Main Drivers Research Articles

Precise photoionisation treatment and hydrodynamic effects in atmospheric modelling of warm and hot Neptunes

Context. Observational breakthroughs in the field of exoplanets in the last decade have motivated the development of numerous theoretical models, such as those describing atmospheres and mass loss, which is believed to be one of the main drivers of planetary evolution. Aims. We outline for which types of close-in planets in the Neptune-mass range the accurate treatment of photoionisation effects is most relevant, particularly with respect to atmospheric mass loss and the parameters relevant for interpreting observations, such as temperature and ion fraction. Methods. We developed the Cloudy e Hydro Ancora INsieme (CHAIN) model, which combines our 1D hydrodynamic upper atmosphere model with the non-local thermodynamical equilibrium (NLTE) photoionisation and radiative transfer code Cloudy accounting for ionisation, dissociation, detailed atomic level populations, and chemical reactions for all chemical elements up to zinc. The hydro-dynamic code is responsible for describing the outflow, while Cloudy solves the photoionisation and heating of planetary atmospheres. We applied CHAIN to model the upper atmospheres of a range of Neptune-like planets with masses between 1 and 50 M⊕, also varying the orbital parameters. Results. For the majority of warm and hot Neptunes, we find slower and denser outflows, with lower ion fractions, compared to the predictions of the hydrodynamic model alone. Furthermore, we find significantly different temperature profiles between CHAIN and the hydrodynamic model alone, though the peak values are similar for similar atmospheric compositions. The mass-loss rates predicted by CHAIN are higher for hot strongly irradiated planets and lower for more moderate planets. All differences between the two models are strongly correlated with the amount of high-energy irradiation. Finally, we find that the hydrodynamic effects significantly impact ionisation and heating. Conclusions. The impact of the precise photoionisation treatment provided by Cloudy strongly depends on the system parameters. This suggests that some of the simplifications typically employed in hydrodynamic modelling might lead to systematic errors when studying planetary atmospheres, even at a population-wide level.

Research funding and citations in papers of Nobel Laureates in Physics, Chemistry and Medicine, 2019-2020

Abstract Purpose The goal of this study is a comparative analysis of the relation between funding (a main driver for scientific research) and citations in papers of Nobel Laureates in physics, chemistry and medicine over 2019-2020 and the same relation in these research fields as a whole. Design/Methodology/Approach This study utilizes a power law model to explore the relationship between research funding and citations of related papers. The study here analyzes 3,539 recorded documents by Nobel Laureates in physics, chemistry and medicine and a broader dataset of 183,016 documents related to the fields of physics, medicine, and chemistry recorded in the Web of Science database. Findings Results reveal that in chemistry and medicine, funded researches published in papers of Nobel Laureates have higher citations than unfunded studies published in articles; vice versa high citations of Nobel Laureates in physics are for unfunded studies published in papers. Instead, when overall data of publications and citations in physics, chemistry and medicine are analyzed, all papers based on funded researches show higher citations than unfunded ones. Originality/Value Results clarify the driving role of research funding for science diffusion that are systematized in general properties: a) articles concerning funded researches receive more citations than (un)funded studies published in papers of physics, chemistry and medicine sciences, generating a high Matthew effect (a higher growth of citations with the increase in the number of papers); b) research funding increases the citations of articles in fields oriented to applied research (e.g., chemistry and medicine) more than fields oriented towards basic research (e.g., physics). Practical Implications The results here explain some characteristics of scientific development and diffusion, highlighting the critical role of research funding in fostering citations and the expansion of scientific knowledge. This finding can support decisionmaking of policymakers and R&D managers to improve the effectiveness in allocating financial resources in science policies to generate a higher positive scientific and societal impact.

Anthropogenic–induced environmental and ecological changes in the Nile Delta over the past half-century

Anthropogenic activities over the past half-century have had a negative impact on the wetland ecosystem in the Nile Delta, which provides essential provisioning and regulating services. Therefore, it is crucial to systematically investigate pollution levels and their ecological consequences at both spatial and temporal scales in order to promote sustainable development. In this study, data on metal pollution in the Manzala Lake were compiled through a systematic review of all published literature from 1968 to 2020. Additionally, agricultural data (including land use, pesticide and fertilizer usage, and discharge) and economic data for the same time period were collected to identify the main drivers of pollution. The results indicated an overall increasing trend in heavy metal concentrations during the study period. The average concentrations of metals, arranged in descending order, were as follows: Fe (15,115.5 μg/g) > Mn (722 μg/g) > Zn (115.4 μg/g) > Cu (65.9 μg/g) > Ni (62.5 μg/g) > Cr (58.1 μg/g) > Pb (54.1 μg/g) > Cd (4.7 μg/g) > Hg (0.1 μg/g). A linear regression model revealed that wastewater discharge, water reuse, and the use of pesticides and fertilizers are the main sources of heavy metal pollution in the Manzala Lake. Consequently, there has been a dramatic decrease in the biodiversity of fish and molluscan communities. The study also found a correlation between heavy metal pollution and socio-economic development, highlighting the urgent need for attention to the conservation, management, and sustainable development of the lake.

A review of wastewater-based epidemiology for antimicrobial resistance surveillance

Antimicrobial resistance (AMR) is recognized as one of the most serious threats to public health. Unparalleled population growth and accelerated rates of AMR emergence and dissemination have resulted in both novel resistance in pathogenic organisms and the re-appearance of infections that were formerly under control. Consequently, this has led to an increased quantity of infectious diseases. One of the main drivers of antimicrobial overuse is inappropriate prescribing in human and veterinary medicine. The ability to rapidly survey the spread of antimicrobial resistance within human populations is key for its prevention, intervention, and control. However, many constraints are present for current clinical surveillance systems and their capacity to determine AMR dynamics in the microbiome of healthy individuals as well as in clinical pathogens causing infections. Wastewater-based epidemiology (WBE) is an emergent technique that has the capacity to act as a supplementary measure for current infectious disease surveillance systems and as an early warning system for infectious disease outbreaks. The development of disease outbreaks to the community level can be monitored in real time through the analysis of population pooled wastewater. This review provides an introduction to using wastewater-based epidemiology to monitor AMR bacteria, as well as an overview of wastewater-based epidemiology and its components.

Policy legacies and energy transitions: Greening policies under sectoral reforms in Argentina and Chile

Under what conditions do greening policies lead to a fast deployment of solar and wind energies? Environmental economics assume that market factors and technological innovations are the main drivers of energy transitions. While these assumptions sometimes hold for well-functioning markets; in emerging economies, the combination of scarce capital, weak institutions, and market distortions creates specific challenges that make their paths to clean energies different from those of developed states. I analyze greening reforms of the electricity sector in Argentina and Chile, exploring instances of success and failure. Using archive data and interviews to stakeholders, I explain how previous sector structures created different market distortions that hindered an effective electricity transition even in the context of significant cost-savings from investment in new technologies. Successful greening policies entailed broader electricity-sector reforms that removed previous binding constraints and restructured incentives for key private-sector stakeholders. I corroborate this argument by employing synthetic control methods to evaluate policies’ impact. I show that broad greening policies led to a significant penetration of renewable energies: by 2020 the share of solar and wind energies in Argentina and Chile were about 7.3% and 13.6% higher than in the counterfactual scenarios in which the greening reforms had not occurred.

Abstract 2027: Serological assessment of cancer associated myo-fibroblast (myCAF) activity by collagen pro-peptide biomarkers provides high prognostic power

Abstract Background: Myofibroblast Cancer Associated Fibroblasts (myCAFs) are the main tumor fibrosis drivers and hence different from inflammatory CAFs (iCAFs). MyCAFs are emerging as an important tool for understanding tumor biology. CAFs produce type III, V, VI and XI collagen that are the essential components of tumor fibrosis. Pro-peptides of these collagens can be quantified both in serum with the PRO-C3, PRO-C5, PRO-C6 and PRO-C11 biomarkers where they are prognostic for poor overall survival in patients with various solid tumor types and may be applied in vitro. Here we investigated the association and difference between myCAFs and iCAFs and their collagen expression profile and related that to data available data on serological assessments of PRO-C3, PRO-C5, PRO-C6 and PRO-C11, and cultured CAFs. Methods: The collagen expression in CAF subtypes were established from publicly available single-cell RNA-Seq dataset from pancreas cancer (PMID: 31273297) and non-small cell lung cancer (PMID: 36973297). In addition, we generated a biomarker profile using PRO-C3, PRO-C5, PRO-C6 and PRO-C11 ELISA to measure in serum of 220 patients with various solid tumor types and 33 healthy controls. We cultured CAFs in vitro and measured the same biomarkers in conditioned medium. We compared the result to historical PRO-C3, PRO-C6 and PRO-C11 prognostic data for pancreas cancer patient data. Results: Based on the single-cell RNA-Seq dataset, while type III and type VI collagen were found expressed in fibroblasts both from normal tissues and tumor tissues whereas type V collagen and XI collagen were found almost exclusively expressed in CAFs (tumor tissue). When further examining the CAF subtypes, type III collagen and VI collagen were found expressed in both myCAFs and iCAFs whereas type V collagen and XI collagen were found almost exclusively expressed in myCAFs and not iCAFs. Moreover, in the 220 patients, PRO-C3 and PRO-C6 was elevated in elevated in a few cancer types (p<0.05-0.01) with an inter-patient variation ~2-fold whereas PRO-C5 and PRO-C11 were elevated in all cancer types (p<0.0001) with a ~5-fold inter-patient variation. These four biomarkers identified different pancreas cancer patients endotypes all with poor overall survival, P<0.001. In direct alignment, collagen pro-peptides we highly upregulated in cultures of CAFs. Conclusions: Profiling collagen expression in fibroblast from PDAC and NSCLC reveals that type V collagen and type XI collagen are exclusively found in myCAF not iCAF. Biomarkers of these collagens can be measured in serum from cancer patients and are prognostic for poor overall survival. Thus, these data suggest that cancer associated myo-fibroblast (myCAF) activity can be assessed non-invasively by specific collagen pro-peptide biomarkers. Citation Format: Nicholas Willumsen, Neel I. Nissen, Morten A. Karsdal. Serological assessment of cancer associated myo-fibroblast (myCAF) activity by collagen pro-peptide biomarkers provides high prognostic power [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2027.

Abstract 7282: Comparing TEAD palmitoylation inhibitors with differential TEAD selectivity in combination efficacy with targeted therapies and in renal safety

Abstract Genetic alterations of the Hippo signaling pathway components resulting in YAP/TAZ activation have been reported in a variety of human malignancies. YAP/TAZ activation and functional requirement have also been linked to resistance to targeted therapies by providing the essential survival signal in drug-tolerant persister/dormant cells. As the main drivers for YAP/TAZ recruitment to chromatin, TEAD transcription factors are the major effectors of the Hippo-YAP/TAZ pathway involved in the regulation of cell proliferation, survival, and cell migration. There are four members in the TEAD family: TEAD1, TEAD2, TEAD3, and TEAD4. All four members have a conserved cysteine residue that gets auto-palmitoylated and a highly conserved central pocket in which the palmitate is buried. TEAD auto-palmitoylation is required for TEAD interaction with coactivator YAP/TAZ and transcriptional activity. We have discovered and developed highly potent and selective TEAD auto-palmitoylation inhibitors that interact directly with TEAD by occupying the central palmitate pocket, disrupt YAP/TAZ-TEAD protein interaction, suppress TEAD transcriptional activity, and selectively block NF2-deficient mesothelioma proliferation in vitro and inhibit NF2 mutant tumor growth in vivo. One of these compounds, VT3989, is being evaluated in an ongoing phase 1 clinical trial, where partial responses in mesothelioma patients have been demonstrated, showing for the first time that the Hippo pathway is druggable and that the Hippo pathway is now a validated target for cancer therapy. It remained a question, however, which TEAD members are more important and whether it would be safer and as efficacious to inhibit one TEAD member than multiple TEAD members. Thus, we utilized our TEAD inhibitors with differential TEAD selectivity to determine the importance of TEAD1 selectivity in anti-tumor efficacy and in renal safety. We evaluated the anti-tumor efficacy of several potent TEAD1-selective and pan-TEAD inhibitors in in vivo combination studies using EGFR mutant/KRAS mutant xenograft models. We found that TEAD1-selective TEAD palmitoylation inhibitors are less efficacious than pan-TEAD/multiple-TEAD inhibitors in combination studies with targeted therapies (as such EGFRi and KRASi). In 14-day/28-day rat studies, TEAD1-selective TEAD inhibitors also exhibited proteinuric nephropathy similar to that observed with pan-/multiple-TEAD inhibitors. Therefore, based on our findings, we can conclude that TEAD1-selective TEAD palmitoylation inhibitors can have similar on-target effect on kidneys as TEAD inhibitors with broader TEAD selectivity while having reduced anti-tumor efficacy and durability of response in combination with targeted therapies. Citation Format: Tracy T. Tang, Leonard Post. Comparing TEAD palmitoylation inhibitors with differential TEAD selectivity in combination efficacy with targeted therapies and in renal safety [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7282.

Abstract 2898: Development of the lipid kinase PIKfyve PROTAC degrader against neuroendocrine prostate cancer

Abstract Therapies targeting the androgen receptor (AR) as the main driver of prostate cancer (PCa) can lead to various mechanisms of resistance and promote progression to castration-resistant PCa (CRPC), which has a median survival of only 13-23 months. Amongst recurrent CRPC, 17%-30% of patients develop neuroendocrine prostate cancer (NEPC), which is a PCa subtype characterized by a unique histology. NEPC exhibits a loss of AR signaling during neuroendocrine transdifferentiation which results in resistance to AR-targeted therapies and gain of cell characteristics resembling poorly differentiated neuroendocrine tumors. Despite advances in the understanding of NEPC development, treatment options remain limited, with platinum-based chemotherapy as the first-line treatment for both de novo and treatment-induced NEPC. However, response to first-line chemotherapy in NEPC is short, with a median survival of only seven months. The poor prognosis of NEPC is attributed in part to late diagnosis and a lack of effective therapeutic agents. Our previous work demonstrated that NEPC and AR-negative PCa exhibit higher dependency on the lipid kinase PIKfyve than AR-positive CRPC. Thus, development of PIKfyve inhibitory therapies targeting the emergent vulnerabilities of NEPC or AR-negative forms of PCa is a promising approach. Using a proteolysis targeting chimera (PROTAC) technology, we designed a class of PIKfyve specific degrader. The in vitro degradation efficiency were determined by immunoblotting, and DC50s (degradation concentration at 50%) were calculated for top candidates. Pharmacokinetic and pharmacodynamic were evaluated for in vivo study. In summary, we have developed a class of PIKfyve specific degrader using the E3 ligase von Hippel-Lindau (VHL) as a ligand via a diverse set of linkers. Mechanistic studies revealed that it induced PIKfyve degradation in a VHL- and proteasome-dependent manner. Citation Format: Yuanyuan Qiao, Chungen Li, Yang Zheng, Xia Jiang, Sarah Nicole Yee, Caleb Cheng, Yi Bao, Yuping Zhang, Yuzhuo Wang, Zhen Wang, Ke Ding, Arul Chinnaiyan. Development of the lipid kinase PIKfyve PROTAC degrader against neuroendocrine prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2898.

On the superior performance of SRI funds

We compare the performance of 1126 US mutual funds deemed socially responsible to that of a matching sample of conventional funds over the three-decade period January 1980–December 2019. The comparisons are made over the entire period as well as the descending (bear) and ascending (bull) market subperiods, classified either according to the NBER method or the regime switching model. Our results indicate that SRI funds outperform their peers over the entire sample period. Additionally, regardless of the method used to the identify market condition or the asset pricing model employed, SRI funds as a group significantly outperform their conventional counterparts during bull markets but insignificantly so during bear markets. However, all-equity SRI funds and those that includes Equity and Fixed Income funds, significantly outperform their peers under either regime, with both methods and for all asset pricing specifications. Further examination indicates that the main driver of differences in the performance of SRI funds and their conventional peers can be attributed to their superior selection ability.

Post-growth theories in a global world: A comparative analysis

Abstract The process of globalisation, the global pecking order, and most international development policies are anchored on the concept of economic growth, which is at the same time increasingly questioned on social and ecological grounds. Increases in global output (GDP) are indeed among the main drivers of energy and natural resources overuse, with potentially destructive consequences for the overall ecological balances sustaining life on the planet. As a consequence, a number of post-growth theories and approaches have emerged over the past few years. This article carries out a comparative analysis of three main post-growth schools of thought in order to trace back their origin, evolution, and policy impacts at the global level. It also investigates the main points of tension and synergy to advance the debate on how best to challenge conventional growth-based policies in the international arena.

Evolutionary patterns and influencing factors of relationships among ecosystem services in the hilly red soil region of Southern China.

As a crucial ecological protection area in China, the Southern hilly red soil region is characterized by uneven spatial and temporal distribution of ecological landscape elements, unpredictable and changeable interrelationships between them, diversified driving factors, and lack of comprehensive consideration of ecosystem services. In order to better understand the interaction between ecosystem services, restore regional ecology, and promote sustainable development, the evolution law and influencing mechanism of ecosystem services and their driving factors are quantitatively analyzed in the study. Based on simulations of different ecosystem services from 2000 to 2020, their spatial and temporal changes and the contributions of main drivers are quantified, their trade-offs and synergies are analyzed, and the changing rules under the influence of natural factors and socioeconomic factors are explored. The results show that (1) the crop production significantly increases in the southwest and north regions, the habitat quality decreases in urban and coastal areas, and the soil retention and water yield show an increasing trend from west to east. (2) Land use/cover is the main driver of carbon storage and habitat quality variation, and precipitation is an important driver of water yield spatial variation. (3) The crop production and the other four ecosystem services show a trade-offs relationship, and the relationship between supporting services and regulating services is the synergetic. (4) The altitude weakens the synergistic relationship between soil retention and habitat quality/carbon storage, while it enhances the synergistic relationship between soil retention and water yield. Driven by precipitation factors, ecosystem services related to water yield have significant differences in the change. The population density enhances the trade-offs of crop production and soil retention, as well as the synergistic relationship between soil retention and habitat quality/carbon storage. In different land use/cover (LULC), the influence of urban land on ecosystem services relationship change is more obvious. Overall, this study can provide scientific bases and policy suggestions for ecosystem protection/restoration in the red soil region of Southern China, which has an important theoretical and practical significance.

Trends in air toxics cancer risk in Southern California, 1998-2018

Air toxics are an important category of air pollutants that are known to cause adverse health effects, including increased cancer risk. Regulatory efforts at federal, state, and local levels have aimed to decrease air toxics emissions over the past several decades. This study evaluated trends in air toxics cancer risks in Southern California using data from 1998 to 2018. We estimated air toxics cancer risk for each of four iterations of the South Coast Air Quality Management District’s Multiple Air Toxics Exposure Study, which included at least one year of measurements at 10 stations and air toxics modeling for each iteration. Cancer risks were calculated using the measured and modeled air toxics concentrations averaged over a one to two year period and multiplied by the corresponding cancer potency factor and combined exposure factor that accounted for multiple exposure pathways and children’s increased sensitivity to the health effects of air pollution. We examined temporal trends in overall air toxics cancer risks and evaluated changes in the air toxics species that contributed most to cancer risk in the region. Both measurement and modeling results show that air toxics cancer risk in Southern California decreased by more than 80% between 1998 and 2018, including a decrease of about 50% from 2012 to 2018. Diesel particulate matter was the main risk driver, followed by benzene, 1,3-butadiene, and formaldehyde. We found that more densely populated communities showed larger decreases than sparsely populated areas. The substantial decrease in air toxics levels over this 20-year period points to the success of air pollution policies aimed at addressing air toxics emissions and can inform future policy efforts to further reduce air toxics health impacts.

Revisiting niche divergence hypothesis in sexually dimorphic birds: Is diet overlap correlated with sexual size dimorphism?

The evolution of sexual size dimorphism (SSD) is a long-standing topic in evolutionary biology, but there is little agreement on the extent to which SSD is driven by the different selective forces. While sexual selection and fecundity selection have traditionally been proposed as the two leading hypotheses, SSD may also result from natural selection through mechanisms such as sexual niche divergence, which might have reduced resource competition between sexes. Here, we revisited the niche divergence hypothesis by testing the relationship between the sexual overlap in diet and SSD of 56 bird species using phylogenetic comparative analyses. We then assessed how SSD variation relates to the three main hypotheses: sexual selection, fecundity selection, and sexual niche divergence using phylogenetic generalized least squares (PGLS). Then, we compared sexual selection, fecundity selection and niche divergence selection as SSD drivers through phylogenetic confirmatory path analyses to disentangle the possible causal evolutionary relationships between SSD and the three hypotheses. Phylogenetic generalized least squares showed that SSD was negatively correlated with diet overlap, that is, the greater the difference in body size between males and females, the less diet overlap. As predicted by sexual selection theory, the difference in body size between sexes was higher in polygynous species. Confirmatory phylogenetic path analyses suggested that the most likely evolutionary path might include the mating system as a main driver in SSD and niche divergence as a result of SSD. We found no evidence of a role of fecundity selection in the evolution of female-biased SSD. Our study provides evidence that sexual selection has likely been the main cause of SSD and that dietary divergence is likely an indirect effect of SSD.

The Role of Gender and Education on Entrepreneurship Performance: The Case of Kenya's Micro and Small Businesses

Although it is believed that entrepreneurship is the main driver of economic growth, it is basically a value-driven activity, and personal values appeared to have a significant impact on both the decision to pursue entrepreneurship as well as how the enterer behaves or performs. The purpose of this study was to investigate the effects of owner/manager gender and educational background on the performance of micro and small businesses in Kenya. A sample of 398 licensed MSEs were chosen from a study population of 65,698 from three counties of Kisumu, Siaya and Vihiga in Western Kenya. Structured questionnaires were used in the study's descriptive survey approach to gather primary data. Descriptive and inferential statistics were used to present the data after it had been evaluated using statistical software (SPSS). The study's findings showed in objective one, that gender has significant difference in the performance of MSEs since (F₀ = 3.895 > F₁ (1, 397) = 3.86; αo = .049 < αc = .05). Objective two, the education level of owner/manager also has significant difference in MSE performance since, (Fo = 187.090> F₁ (1, 397) = 3.86; αo = .001< αc = .05). The study conclusion was that both gender and education characteristic of entrepreneur’s, determine the level of MSE performance. The study recommends combined efforts to support female gender to access necessary resources as well the training and education to expose them to the new technologies. There is need for in-depth study to find out the extent to which gender disparities are affecting the expansion of the MSE sector.

Anti-histone and anti-nucleosome rather than anti-dsDNA antibodies associate with IFN-induced biomarkers in Sudanese and Swedish Systemic Lupus Erythematosus patients.

In SLE, anti-dsDNA can co-occur with autoantibodies against other chromatin components, like histones and nucleosomes. These antibodies induce type-1 interferon production, a hallmark of SLE. We measured antinuclear antibody (ANA) sub-specificities and investigated their associations to inflammatory biomarkers including interferon-regulated chemokines. We included 93 Sudanese and 480 Swedish SLE patients and matched controls (N = 104 + 192). Autoantibodies targeting ANA-subspecificites: dsDNA, Sm, Sm/U1RNPcomplex, U1RNP, SSA/Ro52, SSA/Ro60, SSB/La, ribosomal P, PCNA and histones were quantified in all subjects, anti-nucleosome only in the Swedish patients, with a bead-based multiplex immunoassay. Levels of 72 plasma biomarkers were determined with Proximity Extension Assay technique or ELISA. Among Sudanese patients, the investigated antibodies significantly associated with 9/72 biomarkers. Anti-histone antibodies showed the strongest positive correlations with MCP-3 and S100A12 as well as with interferon I-inducible factors MCP-1 and CXCL10. Anti-dsDNA antibodies associated with CXCL10 and S100A12, but in multivariate analyses, unlike anti-histone, associations lost significance.Among Swedish patients, MCP-1, CXCL10, SA100A12 also demonstrated stronger associations to anti-histone and anti-nucleosome antibodies, compared with anti-dsDNA and other ANA sub-specificities. In multiple regression models, anti-histone/nucleosome retained the strongest associations. When excluding anti-histone or anti-nucleosome positive patients, the associations between MCP-1/CXCL10 and anti-dsDNA were lost. In contrast, when excluding anti-dsDNA positive patients, associations with anti-histone and anti-nucleosome remained significant. In two cohorts of different ethnical origin, autoantibodies targeting chromatin correlate stronger with IFN-induced inflammatory biomarkers than anti-dsDNA or other ANA sub-specificities. Our results suggest that anti-histone/nucleosome autoantibodies may be main drivers of type-1 interferon activity in SLE.

Association of Mutant KRAS Alleles With Morphology and Clinical Outcomes in Pancreatic Ductal Adenocarcinoma.

Mutant KRAS is the main oncogenic driver in pancreatic ductal adenocarcinomas (PDACs). However, the clinical and phenotypic implications of harboring different mutant KRAS alleles remain poorly understood. To characterize the potential morphologic and clinical outcome differences in PDACs harboring distinct mutant KRAS alleles. Cohort 1 consisted of 127 primary conventional PDACs with no neoadjuvant therapy, excluding colloid/mucinous, adenosquamous, undifferentiated, and intraductal papillary mucinous neoplasm-associated carcinomas, for which an in-house 42-gene mutational panel had been performed. A morphologic classification system was devised wherein each tumor was assigned as conventional, papillary/large duct (P+LD, defined as neoplastic glands with papillary structure and/or with length ≥0.5 mm), or poorly differentiated (when the aforementioned component was 60% or more of the tumor). Cohort 2 was a cohort of 88 PDACs in The Cancer Genome Atlas, which were similarly analyzed. In both cohorts, there was significant enrichment of P+LD morphology in PDACs with KRAS G12V and G12R compared with G12D. In the entire combined cohort, Kaplan-Meier analyses showed longer overall survival (OS) with KRAS G12R as compared with G12D (median OS of 1255 versus 682 days, P = .03) and in patients whose PDACs displayed P+LD morphology as compared with conventional morphology (median OS of 1175 versus 684 days, P = .04). In the adjuvant-only subset, KRAS G12R had the longest OS compared with G12D, G12V, and other alleles (median OS unreached/undefined versus 1009, 1129, and 1222 days, respectively). PDACs with different mutant KRAS alleles are associated with distinct morphologies and clinical outcomes, with KRAS G12R allele associated with P+LD morphology and longer OS when compared with G12D using Kaplan-Meier studies.

Assessing Future Hydrological Variability in a Semi-Arid Mediterranean Basin: Soil and Water Assessment Tool Model Projections under Shared Socioeconomic Pathways Climate Scenarios

Climate is one of the main drivers of hydrological processes, and climate change has caused worldwide effects such as water scarcity, frequent floods and intense droughts. The purpose of this study was to analyze the effects of climate change on the water balance components, high flow and low flow stream conditions in a semi-arid basin in Iran. For this reason, the climate outputs of the CanESM5 model under Shared Socioeconomic Pathways (SSP) scenarios SSP126, SSP245, and SSP585 were spatially downscaled by the Statistical Downscaling Model (SDSM). The hydrological process was simulated by the Soil and Water Assessment Tool (SWAT) model. Key findings include a 74% increase in evapotranspiration, a reduction by up to 9.6% in surface runoff, and variations in discharge by up to 53.6%. The temporal analysis of snow melting changes revealed an increase in the volume of snow melting during winter months and a reduction in the volume during spring. The projected climate change is expected to cause notable variations in high and low flow events, particularly under the SSP585 scenario, which anticipates significant peaks in flow rates. This comprehensive analysis underscores the pressing need for adaptive strategies in water resource management to mitigate the anticipated impacts of climate variability.

An integrated approach to explore the microbial biodiversity of natural milk cultures for cheesemaking

The use of natural milk culture (NMC) represents a key factor in PDO Montasio cheeses, contributing to its distinctive sensory profile. The complex microbial ecosystem of NMCs is the result of heat treatment and incubation conditions, which can vary considerably among different production plants. In this study, the microbiota of NMCs collected from 10 PDO Montasio cheese dairies was investigated employing colony counts and metagenomic analysis. Furthermore, residual sugars, organic acids, and volatile profiles were quantitatively investigated. Results showed that Streptococcus thermophilus was the dominant species in all NMCs, and a subdominant population made of other streptococci and L. salivarius was also present. The incubation temperature appeared to be the main driver of biodiversity in NMCs. Metagenomics allowed us to evidence the presence of minor species involving safety (e.g., Staph. aureus) as well as possible functional aspects (Next Generation Probiotics). Statistical analysis based on residual sugars, organic acids, and volatiles' content allowed to correlate the presence of specific microbial groups with metabolites of great technological and sensory relevance, which can contribute to giving value to the artisanal production procedures of NMCs and clarify their role in the creation of the characteristics of PDO Montasio cheese.

People’s perception of the brown bear reintroduction in the Spanish Pyrenees

The brown bear (Ursus arctos) was reintroduced in the Pyrenees during the ‘90s. The bear population has increased in number and distribution, fostering human-wildlife conflicts in areas where the species was absent for more than a century. We analysed 236 questionnaires about people’s perception toward the bear reintroduction in the Spanish Pyrenees, as well as the role of public administration in managing the damages caused by bears using regression trees. Our tree models explained 85% of the observed variability of people’s perceptions being the main drivers of perception whether people consider brown bears to be overabundant, whether these mammals attract nature tourism, if bears represent a danger for humans and finally if the local administration compensates for brown bear damages. We conclude that local administration should create the appropriate social atmosphere for the coexistence of humans and brown bears through information and risk prevention campaigns, compensation of damages, and promoting the public valorisation of the species. These efforts to mitigate human-bear conflicts may promote a positive perception of local people towards this emblematic mammal.

Development of Islamic Economy and Finance in Indonesia through KNEKS Structure in 2019-2024


 
 
 This research discusses the development of Sharia Economics and Finance in Indonesia through the KNEKS Structure in 2019-2024. This research discusses the Direction of Development and Strengthening of Sharia Economics and Finance in Indonesia, of course strengthening the halal value chain with a focus on sectors or clusters that are considered potential and highly competitive; second, strengthening the sharia financial sector whose master plan has been outlined in the Indonesian Sharia Financial Architecture Masterplan or AKSI which has been refined in this master plan; third, strengthening micro, small and medium enterprises or MSMEs as the main drivers of the halal value chain. For the research process on Sharia Economic and Financial Development in Indonesia Through the KNEKS Structure in 2019-2024, this research used the library research method, and we conducted this research where the data study object used library data sourced from several types of books and the internet. as a source for obtaining these data. Then we read, study and understand various kinds of literature related to the research we are doing. And we also use a qualitative observation method by observing data sourced from a book entitled sharia economics, especially at the undergraduate level of higher education. This research is also useful for knowing the direction of development and strengthening of sharia economics and finance in Indonesia through the KNEKS structure in 2019-2024.