bluuebunny/crossref_metadata_2025 huggingface dataset:
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

Generative 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

Simulation 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

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

Understanding 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

Abnormal 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

Periodontitis 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

Pancreatic 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

Despite 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

Resistance 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

Apoptosis 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

Colorectal 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.
Cross-sectional and longitudinal evaluation of heart-to-brachium pulse wave velocity for cardiovascular disease risk
Authors: Sugawara Jun , Tanaka Hirofumi , Yamashina Akira , Tomiyama Hirofumi
Published: August 2024

Heart-brachium pulse wave velocity (hbPWV) is a promising measure of arterial stiffness including the proximal aorta. To characterize age-associated changes and the clinical utilities of hbPWV, we evaluated the impacts of age and cardiovascular disease (CVD) risks on hbPWV cross-sectionally (N = 7868) and longitudinally (N = 3710, followed by 9.1 ± 2.0 years). hbPWV were obtained using two validated equations for arterial path length (with and without considering age-related aortic elongations). Brachial-ankle pulse wave velocity (baPWV) was used as a comparative measure. Repeated-measures correlation (rmcorr) and regression analyses were used to characterize associations of PWVs with age and Framingham’s general CVD risk score (FRS). In the cross-sectional study, hbPWVs derived by both equations showed stronger correlation with age (r = 0.746 ~ 0.796) and FRS (r = 0.714–0.749) than baPWV (r = 0.554 and r = 0.643). Furthermore, hbPWVs correlated with FRS even after controlling for age (r = 0.260 ~ 0.269, P < 0.0001). In the longitudinal study, hbPWVs demonstrated significantly higher rmcorr coefficient with age than baPWV (rrm=0.439–0.511 vs. 0.307, P < 0.0001). Across the adult lifespan, age-related increases in hbPWVs were almost consistent, starting from young adults, while baPWV displayed accelerated increases with age. A receiver operating characteristic curve analysis indicated that hbPWVs depicted more robust ability to stratify general CVD risk compared with baPWV (AUC = 0.896–0.913 vs. 0.833, P < 0.0001). The results of the follow-up study were consistent with the findings of the cross-sectional investigation. Our findings suggest that hbPWV undergoes a linear augmentation with age, commencing from an early adult life stage onward, rendering it a potential marker for discerning CVD risk.
Early warning of trends in commercial wildlife trade through novel machine-learning analysis of patent filing
Authors: Hinsley A. , Challender D. W. S. , Masters S. , Macdonald D. W. , Milner-Gulland E. J. , Fraser J. , Wright J.
Published: August 2024

Unsustainable wildlife trade imperils thousands of species, but efforts to identify and reduce these threats are hampered by rapidly evolving commercial markets. Businesses trading wildlife-derived products innovate to remain competitive, and the patents they file to protect their innovations also provide an early-warning of market shifts. Here, we develop a novel machine-learning approach to analyse patent-filing trends and apply it to patents filed from 1970-2020 related to six traded taxa that vary in trade legality, threat level, and use type: rhinoceroses, pangolins, bears, sturgeon, horseshoe crabs, and caterpillar fungus. We found 27,308 patents, showing 130% per-year increases, compared to a background rate of 104%. Innovation led to diversification, including new fertilizer products using illegal-to-trade rhinoceros horn, and novel farming methods for pangolins. Stricter regulation did not generally correlate with reduced patenting. Patents reveal how wildlife-related businesses predict, adapt to, and create market shifts, providing data to underpin proactive wildlife-trade management approaches.
Tracking the extensive three-dimensional motion of single ions by an engineered point-spread function
Authors: Zhou Yong-zhuang , Zhang Man-chao , Su Wen-bo , Wu Chun-wang , Xie Yi , Chen Ting , Wu Wei , Chen Ping-xing , Zhang Jie
Published: August 2024

Three-dimensional (3D) imaging of individual atoms is a critical tool for discovering new physical phenomena and developing new technologies in microscopic systems. However, the current single-atom-resolved 3D imaging methods are limited to static circumstances or a shallow detection range. Here, we demonstrate a generic dynamic 3D imaging method to track the extensive motion of single ions by exploiting the engineered point-spread function (PSF). We show that the image of a single ion can be engineered into a helical PSF, thus enabling single-snapshot acquisition of the position information of the ion in the trap. A preliminary application of this technique is demonstrated by recording the 3D motion trajectory of a single trapped ion and reconstructing the 3D dynamical configuration transition between the zig and zag structures of a 5-ion crystal. This work opens the path for studies on single-atom-resolved dynamics in both trapped-ion and neutral-atom systems.
A kirigami-based reconfigurable metasurface for selective electromagnetic transmission modulation
Authors: He Shuchang , Wang Chengjun , Tao Jie , Tang Haishan , Wang Zuojia , Song Jizhou
Published: August 2024

Tunable three-dimensional (3D) electromagnetic metasurfaces are essential for achieving selective modulation of polarized waves, but they usually require complex designs and the use of smart materials, posing great implementation challenges. Here, we propose a novel kirigami-based reconfigurable electromagnetic metasurface, which consists of a kirigami-based deformable thin polyimide substrate and periodically arranged copper split-ring resonators. By simple stretch, the two-dimensional (2D) planar metasurface can be uniformly transformed into a 3D state, enabling it to effectively and selectively modulate linearly and circularly polarized waves. Experimental and numerical results reveal the mechanical deformation and transmission characteristics of the metasurface under applied strains. It is shown that the metasurface exhibits good selective transmission tunability while the resonant frequency remains basically unchanged for both transverse electric and transverse magnetic polarized waves. Furthermore, the selective tuning mechanism and the influence of geometrical parameters are also illustrated by the equivalent circuit analysis.
An acidophilic fungus promotes prey digestion in a carnivorous plant
Authors: Sun Pei-Feng , Lu Min R. , Liu Yu-Ching , Shaw Brandon J. P. , Lin Chieh-Ping , Chen Hung-Wei , Lin Yu-fei , Hoh Daphne Z. , Ke Huei-Mien , Wang I-Fan , Lu Mei-Yeh Jade , Young Erica B. , Millett Jonathan , Kirschner Roland , Lin Ying-Chung Jimmy , Chen Ying-Lan , Tsai Isheng Jason
Published: August 2024

Leaves of the carnivorous sundew plants (Drosera spp.) secrete mucilage that hosts microorganisms, but whether this microbiota contributes to prey digestion is unclear. We identified the acidophilic fungus Acrodontium crateriforme as the dominant species in the mucilage microbial communities, thriving in multiple sundew species across the global range. The fungus grows and sporulates on sundew glands as its preferred acidic environment, and its presence in traps increased the prey digestion process. A. crateriforme has a reduced genome similar to other symbiotic fungi. During A. crateriforme–Drosera spatulata coexistence and digestion of prey insects, transcriptomes revealed significant gene co-option in both partners. Holobiont expression patterns during prey digestion further revealed synergistic effects in several gene families including fungal aspartic and sedolisin peptidases, facilitating prey digestion in leaves, as well as nutrient assimilation and jasmonate signalling pathway expression. This study establishes that botanical carnivory is defined by adaptations involving microbial partners and interspecies interactions.
Gastroesophageal reflux disease increases the risk of rheumatoid arthritis: a bidirectional two-sample Mendelian randomization study
Authors: Yuan Quan , Shen Zixiong , Zhang Jiujiang , Liu Qing , Whang Huimin , Li Yang
Published: August 2024

Rheumatoid arthritis (RA) is a common autoimmune disease, and some observational studies have indicated an association between Gastroesophageal Reflux Disease (GERD) and RA. However, the causal relationship between the two remains uncertain. We used Mendelian randomization (MR) to assess the causal relationship between GERD and RA. Two-sample Mendelian randomization analysis was performed using pooled data from large-scale genome-wide association studies. In addition, we performed multivariate MR analyses to exclude confounding factors between GERD and RA, including smoking quantity, drinking frequency, BMI, depression, and education attainment. The MR results for GERD on RA suggested a causal effect of the genetic susceptibility of GERD on RA (discovery dataset, IVW, odds ratio [OR] = 1.41, 95% confidence interval [CI] 1.22–1.63, p = 2.81 × 10−6; validation dataset, IVW, OR = 1.38, 95% CI 1.23–1.55, P = 1.76 × 10−8). Multivariate MR analysis also supports this result. But the results of the reverse MR analysis did not reveal compelling evidence that RA can increase the risk of developing GERD. Our bidirectional Two-Sample Mendelian randomization analysis and multivariate MR analysis provide support for the causal effect of GERD on RA. This discovery could offer new insights for the prevention and treatment of RA.
Long-term strict ant-plant mutualism identity characterises growth rate and leaf shearing resistance of an Amazonian myrmecophyte
Authors: Cárdenas Rafael E. , Rodríguez-Ortega Camila , Utreras Daniel , Forrister Dale L. , Endara María-José , Queenborough Simon A. , Alvia Pablo , Menéndez-Guerrero Pablo A. , Báez Selene , Donoso David A.
Published: August 2024

Over 125 million years of ant-plant interactions have culminated in one of the most intriguing evolutionary outcomes in life history. The myrmecophyte Duroia hirsuta (Rubiaceae) is known for its mutualistic association with the ant Myrmelachista schumanni and several other species, mainly Azteca, in the north-western Amazon. While both ants provide indirect defences to plants, only M. schumanni nests in plant domatia and has the unique behaviour of clearing the surroundings of its host tree from heterospecific plants, potentially increasing resource availability to its host. Using a 12-year survey, we asked how the continuous presence of either only M. schumanni or only Azteca spp. benefits the growth and defence traits of host trees. We found that the continuous presence of M. schumanni improved relative growth rates and leaf shearing resistance of Duroia better than trees with Azteca. However, leaf herbivory, dry matter content, trichome density, and secondary metabolite production were the same in all trees. Survival depended directly on ant association (> 94% of trees died when ants were absent). This study extends our understanding of the long-term effects of strict ant-plant mutualism on host plant traits in the field and reinforces the use of D. hirsuta–M. schumanni as a model system suitable for eco-co-evolutionary research on plant–animal interactions.
Atorvastatin lowers breast cancer risk by reversing an early tumorigenic signature
Authors: Foda Mohamed Y. , Salem Mohamed L. , AlAkwaa Fadhl M. , El-khawaga Omali Y.
Published: August 2024

Breast cancer remains a significant health challenge with complex molecular mechanisms. While many studies have explored genetic markers in breast carcinogenesis, few have studied the potential impact of pharmacological interventions such as Atorvastatin on its genetic landscape. This study aimed to elucidate the molecular distinctions between normal and tumor-adjacent tissues in breast cancer and to investigate the potential protective role of atorvastatin, primarily known for its lipid-lowering effects, against breast cancer. Searching the Gene Expression Omnibus database identified two datasets, GSE9574 and GSE20437, comparing normal breast tissues with tumor-adjacent samples, which were merged, and one dataset, GSE63427, comparing paired pre- and post-treated patients with atorvastatin. Post-ComBat application showed merged datasets' consistency, revealing 116 DEGs between normal and tumor-adjacent tissues. Although initial GSE63427 data analysis suggested a minimal impact of atorvastatin, 105 DEGs post-treatment were discovered. Thirteen genes emerged as key players, both affected by Atorvastatin and dysregulated in tumor-adjacent tissues. Pathway analysis spotlighted the significance of these genes in processes like inflammation, oxidative stress, apoptosis, and cell cycle control. Moreover, there was a noticeable interaction between these genes and the immunological microenvironment in tumor-adjacent tissues, with Atorvastatin potentially altering the suppressive immune landscape to favor anti-tumor immunity. Survival analysis further highlighted the prognostic potential of the 13-gene panel, with 12 genes associated with improved survival outcomes. The 13-gene signature offers promising insights into breast cancer's molecular mechanisms and atorvastatin's potential therapeutic role. The preliminary findings advocate for an in-depth exploration of atorvastatin's impact on.
Exploring the interplay between antiretroviral therapy and the gut-oral microbiome axis in people living with HIV
Authors: Narayanan Aswathy , Kieri Oscar , Vesterbacka Jan , Manoharan Lokeshwaran , Chen Puran , Ghorbani Mahin , Ljunggren Hans-Gustaf , Sällberg Chen Margaret , Aleman Soo , Sönnerborg Anders , Ray Shilpa , Nowak Piotr
Published: August 2024

The gut and oral microbiome is altered in people living with HIV (PLWH). While antiretroviral treatment (ART) is pivotal in restoring immune function in PLWH, several studies have identified an association between specific antiretrovirals, particularly integrase inhibitors (INSTI), and weight gain. In our study, we explored the differences in the oral and gut microbiota of PLWH under different ART regimens, and its correlation to Body Mass Index (BMI). Fecal and salivary samples were collected from PLWH (n = 69) and healthy controls (HC, n = 80). We performed taxonomy analysis to determine the microbial composition and relationship between microbial abundance and ART regimens, BMI, CD4+T-cell count, CD4/CD8 ratio, and ART duration. PLWH showed significantly lower richness compared to HC in both the oral and gut environment. The gut microbiome composition of INSTI-treated individuals was enriched with Faecalibacterium and Bifidobacterium, whereas non-nucleotide reverse transcriptase inhibitor (NNRTI)-treated individuals were enriched with Gordonibacter, Megasphaera, and Staphylococcus. In the oral microenvironment, Veillonella was significantly more abundant in INSTI-treated individuals and Fusobacterium and Alloprevotella in the NNRTI-treated individuals. Furthermore, Bifidobacterium and Dorea were enriched in gut milieu of PLWH with high BMI. Collectively, our findings identify distinct microbial profiles, which are associated with different ART regimens and BMI in PLWH on successful ART, thereby highlighting significant effects of specific antiretrovirals on the microbiome.
The public health impact of COVID-19 variants of concern on the effectiveness of contact tracing in Vermont, United States
Authors: Castonguay François M. , Borah Brian F. , Jeon Seonghye , Rainisch Gabriel , Kelso Patsy , Adhikari Bishwa B. , Daltry Daniel J. , Fischer Leah S. , Greening Bradford , Kahn Emily B. , Kang Gloria J. , Meltzer Martin I.
Published: August 2024

Case investigation and contact tracing (CICT) are public health measures that aim to break the chain of pathogen transmission. Changes in viral characteristics of COVID-19 variants have likely affected the effectiveness of CICT programs. We estimated and compared the cases averted in Vermont when the original COVID-19 strain circulated (Nov. 25, 2020–Jan. 19, 2021) with two periods when the Delta strain dominated (Aug. 1–Sept. 25, 2021, and Sept. 26–Nov. 20, 2021). When the original strain circulated, we estimated that CICT prevented 7180 cases (55% reduction in disease burden), compared to 1437 (15% reduction) and 9970 cases (40% reduction) when the Delta strain circulated. Despite the Delta variant being more infectious and having a shorter latency period, CICT remained an effective tool to slow spread of COVID-19; while these viral characteristics did diminish CICT effectiveness, non-viral characteristics had a much greater impact on CICT effectiveness.
Siponimod treatment response shows partial BDNF dependency in multiple sclerosis models
Authors: Hendek Hasan Hüseyin , Blusch Alina , Heitmann Neele , Oberhagemann Sarah , Demir Seray , Pedreiturria Xiomara , Gold Ralf , Faissner Simon
Published: August 2024

So far, only a small number of medications are effective in progressive multiple sclerosis (MS). The sphingosine-1-phosphate-receptor (S1PR)-1,5 modulator siponimod, licensed for progressive MS, is acting both on peripheral immune cells and in the central nervous system (CNS). So far it remains elusive, whether those effects are related to the neurotrophin brain derived neurotrophic factor (BDNF). We hypothesized that BDNF in immune cells might be a prerequisite to reduce disease activity in experimental autoimmune encephalomyelitis (EAE) and prevent neurotoxicity. MOG35–55 immunized wild type (WT) and BDNF knock-out (BDNFko) mice were treated with siponimod or vehicle and scored daily in a blinded manner. Immune cell phenotyping was performed via flow cytometry. Immune cell infiltration and demyelination of spinal cord were assessed using immunohistochemistry. In vitro, effects on neurotoxicity and mRNA regulation were investigated using dorsal root ganglion cells incubated with EAE splenocyte supernatant. Siponimod led to a dose-dependent reduction of EAE scores in chronic WT EAE. Using a suboptimal dosage of 0.45 µg/day, siponimod reduced clinical signs of EAE independent of BDNF-expression in immune cells in accordance with reduced infiltration and demyelination. Th and Tc cells in secondary lymphoid organs were dose-dependently reduced, paralleled with an increase of regulatory T cells. In vitro, neuronal viability trended towards a deterioration after incubation with EAE supernatant; siponimod showed a slight rescue effect following treatment of WT splenocytes. Neuronal gene expression for CCL2 and CX3CL1 was elevated after incubation with EAE supernatant, which was reversed after siponimod treatment for WT, but not for BNDFko. Apoptosis markers and alternative death pathways were not affected. Siponimod exerts both anti-inflammatory and neuroprotective effects, partially related to BDNF-expression. This might in part explain effectiveness during progression in MS and could be a target for therapy.
Advanced approach combines integrated weight water quality index and potential toxic elements for environmental and health risk assessment supported by simulation technique in Oued Souf, Algeria
Authors: Eid Mohamed Hamdy , Tamma Ahmed A. , Saeed Omar , Székács András , Abukhadra Mostafa R. , El-Sherbeeny Ahmed M. , Bence Czímer , Mikita Viktoria , Kovács Attila , Szűcs Péter
Published: August 2024

The current research study evaluated the health and environmental risks issues associated with potentially toxic elements (PTEs) in the complex terminal aquifer located in the Algerian desert. The methods used included principal component and cluster (dendrogram) analysis to estimate source of ions and contamination. Various indices such as the Heavy Metal Pollution Index (HPI), Metal Index, hazard quotient, hazard index (HI), and cancer risk (CR) were applied to assess both environmental and human health risks. Furthermore, the Monte Carlo method was applied for probabilistic assessment of carcinogenic and non-carcinogenic risks through oral and dermal exposure routes in both adults and children. The results revealed that approximately 16% of the samples fell within the low pollution category (HPI < 100), indicating relatively lower levels of heavy metal contamination. However, the remaining 84% of the samples exhibited high pollution levels, indicating a significant presence of heavy metal pollutants in the northeastern part of the investigated area. The calculated average risk index (RI) for the collected samples was 18.99, with a range from 0.03 to 103.21. This indicates that a large portion, 82% of the samples, could cause low ecological risk (RI < 30), whereas the remaining 18% indicate a significant environmental pollution risk. The HI for oral ingestion showed that adults had HI values ranging from 0.231 to 1.54, while children exhibited higher values, ranging from 0.884 to 5.9 (Fig. 5a). For dermal exposure, HI values in adults ranged from 2.71E−07 to 8.74E−06 and in children, from 2.18E−06 to 7.03E−05. These findings highlight the potential non-carcinogenic risks associated with oral exposure to PTEs and underscore the increased vulnerability of children to metals such as Fe, Mn, Pb, and Cr. Most samples showed CR exceeding 1 × 10−4 for chromium (Cr) and lead (Pb), indicating a significant vulnerability to carcinogenic effects in both children and adults.
AI-enhanced reconstruction of the 12-lead electrocardiogram via 3-leads with accurate clinical assessment
Authors: Mason Federico , Pandey Amitabh C. , Gadaleta Matteo , Topol Eric J. , Muse Evan D. , Quer Giorgio
Published: August 2024

The 12-lead electrocardiogram (ECG) is an integral component to the diagnosis of a multitude of cardiovascular conditions. It is performed using a complex set of skin surface electrodes, limiting its use outside traditional clinical settings. We developed an artificial intelligence algorithm, trained over 600,000 clinically acquired ECGs, to explore whether fewer leads as input are sufficient to reconstruct a 12-lead ECG. Two limb leads (I and II) and one precordial lead (V3) were required to generate a reconstructed 12-lead ECG highly correlated with the original ECG. An automatic algorithm for detection of ECG features consistent with acute myocardial infarction (MI) performed similarly for original and reconstructed ECGs (AUC = 0.95). When interpreted by cardiologists, reconstructed ECGs achieved an accuracy of 81.4 ± 5.0% in identifying ECG features of ST-segment elevation MI, comparable with the original 12-lead ECGs (accuracy 84.6 ± 4.6%). These results will impact development efforts to innovate ECG acquisition methods with simplified tools in non-specialized settings.
Machine learning approaches for influenza A virus risk assessment identifies predictive correlates using ferret model in vivo data
Authors: Kieran Troy J. , Sun Xiangjie , Maines Taronna R. , Belser Jessica A.
Published: August 2024

In vivo assessments of influenza A virus (IAV) pathogenicity and transmissibility in ferrets represent a crucial component of many pandemic risk assessment rubrics, but few systematic efforts to identify which data from in vivo experimentation are most useful for predicting pathogenesis and transmission outcomes have been conducted. To this aim, we aggregated viral and molecular data from 125 contemporary IAV (H1, H2, H3, H5, H7, and H9 subtypes) evaluated in ferrets under a consistent protocol. Three overarching predictive classification outcomes (lethality, morbidity, transmissibility) were constructed using machine learning (ML) techniques, employing datasets emphasizing virological and clinical parameters from inoculated ferrets, limited to viral sequence-based information, or combining both data types. Among 11 different ML algorithms tested and assessed, gradient boosting machines and random forest algorithms yielded the highest performance, with models for lethality and transmission consistently better performing than models predicting morbidity. Comparisons of feature selection among models was performed, and highest performing models were validated with results from external risk assessment studies. Our findings show that ML algorithms can be used to summarize complex in vivo experimental work into succinct summaries that inform and enhance risk assessment criteria for pandemic preparedness that take in vivo data into account.
Hot carriers from intra- and interband transitions in gold-silver alloy nanoparticles
Authors: Ramachandran Shreyas , João Simão M. , Jin Hanwen , Lischner Johannes
Published: August 2024

Hot electrons and holes generated from the decay of localised surface plasmons in metallic nanoparticles can be harnessed for applications in solar energy conversion and sensing. In this paper, we study the generation of hot carriers in large spherical gold-silver alloy nanoparticles using a recently developed atomistic modelling approach that combines a solution of Maxwell’s equations with large-scale tight-binding simulations. We find that hot-carrier properties depend sensitively on the alloy composition. Specifically, nanoparticles with a large gold fraction produce hot carriers under visible light illumination while nanoparticles with a large silver fraction require higher photon energies to produce hot carriers. Moreover, most hot carriers in nanoparticles with a large gold fraction originate from interband transitions which give rise to energetic holes and ‘cold’ electrons near the Fermi level. Increasing the silver fraction enhances the generation rate of hot carriers from intraband transitions which produce energetic electrons and ‘cold’ holes. These findings demonstrate that alloy composition is a powerful tuning parameter for the design of nanoparticles for applications in solar energy conversion and sensing that require precise control of hot-carrier properties.
The rising entropy of English in the attention economy
Authors: Pilgrim Charlie , Guo Weisi , Hills Thomas T.
Published: August 2024

We present evidence that the word entropy of American English has been rising steadily since around 1900. We also find differences in word entropy between media categories, with short-form media such as news and magazines having higher entropy than long-form media, and social media feeds having higher entropy still. To explain these results we develop an ecological model of the attention economy that combines ideas from Zipf’s law and information foraging. In this model, media consumers maximize information utility rate taking into account the costs of information search, while media producers adapt to technologies that reduce search costs, driving them to generate higher entropy content in increasingly shorter formats.
Constructing new bonds to carbon in dihydroquinazolines via hypervalent iodine(iii)-mediated C(sp3)–C(sp3) bond functionalization
Authors: Carlson Haley M. , Marshall Abigail R. , Burton Kaylin M. , Mosey R. Adam
Published: August 2024

A hypervalent iodine(iii)-mediated C(sp3)–C(sp3) bond functionalization reaction for new C–C, C–H, and C–P bond formation in dihydroquinazolines has been developed.
The N-anchoring effect in NH2-functionalized MOF-derived iron–carbon nanomaterials for oxygen reduction
Authors: Shen Yanqiong , Mao Lujiao , Lin Rong , Li Qipeng , Qian Jinjie
Published: August 2024

The inclusion of NH2 groups in MOF-5 promotes Fe(iii) adsorption and effectively prohibits Fe aggregation during pyrolysis. The porous MOF-derived metal–carbon catalyst (MOF5A-Fe@NC) demonstrates competitive ORR performance comparable to Pt/C.
Photocatalytic decarboxylation of free carboxylic acids and their functionalization
Authors: Mondal Subal , Mandal Subham , Mondal Soumya , Midya Siba P. , Ghosh Pradyut
Published: August 2024

This highlight article summarizes the complete development of photodecarboxylative functionalization of free carboxylic acids via a concerted single electron transfer (SET) or energy transfer (ET) pathways.
Chemical catalytic degradation of organic pollutants by using Ag–Cu2O core–shell decorated on rGO
Authors: Chen Lei , Guo Shuang , Park Eungyeong , Zhao Hongkai , Jung Young Mee
Published: August 2024

We successfully fabricated Ag@Cu2O core–shell decorated on reduced graphene oxide (rGO) nanocomposites (ACRN) with a simple and convenient in situ substitution method.
CO residence time modulates multi-carbon formation rates in a zero-gap Cu based CO2 electrolyzer
Authors: Subramanian Siddhartha , Kok Jesse , Gholkar Pratik , Sajeev Kumar Asvin , Iglesias van Montfort Hugo-Pieter , Kortlever Ruud , Urakawa Atsushi , Dam Bernard , Burdyny Thomas
Published: August 2024

This study shows how flow field designs can be used to modulate CO concentrations and hydrocarbon production rates in a zero gap copper based carbon dioxide electrolyzer.
Benign methylformamidinium byproduct induced by cation heterogeneity inhibits local formation of δ-phase perovskites
Authors: Lim Jihoo , Kim Jaehui , Davies-Jones Josh , Danaie Mohsen , Choi Eunyoung , Shim Hongjae , Chen Liang , Kim Jincheol , Kim Judy S. , Davies Philip R. , Seidel Jan , Green Martin A. , Stranks Samuel D. , Il Seok Sang , Yun Jae Sung
Published: August 2024

Methylammonium chloride (MACl) selectively promotes the formation of N-methylformamidinium (MFA+)PbI3 at grain boundaries (GBs) and as clusters near GBs while suppress the formation of δ-FAPbI3.
Identifying initial transformation products during chlorination of the indole moiety and unveiling their formation mechanisms
Authors: Huan MengXue , Liu Yong Dong , Zhong Rugang
Published: August 2024

Initial transformation products and their formation mechanisms in the chlorination of the indole moiety in tryptophan (Trp) are investigated using a quantum chemical computational method.
In pursuit of all solid state batteries (ASSB): advances at the cathode–electrolyte interface for garnet-based ASSB
Authors: Kurian Evan , Pitchai Jayashree , Neelanarayanan Soundarya , Ramesha K.
Published: August 2024

This review focuses on developments at the complex cathode–electrolyte interface (CEI) for garnet Li7La3Zr2O12 (LLZO)-based all solid state batteries.
Chemical synthetic approaches to mimic the TRAIL: promising cancer therapeutics
Authors: Masum Abdullah-Al , Aoki Shin , Rahman Md. Mahbubur , Hisamatsu Yosuke
Published: August 2024

TRAIL induced apoptosis signalling by death receptors (DR4/DR5).