorder. The distribution of misophonia levels differed among sexes (higher representation of women at level 2 [56%], while men mainly were diagnosed at level 3 [50%]) while age only showed tends. Interestingly, the intervention increased 2.71 points the misophonia score obtained in a self-administered questionnaire repeated seven months later and rescued 13.4% of positive diagnoses, suggesting that for the patients to recognize the diagnosis of misophonia in themselves, they must first ­­be aware of this concept. The individuals with less self-concept stability more frequently recognized themselves as misophonic. Besides, 21% of the variance in the change in self-concept was explained by the change in the concept of a close relative. In summary, the lack of self-concept and social representation of misophonia have strong implications for all the actors and are relevant to design interventions to reduce their impact.

Ukrainian Military Hospital retrospective analysis during a decade of conflicts (3995 records) unveils specific mental health ICD-10-CM distribution per rank and the long-lasting impact of active conflict or trench warfare. Most hospitalizations in all years of observation were among soldiers. Anxiety-related disorders have been present since ‘peacetime’, mainly among professional soldiers and high ranks, pointing to the need for rank-tailored psychological training in skills to reduce the anxiety burden. High frequency of psychoactive substance use emerged with acute conflicts and in nonprofessional soldiers during wartime. This dictates the need to strengthen the selection of military personnel, considering the tendency to addiction. Military operations multiply the hospitalizations in psychiatric hospitals. The data warn about a ‘need for free beds effect’, which is worse for soldiers. This is relevant to estimating and planning the need for hospital resources for the current situation where the general population has been recruited for defense. In the current war, tightening the rules of sobriety in units and up to a ban on the sale of alcoholic beverages in areas where hostilities are taking place is recommended. The specific impact on nonprofessional soldiers is relevant to the current war, with the general population of Ukraine recruited for defense and combat.

25 pages, 13 figures, 5 tables, 3 appendixes.-- Code availability: The code of NEMO v4.0.1 and PISCES-v2_RC are publicly available at https://www.nemo-ocean.eu/ (last access: April 2021), https://doi.org/10.5281/zenodo.3878122 (Madec et al., 2022). The PISCES 1D configuration used in this study is available at https://earth.bsc.es/gitlab/mgalitap/p1d_share/-/tree/gapoc/ (last access: May 2021) and https://doi.org/10.5281/zenodo.5243343 (Galí et al., 2021b). The code for the workflow of the genetic algorithm is readily available at https://doi.org/10.5281/zenodo.5205760 (Falls et al., 2021).-- Data availability: These data were collected and made freely available by the international Argo programme and the national programmes that contributes to it (https://argo.ucsd.edu, last access: April 2021; https://www.ocean-ops.org, last access: May 2021). The Argo programme is part of the Global Ocean Observing System. The repository that contains the processed BGC–Argo data and matching PISCES 1D simulations, titled “Datasets for the comparison between POC estimated from BGC–Argo floats and PISCES model simulations”, is readily available at https://doi.org/10.5281/zenodo.5139602 (Galí et al., 20211), When working with Earth system models, a considerable challenge that arises is the need to establish the set of parameter values that ensure the optimal model performance in terms of how they reflect real-world observed data. Given that each additional parameter under investigation increases the dimensional space of the problem by one, simple brute-force sensitivity tests can quickly become too computationally strenuous. In addition, the complexity of the model and interactions between parameters mean that testing them on an individual basis has the potential to miss key information. In this work, we address these challenges by developing a biased random key genetic algorithm (BRKGA) able to estimate model parameters. This method is tested using the one-dimensional configuration of PISCES-v2_RC, the biogeochemical component of NEMO4 v4.0.1 (Nucleus for European Modelling of the Ocean version 4), a global ocean model. A test case of particulate organic carbon (POC) in the North Atlantic down to 1000 m depth is examined, using observed data obtained from autonomous biogeochemical Argo floats. In this case, two sets of tests are run, namely one where each of the model outputs are compared to the model outputs with default settings and another where they are compared with three sets of observed data from their respective regions, which is followed by a cross-reference of the results. The results of these analyses provide evidence that this approach is robust and consistent and also that it provides an indication of the sensitivity of parameters on variables of interest. Given the deviation in the optimal set of parameters from the default, further analyses using observed data in other locations are recommended to establish the validity of the results obtained, This research has been supported by the Fundación Bancaria Caixa d'Estalvis i Pensions de Barcelona (grant no. LCF/BQ/PI18/11630009) and the Ministerio de Ciencia e Innovación (grant nos. PID2019-107952GA-I00 and CGL2017-84493-R), With the institutional support of the ‘Severo Ochoa Centre of Excellence’ accreditation (CEX2019-000928-S)

Low plasma sex hormone-binding globulin (SHBG) levels are present in fatty liver disease, which represents a spectrum of diseases ranging from hepatocellular steatosis through steatohepatitis to fibrosis and irreversible cirrhosis. We have previously determined that fat accumulation reduces SHBG production in different nonalcoholic fatty liver disease mouse models. In the present work, we are interested in elucidating the molecular mechanisms reducing SHBG plasma levels in liver fibrosis. For this purpose, in vivo studies were performed using the human SHBG transgenic mice developing liver fibrosis induced by carbon tetrachloride (CCl

AIM The need to adjust the indications of elective abdominal aortic aneurysm (AAA) repair among patients with a limited life-span deserves a specific evaluation for octogenarians. The aim of this study was to compare the postoperative results and the long-term survival after endovascular repair of abdominal aortic and/or iliac aneurysms (EVAR) in octogenarians compared with patients under 80 years of age. METHODS Retrospective analysis of 241 consecutive patients who underwent an elective EVAR between 2000 and 2017. EVAR was not considered among patients with clear life-limiting conditions. Patients receiving other than commercially standard infra-renal endoprostheses were excluded. RESULTS Seventy patients (29.0%) were octogenarians. They had a lower rate of active smoking (10.0% vs. 30.4%, P

Funding: This research was funded by the European Cooperation in Science and Technology; funding number: EU COST-Action TD1005. Facial expression is a key aspect in observational scales developed to improve pain assessment in individuals with cognitive impairments. Although these scales are used internationally in individuals with different types of cognitive impairments, it is not known whether observing facial expressions of pain might differ between regions or between different types of cognitive impairments. In a pilot study, facial responses to standardized experimental pressure pain were assessed among individuals with different types of cognitive impairments (dementia, mild cognitive impairment, Huntington's disease, and intellectual disability) from different countries (Denmark, Germany, Italy, Israel, and Spain) and were analyzed using facial descriptors from the PAIC scale (Pain Assessment in Impaired Cognition). We found high inter-rater reliability between observers from different countries. Moreover, facial responses to pain did not differ between individuals with dementia from different countries (Denmark, Germany, and Spain). However, the type of cognitive impairment had a significant impact; with individuals with intellectual disability (all being from Israel) showing the strongest facial responses. Our pilot data suggest that the country of origin does not strongly affect how pain is facially expressed or how facial responses are being scored. However, the type of cognitive impairment showed a clear effect in our pilot study, with elevated facial responses in individuals with intellectual disability.

Funding: This work was funded by 2017-SGR-1468 and UAB-GE-260408 to L.G.-L. The colony of 3xTg-AD mice is sustained by ArrestAD H2020 Fet-OPEN-1-2016-2017-737390, European Union's Horizon 2020 research and innovation program under grant agreement No 737390 to L.G.-L. It also received financial support from Memorial Mercedes Llort Sender 2021/80/09241941.8. Acknowledgments: We thank Frank M LaFerla Institute for Memory Impairments and Neurological Disorders, Department of Neurobiology and Behavior, University of California, Irvine, USA, for kindly providing the progenitors of the Spanish colonies of 3xTg-AD and NTg mice. LC-M is recipient of a CONICYT/BECAS CHILE/72180026 grant. This work was funded by 2017-SGR-1468 and UAB-GE-260408 to L.G.-L. The colony of 3xTg-AD mice is sustained by ArrestAD H2020 Fet-OPEN-1-2016-2017-737390, European Union?s Horizon 2020 research and innovation program under grant agreement No 737390 to L.G.-L. It also received financial support from Memorial Mercedes Llort Sender 2021/80/09241941.8. We thank Frank M LaFerla Institute for Memory Impairments and Neurological Disorders, Department of Neurobiology and Behavior, University of California, Irvine, USA, for kindly providing the progenitors of the Spanish colonies of 3xTg-AD and NTg mice. LC-M is recipient of a CONICYT/BECAS CHILE/72180026 grant. Altres ajuts: 2017-SGR-1468 and UAB-GE-260408; BECAS/CHILE/72180026; Memorial Mercedes Llort Sender 2021/80/09241941.8 Gait impairments in Alzheimer's disease (AD) result from structural and functional deficiencies that generate limitations in the performance of activities and restrictions in individual's biopsychosocial participation. In a translational way, we have used the conceptual framework proposed by the International Classification of Disability and Health Functioning (ICF) to classify and describe the functioning and disability on gait and exploratory activity in the 3xTg-AD animal model. We developed a behavioral observation method that allows us to differentiate qualitative parameters of psychomotor performance in animals' gait, similar to the behavioral patterns observed in humans. The functional psychomotor evaluation allows measuring various dimensions of gait and exploratory activity at different stages of disease progression in dichotomy with aging. We included male 3xTg-AD mice and their non-transgenic counterpart (NTg) of 6, 12, and 16 months of age (n = 45). Here, we present the preliminary results. The 3xTg-AD mice show more significant functional impairment in gait and exploratory activity quantitative variables. The presence of movement limitations and muscle weakness mark the functional decline related to the disease severity stages that intensify with increasing age. Motor performance in 3xTg-AD is accompanied by a series of bizarre behaviors that interfere with the trajectory, which allows us to infer poor neurological control. Additionally, signs of physical frailty accompany the functional deterioration of these animals. The use of the ICF as a conceptual framework allows the functional status to be described, facilitating its interpretation and application in the rehabilitation of people with AD.

Research on Alzheimer’s disease (AD) has classically focused on alterations that occur in the brain and their intra- and extracellular neuropathological hallmarks. However, the oxi-inflammation hypothesis of aging may also play a role in neuroimmunoendocrine dysregulation and the disease’s pathophysiology, where the liver emerges as a target organ due to its implication in regulating metabolism and supporting the immune system. In the present work, we demonstrate organ (hepatomegaly), tissue (histopathological amyloidosis), and cellular oxidative stress (decreased glutathione peroxidase and increased glutathione reductase enzymatic activities) and inflammation (increased IL-6 and TNF𝛼) as hallmarks of hepatic dysfunction in 16-month-old male and female 3xTg-AD mice at advanced stages of the disease, and as compared to age- and sex-matched non-transgenic (NTg) counterparts. Moreover, liver–brain axis alterations were found through behavioral (increased neophobia) and HPA axis correlations that were enhanced under forced isolation. In all cases, sex (male) and isolation (naturalistic and forced) were determinants of worse hepatomegaly, oxidative stress, and inflammation progression. In addition, obesity in old male NTg mice was translated into a worse steatosis grade. Further research is underway determine whether these alterations could correlate with a worse disease prognosis and to establish potential integrative system targets for AD research.