bluuebunny/crossref_metadata_2025_split huggingface dataset:
Scaling up in community forest enterprises: the case of central Mexico
Authors: Solís-Mendoza Lesly Elizabeth , Sánchez-Nupan Laura Oliva , Castro-Torres Ricardo Balam , De la Mora de la Mora Gabriela , Kozak Rob , Peterson St Laurent Guillaume , Guerra de la Cruz Vidal , Galicia Leopoldo 
Published: August 2024

AbstractFor community forest enterprises (CFEs) in central Mexico, ‘scaling up’ can be an effective means of achieving the transition to economically attractive and sustainable forest management, but little is known about the potential and challenges that they face in this regard. We used a qualitative case study to evaluate a set of variables that determine the limitations and opportunities for scaling up CFEs in central Mexico and thereby expanding their commercial capacities, activities and outputs. The framework included concepts related to sustainable forest management, natural resource governance and temperate forest ecology. We interviewed leaders of four communities (n = 30) and 15 external actors (regional industry, and national non-governmental organizations). Communities that had developed long-term plans for forest management that embrace conservation values were also those with the greatest capacity to generate sustainable income streams from diverse sources. The robust legal frameworks and community institutions that set up procedures for responsibly harvesting and selling timber, thereby generating income, offer opportunities to enhance the effectiveness of CFEs. Demand continues to grow for wood products involving skilled crafts in central Mexico, but local production remains low; a lack of access to finance imposes limits on investment in the forests and value-added options for the products and services. Market opportunities and growth are also restricted by substandard physical infrastructure (e.g., roads, electricity) limited access to finance (e.g., credit, private-sector investors), and an absence of business plans. There are no formal networks to facilitate learning among these CFEs. Scaling up for these CFEs will require access to markets, innovations, and finance to create sustainable value chains for wood and non-wood forest products. The Mexican government could be instrumental in this by incorporating the notion of scaling up for CFEs when enacting policy that builds on and supports the country’s proven models of community-based forest management. On the other hand, this approach can be useful for developing more robust theoretical and methodological frameworks that capture these complex dynamics, contribute to the theory and practice of enterprise forestry development, sustainable natural resource management, and effective policy formulation.
The coevolution of technology, markets, and culture: the challenging case of AI
Authors: Muñoz Félix-Fernando 
Published: August 2024

AbstractArtificial intelligence (AI) is at the center of economic, social, political, and ethical debate. For the first time in human history, since the appearance of writing, a new type of “intelligence” is impacting the very nature of social relationships. New technologies are not only changing the operating model of markets and value chains in an accelerated way but also in how information is generated and processed, how labor, social relations, and culture evolve, etc. In this paper, we pursue two main goals. First, to set up an analytical framework in which cognitive, technical, and cultural dynamics are intertwined with the processes of deployment of economic action. Secondly, we utilize this framework to explore some key features and challenges of AI and its impact on coevolutionary processes at the cognitive, market, and cultural levels. We devote special attention to the consequences that AI may have for the concept of (economic) rationality and the formation of action plans. We conclude that AI will massively enhance agents’ spaces of action by improving efficiency and exploring new possibilities. However, AI will not change the nature of human action and the structure of the evolution of the economic system.
Auditing and instructing text-to-image generation models on fairness
Authors: Friedrich Felix , Brack Manuel , Struppek Lukas , Hintersdorf Dominik , Schramowski Patrick , Luccioni Sasha , Kersting Kristian 
Published: August 2024

AbstractGenerative AI models have recently achieved astonishing results in quality and are consequently employed in a fast-growing number of applications. However, since they are highly data-driven, relying on billion-sized datasets randomly scraped from the internet, they also suffer from degenerated and biased human behavior, as we demonstrate. In fact, they may even reinforce such biases. To not only uncover but also combat these undesired effects, we present a novel strategy, called Fair Diffusion, to attenuate biases during the deployment of generative text-to-image models. Specifically, we demonstrate shifting a bias in any direction based on human instructions yielding arbitrary proportions for, e.g., identity groups. As our empirical evaluation demonstrates, this introduced control enables instructing generative image models on fairness, requiring no data filtering nor additional training.
Integrated effects of pavement simulation models and scale differences on the thermal environment of tropical cities: physical and numerical modeling experiments
Authors: Kowalski L. F. , Lopes A. M. S. , Masiero E. 
Published: August 2024

AbstractSimulation methods attempt to explain what happens in full-scale environments. However, as simplification procedures, they also have their limitations and opportunities. One of the applications is to use the output data of a physical model to calibrate numerical simulation, or even to use outputs of numerical simulations to analyze urban scale studies. But it is uncertain the error in the interaction between these models. This study aims to analyze the impact of scale analysis and pavements simulation model modification on ambient and surface temperature of asphalt pavement in a physical model of a tropical city street canyons. Therefore, a scaled outdoor experiment was conducted, and a numerical simulation model, using ENVI-met software, was used to investigate the spatiotemporal variation of air and pavement surface temperature, in urban (1:1) and reduced (1:15) scales. For studies on the surface temperature of pavements, within the temperature range of 12 ºC to 37 ºC, it is recommended to calibrate physical models using as input, data derived from numerical simulation models, yielding a mean absolute percentage error (MAPE) of 4.9%. For estimating data in real-world urban scale, within the air temperature range of 15 ºC to 37 ºC, it is proposed to use output data from simulated models in ENVI-met, that presented a mean absolute error (MAE) of ± 0.59 or physical models (MAE =  ± 0.66). These results would be useful for the development of urban surface temperatures parametrizations.
Exploring causal correlations between blood inflammatory cytokines and low back pain: a Mendelian randomization
Authors: Tian Hao , Cheng Jianxin , Zhao Xiaoshuai , Xia Zhongyuan 
Published: August 2024

Abstract
Purpose
Low back pain (LBP) is a common and recurring public health problem that affects sufferers both physically and mentally and warrants further research. A succession of studies have suggested a plausible role for inflammatory cytokines in the pathogenesis of LBP. To date, there is no conclusive mechanism explaining how inflammatory cytokines affects LBP.

Methods
A bidirectional two-sample Mendelian randomization (MR) investigation was undertaken in two stages. The initial phase encompassed 41 inflammatory cytokines as the exposure, with LBP as the outcome, and the subsequent phase adopted the inverse approach. A total of 41 blood inflammatory cytokines were extracted from the genome-wide association study meta-analysis database, encompassing 8,293 individuals. Data pertaining to LBP were acquired from the Finnish biobank. Primary findings were computed using inverse-variance weighting (IVW), while sensitivity analyses accounting for pleiotropy and invalid instruments were conducted utilizing the weighted-median estimator, MR-Egger, and MR Pleiotropy RESidual Sum and Outlier.

Results
Our results suggest that higher levels of Macrophage migration inhibitory factor (MIF) as well as lower levels of C-C motif chemokine ligand 3 (CCL3) are associated with an increased risk of LBP (odds ratio [OR] = 1.134, 95% confidence interval [CI ]= 1.032–1.245, P = 0.009; OR = 0.887, 95% CI = 0.803–0.980, P = 0.018). Moreover, there was no heterogeneity and horizontal pleiotropy observed in the sensitivity analysis. In contrast, in studies of the effect of LBP on inflammatory cytokines, genetically determined LBP had no causal effect on 41 inflammatory cytokines (IVW P > 0.05).

Conclusions
Our study confirms that the levels of circulating MIF and CCL3 may be regarded as valuable circulating inflammatory biomarkers for the management of LBP in clinical practice and as potential molecules for future mechanistic investigation and drug target identification.
Pressure Dependence of Permeability in Cracked Rocks: Experimental Evidence of Non‐Linear Pore‐Pressure Gradients From Local Measurements
Authors: Lin Gang , Chapman Samuel , Garagash Dmitry , Fortin Jérôme , Schubnel Alexandre 
Published: August 2024

AbstractUnderstanding the coupling between rock permeability, pore pressure, and fluid flow is crucial, as fluids play an important role in the Earth's crustal dynamics. We measured the distribution of fluid pressure during fluid‐flow experiments on two typical crustal lithologies, granite and basalt. Our results demonstrate that the pore‐pressure distribution transitions from a linear to a non‐linear profile as the imposed pore‐pressure gradient is increased (from 2.5 to 60 MPa) across the specimen. This non‐linearity results from the effective pressure dependence of permeability, for which two analytical formulations were considered: an empirical exponential and a new micromechanics‐based model. In both cases, the non‐linearity of pore pressure distribution is predicted. Using a compilation of permeability versus Terzaghi's effective pressure data for granites and basalts, we show that our micromechanics‐based model has the potential to predict the pore pressure distribution over the range of effective pressures expected within the brittle crust.
SMC3 contributes to heart development by regulating super-enhancer associated genes
Authors: Zhang Bowen , Zhu Yongchang , Zhang Zhen , Wu Feizhen , Ma Xiaojing , Sheng Wei , Dai Ranran , Guo Zhenglong , Yan Weili , Hao Lili , Huang Guoying , Ma Duan , Hao Bingtao , Ma Jing 
Published: August 2024

AbstractAbnormal cardiac development has been observed in individuals with Cornelia de Lange syndrome (CdLS) due to mutations in genes encoding members of the cohesin complex. However, the precise role of cohesin in heart development remains elusive. In this study, we aimed to elucidate the indispensable role of SMC3, a component of the cohesin complex, in cardiac development and its underlying mechanism. Our investigation revealed that CdLS patients with SMC3 mutations have high rates of congenital heart disease (CHD). We utilized heart-specific Smc3-knockout (SMC3-cKO) mice, which exhibit varying degrees of outflow tract (OFT) abnormalities, to further explore this relationship. Additionally, we identified 16 rare SMC3 variants with potential pathogenicity in individuals with isolated CHD. By employing single-nucleus RNA sequencing and chromosome conformation capture high-throughput genome-wide translocation sequencing, we revealed that Smc3 deletion downregulates the expression of key genes, including Ets2, in OFT cardiac muscle cells by specifically decreasing interactions between super-enhancers (SEs) and promoters. Notably, Ets2-SE-null mice also exhibit delayed OFT development in the heart. Our research revealed a novel role for SMC3 in heart development via the regulation of SE-associated genes, suggesting its potential relevance as a CHD-related gene and providing crucial insights into the molecular basis of cardiac development.
Gingipain from Porphyromonas gingivalis causes insulin resistance by degrading insulin receptors through direct proteolytic effects
Authors: Liu Fen , Zhu Bofeng , An Ying , Zhou Zhifei , Xiong Peiying , Li Xuan , Mi Yang , He Tongqiang , Chen Faming , Wu Buling 
Published: August 2024

AbstractPeriodontitis is a critical risk factor for the occurrence and development of diabetes. Porphyromonas gingivalis may participate in insulin resistance (IR) caused by periodontal inflammation, but the functional role and specific mechanisms of P. gingivalis in IR remain unclear. In the present study, clinical samples were analysed to determine the statistical correlation between P. gingivalis and IR occurrence. Through culturing of hepatocytes, myocytes, and adipocytes, and feeding mice P. gingivalis orally, the functional correlation between P. gingivalis and IR occurrence was further studied both in vitro and in vivo. Clinical data suggested that the amount of P. gingivalis isolated was correlated with the Homeostatic Model Assessment for IR score. In vitro studies suggested that coculture with P. gingivalis decreased glucose uptake and insulin receptor (INSR) protein expression in hepatocytes, myocytes, and adipocytes. Mice fed P. gingivalis tended to undergo IR. P. gingivalis was detectable in the liver, skeletal muscle, and adipose tissue of experimental mice. The distribution sites of gingipain coincided with the downregulation of INSR. Gingipain proteolysed the functional insulin-binding region of INSR. Coculture with P. gingivalis significantly decreased the INSR–insulin binding ability. Knocking out gingipain from P. gingivalis alleviated the negative effects of P. gingivalis on IR in vivo. Taken together, these findings indicate that distantly migrated P. gingivalis may directly proteolytically degrade INSR through gingipain, thereby leading to IR. The results provide a new strategy for preventing diabetes by targeting periodontal pathogens and provide new ideas for exploring novel mechanisms by which periodontal inflammation affects the systemic metabolic state.
Emerging mechanisms and promising approaches in pancreatic cancer metabolism
Authors: Wu Hao , Fu Mengdi , Wu Mengwei , Cao Zhen , Zhang Qiyao , Liu Ziwen 
Published: August 2024

AbstractPancreatic cancer is an aggressive cancer with a poor prognosis. Metabolic abnormalities are one of the hallmarks of pancreatic cancer, and pancreatic cancer cells can adapt to biosynthesis, energy intake, and redox needs through metabolic reprogramming to tolerate nutrient deficiency and hypoxic microenvironments. Pancreatic cancer cells can use glucose, amino acids, and lipids as energy to maintain malignant growth. Moreover, they also metabolically interact with cells in the tumour microenvironment to change cell fate, promote tumour progression, and even affect immune responses. Importantly, metabolic changes at the body level deserve more attention. Basic research and clinical trials based on targeted metabolic therapy or in combination with other treatments are in full swing. A more comprehensive and in-depth understanding of the metabolic regulation of pancreatic cancer cells will not only enrich the understanding of the mechanisms of disease progression but also provide inspiration for new diagnostic and therapeutic approaches.
Triggering of endoplasmic reticulum stress via ATF4-SPHK1 signaling promotes glioblastoma invasion and chemoresistance
Authors: Lan Beiwu , Zhuang Zhoudao , Zhang Jinnan , He Yichun , Wang Nan , Deng Zhuoyue , Mei Lin , Li Yan , Gao Yufei 
Published: August 2024

AbstractDespite advances in therapies, glioblastoma (GBM) recurrence is almost inevitable due to the aggressive growth behavior of GBM cells and drug resistance. Temozolomide (TMZ) is the preferred drug for GBM chemotherapy, however, development of TMZ resistance is over 50% cases in GBM patients. To investigate the mechanism of TMZ resistance and invasive characteristics of GBM, analysis of combined RNA-seq and ChIP-seq was performed in GBM cells in response to TMZ treatment. We found that the PERK/eIF2α/ATF4 signaling was significantly upregulated in the GBM cells with TMZ treatment, while blockage of ATF4 effectively inhibited cell migration and invasion. SPHK1 expression was transcriptionally upregulated by ATF4 in GBM cells in response to TMZ treatment. Blockage of ATF4-SPHK1 signaling attenuated the cellular and molecular events in terms of invasive characteristics and TMZ resistance. In conclusion, GBM cells acquired chemoresistance in response to TMZ treatment via constant ER stress. ATF4 transcriptionally upregulated SPHK1 expression to promote GBM cell aggression and TMZ resistance. The ATF4-SPHK1 signaling in the regulation of the transcription factors of EMT-related genes could be the underlying mechanism contributing to the invasion ability of GBM cells and TMZ resistance. ATF4-SPHK1-targeted therapy could be a potential strategy against TMZ resistance in GBM patients.
PD-L1 induces autophagy and primary resistance to EGFR–TKIs in EGFR-mutant lung adenocarcinoma via the MAPK signaling pathway
Authors: Li Na , Zuo Ran , He Yuchao , Gong Wenchen , Wang Yu , Chen Liwei , Luo Yi , Zhang Cuicui , Liu Zhiyong , Chen Peng , Guo Hua 
Published: August 2024

AbstractResistance to epidermal growth factor receptor (EGFR)–tyrosine kinase inhibitors (TKIs) is a significant cause of treatment failure and cancer recurrence in non-small cell lung cancer (NSCLC). Approximately 30% of patients with EGFR-activating mutations exhibit primary resistance to EGFR–TKIs. However, the potential mechanisms of primary resistance to EGFR–TKIs remain poorly understood. Recent studies have shown that increased expression of programmed death ligand-1 (PD-L1) is associated with EGFR–TKIs resistance. Therefore, the present study aimed to investigate the mechanism of PD-L1 in primary resistance to EGFR–TKIs in EGFR-mutant lung adenocarcinoma (LUAD) cells. We found that PD-L1 was associated with poor prognosis in patients with EGFR-mutant LUAD, while the combination of EGFR–TKIs with chemotherapy could improve its therapeutic efficacy. In vitro and in vivo experiments revealed that PD-L1 promoted the proliferation and autophagy and inhibited the apoptosis of LUAD cells. Mechanistic studies demonstrated that upregulation of PD-L1 was critical in inducing autophagy through the mitogen-activated protein kinase (MAPK) signaling pathway, which was beneficial for tumor progression and the development of gefitinib resistance. Furthermore, we found that gefitinib combined with pemetrexed could synergistically enhance antitumor efficacy in PD-L1-overexpression LUAD cells. Overall, our study demonstrated that PD-L1 contributed to primary resistance to EGFR–TKIs in EGFR-mutant LUAD cells, which may be mediated by inducing autophagy via the MAPK signaling pathway. These findings not only help improve the prognosis of patients with EGFR-mutant LUAD but also provide a reference for the research of other cancer types.
The endoplasmic reticulum pool of Bcl-xL prevents cell death through IP3R-dependent calcium release
Authors: Gadet Rudy , Jabbour Lea , Nguyen Trang Thi Minh , Lohez Olivier , Mikaelian Ivan , Gonzalo Philippe , Luyten Tomas , Chalabi-Dchar Mounira , Wierinckx Anne , Marcillat Olivier , Bultynck Geert , Rimokh Ruth , Popgeorgiev Nikolay , Gillet Germain 
Published: August 2024

AbstractApoptosis plays a role in cell homeostasis in both normal development and disease. Bcl-xL, a member of the Bcl-2 family of proteins, regulates the intrinsic mitochondrial pathway of apoptosis. It is overexpressed in several cancers. Bcl-xL has a dual subcellular localisation and is found at the mitochondria as well as the endoplasmic reticulum (ER). However, the biological significance of its ER localisation is unclear. In order to decipher the functional contributions of the mitochondrial and reticular pools of Bcl-xL, we generated genetically modified mice expressing exclusively Bcl-xL at the ER, referred to as ER-xL, or the mitochondria, referred to as Mt-xL. By performing cell death assays, we demonstrated that ER-xL MEFs show increased vulnerability to apoptotic stimuli but are more resistant to ER stress. Furthermore, ER-xL MEFs displayed reduced 1,4,5-inositol trisphosphate receptor (IP3R)-mediated ER calcium release downstream of Phospholipase C activation. Collectively, our data indicate that upon ER stress, Bcl-xL negatively regulates IP3R-mediated calcium flux from the ER, which prevents ER calcium depletion and maintains the UPR and subsequent cell death in check. This work reveals a moonlighting function of Bcl-xL at the level of the ER, in addition to its well-known role in regulating apoptosis through the mitochondria.
Colorectal cancer risk stratification using a polygenic risk score in symptomatic primary care patients—a UK Biobank retrospective cohort study
Authors: Mallabar-Rimmer Bethan , Merriel Samuel W. D. , Webster Amy P. , Jackson Leigh , Wood Andrew R. , Barclay Matthew , Tyrrell Jessica , Ruth Katherine S. , Thirlwell Christina , Oram Richard , Weedon Michael N. , Bailey Sarah E. R. , Green Harry D. 
Published: August 2024

AbstractColorectal cancer (CRC) is a leading cause of cancer mortality worldwide. Accurate cancer risk assessment approaches could increase rates of early CRC diagnosis, improve health outcomes for patients and reduce pressure on diagnostic services. The faecal immunochemical test (FIT) for blood in stool is widely used in primary care to identify symptomatic patients with likely CRC. However, there is a 6–16% noncompliance rate with FIT in clinic and ~90% of patients over the symptomatic 10 µg/g test threshold do not have CRC. A polygenic risk score (PRS) quantifies an individual’s genetic risk of a condition based on many common variants. Existing PRS for CRC have so far been used to stratify asymptomatic populations. We conducted a retrospective cohort study of 50,387 UK Biobank participants with a CRC symptom in their primary care record at age 40+. A PRS based on 201 variants, 5 genetic principal components and 22 other risk factors and markers for CRC were assessed for association with CRC diagnosis within 2 years of first symptom presentation using logistic regression. Associated variables were included in an integrated risk model and trained in 80% of the cohort to predict CRC diagnosis within 2 years. An integrated risk model combining PRS, age, sex, and patient-reported symptoms was predictive of CRC development in a testing cohort (receiver operating characteristic area under the curve, ROCAUC: 0.76, 95% confidence interval: 0.71–0.81). This model has the potential to improve early diagnosis of CRC, particularly in cases of patient noncompliance with FIT.