| 61. |
- El Bairi, Khalid, et al.
(author)
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The tale of TILs in breast cancer: A report from The International Immuno-Oncology Biomarker Working Group
- 2021
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In: npj Breast Cancer. - : Springer Science and Business Media LLC. - 2374-4677. ; 7:1
-
Research review (peer-reviewed)abstract
- The advent of immune-checkpoint inhibitors (ICI) in modern oncology has significantly improved survival in several cancer settings. A subgroup of women with breast cancer (BC) has immunogenic infiltration of lymphocytes with expression of programmed death-ligand 1 (PD-L1). These patients may potentially benefit from ICI targeting the programmed death 1 (PD-1)/PD-L1 signaling axis. The use of tumor-infiltrating lymphocytes (TILs) as predictive and prognostic biomarkers has been under intense examination. Emerging data suggest that TILs are associated with response to both cytotoxic treatments and immunotherapy, particularly for patients with triple-negative BC. In this review from The International Immuno-Oncology Biomarker Working Group, we discuss (a) the biological understanding of TILs, (b) their analytical and clinical validity and efforts toward the clinical utility in BC, and (c) the current status of PD-L1 and TIL testing across different continents, including experiences from low-to-middle-income countries, incorporating also the view of a patient advocate. This information will help set the stage for future approaches to optimize the understanding and clinical utilization of TIL analysis in patients with BC.
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| 62. |
- Ferrando, Carlos, et al.
(author)
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Clinical features, ventilatory management, and outcome of ARDS caused by COVID-19 are similar to other causes of ARDS
- 2020
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In: Intensive Care Medicine. - : SPRINGER. - 0342-4642 .- 1432-1238. ; 46:12, s. 2200-2211
-
Journal article (peer-reviewed)abstract
- Purpose The main characteristics of mechanically ventilated ARDS patients affected with COVID-19, and the adherence to lung-protective ventilation strategies are not well known. We describe characteristics and outcomes of confirmed ARDS in COVID-19 patients managed with invasive mechanical ventilation (MV). Methods This is a multicenter, prospective, observational study in consecutive, mechanically ventilated patients with ARDS (as defined by the Berlin criteria) affected with with COVID-19 (confirmed SARS-CoV-2 infection in nasal or pharyngeal swab specimens), admitted to a network of 36 Spanish and Andorran intensive care units (ICUs) between March 12 and June 1, 2020. We examined the clinical features, ventilatory management, and clinical outcomes of COVID-19 ARDS patients, and compared some results with other relevant studies in non-COVID-19 ARDS patients. Results A total of 742 patients were analysed with complete 28-day outcome data: 128 (17.1%) with mild, 331 (44.6%) with moderate, and 283 (38.1%) with severe ARDS. At baseline, defined as the first day on invasive MV, median (IQR) values were: tidal volume 6.9 (6.3-7.8) ml/kg predicted body weight, positive end-expiratory pressure 12 (11-14) cmH(2)O. Values of respiratory system compliance 35 (27-45) ml/cmH(2)O, plateau pressure 25 (22-29) cmH(2)O, and driving pressure 12 (10-16) cmH(2)O were similar cto values from non-COVID-19 ARDS observed in other studies. Recruitment maneuvers, prone position and neuromuscular blocking agents were used in 79%, 76% and 72% of patients, respectively. The risk of 28-day mortality was lower in mild ARDS [hazard ratio (RR) 0.56 (95% CI 0.33-0.93),p = 0.026] and moderate ARDS [hazard ratio (RR) 0.69 (95% CI 0.47-0.97),p = 0.035] when compared to severe ARDS. The 28-day mortality was similar to other observational studies in non-COVID-19 ARDS patients. Conclusions In this large series, COVID-19 ARDS patients have features similar to other causes of ARDS, compliance with lung-protective ventilation was high, and the risk of 28-day mortality increased with the degree of ARDS severity.
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| 63. |
- Holguin-Veras, Jose, et al.
(author)
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A Multiclass Tour Flow Model and Its Role in Multiclass Freight Tour Synthesis
- 2020
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In: Transportation Science. - : Institute for Operations Research and the Management Sciences (INFORMS). - 0041-1655 .- 1526-5447. ; 54:3, s. 631-650
-
Journal article (peer-reviewed)abstract
- This paper summarizes the research conducted by the authors concerning the development of an analytical freight demand model that explicitly considers freight pickup and delivery flows by industry sector, the multiclass tour flow model (MC-TFM). The mathematical properties of the resultant model are investigated, including the convexity of the optimization model, the interconnection between the MC-TFM and the family of gravity models, and the MC-TFM's elasticities. The MC-TFM is then integrated into a multiclass freight tour synthesis model (MC-FTS) that is capable of inferring freight tour demand on the basis of secondary data such as traffic counts and estimates of freight trip generation by industry sector. The ability of the resulting MC-FTS is tested by means of numerical experiments involving test cases.
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| 64. |
- Martinez-Manuel, Leopoldo, et al.
(author)
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A comprehensive analysis of the optical and thermal performance of solar absorber coatings under concentrated flux conditions
- 2022
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In: Solar Energy. - : Elsevier BV. - 0038-092X .- 1471-1257. ; 239, s. 319-336
-
Journal article (peer-reviewed)abstract
- Solar Absorber Coatings (SACs) are widely used materials for improving thermal efficiencies of solar receivers. Traditionally, these SACs are investigated using heat treatments to test their optical-thermal properties; however, tests under concentrated flux conditions are still required. In this work, the thermal efficiency of different SACs is experimentally evaluated and compared. The analyzed SACs are: (1) Pyromark®2500, (2) Solkote®, (3) Thurmalox®250, (4) Comex® and (5) a new Soot from Forest Biomass (SFB) based coating. To assess the SACs performance, a High Flux Solar Simulator along with a calorimetric test bench are implemented under a well-controlled indoor environment applying two levels of concentrated irradiance of 100 ± 3 kW/m2 and 415 ± 12 kW/m2 named low and high flux level, respectively. Results show that, for a low flux level, the analyzed coatings present thermal efficiencies in a range from 91.74% to 83.24%, exhibiting a slightly close performance in most of the cases. Correspondingly, for a high flux level, the efficiencies range from 88.69% to 72.69%, with Pyromark®2500 being the most efficient in both cases. In addition, variations in the optical properties are reported for the experimental campaign with the high flux level, observing slight changes in the spectral absorptance and emittance. From these results, Pyromark presents the highest drop in solar absorptance of 1.22%, which is attributed to microcracks observed through the Scanning Electron Microscope (SEM). Thus, the presented approach can provide valuable information about the effects that concentrated flux levels can have in the optical-thermal performance of the analyzed samples.
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| 65. |
- Nishi, Stephanie K., et al.
(author)
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Mediterranean, DASH, and MIND Dietary Patterns and Cognitive Function : The 2-Year Longitudinal Changes in an Older Spanish Cohort
- 2021
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In: Frontiers in Aging Neuroscience. - : Frontiers Media SA. - 1663-4365. ; 13
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Journal article (peer-reviewed)abstract
- Background and Aims: Plant-forward dietary patterns have been associated with cardiometabolic health benefits, which, in turn, have been related to cognitive performance with inconsistent findings. The objective of this study was to examine the relationship between baseline adherence to three a priori dietary patterns (Mediterranean, DASH, and MIND diets) with 2-year changes in cognitive performance in older adults with overweight or obesity and high cardiovascular disease risk. Methods: A prospective cohort analysis was conducted within the PREDIMED-Plus trial, involving 6,647 men and women aged 55–75 years with overweight or obesity and metabolic syndrome. Using a validated, semiquantitative 143-item food frequency questionnaire completed at baseline, the dietary pattern adherence scores were calculated. An extensive neuropsychological test battery was administered at baseline and 2-year follow-up. Multivariable-adjusted linear regression models were used to assess associations between 2-year changes in cognitive function z-scores across tertiles of baseline adherence to the a priori dietary patterns. Results: Adherence to the Mediterranean diet at baseline was associated with 2-year changes in the general cognitive screening Mini-Mental State Examination (MMSE, β: 0.070; 95% CI: 0.014, 0.175, P-trend = 0.011), and two executive function-related assessments: the Trail Making Tests Part A (TMT-A, β: −0.054; 95% CI: −0.110, − 0.002, P-trend = 0.047) and Part B (TMT-B, β: −0.079; 95% CI: −0.134, −0.024, P-trend = 0.004). Adherence to the MIND diet was associated with the backward recall Digit Span Test assessment of working memory (DST-B, β: 0.058; 95% CI: 0.002, 0.114, P-trend = 0.045). However, higher adherence to the DASH dietary pattern was not associated with better cognitive function over a period of 2 years. Conclusion: In older Spanish individuals with overweight or obesity and at high cardiovascular disease risk, higher baseline adherence to the Mediterranean dietary pattern may be associated with better cognitive performance than lower adherence over a period of 2 years.
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| 66. |
- Patiño, Jairo, et al.
(author)
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Unveiling the nature of a miniature world : a horizon scan of fundamental questions in bryology
- 2022
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In: Journal of Bryology. - : Informa UK Limited. - 0373-6687 .- 1743-2820. ; 44:1, s. 1-34
-
Journal article (peer-reviewed)abstract
- Introduction. Half a century since the creation of the International Association of Bryologists, we carried out a review to identify outstanding challenges and future perspectives in bryology. Specifically, we have identified 50 fundamental questions that are critical in advancing the discipline.Methods. We have adapted a deep-rooted methodology of horizon scanning to identify key research foci. An initial pool of 258 questions was prepared by a multidisciplinary and international working group of 32 bryologists. A series of online surveys completed by a broader community of researchers in bryology, followed by quality-control steps implemented by the working group, were used to create a list of top-priority questions. This final list was restricted to 50 questions with a broad conceptual scope and answerable through realistic research approaches.Key results. The top list of 50 fundamental questions was organised into four general topics: Bryophyte Biodiversity and Biogeography; Bryophyte Ecology, Physiology and Reproductive Biology; Bryophyte Conservation and Management; and Bryophyte Evolution and Systematics. These topics included 9, 19, 14 and 8 questions, respectively.Conclusions. Although many of the research challenges identified are not newly conceived, our horizon-scanning exercise has established a significant foundation for future bryological research. We suggest analytical and conceptual strategies and novel developments for potential use in advancing the research agenda for bryology.
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| 67. |
- Salloum, Fadi N., et al.
(author)
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Priorities in Cardio-Oncology Basic and Translational Science : GCOS 2023 Symposium Proceedings: JACC: CardioOncology State-of-the-Art Review
- 2023
-
In: JACC: CardioOncology. - 2666-0873. ; 5:6, s. 715-731
-
Research review (peer-reviewed)abstract
- Despite improvements in cancer survival, cancer therapy–related cardiovascular toxicity has risen to become a prominent clinical challenge. This has led to the growth of the burgeoning field of cardio-oncology, which aims to advance the cardiovascular health of cancer patients and survivors, through actionable and translatable science. In these Global Cardio-Oncology Symposium 2023 scientific symposium proceedings, we present a focused review on the mechanisms that contribute to common cardiovascular toxicities discussed at this meeting, the ongoing international collaborative efforts to improve patient outcomes, and the bidirectional challenges of translating basic research to clinical care. We acknowledge that there are many additional therapies that are of significance but were not topics of discussion at this symposium. We hope that through this symposium-based review we can highlight the knowledge gaps and clinical priorities to inform the design of future studies that aim to prevent and mitigate cardiovascular disease in cancer patients and survivors.
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| 68. |
- Schank, Jesse R., et al.
(author)
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Increased Alcohol Consumption in Mice Lacking Sodium Bicarbonate Transporter NBCn1
- 2020
-
In: Scientific Reports. - : NATURE PUBLISHING GROUP. - 2045-2322. ; 10:1
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Journal article (peer-reviewed)abstract
- The previous reports on an addiction vulnerability marker in the human SLC4A7 gene encoding the Na/HCO3 transporter NBCn1 suggest that this pH-regulating protein may affect alcohol-related behavior and response. Here, we examined alcohol consumption and sensitivity to the sedative effects of alcohol in male NBCn1 knockout mice. These mice displayed lower pH in neurons than wildtype controls, determined by intracellular pH in hippocampal neuronal cultures. Neurons from knockout mice had a higher action potential threshold and a more depolarized membrane potential, thus reducing membrane excitability. In a two-bottle free choice procedure, knockout mice consumed more alcohol than controls and consistently increased alcohol consumption after repeated alcohol deprivation periods. Quinine and sucrose preference was similar between genotypes. Knockout mice showed increased propensity for alcohol-induced conditioned place preference. In loss of righting reflex assessment, knockout mice revealed increased sensitivity to alcohol-induced sedation and developed tolerance to the sedation after repeated alcohol administrations. Furthermore, chronic alcohol consumption caused NBCn1 downregulation in the hippocampus and striatum of mice and humans. These results demonstrate an important role of NBCn1 in regulation of alcohol consumption and sensitivity to alcohol-induced sedation.
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| 69. |
- Sheppard, Eleanor C., et al.
(author)
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Genomic associations with poxvirus across divergent island populations in Berthelot's pipit
- 2022
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In: Molecular Ecology. - : John Wiley & Sons. - 0962-1083 .- 1365-294X. ; 31:11, s. 3154-3173
-
Journal article (peer-reviewed)abstract
- Understanding the mechanisms and genes that enable animal populations to adapt to pathogens is important from an evolutionary, health and conservation perspective. Berthelot's pipit (Anthus berthelotii) experiences extensive and consistent spatial heterogeneity in avian pox infection pressure across its range of island populations, thus providing an excellent system with which to examine how pathogen-mediated selection drives spatial variation in immunogenetic diversity. Here, we test for evidence of genetic variation associated with avian pox at both an individual and population-level. At the individual level, we find no evidence that variation in MHC class I and TLR4 (both known to be important in recognising viral infection) was associated with pox infection within two separate populations. However, using genotype-environment association (Bayenv) in conjunction with genome-wide (ddRAD-seq) data, we detected strong associations between population-level avian pox prevalence and allele frequencies of single nucleotide polymorphisms (SNPs) at a number of sites across the genome. These sites were located within genes involved in cellular stress signalling and immune responses, many of which have previously been associated with responses to viral infection in humans and other animals. Consequently, our analyses indicate that pathogen-mediated selection may play a role in shaping genomic variation among relatively recently colonised island bird populations and highlight the utility of genotype-environment associations for identifying candidate genes potentially involved in host-pathogen interactions.
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| 70. |
- Sheppard, Eleanor C., et al.
(author)
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Genotype-environment associations reveal genes potentially linked to avian malaria infection in populations of an endemic island bird
- 2024
-
In: Molecular Ecology. - : John Wiley & Sons. - 0962-1083 .- 1365-294X. ; 33:8
-
Journal article (peer-reviewed)abstract
- Patterns of pathogen prevalence are, at least partially, the result of coevolutionary host–pathogen interactions. Thus, exploring the distribution of host genetic variation in relation to infection by a pathogen within and across populations can provide important insights into mechanisms of host defence and adaptation. Here, we use a landscape genomics approach (Bayenv) in conjunction with genome-wide data (ddRADseq) to test for associations between avian malaria (Plasmodium) prevalence and host genetic variation across 13 populations of the island endemic Berthelot's pipit (Anthus berthelotii). Considerable and consistent spatial heterogeneity in malaria prevalence was observed among populations over a period of 15 years. The prevalence of malaria infection was also strongly positively correlated with pox (Avipoxvirus) prevalence. Multiple host loci showed significant associations with malaria prevalence after controlling for genome-wide neutral genetic structure. These sites were located near to or within genes linked to metabolism, stress response, transcriptional regulation, complement activity and the inflammatory response, many previously implicated in vertebrate responses to malarial infection. Our findings identify diverse genes – not just limited to the immune system – that may be involved in host protection against malaria and suggest that spatially variable pathogen pressure may be an important evolutionary driver of genetic divergence among wild animal populations, such as Berthelot's pipit. Furthermore, our data indicate that spatio-temporal variation in multiple different pathogens (e.g. malaria and pox in this case) may have to be studied together to develop a more holistic understanding of host pathogen-mediated evolution.
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