bluuebunny/crossref_metadata_2025 huggingface dataset:
Unveiling the Real Madrid effect: the impact of football-related acrimony on elections
Authors: Alfano Vincenzo , Ercolano Salvatore
Published: October 2023

Contributing to the literature on so-called irrelevant events, this article aims to investigate the existence of a relation between football results and voters’ behaviour. There are indeed reasons to believe that football-related acrimony could influence electoral behaviour. More precisely, does the rank of a rival team and the distance between it and local teams influence the behaviour of the electorate? Spain seems to be the perfect case for study of this relationship, since the presence of football teams representing both local (comunidad) and central authorities (the Spanish Crown) allows us to study the effect of an important cleavage: the centre-periphery. This means that sport disputes may be reflected in voting preferences for ethno-regionalist parties. Following this reasoning, the better Real Madrid (the team representing the Crown) performs, and the closer the local team is to it (and thus actually competing), the stronger local supporters’ sense of acrimony and desire for payback will be. By means of a quantitative approach, using data on election results and Spanish Liga rankings, our analysis confirms the existence of a negative correlation between Real Madrid’s ranking and distance from local teams, and the share of votes in ethno-regionalist parties.
Between precarity and professionalism: the effect of uncertainty on adult educators’ participation in continuing education
Authors: Werner Karoline , Martin Andreas
Published: October 2023

Continuous participation in further education activities is considered to be a driving factor for the professionalism of adult educators. However, especially in this field, the decision to participate is often embedded in a context of disadvantageous socio-economic living conditions and atypical employment, which is described as precarious in research on continuing education. For this reason, we are studying the influence of precarious employment on the participation of adult educators. In doing so, we focus on the uncertainty in planning one’s professional career, which is typical of precarious life situations. Based on a modification of the classical theory of subjective expected utility, we formulate the assumption that uncertainty in the evaluation of one’s own career development opportunities reduces participation in continuing education. To test our hypothesis, we use data from the wb-personalmonitor and estimate linear and logistic regressions using an inverse-probability-weighted regression-adjustment. The results show that uncertainty reduces the number of continuing education courses attended.
The impact of using natural waste biopolymer cement on the properties of traditional/fibrous concrete
Authors: Yehia Sameh , Ibrahim Arafa M. , Ahmed Doaa F.
Published: October 2023

The naturally occurring wastes contain a large number of active groups. In this study, shrimp shell wastes were modified chemically to form chitosan. When mixing concrete with a natural polymer the result revealed a synergistic impact on the characteristics and functionality of the concrete structure. The formed chitosan was characterized by Fourier-Transform Infrared Spectroscopy (FT-IR), Thermogravimetric Analysis (TGA), X-ray Diffraction (XRD), and Scanning Electron Microscopy (SEM). Five concrete mixes were designed to achieve the study objective. For certain concrete mixes, admixtures such as a natural polymer (chitosan), and chemical (superplasticizer) were added with 0.05% by weight of the cement content. Those admixtures were added to study their behavior on the characteristics of the concrete mixes, and then compare test results with control concrete mixes. Also, the purpose of the experiment was expanded to study the impact of adding the admixtures to fibrous concrete, as this fibrous concrete faces interlocking due to steel fiber's presence in the fresh concrete mixture. The results indicated that concrete-embedded chitosan exhibited significant enhancement in the mechanical properties. Further, the surface shape of concrete was characterized by the presence of chitosan crystallites which spread and filled the spaces in the chitosan structure. Also, it’s noted that chitosan can delay the rate of cement hydration to a small value, which may help in hot weathering concrete.
Anticonvulsant effects of isopimpinellin and its interactions with classic antiseizure medications and borneol in the mouse tonic–clonic seizure model: an isobolographic transformation
Authors: Łuszczki Jarogniew J. , Bojar Hubert , Jankiewicz Katarzyna , Florek-Łuszczki Magdalena , Chmielewski Jarosław , Skalicka-Woźniak Krystyna
Published: October 2023

Background

Overwhelming evidence indicates that some naturally occurring coumarins and terpenes are widely used in folk medicine due to their various therapeutic effects affecting the brain. Antiseizure medications (ASMs) are the principal treatment option for epilepsy patients, although some novel strategies based on naturally occurring substances are intensively investigated. This study was aimed at determining the influence of isopimpinellin (ISOP—a coumarin) when administered either separately or in combination with borneol (BOR—a monoterpenoid), on the antiseizure potencies of four classic ASMs (carbamazepine (CBZ), phenytoin (PHT), phenobarbital (PB), and valproate (VPA)) in the mouse model of maximal electroshock-induced (MES) tonic–clonic seizures.

Materials

Tonic–clonic seizures were evoked experimentally in mice after systemic (ip) administration of the respective doses of ISOP, BOR, and classic ASMs. Interactions for two-drug (ISOP + a classic ASM) and three-drug (ISOP + BOR + a classic ASM) mixtures were assessed isobolographically in the mouse MES model.

Results

ISOP (administered alone) had no impact on the anticonvulsant potencies of four classic ASMs. Due to the isobolographic transformation of data, the combination of ISOP + VPA exerted an antagonistic interaction, whereas the two-drug mixtures of ISOP + CBZ, ISOP + PHT, and ISOP + PB produced additive interactions in the mouse MES model. The three-drug combinations of ISOP + BOR with CBZ and PHT produced additive interactions, while the three-drug combinations of ISOP + BOR with PB and VPA exerted synergistic interactions in the mouse MES model.

Conclusions

The most intriguing interaction was that for ISOP + VPA, for which the addition of BOR evoked a transition from antagonism to synergy in the mouse MES model.
Towards a social constructionist, criticalist, Foucauldian-informed qualitative research approach: Opportunities and challenges
Authors: Phillips Matthew J.
Published: October 2023

In this paper, I delve into the application of a social constructionist, critical, and Foucauldian approach, and shed light on the complexities and nuances that arise when studying human behaviour and societal dynamics. While social constructionism offers valuable insights into how social action is constructed within everyday interactions in political and socio-cultural contexts, it also prompts further inquiries that extend beyond its epistemological scope. To address these broader questions, I propose a threefold approach that combines a critical perspective, a Foucauldian methodology, and social constructionism. By incorporating these complementary lenses, researchers can more effectively explore the intricate relationship between participant meaning and power imbalances within society. Additionally, this approach allows for an examination of how specific ways of being and doing become privileged as truth, while alternative perspectives and experiences are marginalised or excluded. The article serves as a theoretical foundation for understanding social constructionism, critical psychology, and Foucauldian methodology. It offers readers a comprehensive guide and a set of reflective tools to enhance their qualitative research practices. By considering the complexities of social legitimacy, critique, power imbalances, and the construction of truth, researchers can gain a deeper understanding of the phenomena they investigate. Ultimately, this multifaceted approach contributes to a more nuanced and insightful analysis of social phenomena and facilitates a more inclusive exploration of diverse perspectives and versions of reality.
Dietary protein recommendations to support healthy muscle ageing in the 21st century and beyond: considerations and future directions
Authors: Morgan Paul T. , Witard Oliver C. , Højfeldt Grith , Church David D. , Breen Leigh
Published: October 2023

This review explores the evolution of dietary protein intake requirements and recommendations, with a focus on skeletal muscle remodelling to support healthy ageing based on presentations at the 2023 Nutrition Society summer conference. In this review, we describe the role of dietary protein for metabolic health and ageing muscle, explain the origins of protein and amino acid (AA) requirements and discuss current recommendations for dietary protein intake, which currently sits at about 0⋅8 g/kg/d. We also critique existing (e.g. nitrogen balance) and contemporary (e.g. indicator AA oxidation) methods to determine protein/AA intake requirements and suggest that existing methods may underestimate requirements, with more contemporary assessments indicating protein recommendations may need to be increased to >1⋅0 g/kg/d. One example of evolution in dietary protein guidance is the transition from protein requirements to recommendations. Hence, we discuss the refinement of protein/AA requirements for skeletal muscle maintenance with advanced age beyond simply the dose (e.g. source, type, quality, timing, pattern, nutrient co-ingestion) and explore the efficacy and sustainability of alternative protein sources beyond animal-based proteins to facilitate skeletal muscle remodelling in older age. We conclude that, whilst a growing body of research has demonstrated that animal-free protein sources can effectively stimulate and support muscle remodelling in a manner that is comparable to animal-based proteins, food systems need to sustainably provide a diversity of both plant and animal source foods, not least for their protein content but other vital nutrients. Finally, we propose some priority research directions for the field of protein nutrition and healthy ageing.
Similarity and the coordination of ownership
Authors: Grüning David J. , Krueger Joachim I.
Published: October 2023

We discuss and expand Boyer's idea of ownership coordination. Interpersonal similarity, we suggest, can moderate the attainment of coordination: Perceived similarity predicts coordination costs, whereas actual similarity dictates coordination success and the severity of illusory assumptions regarding a shared understanding of ownership. The example of similarity highlights the complexity of the social projection process uncritically assumed behind ownership coordination.
The recursive nature of ownership intuitions
Authors: Shechter Anat , Gilead Michael , Bereby-Meyer Yoella
Published: October 2023

The proposed model overlooks the self-referential and self-perpetuating nature of ownership intuitions. Human knowledge is primarily formed through social interaction within power dynamics. Accordingly, we suggest that legitimate ownership of one object can influence perceptions of legitimate ownership of another object. Ultimately, we argue that ownership intuitions are not independent but embedded in a self-referential system that perpetuates inequality.
The symptom burden and the assessment of palliative symptoms in patients with metastatic upper gastrointestinal cancer: A qualitative interview study
Authors: Sønderup Tarp Maja , Rosenberg Jacob
Published: October 2023

Objectives

Patients with metastatic upper gastrointestinal (GI) cancer may experience a large physical symptom burden. However, less is known about existential, social, and psychological symptoms. To provide the patient with palliative care, quality-of-life questionnaires are used for structured needs assessment. These are sporadically implemented, and there seems to be uncertainty to the efficiency of current practice. The aim of study was to explore the experienced assessment-process and treatment of palliative symptoms, as well as the experienced symptom burden, in patients with metastatic upper GI cancer.

Methods

Qualitative, semi-structured interviews were conducted in 10 patients with metastatic upper GI cancer. Data were analyzed using content analysis.

Results

The patients did not expect treatment for all physical symptoms. Existential symptoms revolved around death and dying, social issues were mainly related to family, and psychological issues were based in the continuous dealing with serious illness. Existential, social, and psychological symptoms were mostly not considered part of the expected care when admitted to hospital. Patients had only vague recollections of their experiences with structured needs assessment, and the process had been inconsequential in the treatment of symptoms.

Significance of results

Patients with upper GI cancer experience symptoms related to all 4 areas of palliative care being physical, existential, social, and psychological, but these are differentiated in the way patients perceive their origins and treatability. Structured needs assessment was not routinely carried out, and in cases where this had been done, no follow-up was effectuated. This calls for increased focus and proper implementation for the process to be relevant in the treatment of palliative symptoms.
Qualitative analysis of expressions used in the end-of-life discussions and their associated factors
Authors: Abe Akiko , Takeuchi Mari , Kobayashi Masato , Kohno Takashi , Mimura Masaru , Fujisawa Daisuke
Published: October 2023

Objectives

Discussing end-of-life (EOL) issues with patients remains challenging for health professionals. Physicians may use various expressions, including euphemistic ones, when disclosing the prognosis to their patients to reduce their psychological impact. However, the actual expressions of EOL disclosure in clinical practice are unclear. This study aims to investigate the expressions used in EOL disclosures and explore their associated factors.

Methods

A retrospective chart review was conducted enrolling all the patients who died in a university-affiliated hospital. Expressions used in the EOL disclosure were qualitatively analyzed. The patients’ participation rate and length from the discussion to death were investigated.

Results

EOL disclosures were observed in 341 of 358 patients. The expressions used by the physicians were categorized into 4 groups; Group 1: Clear presentation of life expectancy (n = 106; 31.1%), Group 2: Euphemistic presentation of life expectancy (n = 24; 7.0%), Group 3: Presentation of risk of sudden death (n = 147; 43.1%), Group 4: No mention on life expectancy (n = 64; 18.8%). The proportion of male patients was higher in Group 2 (79%) and lower in Group 4 (56%). Patients with cancer accounted for approximately 70% of Groups 1 and 4, but only approximately 30% of Group 3. The patient participation rate was highest in Group4 (84.4%), followed by Group 2 (50.0%). The median time from EOL disclosure to death was longer in Groups 1 and 4 (26 and 29.5 days, respectively), compared to Groups 2 and 3 (18.5 and 16 days, respectively).

Significance of results

A variety of expressions are used in EOL disclosure. Patterns of communication are influenced by patients’ gender and type of illness (cancer or noncancer). Euphemisms do not seem to facilitate timely disclosure of life expectancy or patient participation. For health professionals, not only devising the expressions to alleviate their patients’ distress when breaking bad news but also considering the communication process and patient background are essential.
Disruption as an opportunity or threat: A qualitative analysis of factors influencing the attitudes of experts in serious illness care toward psychedelic-assisted therapies
Authors: Sholevar Roxanne , Peteet John , Sanders Justin , Beaussant Yvan
Published: October 2023

Background

Psychedelic-assisted therapies (PAT) are emerging as a promising treatment for psycho-existential distress in patients with serious illness. A recent qualitative analysis of perspectives of 17 experts in serious illness care and/or PAT research identified divergent views on the therapeutic potential and safety of PAT in patients with serious illness. This paper further analyzes the factors that may influence these views.

Objectives

To identify factors underlying the attitudes of experts in serious illness care and/or PAT toward PAT and its potential role in serious illness care.

Methods

Semi-structured interviews of 17 experts in serious illness care and/or PAT from the United States and Canada were analyzed to identify factors cited as influencing their views on PAT.

Results

Five factors were identified as influencing experts’ attitudes toward PAT: perception of unmet need, knowledge of empirical studies of PAT, personal experience with psychedelics, professional background, and age/generation. In addition, an integrative theme emerged from the analysis, namely PAT’s disruptive potential at 4 levels relevant to serious illness care: patient’s experience of self, illness, and death; relationships with loved ones and health-care providers; existing clinical models of serious illness care; and societal attitudes toward death. Whether this disruptive potential was viewed as a therapeutic opportunity, or an undue risk, was central in influencing experts’ level of support. Experts’ perception of this disruptive potential was directly influenced by the 5 identified factors.

Significance of results

Points of disruption potentially invoked by PAT in serious illness care highlight important practical and philosophical considerations when working to integrate PAT into serious illness care delivery in a safe and effective way.
Advanced operation of heated fluidic resonators via mechanical and thermal loss reduction in vacuum
Authors: Ko Juhee , Lee Bong Jae , Lee Jungchul
Published: October 2023

For simultaneous and quantitative thermophysical measurements of ultrasmall liquid volumes, we have recently developed and reported heated fluidic resonators (HFRs). In this paper, we improve the precision of HFRs in a vacuum by significantly reducing the thermal loss around the sensing element. A vacuum chamber with optical, electrical, and microfluidic access is custom-built to decrease the convection loss by two orders of magnitude under 10-4 mbar conditions. As a result, the measurement sensitivities for thermal conductivity and specific heat capacity are increased by 4.1 and 1.6 times, respectively. When differentiating between deionized water (H2O) and heavy water (D2O) with similar thermophysical properties and ~10% different mass densities, the signal-to-noise ratio (property differences over standard error) for H2O and D2O is increased by 9 and 5 times for thermal conductivity and specific heat capacity, respectively.
Brainmask: an ultrasoft and moist micro-electrocorticography electrode for accurate positioning and long-lasting recordings
Authors: Ji Bowen , Sun Fanqi , Guo Jiecheng , Zhou Yuhao , You Xiaoli , Fan Ye , Wang Longchun , Xu Mengfei , Zeng Wen , Liu Jingquan , Wang Minghao , Hu Huijing , Chang Honglong
Published: October 2023

Bacterial cellulose (BC), a natural biomaterial synthesized by bacteria, has a unique structure of a cellulose nanofiber-weaved three-dimensional reticulated network. BC films can be ultrasoft with sufficient mechanical strength, strong water absorption and moisture retention and have been widely used in facial masks. These films have the potential to be applied to implantable neural interfaces due to their conformality and moisture, which are two critical issues for traditional polymer or silicone electrodes. In this work, we propose a micro-electrocorticography (micro-ECoG) electrode named “Brainmask”, which comprises a BC film as the substrate and separated multichannel parylene-C microelectrodes bonded on the top surface. Brainmask can not only guarantee the precise position of microelectrode sites attached to any nonplanar epidural surface but also improve the long-lasting signal quality during acute implantation with an exposed cranial window for at least one hour, as well as the in vivo recording validated for one week. This novel ultrasoft and moist device stands as a next-generation neural interface regardless of complex surface or time of duration.
An implantable, wireless, battery-free system for tactile pressure sensing
Authors: Du Lin , Hao Han , Ding Yixiao , Gabros Andrew , Mier Thomas C. E. , Van der Spiegel Jan , Lucas Timothy H. , Aflatouni Firooz , Richardson Andrew G. , Allen Mark G.
Published: October 2023

The sense of touch is critical to dexterous use of the hands and thus an essential component of efforts to restore hand function after amputation or paralysis. Prosthetic systems have addressed this goal with wearable tactile sensors. However, such wearable sensors are suboptimal for neuroprosthetic systems designed to reanimate a patient’s own paralyzed hand. Here, we developed an implantable tactile sensing system intended for subdermal placement. The system is composed of a microfabricated capacitive pressure sensor, a custom integrated circuit supporting wireless powering and data transmission, and a laser-fused hermetic silica package. The miniature device was validated through simulations, benchtop assessment, and testing in a primate hand. The sensor implanted in the fingertip accurately measured applied skin forces with a resolution of 4.3 mN. The output from this novel sensor could be encoded in the brain with microstimulation to provide tactile feedback. More broadly, the materials, system design, and fabrication approach establish new foundational capabilities for various applications of implantable sensing systems.
Eosinophils promote pulmonary matrix destruction and emphysema via Cathepsin L
Authors: Xu Xia , Yu Tao , Dong Lingling , Glauben Rainer , Wu Siyuan , Huang Ronghua , Qumu Shiwei , Chang Chenli , Guo Jing , Pan Lin , Yang Ting , Lin Xin , Huang Ke , Chen Zhihua , Wang Chen
Published: October 2023

Patients with chronic obstructive pulmonary disease (COPD) who exhibit elevated blood eosinophil levels often experience worsened lung function and more severe emphysema. This implies the potential involvement of eosinophils in the development of emphysema. However, the precise mechanisms underlying the development of eosinophil-mediated emphysema remain unclear. In this study, we employed single-cell RNA sequencing to identify eosinophil subgroups in mouse models of asthma and emphysema, followed by functional analyses of these subgroups. Assessment of accumulated eosinophils unveiled distinct transcriptomes in the lungs of mice with elastase-induced emphysema and ovalbumin-induced asthma. Depletion of eosinophils through the use of anti-interleukin-5 antibodies ameliorated elastase-induced emphysema. A particularly noteworthy discovery is that eosinophil-derived cathepsin L contributed to the degradation of the extracellular matrix, thereby leading to emphysema in pulmonary tissue. Inhibition of cathepsin L resulted in a reduction of elastase-induced emphysema in a mouse model. Importantly, eosinophil levels correlated positively with serum cathepsin L levels, which were higher in emphysema patients than those without emphysema. Expression of cathepsin L in eosinophils demonstrated a direct association with lung emphysema in COPD patients. Collectively, these findings underscore the significant role of eosinophil-derived cathepsin L in extracellular matrix degradation and remodeling, and its relevance to emphysema in COPD patients. Consequently, targeting eosinophil-derived cathepsin L could potentially offer a therapeutic avenue for emphysema patients. Further investigations are warranted to explore therapeutic strategies targeting cathepsin L in emphysema patients.
Predicting individual cases of major adolescent psychiatric conditions with artificial intelligence
Authors: de Lacy Nina , Ramshaw Michael J. , McCauley Elizabeth , Kerr Kathleen F. , Kaufman Joan , Nathan Kutz J.
Published: October 2023

Three-quarters of lifetime mental illness occurs by the age of 24, but relatively little is known about how to robustly identify youth at risk to target intervention efforts known to improve outcomes. Barriers to knowledge have included obtaining robust predictions while simultaneously analyzing large numbers of different types of candidate predictors. In a new, large, transdiagnostic youth sample and multidomain high-dimension data, we used 160 candidate predictors encompassing neural, prenatal, developmental, physiologic, sociocultural, environmental, emotional and cognitive features and leveraged three different machine learning algorithms optimized with a novel artificial intelligence meta-learning technique to predict individual cases of anxiety, depression, attention deficit, disruptive behaviors and post-traumatic stress. Our models tested well in unseen, held-out data (AUC ≥ 0.94). By utilizing a large-scale design and advanced computational approaches, we were able to compare the relative predictive ability of neural versus psychosocial features in a principled manner and found that psychosocial features consistently outperformed neural metrics in their relative ability to deliver robust predictions of individual cases. We found that deep learning with artificial neural networks and tree-based learning with XGBoost outperformed logistic regression with ElasticNet, supporting the conceptualization of mental illnesses as multifactorial disease processes with non-linear relationships among predictors that can be robustly modeled with computational psychiatry techniques. To our knowledge, this is the first study to test the relative predictive ability of these gold-standard algorithms from different classes across multiple mental health conditions in youth within the same study design in multidomain data utilizing >100 candidate predictors. Further research is suggested to explore these findings in longitudinal data and validate results in an external dataset.
IGF2BP2 acts as a m6A modification regulator in laryngeal squamous cell carcinoma through facilitating CDK6 mRNA stabilization
Authors: Tang Xiaojun , Tang Qinglai , Li Shisheng , Li Mengmeng , Yang Tao
Published: October 2023

Laryngeal squamous cell carcinoma (LSCC) is one of the most commonly seen cancers in the head and neck region with increasing morbidity and mortality globally. N6-methyladenosine (m6A) modification plays a critical role in the carcinogenesis of LSCC. In this study, two datasets from online database were analyzed for differentially expressed genes (DEGs) between LSCC and normal samples. Furthermore, we carried out a series of experiments, including hematoxylin & eosin staining, immunohistochemical (IHC) staining, CCK-8, colony formation, transwell, flow cytometry, xenograft tumor model assays, actinomycin D assay, cycloheximide (CHX) assay, methylated m6A RNA immunoprecipitation (Me-RIP), RNA immunoprecipitation (RIP) assay, to verify the relevant findings in vivo and in vitro. Insulin like growth factor 2 mRNA binding protein 2 (IGF2BP2) was identified as an up-regulated m6A regulator in LSCC samples. Lower IGF2BP2 expression was linked to higher survival probability in LSCC and other head and neck squamous cell carcinoma patients. In LSCC cells, IGF2BP2 knockdown attenuated cancer cell aggressiveness, possibly through modulating cell cycle arrest. In the xenograft tumor model derived from IGF2BP2 knocked-down LSCC cells, IGF2BP2 knockdown inhibited tumor growth. IGF2BP2 up-regulated CDK6 expression through facilitating the stability of CDK6 mRNA and protein. CDK6 knockdown caused no changes in IGF2BP2 expression, but partially eliminated the promotive effects of IGF2BP2 overexpression on LSCC cells’ aggressiveness. Overexpressed IGF2BP2 in LSCC serves as an oncogenic factor, promoting LSCC cell proliferation and invasion in vitro and tumor growth in a xenograft tumor model in vivo through facilitating CDK6 mRNA stabilization.
Self-recruited neutrophils trigger over-activated innate immune response and phenotypic change of cardiomyocytes in fulminant viral myocarditis
Authors: Li Huihui , Zhang Mingzhi , Zhao Quanyi , Zhao Wanqing , Zhuang Yan , Wang Jin , Hang Weijian , Wen Zheng , Wang Li , Chen Chen , Wang Dao Wen
Published: October 2023

Fulminant myocarditis (FM) is a life-threatening inflammatory disease. However, the mechanisms underlying its acute onset are unknown. By dynamic cardiac function measurement, we discovered that the initiation of sudden hemodynamic collapse was on day 4 in the mouse model of FM. Single-cell RNA-sequencing study revealed that healthy cardiomyocytes (CMs) lost their contractile and metabolic function and differentiated into pro-angiogenic and pro-inflammatory CMs. Meanwhile, neutrophils, the most expanded immune cells, exhibited a unique developmental trajectory only after migrating to the heart, where they continuously attracted peripheral neutrophils via Cxcl2/Cxcl3, resulting in the acute accumulation of neutrophils in the heart. Well-differentiated cardiac-infiltrating neutrophils, rather than viruses, induced phenotypic changes in CMs. Moreover, neutrophils could amplify cytokine storm by recruiting and activating pro-inflammatory monocytes. Blockade of the self-recruiting loop of neutrophils by targeting the Cxcl2/Cxcl3-Cxcr2 axis substantially alleviated FM in mice. Collectively, we provide a comprehensive single-cell atlas of immune cells and CMs in FM, elucidate the disease pathogenesis, and suggest potential therapeutic strategies.
Climate-induced decline in the quality and quantity of European hops calls for immediate adaptation measures
Authors: Mozny Martin , Trnka Miroslav , Vlach Vojtech , Zalud Zdenek , Cejka Tomas , Hajkova Lenka , Potopova Vera , Semenov Mikhail A. , Semeradova Daniela , Büntgen Ulf
Published: October 2023

A recent rise in the global brewery sector has increased the demand for high-quality, late summer hops. The effects of ongoing and predicted climate change on the yield and aroma of hops, however, remain largely unknown. Here, we combine meteorological measurements and model projections to assess the climate sensitivity of the yield, alpha content and cone development of European hops between 1970 and 2050 CE, when temperature increases by 1.4 °C and precipitation decreases by 24 mm. Accounting for almost 90% of all hop-growing regions, our results from Germany, the Czech Republic and Slovenia show that hop ripening started approximately 20 days earlier, production declined by almost 0.2 t/ha/year, and the alpha content decreased by circa 0.6% when comparing data before and after 1994 CE. A predicted decline in hop yield and alpha content of 4–18% and 20–31% by 2050 CE, respectively, calls for immediate adaptation measures to stabilize an ever-growing global sector.
Kupffer cells prevent pancreatic ductal adenocarcinoma metastasis to the liver in mice
Authors: Thomas Stacy K. , Wattenberg Max M. , Choi-Bose Shaanti , Uhlik Mark , Harrison Ben , Coho Heather , Cassella Christopher R. , Stone Meredith L. , Patel Dhruv , Markowitz Kelly , Delman Devora , Chisamore Michael , Drees Jeremy , Bose Nandita , Beatty Gregory L.
Published: October 2023

Although macrophages contribute to cancer cell dissemination, immune evasion, and metastatic outgrowth, they have also been reported to coordinate tumor-specific immune responses. We therefore hypothesized that macrophage polarization could be modulated therapeutically to prevent metastasis. Here, we show that macrophages respond to β-glucan (odetiglucan) treatment by inhibiting liver metastasis. β-glucan activated liver-resident macrophages (Kupffer cells), suppressed cancer cell proliferation, and invoked productive T cell-mediated responses against liver metastasis in pancreatic cancer mouse models. Although excluded from metastatic lesions, Kupffer cells were critical for the anti-metastatic activity of β-glucan, which also required T cells. Furthermore, β-glucan drove T cell activation and macrophage re-polarization in liver metastases in mice and humans and sensitized metastatic lesions to anti-PD1 therapy. These findings demonstrate the significance of macrophage function in metastasis and identify Kupffer cells as a potential therapeutic target against pancreatic cancer metastasis to the liver.
Cryo-EM structure of severe fever with thrombocytopenia syndrome virus
Authors: Du Shouwen , Peng Ruchao , Xu Wang , Qu Xiaoyun , Wang Yuhang , Wang Jiamin , Li Letian , Tian Mingyao , Guan Yudong , Wang Jigang , Wang Guoqing , Li Hao , Deng Lingcong , Shi Xiaoshuang , Ma Yidan , Liu Fengting , Sun Minhua , Wei Zhengkai , Jin Ningyi , Liu Wei , Qi Jianxun , Liu Quan , Liao Ming , Li Chang
Published: October 2023

The severe fever with thrombocytopenia syndrome virus (SFTSV) is a tick-borne human-infecting bunyavirus, which utilizes two envelope glycoproteins, Gn and Gc, to enter host cells. However, the structure and organization of these glycoproteins on virion surface are not yet known. Here we describe the structure of SFTSV determined by single particle reconstruction, which allows mechanistic insights into bunyavirus assembly at near-atomic resolution. The SFTSV Gn and Gc proteins exist as heterodimers and further assemble into pentameric and hexameric peplomers, shielding the Gc fusion loops by both intra- and inter-heterodimer interactions. Individual peplomers are associated mainly through the ectodomains, in which the highly conserved glycans on N914 of Gc play a crucial role. This elaborate assembly stabilizes Gc in the metastable prefusion conformation and creates some cryptic epitopes that are only accessible in the intermediate states during virus entry. These findings provide an important basis for developing vaccines and therapeutic drugs.
Meteorological drivers of resource adequacy failures in current and high renewable Western U.S. power systems
Authors: Sundar Srihari , Craig Michael T. , Payne Ashley E. , Brayshaw David J. , Lehner Flavio
Published: October 2023

Power system resource adequacy (RA), or its ability to continually balance energy supply and demand, underpins human and economic health. How meteorology affects RA and RA failures, particularly with increasing penetrations of renewables, is poorly understood. We characterize large-scale circulation patterns that drive RA failures in the Western U.S. at increasing wind and solar penetrations by integrating power system and synoptic meteorology methods. At up to 60% renewable penetration and across analyzed weather years, three high pressure patterns drive nearly all RA failures. The highest pressure anomaly is the dominant driver, accounting for 20-100% of risk hours and 43-100% of cumulative risk at 60% renewable penetration. The three high pressure patterns exhibit positive surface temperature anomalies, mixed surface solar radiation anomalies, and negative wind speed anomalies across our region, which collectively increase demand and decrease supply. Our characterized meteorological drivers align with meteorology during the California 2020 rolling blackouts, indicating continued vulnerability of power systems to these impactful weather patterns as renewables grow.
High-temperature electrothermal remediation of multi-pollutants in soil
Authors: Deng Bing , Carter Robert A. , Cheng Yi , Liu Yuan , Eddy Lucas , Wyss Kevin M. , Ucak-Astarlioglu Mine G. , Luong Duy Xuan , Gao Xiaodong , JeBailey Khalil , Kittrell Carter , Xu Shichen , Jana Debadrita , Torres Mark Albert , Braam Janet , Tour James M.
Published: October 2023

Soil contamination is an environmental issue due to increasing anthropogenic activities. Existing processes for soil remediation suffer from long treatment time and lack generality because of different sources, occurrences, and properties of pollutants. Here, we report a high-temperature electrothermal process for rapid, water-free remediation of multiple pollutants in soil. The temperature of contaminated soil with carbon additives ramps up to 1000 to 3000 °C as needed within seconds via pulsed direct current input, enabling the vaporization of heavy metals like Cd, Hg, Pb, Co, Ni, and Cu, and graphitization of persistent organic pollutants like polycyclic aromatic hydrocarbons. The rapid treatment retains soil mineral constituents while increases infiltration rate and exchangeable nutrient supply, leading to soil fertilization and improved germination rates. We propose strategies for upscaling and field applications. Techno-economic analysis indicates the process holds the potential for being more energy-efficient and cost-effective compared to soil washing or thermal desorption.
LptM promotes oxidative maturation of the lipopolysaccharide translocon by substrate binding mimicry
Authors: Yang Yiying , Chen Haoxiang , Corey Robin A. , Morales Violette , Quentin Yves , Froment Carine , Caumont-Sarcos Anne , Albenne Cécile , Burlet-Schiltz Odile , Ranava David , Stansfeld Phillip J. , Marcoux Julien , Ieva Raffaele
Published: October 2023

Insertion of lipopolysaccharide (LPS) into the bacterial outer membrane (OM) is mediated by a druggable OM translocon consisting of a β-barrel membrane protein, LptD, and a lipoprotein, LptE. The β-barrel assembly machinery (BAM) assembles LptD together with LptE at the OM. In the enterobacterium Escherichia coli, formation of two native disulfide bonds in LptD controls translocon activation. Here we report the discovery of LptM (formerly YifL), a lipoprotein conserved in Enterobacteriaceae, that assembles together with LptD and LptE at the BAM complex. LptM stabilizes a conformation of LptD that can efficiently acquire native disulfide bonds, whereas its inactivation makes disulfide bond isomerization by DsbC become essential for viability. Our structural prediction and biochemical analyses indicate that LptM binds to sites in both LptD and LptE that are proposed to coordinate LPS insertion into the OM. These results suggest that, by mimicking LPS binding, LptM facilitates oxidative maturation of LptD, thereby activating the LPS translocon.
Predicting discrete-time bifurcations with deep learning
Authors: Bury Thomas M. , Dylewsky Daniel , Bauch Chris T. , Anand Madhur , Glass Leon , Shrier Alvin , Bub Gil
Published: October 2023

Many natural and man-made systems are prone to critical transitions—abrupt and potentially devastating changes in dynamics. Deep learning classifiers can provide an early warning signal for critical transitions by learning generic features of bifurcations from large simulated training data sets. So far, classifiers have only been trained to predict continuous-time bifurcations, ignoring rich dynamics unique to discrete-time bifurcations. Here, we train a deep learning classifier to provide an early warning signal for the five local discrete-time bifurcations of codimension-one. We test the classifier on simulation data from discrete-time models used in physiology, economics and ecology, as well as experimental data of spontaneously beating chick-heart aggregates that undergo a period-doubling bifurcation. The classifier shows higher sensitivity and specificity than commonly used early warning signals under a wide range of noise intensities and rates of approach to the bifurcation. It also predicts the correct bifurcation in most cases, with particularly high accuracy for the period-doubling, Neimark-Sacker and fold bifurcations. Deep learning as a tool for bifurcation prediction is still in its nascence and has the potential to transform the way we monitor systems for critical transitions.
Multidimensional responses of grassland stability to eutrophication
Authors: Chen Qingqing , Wang Shaopeng , Borer Elizabeth T. , Bakker Jonathan D. , Seabloom Eric W. , Harpole W. Stanley , Eisenhauer Nico , Lekberg Ylva , Buckley Yvonne M. , Catford Jane A. , Roscher Christiane , Donohue Ian , Power Sally A. , Daleo Pedro , Ebeling Anne , Knops Johannes M. H. , Martina Jason P. , Eskelinen Anu , Morgan John W. , Risch Anita C. , Caldeira Maria C. , Bugalho Miguel N. , Virtanen Risto , Barrio Isabel C. , Niu Yujie , Jentsch Anke , Stevens Carly J. , Gruner Daniel S. , MacDougall Andrew S. , Alberti Juan , Hautier Yann
Published: October 2023

Eutrophication usually impacts grassland biodiversity, community composition, and biomass production, but its impact on the stability of these community aspects is unclear. One challenge is that stability has many facets that can be tightly correlated (low dimensionality) or highly disparate (high dimensionality). Using standardized experiments in 55 grassland sites from a globally distributed experiment (NutNet), we quantify the effects of nutrient addition on five facets of stability (temporal invariability, resistance during dry and wet growing seasons, recovery after dry and wet growing seasons), measured on three community aspects (aboveground biomass, community composition, and species richness). Nutrient addition reduces the temporal invariability and resistance of species richness and community composition during dry and wet growing seasons, but does not affect those of biomass. Different stability measures are largely uncorrelated under both ambient and eutrophic conditions, indicating consistently high dimensionality. Harnessing the dimensionality of ecological stability provides insights for predicting grassland responses to global environmental change.
Enhanced joint impact of western hemispheric precursors increases extreme El Niño frequency under greenhouse warming
Authors: Jo Hyun-Su , Ham Yoo-Geun
Published: October 2023

Sea surface temperature variability over the north tropical Atlantic (NTA) and over the subtropical northeast Pacific (SNP), which is referred to as the North Pacific Meridional Mode, during the early boreal spring is known to trigger El Niño–Southern Oscillation (ENSO) events. The future changes of the influence of those northwestern hemispheric precursors on ENSO are usually examined separately, even though their joint impacts significantly differ from the individual impacts. Here, we show that the impacts of both NTA and SNP on ENSO significantly increase under greenhouse warming and that the degrees of enhancement are closely linked. The wetter mean state over the off-equatorial eastern Pacific is a single contributor that controls the impacts of both NTA and SNP on ENSO. The enhanced joint impacts of the northwestern hemispheric precursors on ENSO increase the occurrences of extreme El Niño events and the ENSO predictability under greenhouse warming.
Chirality-induced avalanche magnetization of magnetite by an RNA precursor
Authors: Ozturk S. Furkan , Bhowmick Deb Kumar , Kapon Yael , Sang Yutao , Kumar Anil , Paltiel Yossi , Naaman Ron , Sasselov Dimitar D.
Published: October 2023

Homochirality is a hallmark of life on Earth. To achieve and maintain homochirality within a prebiotic network, the presence of an environmental factor acting as a chiral agent and providing a persistent chiral bias to prebiotic chemistry is highly advantageous. Magnetized surfaces are prebiotically plausible chiral agents due to the chiral-induced spin selectivity (CISS) effect, and they were utilized to attain homochiral ribose-aminooxazoline (RAO), an RNA precursor. However, natural magnetic minerals are typically weakly magnetized, necessitating mechanisms to enhance their magnetization for their use as effective chiral agents. Here, we report the magnetization of magnetic surfaces by crystallizing enantiopure RAO, whereby chiral molecules induce a uniform surface magnetization due to the CISS effect, which spreads across the magnetic surface akin to an avalanche. Chirality-induced avalanche magnetization enables a feedback between chiral molecules and magnetic surfaces, which can amplify a weak magnetization and allow for highly efficient spin-selective processes on magnetic minerals.
HLA3DB: comprehensive annotation of peptide/HLA complexes enables blind structure prediction of T cell epitopes
Authors: Gupta Sagar , Nerli Santrupti , Kutti Kandy Sreeja , Mersky Glenn L. , Sgourakis Nikolaos G.
Published: October 2023

The class I proteins of the major histocompatibility complex (MHC-I) display epitopic peptides derived from endogenous proteins on the cell surface for immune surveillance. Accurate modeling of peptides bound to the human MHC, HLA, has been mired by conformational diversity of the central peptide residues, which are critical for recognition by T cell receptors. Here, analysis of X-ray crystal structures within our curated database (HLA3DB) shows that pHLA complexes encompassing multiple HLA allotypes present a discrete set of peptide backbone conformations. Leveraging these backbones, we employ a regression model trained on terms of a physically relevant energy function to develop a comparative modeling approach for nonamer pHLA structures named RepPred. Our method outperforms the top pHLA modeling approach by up to 19% in structural accuracy, and consistently predicts blind targets not included in our training set. Insights from our work may be applied towards predicting antigen immunogenicity, and receptor cross-reactivity.
Visible light-triggered selective C(sp2)-H/C(sp3)-H coupling of benzenes with aliphatic hydrocarbons
Authors: Li Qian-Yu , Cheng Shiyan , Ye Ziqi , Huang Tao , Yang Fuxing , Lin Yu-Mei , Gong Lei
Published: October 2023

The direct and selective coupling of benzenes with aliphatic hydrocarbons is a promising strategy for C(sp2)-C(sp3) bond formation using readily available starting materials, yet it remains a significant challenge. In this study, we have developed a simplified photochemical system that incorporates catalytic amounts of iron(III) halides as multifunctional reagents and air as a green oxidant to address this synthetic problem. Under mild conditions, the reaction between a strong C(sp2)-H bond and a robust C(sp3)-H bond has been achieved, affording a broad range of cross-coupling products with high yields and commendable chemo-, site-selectivity. The iron halide acts as a multifunctional reagent that responds to visible light, initiates C-centered radicals, induces single-electron oxidation to carbocations, and participates in a subsequent Friedel-Crafts-type process. The gradual release of radical species and carbocation intermediates appears to be critical for achieving desirable reactivity and selectivity. This eco-friendly, cost-efficient approach offers access to various building blocks from abundant hydrocarbon feedstocks, and demonstrates the potential of iron halides in sustainable synthesis.
Symmetric carbon tetramers forming spin qubits in hexagonal boron nitride
Authors: Benedek Zsolt , Babar Rohit , Ganyecz Ádám , Szilvási Tibor , Legeza Örs , Barcza Gergely , Ivády Viktor
Published: October 2023

Point defect quantum bits in semiconductors have the potential to revolutionize sensing at atomic scales. Currently, vacancy-related defects are at the forefront of high spatial resolution and low-dimensional sensing. On the other hand, it is expected that impurity-related defect structures may give rise to new features that could further advance quantum sensing in low dimensions. Here, we study the symmetric carbon tetramer clusters in hexagonal boron nitride and propose them as spin qubits for sensing. We utilize periodic-DFT and quantum chemistry approaches to reliably and accurately predict the electronic, optical, and spin properties of the studied defect. We show that the nitrogen-centered symmetric carbon tetramer gives rise to spin state-dependent optical signals with strain-sensitive intersystem crossing rates. Furthermore, the weak hyperfine coupling of the defect to their spin environments results in a reduced electron spin resonance linewidth that can enhance sensitivity.