bluuebunny/crossref_metadata_2025 huggingface dataset:
Philanthropic supported innovation: trends, areas, and impact
Authors: Li Guan Cheng , He Lingyun , Fleming Lee
Published: August 2023

Philanthropy provides substantial support for science and research—does it do the same for technology and invention? We match patenting outcomes in the United States with philanthropic organizations as listed in the Candid database and find that at least 0.2% of U.S. patenting since 1976 received philanthropic support. After matching philanthropic patents to non-philanthropic patents based on technology, time, and the number of inventors, we find that philanthropic invention is more likely to be done by smaller teams and U.S. based inventors and less likely to rely on science research and non-U.S. prior art. Renewal rates are not significantly different from non-philanthropic patents and philanthropic patents are not more likely to be in underserved areas of technology. Philanthropic supported patents receive significantly fewer future prior art citations, thus implying that philanthropy supported patents are not exceptionally valuable.
The Rhetoric of Solidarity: Nature and Measurement of Social Cohesion in the Self-representation of Civil Society Organizations
Authors: Neumann Rico , Pfetsch Barbara , Hutter Swen , Koschut Simon , Schieferdecker David , Specht Jule
Published: August 2023

Scholars have called to study how social cohesion is discursively negotiated and produced in communication behavior. However, empirical evidence remains scarce. In this study, we investigate to what extent and how civil society organizations (CSOs), part of the backbone of social integration in modern democracies, make references to social cohesion in their public self-portrayals. We develop a standardized measure for content analyzing the manifestation of social cohesion along three theoretical dimensions: social relations, connectedness, and orientation towards the common good. We apply our innovative content measure to the external communication of an original sample of nearly 800 CSOs in Germany, using their websites. Subsequently, we use data from an accompanying organizational survey of these institutions to investigate whether and how certain organizational features help explain variance in social cohesion rhetoric. Findings suggest that CSOs’ external communications employ themes from all key dimensions of social cohesion, revealing a fair amount of variation on all three subdimensions and a summary index of the overall strength social cohesion rhetoric. These different emphases are contingent upon various organizational characteristics, namely the spheres in which CSOs are primarily active, their locations, and their target groups. Whereas culturally and media-oriented organizations as well as sports clubs are largely reluctant to make references to social cohesion, politically active CSOs and those addressing socially disadvantaged communities tend to push more in this direction. The latter tend to operate in more professionalized structures, indicating that referencing social cohesion legitimizes these groups’ political and social purposes in the public sphere.
Sexual dimorphism in peripheral blood cell characteristics linked to recanalization success of endovascular thrombectomy in acute ischemic stroke
Authors: Overmars L. Malin , van Solinge Wouter W. , Ruijter Hester M. den , van der Worp H. Bart , Van Es Bram , Hulsbergen-Veelken Cornelia A. R. , Biessels Geert Jan , Exalto Lieza G. , Haitjema Saskia
Published: August 2023

Endovascular thrombectomy (EVT) success to treat acute ischemic stroke varies with factors like stroke etiology and clot composition, which can differ between sexes. We studied if sex-specific blood cell characteristics (BCCs) are related to recanalization success. We analyzed electronic health records of 333 EVT patients from a single intervention center, and extracted 71 BCCs from the Sapphire flow cytometry analyzer. Through Sparse Partial Least Squares Discriminant Analysis, incorporating cross-validation and stability selection, we identified BCCs associated with successful recanalization (TICI 3) in both sexes. Stroke etiology was considered, while controlling for cardiovascular risk factors. Of the patients, successful recanalization was achieved in 51% of women and 49% of men. 21 of the 71 BCCs showed significant differences between sexes  (pFDR-corrected < 0.05). The female-focused recanalization model had lower error rates than both combined [t(192.4) = 5.9, p < 0.001] and male-only models [t(182.6) = − 15.6, p < 0.001]. In women, successful recanalization and cardioembolism were associated with a higher number of reticulocytes, while unsuccessful recanalization and large artery atherosclerosis (LAA) as cause of stroke were associated with a higher mean corpuscular hemoglobin concentration. In men, unsuccessful recanalization and LAA as cause of stroke were associated with a higher coefficient of variance of lymphocyte complexity of the intracellular structure. Sex-specific BCCs related to recanalization success varied and were linked to stroke etiology. This enhanced understanding may facilitate personalized treatment for acute ischemic stroke.
Serpina3n/serpina3 alleviates cyclophosphamide-induced interstitial cystitis by activating the Wnt/β-catenin signal
Authors: Fang Weilin , Song Qixiang , Lv Tingting , Lv Jianwei , Cai Zhikang , Wang Zhong , Song Xin , Ji Xiang , Huang Jin
Published: August 2023

Background/objective

Serpina3n/Serpina3 has been identified to be implicated in inflammatory diseases, but its role in interstitial cystitis/bladder pain syndrome (IC/BPS) remains unknown. Here, we aimed to reveal serpina3n/serpina3 role in IC/BPS in vivo and in vitro.

Methods

The IC/BPS model in mice was induced by intraperitoneal injection of 150 mg/kg of cyclophosphamide (CYP). HE and toluidine blue staining were used for histology assessment. Serpina3n/serpina3 expression in the bladder tissues from IC/BPS patients and mouse models were determined by qPCR, immunohistochemistry and western blotting. XAV-939 treatment was applied to inhibit β-catenin activation. Serpina3 role in modulating the growth and apoptosis of HBlEpCs, a human primary bladder epithelial cell line, was assessed by CCK-8 and flow cytometry assays.

Results

Serpina3n/serpina3 expression was decreased in both human and mice bladder tissues with IC/BPS. Upregulation of serpina3n significantly alleviated CYP-induced bladder injury, with decreased mast cells and pro-inflammatory factor levels, including IL-1β, IL-6, and TNF-α, while increased IL-10 level. In addition, serpina3 overexpression inhibited the apoptosis of HBlEpCs, and increased cell growth. In mechanism, we found that serpina3 overexpression promoted the activation of wnt/β-catenin signaling. And, the inhibition of wnt/β-catenin signaling with XAV-939 abolished serpina3n/serpina3 role in protecting bladder tissues from CYP-induced cystitis, as well as inhibiting HBlEpC apoptosis.

Conclusion

Serpina3n/serpina3 expression was decreased in IC/BPS. Overexpression of serpina3n could alleviate CYP-induced IC/BPS by activating the Wnt/β-catenin signal. This study may provide a new therapeutic strategy for IC/BPS.
Investigating state and trait aspects of resilience using Generalizability theory
Authors: Child Lucy E. , Medvedev Oleg N.
Published: August 2023

Challenges of modern living such as burden of disease, a global COVID-19 pandemic and workplace stress leading to anxiety and depression raise the importance of psychological resilience. Psychological interventions should increase trait resilience that involves reinforcing state resilience and requires a clear distinction between state and trait aspects of the construct. Generalizability theory is the appropriate method increasingly used to distinguish between state and trait and to establish reliability of psychological assessment. G-theory was applied to examine five major resilience scales completed at 3 time-points by the sample (n = 94) that possess adequate statistical power for such analyses. All five resilience scales demonstrated strong reliability and generalizability of scores across occasions and sample population as expected for a valid trait measure (G > 0.90). However, eight state aspects of resilience were identified from all five resilience scales including adaptation to change; perseverance; self-confidence while facing adversity; self-efficacy; trust in instincts; ability to follow plans; non-reactivity; and ability to plan. State aspects of resilience appear to show more variability and, pending further research, could potentially be a target for resilience-building interventions. All five measures of resilience are useful to assess long-lasting changes in resilience. Development of a state resilience scale is warranted.
Potato Tuber Lenticels: A Review of Their Development, Structure, Function, and Disease Susceptibility
Authors: Bethke Paul Carl
Published: August 2023

Potato tuber lenticels are essential components of the potato skin. This review draws on more than a century of published literature to give a comprehensive overview of potato tuber lenticels. This review describes the development and structure of lenticels, as well as the number of lenticels per tuber. Lenticels facilitate gas exchange between the atmosphere and the interior of the tuber, and data on lenticel permeability to oxygen and carbon dioxide are summarized. Conditions that promote proliferation of filling cells and lenticel enlargement are described in the context of laboratory experiments and observations from the field. Lenticels are potential sites of infection by plant pathogens including common scab, powdery scab and late blight. Research demonstrating interactions between lenticels and various diseases is presented, with an emphasis on potato soft rot. Many aspects of lenticel biology remain poorly understood and a few compelling unanswered questions are highlighted.
An improved blood hemorrhaging treatment using diatoms frustules, by alternating Ca and light levels in cultures
Authors: Li Qinfeng , He Zheng , Rozan Hussein. E. , Feng Chao , Cheng Xiaojie , Chen Xiguang
Published: August 2023

Hemorrhage control requires hemostatic materials that are both effective and biocompatible. Among these, diatom biosilica (DBs) could significantly improve hemorrhage control, but it induces hemolysis (the hemolysis rate > 5%). Thus, the purpose of this study was to explore the influence of Ca2+ biomineralization on DBs for developing fast hemostatic materials with a low hemolysis rate. Here, CaCl2 was added to the diatom medium under high light (cool white, fluorescent lamps, 67.5 µmol m−2 s−1), producing Ca-DBs-3 with a particle size of 40–50 μm and a Ca2+ content of Ca-DBs-3 obtained from the higher concentration CaCl2 group (6.7 mmol L−1) of 0.16%. The liquid absorption capacity of Ca-DBs-3 was 30.43 ± 0.57 times its dry weight; the in vitro clotting time was comparable to QuikClot® zeolite; the hemostatic time and blood loss using the rat tail amputation model were 36.40 ± 2.52 s and 0.39 ± 0.12 g, which were 40.72% and 19.50% of QuikClot® zeolite, respectively. Ca-DBs-3 showed no apparent toxicity to L929 cells (cell viability > 80%) and was non-hemolysis (the hemolysis rate < 2%). This study prepared Ca-DBs-3 with a rapid hemostatic effect and good biocompatibility, providing a path to develop diatom biosilica hemostatic materials.
Large yellow croaker (Larimichthys crocea) mitofusin 2 inhibits type I IFN responses by degrading MAVS via enhanced K48-linked ubiquitination
Authors: Li Wen-Xing , Wang Xiao-Hong , Lin Yi-Jun , Zhou Yuan-Yuan , Li Jun , Zhang Xiang-Yang , Chen Xin-Hua
Published: August 2023

In mammals, mitofusin 2 (MFN2) is involved in mitochondrial fusion, and suppresses the virus-induced RIG-I-like receptor (RLR) signaling pathway. However, little is known about the function of MFN2 in non-mammalian species. In the present study, we cloned an MFN2 ortholog (LcMFN2) in large yellow croaker (Larimichthys crocea). Phylogenetic analysis showed that MFN2 emerged after the divergence of amphioxus and vertebrates. The protein sequences of MFN2 were well conserved from fish to mammals. LcMFN2 was expressed in all the tissues/organs examined at different levels, and its expression was upregulated in response to poly(I:C) stimulation. Overexpression of LcMFN2 inhibited MAVS-induced type I interferon (IFN) promoter activation and antiviral gene expression. In contrast, knockdown of endogenous LcMFN2 enhanced poly(I:C) induced production of type I IFNs. Additionally, LcMFN2 enhanced K48-linked polyubiquitination of MAVS, promoting its degradation. Also, overexpression of LcMFN2 impaired the cellular antiviral response, as evidenced by the increased expression of viral genes and more severe cytopathic effects (CPE) in cells infected with spring viremia of carp virus (SVCV). These results indicated that LcMFN2 inhibited type I IFN response by degrading MAVS, suggesting its negative regulatory role in cellular antiviral response. Therefore, our study sheds a new light on the regulatory mechanisms of the cellular antiviral response in teleosts.
Evaluation of the effect of different conventional roof types and industrial activity on harvested rainwater in Southern Nigeria
Authors: Nicholas Eno-obong Sunday , Ukoha Pius Onyeoziri
Published: August 2023

Harvested rainwater is still the only source of acceptable drinking water for rural communities in Nigeria and in some countries, where there are no water networks and it is the rooftop rainwater harvesting that is being exercised for the potable and non-potable usages. This study was aimed at evaluating the effect of roof types and industrial activity on rainwater quality by analysing the physico-chemical/bacteriological characteristics, heavy metals and investigating the metal composition of the roof types. Rainwater was harvested from long-span aluminium, asbestos, corrugated iron, Cameroon zinc, stone-coated tiles roof run-offs and directly from the sky in the urban and rural areas of Imo State between the months of April-July, 2017. The results were compared with water quality standards (NAFDAC, USEPA, WHO and NSDWQ) for drinking water and Water Quality Index (WQI) ratings since there is no standard for rainwater quality. Roofs ages from < 5, 5–10, 15–20, and > 25 years in use were considered. Heavy metals were analysed using Flame-AAS; other parameters were analysed using standard methods. The WQI ratings were calculated using the weighted arithmetic method. Results show mean values ranging from 5.70 to 6.60 for pH, E.coli (not detected) and heavy metals (mg/L) burden of 0.00–0.09 for Pb, Cr (0.00–0.79), Zn (0.00–0.06), Fe (0.00–0.50) and Al (0.00–0.63). The WQI ratings gave excellent water to unfit for drinking water quality in both urban and rural areas. Since the harvested rainwater was not free of contamination, a few helpful recommendations were suggested for positive impacts in Nigeria as a whole.
Generalized Ricci Solitons on Three-Dimensional Lorentzian Walker Manifolds
Authors: Pirhadi Vahid , Fasihi-Ramandi Ghodratallah , Azami Shahroud
Published: August 2023

In this paper, we characterize the generalized Ricci soliton equation on the three-dimensional Lorentzian Walker manifolds. We prove that every generalized Ricci soliton with $$C, \beta ,\mu \ne 0$$

C
,
β
,
μ
≠
0

on a three-dimensional Lorentzian Walker manifold is steady. Moreover, non-trivial solutions for strictly Lorentzian Walker manifolds are derived. Finally, we give some conditions on the defining function f under which a generalized Ricci soliton on a three-dimensional Lorentzian Walker manifold to be gradient.
Migration–contagion processes
Authors: Baccelli F. , Foss S. , Shneer S.
Published: August 2023

Consider the following migration process based on a closed network of N queues with
$K_N$
customers. Each station is a
$\cdot$
/M/
$\infty$
queue with service (or migration) rate
$\mu$
. Upon departure, a customer is routed independently and uniformly at random to another station. In addition to migration, these customers are subject to a susceptible–infected–susceptible (SIS) dynamics. That is, customers are in one of two states: I for infected, or S for susceptible. Customers can swap their state either from I to S or from S to I only in stations. More precisely, at any station, each susceptible customer becomes infected with the instantaneous rate
$\alpha Y$
if there are Y infected customers in the station, whereas each infected customer recovers and becomes susceptible with rate
$\beta$
. We let N tend to infinity and assume that
$\lim_{N\to \infty} K_N/N= \eta $
, where
$\eta$
is a positive constant representing the customer density. The main problem of interest concerns the set of parameters of such a system for which there exists a stationary regime where the epidemic survives in the limiting system. The latter limit will be referred to as the thermodynamic limit. We use coupling and stochastic monotonicity arguments to establish key properties of the associated Markov processes, which in turn allow us to give the structure of the phase transition diagram of this thermodynamic limit with respect to
$\eta$
. The analysis of the Kolmogorov equations of this SIS model reduces to that of a wave-type PDE for which we have found no explicit solution. This plain SIS model is one among several companion stochastic processes that exhibit both random migration and contagion. Two of them are discussed in the present paper as they provide variants to the plain SIS model as well as some bounds and approximations. These two variants are the departure-on-change-of-state (DOCS) model and the averaged-infection-rate (AIR) model, which both admit closed-form solutions. The AIR system is a classical mean-field model where the infection mechanism based on the actual population of infected customers is replaced by a mechanism based on some empirical average of the number of infected customers in all stations. The latter admits a product-form solution. DOCS features accelerated migration in that each change of SIS state implies an immediate departure. This model leads to another wave-type PDE that admits a closed-form solution. In this text, the main focus is on the closed stochastic networks and their limits. The open systems consisting of a single station with Poisson input are instrumental in the analysis of the thermodynamic limits and are also of independent interest. This class of SIS dynamics has incarnations in virtually all queueing networks of the literature.
Excessive Pricing in Pharmaceuticals under Article 102 TFEU
Authors: Veraldi Jacquelyn D.
Published: August 2023

High pharmaceutical pricing practices in Europe have been increasingly on the radar of the European Union, academia and civil society as a risk to Member State health budgets. It is therefore hardly surprising that, in recent years, competition authorities have resuscitated the excessive pricing prohibition contained in Article 102(a) TFEU. Focusing on this phenomenon, this piece highlights the diverse ways in which the United Brands test has been applied in pharmaceuticals by conducting a comparative study of the decisional practice of national competition authorities. Several observations and arguments are then derived therefrom, demonstrating that, while difficult (most notably in respect to patent-protected products), competition authorities and courts have established sophisticated ways of determining whether a pharmaceutical price is excessive in the sense of Article 102(a) TFEU. These findings should encourage hesitant competition authorities and private plaintiffs to at least carry out preliminary investigations when they suspect excessive pricing in pharmaceuticals is taking place.
Acceptable Risks in Europe’s Proposed AI Act: Reasonableness and Other Principles for Deciding How Much Risk Management Is Enough
Authors: Fraser Henry , Bello y Villarino José-Miguel
Published: August 2023

This paper critically evaluates the European Commission’s proposed AI Act’s approach to risk management and risk acceptability for high-risk artificial intelligence systems that pose risks to fundamental rights and safety. The Act aims to promote “trustworthy” AI with a proportionate regulatory burden. Its provisions on risk acceptability require residual risks from high-risk systems to be reduced or eliminated “as far as possible”, having regard for the “state of the art”. This criterion, especially if interpreted narrowly, is unworkable and promotes neither proportionate regulatory burden nor trustworthiness. By contrast, the Parliament’s most recent draft amendments to the risk management provisions introduce “reasonableness” and cost–benefit analyses and are more transparent regarding the value-laden and contextual nature of risk acceptability judgments. This paper argues that the Parliament’s approach is more workable and better balances the goals of proportionality and trustworthiness. It explains what reasonableness in risk acceptability judgments would entail, drawing on principles from negligence law and European medical devices regulation. It also contends that the approach to risk acceptability judgments needs a firm foundation of civic legitimacy, including detailed guidance or involvement from regulators and meaningful input from affected stakeholders.
Tame or wild Toeplitz shifts
Authors: FUHRMANN GABRIEL , KELLENDONK JOHANNES , YASSAWI REEM
Published: August 2023

We investigate tameness of Toeplitz shifts. By introducing the notion of extended Bratteli–Vershik diagrams, we show that such shifts with finite Toeplitz rank are tame if and only if there are at most countably many orbits of singular fibres over the maximal equicontinuous factor. The ideas are illustrated using the class of substitution shifts. A body of elaborate examples shows that the assumptions of our results cannot be relaxed.
COVID-19 fear and its associated correlates among type-2 diabetes patients in Bangladesh: A hospital-based study
Authors: Shuvo Suvasish Das , Hossen Md Toufik , Hossain Md Sakhawot , Khatun Asma , Mazumdar Sanaullah , Riazuddin Md , Roy Deepa
Published: August 2023

The outbreak of COVID-19 has caused widespread fear among people around the world, particularly those with underlying health conditions such as type-2 diabetes. This study aimed to investigate COVID-19 fear and its associated potential factors among type-2 diabetes patients in Bangladesh. A total of 1,036 type-2 diabetes patients residing in the Jashore district of Bangladesh were interviewed using the COVID-19 Fear Scale in Bengali language. A pre-validated questionnaire was used to collect data on sociodemographic, lifestyle-related characteristics, and COVID-19-related information. Logistic regression was performed to identify factors associated with perceived fear of COVID-19. The mean score of the COVID-19 fear was 18.1 ± 5.6. Approximately 45 and 39% were most afraid and uncomfortable thinking about COVID-19, respectively. Regression analysis revealed that gender, age, occupation, residence, physical activity, smoking, and dietary diversity score were associated with fear. Additionally, respondents who had limited self-care practice, unaffordable medicine, medicine shortages, a close friend or family member diagnosed with COVID-19, and financial problems during COVID-19 were significant predictors of COVID-19 fear. Healthcare providers should implement interventions, including appropriate education and counseling, to address the psychological impact of the COVID-19 pandemic on type-2 diabetes patients in Bangladesh.
Starch Analyses on Culinary Equipment from Chavin de Huantar
Authors: Mesía-Montenegro Christian , Weber Sadie L.
Published: August 2023

Excavations at the Wacheqsa sector from Chavin de Huantar identified contexts from the Middle Formative (1100–900 BC) and Late Formative (900–550 BC) periods. We present results of starch analysis conducted in culinary equipment (ceramics) retrieved from domestic occupations and a large midden. Microbotanical analysis revealed a variety of plant food resources, such as maize, beans, olluco, and possibly chili peppers.
The blood of Christ: Sacrificial death or moral authority?
Authors: Wiese Tammy
Published: August 2023

The phrase blood of Christ has traditionally been interpreted as and used interchangeably with Christ's sacrificial death. As such, Jesus’ death is seen to be more crucial to salvation than his incarnation and resurrection. The blood of Christ language in the New Testament books of Hebrews and Romans echoes Old Testament cultic atonement language. Given recent and ample exegetical biblical scholarship that suggests blood of Christ language might refer to Christ's incarnational, resurrected life, we should explore the resulting soteriological implications. What salvific significance is there to the cross if Jesus Christ entered the Most Holy Place with his lifeblood flowing in his veins as David Moffitt asserts? I propose that the cross reveals God's legal and moral authority to forgive sin without minimising the law.
Seeking contexts that promote neurodiverse social success: Patterns of behavior during minimally-structured interaction settings in autistic and non-autistic youth
Authors: McNair Morgan L. , Keenan Elliot Gavin , Houck Abigail P. , Lerner Matthew D.
Published: August 2023

While peer interaction differences are considered a central feature of autism, little is known regarding the nature of these interactions via directly-observed measurement of naturalistic (i.e., minimally-structured) groups of autistic and non-autistic adolescent peers. 148 autistic and non-autistic adolescents (111 male, Mage = 14.22, SDage = 1.90; MIQ = 103.22, SDIQ = 15.80) participated in a 50-minute, minimally-structured, naturalistic peer interaction paradigm with activities of varying social demands: an incidental social demand (eating in a room with peers), a physical social demand (playing a physically-interactive game), and a verbal social demand (playing a verbal game). While autistic youth exhibited fewer overall interaction behaviors than non-autistic youth, the two groups did not differ in amount of positive, negative, and low-level interaction behaviors. Within activities, autistic and non-autistic youth only differed in positive interaction behaviors during the context of a verbal social demand. Youth who displayed more positive interaction behaviors during this same activity had less autism spectrum disorder symptomatology, controlling for nested group effects and relevant covariates. These results point toward subtle differences in social demands across naturalistic settings that can either support or impede prosocial interaction for autistic youth, providing a guidepost for identifying settings that best promote social success for neurodiverse populations.
New Histories of and for Europe: Narrating the European Project
Authors: Krawatzek Félix , Pestel Friedemann
Published: August 2023

Approaching Europe's historical trajectories to explain its present condition is an ever-growing genre. More than 200 years after the Congress of Vienna, more than 100 years after the First World War, more than sixty years after the Treaty of Rome, more than half a decade after the Brexit referendum – and after more than a year of open warfare in Ukraine, the European project remains in constant flux. A seemingly endless sequence of junctures over the last two decades has raised the demand for historically grounded analyses of Europe. The desire for such publications, both academic and for a broader audience, is thus far from exhausted. Every turn in European politics gives rise to a new take on Europe's past by historians and scholars working in related disciplines.
Future Temperature‐Related Deaths in the U.S.: The Impact of Climate Change, Demographics, and Adaptation
Authors: Lee Jangho , Dessler Andrew E.
Published: August 2023

Mortality due to extreme temperatures is one of the most worrying impacts of climate change. In this analysis, we use historic mortality and temperature data from 106 cities in the United States to develop a model that predicts deaths attributable to temperature. With this model and projections of future temperature from climate models, we estimate temperature‐related deaths in the United States due to climate change, changing demographics, and adaptation. We find that temperature‐related deaths increase rapidly as the climate warms, but this is mainly due to an expanding and aging population. For global average warming below 3°C above pre‐industrial levels, we find that climate change slightly reduces temperature‐related mortality in the U.S. because the reduction of cold‐related mortality exceeds the increase in heat‐related deaths. Above 3°C warming, whether the increase in heat‐related deaths exceeds the decrease in cold‐related deaths depends on the level of adaptation. Southern U.S. cities are already well adapted to hot temperatures and the reduction of cold‐related mortality drives overall lower mortality. Cities in the Northern U.S. are not well adapted to high temperatures, so the increase in heat‐related mortality exceeds the reduction in cold‐related mortality. Thus, while the total number of climate‐related mortality may not change much, climate change will shift mortality in the U.S. to higher latitudes.
Storylines of Sahel Precipitation Change: Roles of the North Atlantic and Euro‐Mediterranean Temperature
Authors: Monerie Paul‐Arthur , Biasutti Michela , Mignot Juliette , Mohino Elsa , Pohl Benjamin , Zappa Giuseppe
Published: August 2023

Future changes in Sahel precipitation are uncertain because of large differences among projections from various models. In order to explore this uncertainty, we use a storyline approach which seeks to identify alternative plausible evolutions of Sahel precipitation and their driving factors. By analyzing projections from the CMIP6 climate models, we show that changes in North Atlantic and in Euro‐Mediterranean temperatures explain up to 60% of the central Sahel precipitation change uncertainty. We then construct several storylines of Sahel precipitation change based on future plausible changes in North Atlantic and Euro‐Mediterranean temperatures. In one storyline, an amplified warming of both the North Atlantic and the Euro‐Mediterranean areas promotes a northward shift of the West African monsoon, increasing precipitation over the central Sahel, while, in the opposite storyline, a moderate warming in both regions is associated with a small change in precipitation over the central Sahel and a decrease in precipitation over the western Sahel, at the end of the 21st century. These results indicate that Sahel precipitation uncertainty will not be substantially reduced unless the uncertainty in the future warming of the North Atlantic and the Euro‐Mediterranean areas is constrained.
FBXO28 suppresses liver cancer invasion and metastasis by promoting PKA-dependent SNAI2 degradation
Authors: Qiao Xinran , Lin Jingyu , Shen Jiajia , Chen Yang , Zheng Liyun , Ren Hangjiang , Zhao Xiaoli , Yang Hang , Li Pengyu , Wang Zhen
Published: August 2023

FBXO28 is a member of F-box proteins that are the substrate receptors of SCF (SKP1, CULLIN1, F-box protein) ubiquitin ligase complexes. Despite the implications of its role in cancer, the function of FBXO28 in epithelial-mesenchymal transition (EMT) process and metastasis for cancer remains largely unknown. Here, we report that FBXO28 is a critical negative regulator of migration, invasion and metastasis in human hepatocellular carcinoma (HCC) in vitro and in vivo.FBXO28expression is upregulated in human epithelial cancer cell lines relative to mesenchymal counterparts. Mechanistically, by directly binding to SNAI2, FBXO28 functions as an E3 ubiquitin ligase that targets the substrate for degradation via ubiquitin proteasome system. Importantly, we establish a cooperative function for PKA in FBXO28-mediated SNAI2 degradation. In clinical HCC specimens, FBXO28 protein levels positively whereas negatively correlate with PKAα and SNAI2 levels, respectively. LowFBXO28orPRKACAexpression is associated with poor prognosis of HCC patients. Together, these findings elucidate the novel function of FBXO28 as a critical inhibitor of EMT and metastasis in cancer and provide a mechanistic rationale for its candidacy as a new prognostic marker and/or therapeutic target in human aggressive HCC.
Hornerin mediates phosphorylation of the polo-box domain in Plk1 by Chk1 to induce death in mitosis
Authors: Song Haiyu , Kim Eun Ho , Hong Jihee , Gwon Dasom , Kim Jee Won , Bae Gyu-Un , Jang Chang-Young
Published: August 2023

The centrosome assembles a bipolar spindle for faithful chromosome segregation during mitosis. To prevent the inheritance of DNA damage, the DNA damage response (DDR) triggers programmed spindle multipolarity and concomitant death in mitosis through a poorly understood mechanism. We identified hornerin, which forms a complex with checkpoint kinase 1 (Chk1) and polo-like kinase 1 (Plk1) to mediate phosphorylation at the polo-box domain (PBD) of Plk1, as the link between the DDR and death in mitosis. We demonstrate that hornerin mediates DDR-induced precocious centriole disengagement through a dichotomous mechanism that includes sequestration of Sgo1 and Plk1 in the cytoplasm through phosphorylation of the PBD in Plk1 by Chk1. Phosphorylation of the PBD in Plk1 abolishes the interaction with Sgo1 and phosphorylation-dependent Sgo1 translocation to the centrosome, leading to precocious centriole disengagement and spindle multipolarity. Mechanistically, hornerin traps phosphorylated Plk1 in the cytoplasm. Furthermore, PBD phosphorylation inactivates Plk1 and disrupts Cep192::Aurora A::Plk1 complex translocation to the centrosome and concurrent centrosome maturation. Remarkably, hornerin depletion leads to chemoresistance against DNA damaging agents by attenuating DDR-induced death in mitosis. These results reveal how the DDR eradicates mitotic cells harboring DNA damage to ensure genome integrity during cell division.
CRISPR screen identifies the role of RBBP8 in mediating unfolded protein response induced liver damage through regulating protein synthesis
Authors: Wang Heting , Pan Xuya , Xiang Xiaoxin , Zhang Yang , Chen Jianning , Wen Shiyi , Wang Jin , Gao Rong , Yang Jifeng , Zhi Yaping , Wen Siying , Zheng Yubao , Li Ting , Ai Heying , He Xuemin , Lu Yan , Zhu Yanhua , Li Chunliang , Chen Yanming , Shi Guojun
Published: August 2023

Unfolded protein response (UPR) maintains the endoplasmic reticulum (ER) homeostasis, survival, and physiological function of mammalian cells. However, how cells adapt to ER stress under physiological or disease settings remains largely unclear. Here by a genome-wide CRISPR screen, we identified that RBBP8, an endonuclease involved in DNA damage repair, is required for ATF4 activation under ER stress in vitro. RNA-seq analysis suggested that RBBP8 deletion led to impaired cell cycle progression, retarded proliferation, attenuated ATF4 activation, and reduced global protein synthesis under ER stress. Mouse tissue analysis revealed that RBBP8 was highly expressed in the liver, and its expression is responsive to ER stress by tunicamycin intraperitoneal injection. Hepatocytes with RBBP8 inhibition by adenovirus-mediated shRNA were resistant to tunicamycin (Tm)-induced liver damage, cell death, and ER stress response. To study the pathological role of RBBP8 in regulating ATF4 activity, we illustrated that both RBBP8 and ATF4 were highly expressed in liver cancer tissues compared with healthy controls and highly expressed in Ki67-positive proliferating cells within the tumors. Interestingly, overexpression of RBBP8 in vitro promoted ATF4 activation under ER stress, and RBBP8 expression showed a positive correlation with ATF4 expression in liver cancer tissues by co-immunostaining. Our findings provide new insights into the mechanism of how cells adapt to ER stress through the crosstalk between the nucleus and ER and how tumor cells survive under chemotherapy or other anticancer treatments, which suggests potential therapeutic strategies against liver disease by targeting DNA damage repair, UPR or protein synthesis.
m6A methylation: a potential key player in understanding and treating COVID-2019 infection
Authors: Qian Weiwei , Zhou Jian , Duan Ligeng , Wang Haoyu , Xu Shuyun , Cao Yu
Published: August 2023

Since its discovery in 2019, coronavirus disease 2019 (COVID-2019) spans a wide clinical spectrum from the asymptomatic stage, mild infection, to severe pneumonia. In patients with COVID-2019, factors such as advanced age, diabetes, or hypertension are associated with a significantly increased risk of severe diseases and death. Of note, the mechanisms underlying differences in the risk and symptoms of COVID-2019 among different populations are still poorly characterized. Accordingly, it is imperative to elucidate potential pathophysiological mechanisms and develop targeted therapeutic approaches for COVID-2019 infection. N6-methyladenosine (m6A) is one of the most common modifications in mammalian RNA transcripts and is widely found in messenger RNAs and some non-coding RNAs. It has been reported that m6A methylation modifications are present in viral RNA transcripts, which are of great significance for the regulation of the viral life cycle. Furthermore, m6A methylation has recently been found to be strongly associated with COVID-2019 infection. Therefore, this article reviews recent advances in studies related to the role of m6A methylation in COVID-2019 infection.
Effect of the blend ratio of cyclic and linear polyethylene blends on isothermal crystallization in the quiescent state
Authors: Kobayashi Keiko , Atarashi Hironori , Yamazaki Shinichi , Kimura Kunio
Published: August 2023

The role of entanglements that form between cyclic and linear polymers in crystallization is of particular interest, but it is not fully understood. We investigated the crystallization behaviors of blends of cyclic polyethylene (C-PE) and linear polyethylene (L-PE) in a quiescent state to elucidate the role of this novel entanglement in crystallization. The samples were prepared by mixing the prepared C-PE and L-PE specimens at L-PE weight fraction (ΦL-PE) values of 0–100 wt%, with the weight average molecular weights of C-PE and L-PE being 175 × 103 and 154 × 103, respectively. The isothermal crystallization behaviors were analyzed through polarizing optical microscopy (POM) and differential scanning calorimetry (DSC). The morphology observed through POM was similar to that of ΦL-PE. From the time evolution of the heat flow measured via DSC, we obtained the half-crystallization time (t1/2) values as functions of ΦL-PE at different degrees of supercooling (ΔT). The 1/t1/2 values of the C-PE and L-PE homopolymers were approximately the same at ΔT = 25.5 and 26.5 K. At a larger ΔT value, the 1/t1/2 value of C-PE was significantly larger than that of L-PE. In contrast, 1/t1/2 reached a minimum value at ΦL-PE = 30–40 wt%, irrespective of ΔT. As the entanglement density increased with increasing ΦL-PE, the crystallization rate was expected to decrease monotonically. By considering the experimental relationship between 1/t1/2 and ΦL-PE, we speculated that the suppression of crystallization in the blended system was caused by a novel entanglement formed by the penetration of the L-PE chain into the C-PE chain.
Spatial transcriptomics reveals distinct and conserved tumor core and edge architectures that predict survival and targeted therapy response
Authors: Arora Rohit , Cao Christian , Kumar Mehul , Sinha Sarthak , Chanda Ayan , McNeil Reid , Samuel Divya , Arora Rahul K. , Matthews T. Wayne , Chandarana Shamir , Hart Robert , Dort Joseph C. , Biernaskie Jeff , Neri Paola , Hyrcza Martin D. , Bose Pinaki
Published: August 2023

The spatial organization of the tumor microenvironment has a profound impact on biology and therapy response. Here, we perform an integrative single-cell and spatial transcriptomic analysis on HPV-negative oral squamous cell carcinoma (OSCC) to comprehensively characterize malignant cells in tumor core (TC) and leading edge (LE) transcriptional architectures. We show that the TC and LE are characterized by unique transcriptional profiles, neighboring cellular compositions, and ligand-receptor interactions. We demonstrate that the gene expression profile associated with the LE is conserved across different cancers while the TC is tissue specific, highlighting common mechanisms underlying tumor progression and invasion. Additionally, we find our LE gene signature is associated with worse clinical outcomes while TC gene signature is associated with improved prognosis across multiple cancer types. Finally, using an in silico modeling approach, we describe spatially-regulated patterns of cell development in OSCC that are predictably associated with drug response. Our work provides pan-cancer insights into TC and LE biology and interactive spatial atlases (http://www.pboselab.ca/spatial_OSCC/; http://www.pboselab.ca/dynamo_OSCC/) that can be foundational for developing novel targeted therapies.
An idiosyncratic zonated stroma encapsulates desmoplastic liver metastases and originates from injured liver
Authors: Fernández Moro Carlos , Geyer Natalie , Harrizi Sara , Hamidi Yousra , Söderqvist Sara , Kuznyecov Danyil , Tidholm Qvist Evelina , Salmonson Schaad Media , Hermann Laura , Lindberg Amanda , Heuchel Rainer L. , Martín-Bernabé Alfonso , Dhanjal Soniya , Navis Anna C. , Villard Christina , del Valle Andrea C. , Bozóky Lorand , Sparrelid Ernesto , Dirix Luc , Strell Carina , Östman Arne , Schmierer Bernhard , Vermeulen Peter B. , Engstrand Jennie , Bozóky Béla , Gerling Marco
Published: August 2023

A perimetastatic capsule is a strong positive prognostic factor in liver metastases, but its origin remains unclear. Here, we systematically quantify the capsule’s extent and cellular composition in 263 patients with colorectal cancer liver metastases to investigate its clinical significance and origin. We show that survival improves proportionally with increasing encapsulation and decreasing tumor-hepatocyte contact. Immunostaining reveals the gradual zonation of the capsule, transitioning from benign-like NGFRhigh stroma at the liver edge to FAPhigh stroma towards the tumor. Encapsulation correlates with decreased tumor viability and preoperative chemotherapy. In mice, chemotherapy and tumor cell ablation induce capsule formation. Our results suggest that encapsulation develops where tumor invasion into the liver plates stalls, representing a reparative process rather than tumor-induced desmoplasia. We propose a model of metastases growth, where the efficient tumor colonization of the liver parenchyma and a reparative liver injury reaction are opposing determinants of metastasis aggressiveness.
Heavy quasiparticles and cascades without symmetry breaking in twisted bilayer graphene
Authors: Datta Anushree , Calderón M. J. , Camjayi A. , Bascones E.
Published: August 2023

Among the variety of correlated states exhibited by twisted bilayer graphene, cascades in the spectroscopic properties and in the electronic compressibility occur over larger ranges of energy, twist angle and temperature compared to other effects. This suggests a hierarchy of phenomena. Using a combined dynamical mean-field theory and Hartree calculation, we show that the spectral weight reorganisation associated with the formation of local moments and heavy quasiparticles can explain the cascade of electronic resets without invoking symmetry breaking orders. The phenomena reproduced here include the cascade flow of spectral weight, the oscillations of remote band energies, and the asymmetric jumps of the inverse compressibility. We also predict a strong momentum differentiation in the incoherent spectral weight associated with the fragile topology of twisted bilayer graphene.
Management of patients at the hepatopancreatobiliary unit of a London teaching hospital during the COVID-19 pandemic
Authors: Staubli Sebastian M. , Raptis Dimitri A. , Ghani Shahi , Davidson Brian R. , Fusai Giuseppe K. , Imber Charles , Iype Sateesh , Nasralla David , Pissanou Theodora , Rahman Sakhawat , Sharma Dinesh , Tinguely Pascale , Haddad Fares , Dodd Miranda , Dann Chris , Walker David , Pollok Joerg-Matthias ,   On behalf of the Royal Free Hospital London HPB team, Banerjee Abhirup , Mohamed Ahmed , Obalogun Aleem , Ramirez Alejandro , Rothnie Alex , Grajn Andrej , Chikkala Bhargava , Ojo-Williams Bose , Hidalgo-Salinas Camilla , Ceresa Carlo , Frola Carlo , Tsakiris Charalampos , Shaw Conrad , Chasiotis Dimitrios , Kontis Elissaios , Froghi Farid , Venkatakrishnan Guhan , Tzerbinis Helen , Kostakis Ioannis D. , Whitehead James , Costa Joao , Patel Krishnakumure , Kathirvel Manikandan , Sharma Mitesh , Elnagar Mohamed , Somasundaram Murali , Dimitrokallis Nikolaos , Morare Nolitha , Kupfuwa Nyasharenee , Bulathsinhala Sandun , Makhdoom Shahroo , Pericleous Stephanos , Kunnuru Supreeth , Ramos-Vazquez Susana , Ibraheem Tameem , Keating Gemma , Lightfoot Linda , Brown Sophie , Gyamfi Lucy , Modi Kajal , Tufuo Vanessa , Walker Harriet Louise
Published: August 2023

To mitigate COVID-19-related shortage of treatment capacity, the hepatopancreatobiliary (HPB) unit of the Royal Free Hospital London (RFHL) transferred its practice to independent hospitals in Central London through the North Central London Cancer Alliance. The aim of this study was to critically assess this strategy and evaluate perioperative outcomes. Prospectively collected data were reviewed on all patients who were treated under the RFHL HPB unit in six hospitals between November 2020 and October 2021. A total of 1541 patients were included, as follows: 1246 (81%) at the RFHL, 41 (3%) at the Chase Farm Hospital, 23 (2%) at the Whittington Hospital, 207 (13%) at the Princess Grace Hospital, 12 (1%) at the Wellington Hospital and 12 (1%) at the Lister Hospital, Chelsea. Across all institutions, overall complication rate were 40%, major complication (Clavien–Dindo grade ≥ 3a) rate were 11% and mortality rates were 1.4%, respectively. In COVID-19-positive patients (n = 28), compared with negative patients, complication rate and mortality rates were increased tenfold. Outsourcing HPB patients, including their specialist care, to surrounding institutions was safe and ensured ongoing treatment with comparable outcomes among the institutions during the COVID-19 pandemic. Due to the lack of direct comparison with a non-pandemic cohort, these results can strictly only be applied within a pandemic setting.