bluuebunny/crossref_metadata_2025 huggingface dataset:
Conceptualising State-Centric Mediation: An Analysis of China's Foreign Investment Complaints Mechanism
Authors: McLaughlin Mark
Published: February 2024

This article argues that China's foreign investor complaints system constitutes ‘state-centric investment mediation’. The Rules on Handling Complaints of Foreign-Invested Enterprises, which entered into force on 1 October 2020, place a state agency in the position of facilitating negotiations between a foreign investor and the agency being complained against. The prospects for this complaints system depend on how the state-as-mediator dynamic is perceived by foreign investors. To this end, it will be argued that settlement agreements reached pursuant to this system may be enforceable under the Singapore Convention on Mediation in certain circumstances. Investors and government entities operating similar systems worldwide should be cognisant of the broad drafting terminology of the Singapore Convention. Moreover, it is proposed that further clarification of the procedural rules and the inclusion of China's foreign-related dispute resolution institutions may enhance investor confidence and encourage use of the complaints system.
Waste not, want not: Value chain stakeholder attitudes to surplus dairy calf management in Australia
Authors: Bolton Sarah E , Vandresen Bianca , von Keyserlingk Marina AG
Published: February 2024

The management of surplus dairy calves in Australia has traditionally been influenced by the economic viability of different practices. When beef prices are favourable, more surplus calves are raised for beef, and when beef prices are low, more calves are killed in the first few days of life. Early life killing of surplus calves may however threaten the dairy industry’s social licence to operate. The aim of this study was to describe the views of value chain stakeholders regarding the management of surplus calves. Representatives from seven post-farm gate organisations participated in semi-structured interviews and were asked about their views on current practices, alternatives to early life killing and how best to implement change. Responses were analysed using inductive thematic analysis and were organised into three themes: (1) ethics of surplus calf management; (2) economics of surplus calf management; and (3) moving towards solutions including approaches to affecting change. We conclude that stakeholders widely recognised early life killing of surplus calves as a threat to the industry’s social licence. Whilst technical solutions such as beef on dairy breeding programmes were cited as important, participants emphasised that implementing sustainable solutions will require collaboration, leadership, and commitment by all stakeholders along the value chain.
To Blockade or Not To Blockade? The Legal Status of Russia's Suspension of Shipping in the Sea of Azov
Authors: Friedman Shani
Published: February 2024

This article explores the legal situation relating to the Sea of Azov in the light of the Russian suspension of shipping on 24 February 2022. While this act received little scholarly or political attention, there is a debate concerning the legality of the suspension of shipping, mainly whether it is governed by the law of naval blockade under the laws of naval warfare. The article analyses the situation from the perspectives of both international humanitarian law (IHL) and the law of the sea (LOS) and examines how the interaction between the two legal regimes affects the analysis. The article supports the conclusion that the Russian conduct does not constitute a naval blockade but may be an accepted practice within the legal regime of naval warfare. In addition, it holds that LOS affects both the laws of naval warfare and the status of the Sea of Azov. Furthermore, the article raises doubts as to the relevance and applicability of the legal concept of naval blockade in modern international law.
Detrimental effects of electromagnetic radiation emitted from cell phone on embryo morphokinetics and blastocyst viability in mice
Authors: Seify Mohammad , Khalili Mohammad Ali , Anbari Fatemeh , Koohestanidehaghi Yeganeh
Published: February 2024

Electromagnetic radiation (EMR) has deleterious effects on sperm motility and viability, as well as oocyte membrane and organelle structure. The aim was to assess the effects of cell phone radiation on preimplantation embryo morphokinetics and blastocyst viability in mice. For superovulation, 20 female mice were treated with intraperitoneal (IP) injections of 10 IU pregnant mare’s serum gonadotropin (Folligon® PMSG), followed by 10 IU of human chorionic gonadotropin (hCG) after 48 h. The zygotes (n = 150) from the control group were incubated for 4 days. The experimental zygotes (n = 150) were exposed to a cell phone emitting EMR with a frequency range 900–1800 MHz for 30 min on day 1. Then, all embryos were cultured in the time-lapse system and annotated based on time points from the 2-cell stage (t2) to hatched blastocyst (tHDyz), as well as abnormal cleavage patterns. Blastocyst viability was assessed using Hoechst and propidium iodide staining. Significant increases (P < 0.05) were observed in the cleavage division time points of t2, t8, t10, and t12 of the experimental group compared with the controls. In terms of blastocyst formation parameters, a delay in embryo development was observed in the experimental group compared with the controls. Data analysis of the time intervals between the two groups showed a significant difference in the s3 time interval (P < 0.05). Also, the rates of fragmentation, reverse cleavage, vacuole formation, and embryo arrest were significantly higher in the experimental group (P < 0.05). Furthermore, the cell survival rate in the experimental group was lower than the control group (P < 0.05). Exposure to EMR has detrimental consequences for preimplantation embryo development in mice. These effects can manifest as defects in the cleavage stage and impaired blastocyst formation, leading to lower cell viability.
Variability in phenolic compounds, antioxidant capacity and essential oil profile in different tissues of Ferula assa-foetida L. populations in Iran: an opportunity for industrial products
Authors: Jalili Batool , Saeidi-sar Sakineh , Masoudian Nahid , Zarban Asghar , Namaei Mohammad Hasan
Published: February 2024

Plant responses to multiple environmental conditions in the habitat are characterized by intra-species variety. Ferula assa-foetida L. is a native medical plant in Iran, which has a wide range of therapeutic and pharmacological properties. The objective of the current study was to identify changes in phenolic content, antioxidant capacity and essential oil (EO) composition in different tissues (leaf, flower and fruit) of three populations of F. assa-foetida L. (Sarbisheh, Nehbandan, located in South Khorasan province of Iran). The results showed that total phenolic content (TPC), total flavonoid content (TFC) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging activity in the leaves of Sarbisheh were higher than in other treatments. The amount of TPC, TFC and DPPH scavenging activity in leaves was higher than in other tissues in the Sarbisheh population, increasing by 31 and 70%, 41 and 20%, 8 and 13%, respectively, over that of flowers and fruits. The main EO compounds of leaves were α-pinene (11.86–13.56%), β-pinene (6.80–7.99%), bornyl acetate (15.80–17.33%). The main EO constitutes of flowers were Z-propenyl-sec-butyldisulfide (10.12–12.4%), eco-fenchyl acetate (10.87–12.4%), myrcisticin (13.43–15.87%) and α-bisabolol (11.23–13.76%). The primary compounds of fruit EO were β-pinene (9.32–11.26%), (Z)-1-propenyl sec butyldisulf (17.54–18.87%) and (E)-1-propenyl sec butyldisulf (28.32–30.02%). The agglomerative hierarchical clustering showed that three distinguished clusters were identified for population, where Nehbandan and Qaen had the higher similarity and Sarbisheh completely differed from the two ones. Different plant tissues contain varying types of chemicals, with leaves exhibiting higher levels of phenolic content and antioxidant capacity. This characteristic can be beneficial for industries such as food and pharmaceuticals.
Delphine von Schauroth, Corinna-Sister
Authors: Lalonde Amanda
Published: February 2024

Despite her current marginal position, the nineteenth-century pianist and composer Delphine von Schauroth (1813–1887) once ranked among the most prominent virtuosos of the nineteenth century and had connections with Fanny Hensel, Ferdinand Hiller, Josephine Lang, Franz Liszt, Felix Mendelssohn, Robert Schumann and others. Drawing on large body of music criticism, as well as compositions, letters, images and literary works, this article presents a portrait of Schauroth as an artist, with an emphasis on the role of improvisation and the improvisatory in her pianism. In particular, the article fleshes out Robert Schumann's characterization of Schauroth as a ‘Corinna-sister’, a reference to the improvising poetess of Madame de Stäel's novel Corinne, or Italy. The article suggests that Schumann's comparison highlights key facets of Schauroth's status and character as a pianist and composer. Firstly, like Corinne, Schauroth was widely renowned as an eminent performer and was celebrated as a genius by critics, which was particularly notable for a woman musician in the early nineteenth century. Secondly, Schauroth was received as a creator, not only for her compositions, but also for her performances: in the late 1820s and early 1830s, in particular, critics responded to these performances with images of magical creation and an emphasis on the newness of her performance over the composer's work. Thirdly, Schauroth displayed a varied practice of improvisation, and her compositions were understood as having an improvisatory character.
The Link between Abstract Thinking Style and Subjective Well-Being: Its Impact when People are in (Real or Perceived) Financial Scarcity
Authors: Caballero González Amparo , Fernández Sedano Itziar , Laforet Bronwyn , Carrera Levillain Pilar
Published: February 2024

Across three studies, we explored the link between an abstract mindset and subjective well-being (SWB) in participants with real and/or perceived financial scarcity. In Studies 1 and 2, samples presented real objective financial vulnerability: Adolescents from lower-middle income districts (Study 1; N = 256), and adults without higher education and with very low incomes (Study 2; N = 210). In Studies 1 and 2 participants completed a survey including measures of thinking style and SWB. In Studies 2 and 3 perception of financial difficulty and SWB were also measured. Study 3 (N = 161) used a sample of university students and employed an experimental design manipulating participants’ thinking style (i.e., concrete versus abstract mindset conditions); additionally, all participants were induced to perceive financial scarcity. Correlations revealed a significant and positive relationship between an abstract thinking style and SWB (Studies 1 and 2). Thus, these results showed that a relatively more abstract thinking style was associated with greater life satisfaction. In Studies 2 and 3 mediation analyses indicated that adults who presented a more abstract thinking style, perceived lower financial difficulties and then reported greater SWB. Overall, given that an abstract thinking style can be induced, these results offer a new intervention approach for improving the SWB of people living in situations of financial scarcity.
Earth Observation to Address Inequities in Post‐Flood Recovery
Authors: Friedrich H. K. , Tellman B. , Sullivan J. A. , Saunders A. , Zuniga‐Teran A. A. , Bakkensen L. A. , Cawley M. , Dolk M. , Emberson R. A. , Forrest S. A. , Gupta N. , Gyawali N. , Hall C. A. , Kettner A. J. , Lozano J. L. Sanchez , Bola G. B.
Published: February 2024

Floods impact communities worldwide, resulting in loss of life, damaged infrastructure and natural assets, and threatened livelihoods. Climate change and urban development in flood‐prone areas will continue to worsen flood‐related losses, increasing the urgency for effective tools to monitor recovery. Many Earth Observation (EO) applications exist for flood‐hazard monitoring and provide insights on location, timing, and extent in near real‐time and historically to estimate flood risk. Less attention has been paid to flood recovery, even though differing recovery rates and outcomes can have immediate and enduring distributional effects within communities. EO data are uniquely positioned to monitor post‐flood recovery and inform policy on hazard mitigation and adaptation but remain underutilized. We encourage the EO and flood research community to refocus on developing flood recovery applications to address growing risk. Translation of EO insights on flood recovery among flood‐affected communities and decision‐makers is necessary to address underlying social vulnerabilities that exacerbate inequitable recovery outcomes and advocate for redressing injustices where disparate recovery is observed. We identify an unequivocal need for EO to move beyond mapping flood hazard and exposure toward post‐flood recovery monitoring to inform recovery across geographic contexts. This commentary proposes a framework for remote sensing scientists to engage community‐based partners to integrate EO with non‐EO data to advance flood recovery monitoring, characterize inequitable recovery, redistribute resources to mitigate inequities, and support risk reduction of future floods.
Paternal cocaine-seeking motivation defines offspring’s vulnerability to addiction by down-regulating GABAergic GABRG3 in the ventral tegmental area
Authors: Cui Jian , Huang Nan , Fan Guangyuan , Pan Tao , Han Kunxiu , Jiang Changyou , Liu Xing , Wang Feifei , Ma Lan , Le Qiumin
Published: February 2024

Epidemiological investigations indicate that parental drug abuse experiences significantly influenced the addiction vulnerability of offspring. Studies using animal models have shown that paternal cocaine use and highly motivated drug-seeking behavior are important determinants of offspring addiction susceptibility. However, the key molecules contributing to offspring addiction susceptibility are currently unclear. The motivation for cocaine-seeking behavior in offspring of male rats was compared between those whose fathers self-administered cocaine (SA) and those who were yoked with them and received non-contingent cocaine administrations (Yoke). We found that paternal experience with cocaine-seeking behavior, but not direct cocaine exposure, could lead to increased lever-pressing behavior in male F1 offspring. This effect was observed without significant changes to the dose-response relationship. The transcriptomes of ventral tegmental area (VTA) in offspring were analyzed under both naive state and after self-administration training. Specific transcriptomic changes in response to paternal cocaine-seeking experiences were found, which mainly affected biological processes such as synaptic connections and receptor signaling pathways. Through joint analysis of these candidate genes and parental drug-seeking motivation scores, we found that gamma-aminobutyric acid receptor subunit gamma-3 (Gabrg3) was in the hub position of the drug-seeking motivation-related module network and highly correlated with parental drug-seeking motivation scores. The downregulation ofGabrg3expression, caused by paternal motivational cocaine-seeking, mainly occurred in GABAergic neurons in the VTA. Furthermore, down-regulating GABAergicGabrg3in VTA resulted in an increase in cocaine-seeking behavior in the Yoke F1 group. This down-regulation also reduced transcriptome differences between the Yoke and SA groups, affecting processes related to synaptic formation and neurotransmitter transmission. Taken together, we propose that paternal cocaine-seeking behavior, rather than direct drug exposure, significantly influences offspring addiction susceptibility through the downregulation ofGabrg3in GABAergic neurons of the VTA, highlighting the importance of understanding specific molecular pathways in the intergenerational inheritance of addiction vulnerability.
TcrXY is an acid-sensing two-component transcriptional regulator of Mycobacterium tuberculosis required for persistent infection
Authors: Stupar Miljan , Tan Lendl , Kerr Edward D. , De Voss Christopher J. , Forde Brian M. , Schulz Benjamin L. , West Nicholas P.
Published: February 2024

The ability ofMycobacterium tuberculosis(Mtb) to persist in the host complicates and prolongs tuberculosis (TB) patient chemotherapy. Here we demonstrate that a neglected two-component system (TCS) of Mtb, TcrXY, is an autoregulated acid-sensing TCS that controls a functionally diverse 70-gene regulon required for bacterial persistence. Characterisation of two representatives of this regulon,Rv3706candRv3705A, implicate these genes as key determinants for the survival of Mtb in vivo by serving as important effectors to mitigate redox stress at acidic pH. We show that genetic silencing of the response regulatortcrXusing CRISPR interference attenuates the persistence of Mtb during chronic mouse infection and improves treatment with the two front-line anti-TB drugs, rifampicin and isoniazid. We propose that targeting TcrXY signal transduction blocks the ability of Mtb to sense and respond to acid stress, resulting in a disordered program of persistence to render the organism vulnerable to existing TB chemotherapy.
Porphyromonas gingivalis aggravates colitis via a gut microbiota-linoleic acid metabolism-Th17/Treg cell balance axis
Authors: Jia Lu , Jiang Yiyang , Wu Lili , Fu Jingfei , Du Juan , Luo Zhenhua , Guo Lijia , Xu Junji , Liu Yi
Published: February 2024

Periodontitis is closely related to inflammatory bowel disease (IBD). An excessive and non-self-limiting immune response to the dysbiotic microbiome characterizes the two. However, the underlying mechanisms that overlap still need to be clarified. We demonstrate that the critical periodontal pathogen Porphyromonas gingivalis (Pg) aggravates intestinal inflammation and Th17/Treg cell imbalance in a gut microbiota-dependent manner. Specifically, metagenomic and metabolomic analyses shows that oral administration of Pg increases levels of the Bacteroides phylum but decreases levels of the Firmicutes, Verrucomicrobia, and Actinobacteria phyla. Nevertheless, it suppresses the linoleic acid (LA) pathway in the gut microbiota, which was the target metabolite that determines the degree of inflammation and functions as an aryl hydrocarbon receptor (AHR) ligand to suppress Th17 differentiation while promoting Treg cell differentiation via the phosphorylation of Stat1 at Ser727. Therapeutically restoring LA levels in colitis mice challenged with Pg exerts anti-colitis effects by decreasing the Th17/Treg cell ratio in an AHR-dependent manner. Our study suggests that Pg aggravates colitis via a gut microbiota-LA metabolism-Th17/Treg cell balance axis, providing a potential therapeutically modifiable target for IBD patients with periodontitis.
Microbes translocation from oral cavity to nasopharyngeal carcinoma in patients
Authors: Liao Ying , Wu Yan-Xia , Tang Minzhong , Chen Yi-Wei , Xie Jin-Ru , Du Yan , Wang Tong-Min , He Yong-Qiao , Xue Wen-Qiong , Zheng Xiao-Hui , Liu Qiao-Yun , Zheng Mei-Qi , Jia Yi-Jing , Tong Xia-Ting , Zhou Ting , Li Xi-Zhao , Yang Da-Wei , Diao Hua , Jia Wei-Hua
Published: February 2024

The presence of oral microbes in extra-oral sites is linked to gastrointestinal cancers. However, their potential ectopically colonization in the nasopharynx and impact on local cancer development remains uncertain. Our study involving paired nasopharyngeal-oral microbial samples from nasopharyngeal carcinoma (NPC) patients and controls unveils an aberrant oral-to-nasopharyngeal microbial translocation associated with increased NPC risk (OR = 4.51, P = 0.012). Thirteen species are classified as oral-translocated and enriched in NPC patients. Among these, Fusobacterium nucleatum and Prevotella intermedia are validated through culturomics and clonal strain identification. Nasopharyngeal biopsy meta-transcriptomes confirm these microbes within tumors, influencing local microenvironment and cytokine response. These microbes correlate significantly with the Epstein-Barr virus (EBV) loads in the nasopharynx, exhibiting an increased dose-response relationship. Collectively, our study identifies oral microbes migrating to the nasopharynx, infiltrating tumors, impacting microenvironments and linking with EBV infection. These results enhance our understanding of abnormal microbial communication and their roles in carcinogenesis.
Protein design using structure-based residue preferences
Authors: Ding David , Shaw Ada Y. , Sinai Sam , Rollins Nathan , Prywes Noam , Savage David F. , Laub Michael T. , Marks Debora S.
Published: February 2024

Recent developments in protein design rely on large neural networks with up to 100s of millions of parameters, yet it is unclear which residue dependencies are critical for determining protein function. Here, we show that amino acid preferences at individual residues—without accounting for mutation interactions—explain much and sometimes virtually all of the combinatorial mutation effects across 8 datasets (R2 ~ 78-98%). Hence, few observations (~100 times the number of mutated residues) enable accurate prediction of held-out variant effects (Pearson r > 0.80). We hypothesized that the local structural contexts around a residue could be sufficient to predict mutation preferences, and develop an unsupervised approach termed CoVES (Combinatorial Variant Effects from Structure). Our results suggest that CoVES outperforms not just model-free methods but also similarly to complex models for creating functional and diverse protein variants. CoVES offers an effective alternative to complicated models for identifying functional protein mutations.
Anthropogenic carbon pathways towards the North Atlantic interior revealed by Argo-O2, neural networks and back-calculations
Authors: Asselot Rémy , Carracedo Lidia I. , Thierry Virginie , Mercier Herlé , Bajon Raphaël , Pérez Fiz F.
Published: February 2024

The subpolar North Atlantic (SPNA) is a region of high anthropogenic CO2 (Cant) storage per unit area. Although the average Cant distribution is well documented in this region, the Cant pathways towards the ocean interior remain largely unresolved. We used observations from three Argo-O2 floats spanning 2013-2018 within the SPNA, combined with existing neural networks and back-calculations, to determine the Cant evolution along the float pathways from a quasi-lagrangian perspective. Our results show that Cant follows a stepwise deepening along its way through the SPNA. The upper subtropical waters have a stratified Cant distribution that homogenizes within the winter mixed layer by Subpolar Mode Water formation in the Iceland Basin. In the Irminger and Labrador Basins, the high-Cant footprint (> 55 μmol kg−1) is mixed down to 1400 and 1800 dbar, respectively, by deep winter convection. As a result, the maximum Cant concentration is diluted (<45 μmol kg−1). Our study highlights the role of water mass transformation as a first-order mechanism for Cant penetration into the ocean. It also demonstrates the potential of Argo-O2 observations, combined with existing methods, to obtain reliable Cant estimates, opening ways to study the oceanic Cant content at high spatio-temporal resolution.
Value of the NF-κB signalling pathway and the DNA repair gene PARP1 in predicting distant metastasis after breast cancer surgery
Authors: Pan Kaiyong , Li Xiabin , He Junfang , Lei Yuxi , Yang Yongxin , Jiang Deyong , Tang Yan
Published: February 2024

The DNA repair gene PARP1 and NF-κB signalling pathway affect the metastasis of breast cancer by influencing the drug resistance of cancer cells. Therefore, this study focused on the value of the DNA repair gene PARP1 and NF-κB pathway proteins in predicting the postoperative metastasis of breast cancer. A nested case‒control study was performed. Immunohistochemical methods were used to detect the expression of these genes in patients. ROC curves were used to analyse the predictive effect of these factors on distant metastasis. The COX model was used to evaluate the effects of PARP1 and TNF-α on distant metastasis. The results showed that the expression levels of PARP1, IKKβ, p50, p65 and TNF-α were significantly increased in the metastasis group (P < 0.001). PARP1 was correlated with IKKβ, p50, p65 and TNF-α proteins (P < 0.001). There was a correlation between IKKβ, p50, p65 and TNF-α proteins (P < 0.001). ROC curve analysis showed that immunohistochemical scores for PARP1 of > 6, IKKβ of > 4, p65 of > 4, p50 of > 2, and TNF-α of > 4 had value in predicting distant metastasis (SePARP1 = 78.35%, SpPARP1 = 79.38%, AUCPARP1 = 0.843; Sep50 = 64.95%, Spp50 = 70.10%, AUCp50 = 0.709; SeTNF-α = 60.82%, SpTNF-α = 69.07%, AUCTNF-α = 0.6884). Cox regression analysis showed that high expression levels of PARP1 and TNF-α were a risk factor for distant metastasis after breast cancer surgery (RRPARP1 = 4.092, 95% CI 2.475–6.766, P < 0.001; RRTNF-α = 1.825, 95% CI 1.189–2.799, P = 0.006). Taken together, PARP1 > 6, p50 > 2, and TNF-α > 4 have a certain value in predicting breast cancer metastasis, and the predictive value is better when they are combined for diagnosis (Secombine = 97.94%, Spcombine = 71.13%).
Fetal face shape analysis from prenatal 3D ultrasound images
Authors: Sivera Raphael , Clark Anna E. , Dall’Asta Andrea , Ghi Tullio , Schievano Silvia , Lees Christoph C.
Published: February 2024

3D ultrasound imaging of fetal faces has been predominantly confined to qualitative assessment. Many genetic conditions evade diagnosis and identification could assist with parental counselling, pregnancy management and neonatal care planning. We describe a methodology to build a shape model of the third trimester fetal face from 3D ultrasound and show how it can objectively describe morphological features and gestational-age related changes of normal fetal faces. 135 fetal face 3D ultrasound volumes (117 appropriately grown, 18 growth-restricted) of 24-34 weeks gestation were included. A 3D surface model of each face was obtained using a semi-automatic segmentation workflow. Size normalisation and rescaling was performed using a growth model giving the average size at every gestation. The model demonstrated a similar growth rate to standard head circumference reference charts. A landmark-free morphometry model was estimated to characterize shape differences using non-linear deformations of an idealized template face. Advancing gestation is associated with widening/fullness of the cheeks, contraction of the chin and deepening of the eyes. Fetal growth restriction is associated with a smaller average facial size but no morphological differences. This model may eventually be used as a reference to assist in the prenatal diagnosis of congenital anomalies with characteristic facial dysmorphisms.
Mechanism exploration and biomarker identification of glycemic deterioration in patients with diseases of the exocrine pancreas
Authors: Wang Zhen , Zhang Guolin , Fu Jixian , Li Guangxing , Zhao Zhihao , Choe HyokChol , Ding Kaiyue , Ma Junnan , Wei Jing , Shang Dong , Zhang Lin
Published: February 2024

The damage to the endocrine pancreas among patients with diseases of the exocrine pancreas (DP) leads to reduced glycemic deterioration, ultimately resulting in diabetes of the exocrine pancreas (DEP). The present research aims to investigate the mechanism responsible for glycemic deterioration in DP patients, and to identify useful biomarkers, with the ultimate goal of enhancing clinical practice awareness. Gene expression profiles of patients with DP in this study were acquired from the Gene Expression Omnibus database. The original study defines DP patients to belong in one of three categories: non-diabetic (ND), impaired glucose tolerance (IGT) and DEP, which correspond to normoglycemia, early and late glycemic deterioration, respectively. After ensuring quality control, the discovery cohort included 8 ND, 20 IGT, and 12 DEP, while the validation cohort included 27 ND, 15 IGT, and 20 DEP. Gene set enrichment analysis (GSEA) employed differentially expressed genes (DEGs), while immunocyte infiltration was determined using single sample gene set enrichment analysis (ssGSEA). Additionally, correlation analysis was conducted to establish the link between clinical characteristics and immunocyte infiltration. The least absolute shrinkage and selection operator regression and random forest combined to identify biomarkers indicating glycemic deterioration in DP patients. These biomarkers were further validated through independent cohorts and animal experiments. With glycemic deterioration, biological processes in the pancreatic islets such as nutrient metabolism and complex immune responses are disrupted in DP patients. The expression of ACOT4, B2M, and ACKR2 was upregulated, whereas the expression of CACNA1F was downregulated. Immunocyte infiltration in the islet microenvironment showed a significant positive correlation with the age, body mass index (BMI), HbA1c and glycemia at the 2-h of patients. It was a crucial factor in glycemic deterioration. Additionally, B2M demonstrated a significant positive correlation with immunocyte infiltration and clinical features. Quantitative real-time PCR (qRT-PCR) and western blotting confirmed the upregulation in B2M. Immunofluorescent staining suggested the alteration of B2M was mainly in the alpha cells and beta cells. Overall, the study showed that gradually increased immunocyte infiltration was a significant contributor to glycemic deterioration in patients with DP, and it also highlighted B2M as a biomarker.
A materials informatics driven fine-tuning of triazine-based electron-transport layer for organic light-emitting devices
Authors: Sato Kosuke , Hattori Kazuki , Uehara Fuminari , Kitaguni Tomoko , Nishiura Toshiki , Yamagata Takuya , Nomura Keisuke , Matsumoto Naoki , Tanaka Tsuyoshi , Aihara Hidenori
Published: February 2024

Materials informatics in the development of organic light-emitting diode (OLED) related materials have been performed and exhibited the effectiveness for finding promising compounds with a desired property. However, the molecular structure optimization of the promising compounds through the conventional approach, namely the fine-tuning of molecules, still involves a significant amount of trial and error. This is because it is challenging to endow a single molecule with all the properties required for practical applications. The present work focused on fine-tuning triazine-based electron-transport materials using machine learning (ML) techniques. The prediction models based on localized datasets containing only triazine derivatives showed high prediction accuracy. The descriptors from density functional theory calculations enhanced the prediction of the glass transition temperature. The proposed multistep virtual screening approach extracted the promising triazine derivatives with the coexistence of higher electron mobility and glass transition temperature. Nine selected triazine compounds from 3,670,000 of the initial search space were synthesized and used as the electron transport layer for practical OLED devices. Their observed properties matched the predicted properties, and they enhanced the current efficiency and lifetime of the device. This paper provides a successful model for the ML assisted fine-tuning that effectively accelerates the development of practical materials.
Using thermokinetic methods to enhance properties of epoxy resins with amino acids as biobased curing agents by achieving full crosslinking
Authors: Walter Melissa , Neubacher Marcel , Fiedler Bodo
Published: February 2024

Fibre-reinforced polymers (FRPs) are used in numerous industrial sectors and contribute to reducing CO2 emissions due to their outstanding properties in lightweight design. However, sustainable alternatives must be developed since the matrix polymers utilised contain substances hazardous to health and the environment. In widely used epoxy resins, the curing agents are mainly critical. Using biomolecules instead of synthetic curing agents can significantly reduce composites' toxicity and petrol-based carbon content. This study considerably exceeds the thermo-mechanical properties of epoxies cured with amino acids described in the literature until now. It demonstrates competitive or even better properties than state-of-the-art epoxies cured with petrol-based amine curing agents. For instance, the tensile strength of arginine-cured epoxy is more than twice as high as reported before and 13.5% higher compared to the petrol-based reference. At the same time, a high elongation at break of over 6% was accomplished, making these polymers suitable as matrix materials in FRPs. Furthermore, the glass transition onset of up to 130 °C is sufficiently high for many applications. The key to success is the development of individual curing profiles based on thermokinetic analysis. The work provides the development and analysis of several biomolecule-cured epoxies with promising property spectra.
Increased monocytic myeloid-derived suppressor cells in type 2 diabetes correlate with hyperglycemic and was a risk factor of infection and tumor occurrence
Authors: Zhou Ji , Zhang Mengjie , Ju Xiaodi , Wang Huiping , Xiao Hao , Zhai Zhimin , Zhong Xing , Hong Jingfang
Published: February 2024

To investigate the frequency of monocytic myeloid-derived suppressor cells (M-MDSCs) in type 2 diabetes mellitus (T2DM) patients and explore the potential associations between M-MDSCs, glycemic control, and the occurrence of infections and tumor. 102 healthy and 77 T2DM individuals were enrolled. We assessed the M-MDSCs frequency, levels of fasting plasma glucose (FPG), haemoglobin A1c (HbA1c), and other relevant indicators. Each patient underwent a follow-up of at least 6 months after M-MDSCs detection. The M-MDSCs frequency was significantly higher in patients with poor glycemic control (PGC) compared to the healthy population (P < 0.001), whereas there was no significant difference between patients with good glycemic control and the healthy (P > 0.05). There was a positive correlation between the M-MDSCs frequency and FPG, HbA1c (R = 0.517 and 0.315, P < 0.001, respectively). T2DM patients with abnormally increased M-MDSCs have a higher incidence of infection and tumor (48.57% and 11.43% respectively). Our results shed new light on the pathogenesis of T2DM, help to understand why T2DM patients are susceptible to infection and tumor and providing novel insights for future prevention and treatment of T2DM.
Effect of fiber addition on strength and toughness of rubberized concretes
Authors: Mohamed Sameh , Elemam Hesham , Seleem Mohamed H. , Sallam Hossam El-Din M.
Published: February 2024

In this paper, an experimental study was conducted to examine the static and dynamic behaviors of rubberized fiber-reinforced concrete (RFRC). Crumb rubber was partially replaced from sand at volume fractions of 0%, 5%, 10%, 15%, and 20%. Steel fibers (SFs) with fiber volume fractions (Vf%) of 0%, 0.5%, 1%, and 1.5% were used for the production of FRCs, while polypropylene fiber (PPF) with Vf% = 0.4% was adopted to produce others FRCs. A combination of 0.4% PPF and 1% SF was used for hybrid FRC. The static properties were evaluated through compression, indirect tension, and flexural tests. However, the drop weight impact test was conducted to assess the dynamic property by estimating the impact energy. It was observed that the replacement of sand with rubber reduced all mechanical properties of concrete. In the case of RFRC, a reduction in compressive strength, compared to samples without fibers, was noted, and this reduction increased with higher Vf%. Both toughness indices and fracture energy were affected slightly by increasing rubber percentages while markedly increased with higher Vf%. However, adding rubber and/or fibers enhanced the impact energy of concrete.
Rapid loss of maternal immunity and increase in environmentally mediated antibody generation in urban gulls
Authors: Lamb Juliet S. , Tornos Jérémy , Lejeune Mathilde , Boulinier Thierry
Published: February 2024

Monitoring pathogen circulation in wildlife sentinel populations can help to understand and predict the spread of disease at the wildlife-livestock-human interface. Immobile young provide a useful target population for disease surveillance, since they can be easily captured for sampling and their levels of antibodies against infectious agents can provide an index of localized circulation. However, early-life immune responses include both maternally-derived antibodies and antibodies resulting from exposure to pathogens, and disentangling these two processes requires understanding their individual dynamics. We conducted an egg-swapping experiment in an urban-nesting sentinel seabird, the yellow-legged gull, and measured antibody levels against three pathogens of interest (avian influenza virus AIV, Toxoplasma gondii TOX, and infectious bronchitis virus IBV) across various life stages, throughout chick growth, and between nestlings raised by biological or non-biological parents. We found that levels of background circulation differed among pathogens, with AIV antibodies widely present across all life stages, TOX antibodies rarer, and IBV antibodies absent. Antibody titers declined steadily from adult through egg, nestling, and chick stages. For the two circulating pathogens, maternal antibodies declined exponentially after hatching at similar rates, but the rate of linear increase due to environmental exposure was significantly higher in the more prevalent pathogen (AIV). Differences in nestling antibody levels due to parental effects also persisted longer for AIV (25 days, vs. 14 days for TOX). Our results suggest that yellow-legged gulls can be a useful sentinel population of locally transmitted infectious agents, provided that chicks are sampled at ages when environmental exposure outweighs maternal effects.
Inclusion of a computerized test in ADHD diagnosis process can improve trust in the specialists’ decision and elevate adherence levels
Authors: Grossman Ephraim S. , Berger Itai
Published: February 2024

Attention deficit and hyperactivity disorder (ADHD) affects many life aspects of children and adults. Accurate identification, diagnosis and treatment of ADHD can facilitate better care. However, ADHD diagnosis and treatment methods are subject of controversy. Objective measures can elevate trust in specialist’s decision and treatment adherence. In this observational study we asked whether knowing that a computerized test was included in ADHD diagnosis process results in more trust and intention to adhere with treatment recommendations. Questionnaires were administered to 459 people, 196 men, average age = 40.57 (8.90). Questions regarding expected trust and adherence, trust trait, trust in physician and health-care-institutions, and ADHD scales followed a scenario about parents referred to a neurologist for sons’ ADHD diagnosis. The scenario presented to the test group (n = 185) mentioned that a computerized test was part of the diagnostic process. The control group scenario didn’t mention any computerized test in the diagnostic process. Test group participants expressed more trust in the diagnosis and greater levels of intention for treatment adherence. Group differences in intention for treatment adherence were mediated by trust in decision. Inclusion of a computerized test in ADHD diagnosis process can improve trust in the specialists’ decision and elevate adherence levels.
Political context of the European vaccine debate on Twitter
Authors: Paoletti Giordano , Dall’Amico Lorenzo , Kalimeri Kyriaki , Lenti Jacopo , Mejova Yelena , Paolotti Daniela , Starnini Michele , Tizzani Michele
Published: February 2024

At the beginning of the COVID-19 pandemic, fears grew that making vaccination a political (instead of public health) issue may impact the efficacy of this life-saving intervention, spurring the spread of vaccine-hesitant content. In this study, we examine whether there is a relationship between the political interest of social media users and their exposure to vaccine-hesitant content on Twitter. We focus on 17 European countries using a multilingual, longitudinal dataset of tweets spanning the period before COVID, up to the vaccine roll-out. We find that, in most countries, users’ endorsement of vaccine-hesitant content is the highest in the early months of the pandemic, around the time of greatest scientific uncertainty. Further, users who follow politicians from right-wing parties, and those associated with authoritarian or anti-EU stances are more likely to endorse vaccine-hesitant content, whereas those following left-wing politicians, more pro-EU or liberal parties, are less likely. Somewhat surprisingly, politicians did not play an outsized role in the vaccine debates of their countries, receiving a similar number of retweets as other similarly popular users. This systematic, multi-country, longitudinal investigation of the connection of politics with vaccine hesitancy has important implications for public health policy and communication.
Exploring the association between cancer and cognitive impairment in the Australian Imaging Biomarkers and Lifestyle (AIBL) study
Authors: Ma Liwei , Low Yi Ling Clare , Zhuo Yuanhao , Chu Chenyin , Wang Yihan , Fowler Christopher J. , Tan Edwin C. K. , Masters Colin L. , Jin Liang , Pan Yijun
Published: February 2024

An inverse association between cancer and Alzheimer’s disease (AD) has been demonstrated; however, the association between cancer and mild cognitive impairment (MCI), and the association between cancer and cognitive decline are yet to be clarified. The AIBL dataset was used to address these knowledge gaps. The crude and adjusted odds ratios for MCI/AD and cognitive decline were compared between participants with/without cancer (referred to as C+ and C− participants). A 37% reduction in odds for AD was observed in C+ participants compared to C− participants after adjusting for all confounders. The overall risk for MCI and AD in C+ participants was reduced by 27% and 31%, respectively. The odds of cognitive decline from MCI to AD was reduced by 59% in C+ participants after adjusting for all confounders. The risk of cognitive decline from MCI to AD was halved in C+ participants. The estimated mean change in Clinical Dementia Rating-Sum of boxes (CDR-SOB) score per year was 0.23 units/year higher in C− participants than in C+ participants. Overall, an inverse association between cancer and MCI/AD was observed in AIBL, which is in line with previous reports. Importantly, an inverse association between cancer and cognitive decline has also been identified.
Association of systemic anticholinergic medication use and accelerated decrease in lung function in older adults
Authors: Svensson Markus , Elmståhl Sölve , Sanmartin Berglund Johan , Rosso Aldana
Published: February 2024

Older adults are frequently exposed to medicines with systemic anticholinergic properties, which are linked to increased risk of negative health outcomes. The association between systemic anticholinergics and lung function has not been reported. The aim of this study was to investigate if exposure to systemic anticholinergics influences lung function in older adults. Participants of the southernmost centres of the Swedish National study on Aging and Care (SNAC) were followed from 2001 to 2021. In total, 2936 subjects (2253 from Good Aging in Skåne and 683 from SNAC-B) were included. An extensive medical examination including spirometry assessments was performed during the study visits. The systemic anticholinergic burden was described using the anticholinergic cognitive burden scale. The effect of new use of systemic anticholinergics on the annual change in forced expiratory volume (FEV1s) was estimated using mixed models. During follow-up, 802 (27.3%) participants were exposed to at least one systemic anticholinergic medicine. On average, the FEV1s of participants without systemic anticholinergic exposure decreased 37.2 ml/year (95% CI [33.8; 40.6]) while participants with low and high exposure lose 47.2 ml/year (95% CI [42.4; 52.0]) and 43.7 ml/year (95% CI [25.4; 62.0]). A novel association between new use of medicines with systemic anticholinergic properties and accelerated decrease in lung function in older adults was found. The accelerated decrease is comparable to that observed in smokers. Studies are needed to further explore this potential side effect of systemic anticholinergics.
Spectrum analysis of digital UPWM signals generated from random modulating signals
Authors: Kaleris Konstantinos , Psarakis Emmanouil , Mourjopoulos John
Published: February 2024

This work studies the spectrum of discrete-time Uniform-sampling pulse width modulation (UPWM) signals originating from stochastic input signals. It demonstrates that for ergodic input sequences of independent and identically distributed random variables, the Discrete Fourier Transform (DFT) of the UPWM signals can be directly estimated from the input signal’s statistics. Consequently, it is shown that if the input signal can be modeled as such a random sequence, only statistical information of the sequence is required for the accurate estimation of the DFT of the UPWM signal. This is achieved here by proving that the DFT estimators obtained by observation of the input sequence within a time window are consistent estimators of the DFT coefficients of the underlying random process. Moreover, for signals whose generalized probability density functions can be expressed as functions of a small number of parameters, the DFT coefficients can be estimated or even calculated via closed-form expressions with linear complexity. Examples are given for input signals derived from symmetric and asymmetric distributions. The results are validated by comparison with evaluations of the UPWM signal’s DFT via the Fast Fourier Transform (FFT). The proposed method provides a mathematical framework for the analysis and design of UPWM systems whose inputs have known statistical properties.
Health anxiety amplifies fearful responses to illness-related imagery
Authors: Benke Christoph , Wallenfels Laura-Marie , Bleichhardt Gaby M. , Melzig Christiane A.
Published: February 2024

Severe health anxiety (HA) is characterized by excessive worry and anxiety about one's health, often accompanied by distressing intrusive imagery of signs of a serious illness or potentially receiving bad news about having a life-threatening disease. However, the emotional responses to these illness-related mental images in relation to HA have not been fully elucidated. Emotional responses to mental imagery of 142 participants were assessed in a well-controlled script-driven imagery task, systematically comparing emotional responses to illness-related imagery with neutral and standard fear imagery. The results revealed that participants reported higher anxiety, aversion, emotional arousal, and a stronger avoidance tendency during imagery of fear and illness-related scenes compared to neutral scenes. Importantly, the emotional modulation varied by the level of HA, indicating that individuals with higher HA experienced stronger emotional responses to illness-related imagery. This association between HA and fearful imagery could not be better accounted for by other psychological factors such as trait anxiety, anxiety sensitivity, somatic symptom severity, or symptoms of depression and anxiety. Fearful responding to standard threat material was not associated with HA. The present findings highlight the importance of considering fear responding to mental imagery in understanding and addressing HA.