bluuebunny/crossref_metadata_2025 huggingface dataset:
Indicadores de intensificación y aprovechamiento alimenticio de camélidos en la Puna de Salta, Argentina
Authors: Orsi Juan Pablo
Published: January 2025

Se presenta evidencia arqueofaunística para estudiar indicadores de intensificación y discutir los cambios en el aprovechamiento alimenticio de camélidos de la Puna de Salta, noroeste de Argentina. El registro proviene del sitio Alero Cuevas, ubicado en la cuenca de Pastos Grandes, 4.400 m snm. Este sitio presenta una secuencia larga de ocupación que permite abordar el uso de los recursos animales entre aproximadamente 10.000 y 4000 años aP. Los resultados indican estrategias de aprovechamiento alimenticio que tienden a la intensificación de la explotación de los camélidos hacia los 4000 años aP. En este sentido, la información arqueofaunística presentada es útil para integrarla a la discusión planteada sobre los procesos de intensificación de uso de camélidos propuestos para la puna argentina.
Regional Chronologies and Hidden Transcripts: Defining the Initial Late Formative Period in the Southern Lake Titicaca Basin, Bolivia
Authors: Smith Scott C. , Pérez Arias Maribel , Pérez Arias Adolfo E. , Flores Pérez Andrea , DeRego Karli , Rohrer Genevieve , Marsh Erik J.
Published: January 2025

The excavation of a stratified sequence of deposits spanning the Initial Late Formative period (250 BC–AD 120) at Iruhito, in the upper Desaguadero Valley of Bolivia, provides insight into this previously unrecognized, four-century period separating the well-documented Middle Formative (800–250 BC) from the Late Formative (~AD 120–590) period. By tracking subtle shifts in ceramic, architectural, lithic, and faunal data, we can explore tempos of change in social life during this dynamic time. These data lead us to suggest that, rather than being a “transitional” period or a “hiatus” in regional occupation, the Initial Late Formative period was a distinct mode of sociality characterized by the realignment and expansion of interaction networks, on the one hand, and rejection of the decorative aesthetics, monumentality, and public-oriented performances of earlier periods, on the other. We argue that the Late Formative period centers emerging after ~AD 120 intentionally cited architecture and aesthetics that were distant in time and space, constituting a sophisticated political strategy. Finally, these data suggest that the chronological schemata we use to build regional histories often obscure social variability.
Italian vermouth on the international market (1890–1960): a success story
Authors: Mazzotti Omar , Maffi Luciano , Magagnoli Stefano
Published: January 2025

This article examines the causes and geographical trajectories of the globalisation of vermouth, one of the most famous Made in Italy products in the world. Of all the fortified wines, vermouth stands out for its unique history. Originally a product of Piedmont consumed mainly by the aristocracy and the emerging bourgeoisie, vermouth became the subject of a growing export trade between the nineteenth and twentieth centuries, gaining credibility thanks to the prizes won at international exhibitions and the marketing strategies of the main companies in the sector (Martini & Rossi, Carpano, Gancia, Cinzano). Despite the commercial difficulties it experienced in the twentieth century as a result of protectionist measures, the effects of war, the heterogeneous policies applied to the alcoholic beverage industry and widespread imitation and counterfeiting, vermouth has managed to maintain an appeal that has made it an international icon and one of the most resilient products in the medium to long term. This is partly the result of a media representation that was capable of deeply influencing the collective imagination of consumers.
Sport at the Conjuncture: Sport History, Sexual Abuse, and Resistance
Authors: Ross MacIntosh , Di Gravio Michael , Abu-Jazar Aram , Drozdowsky Daniel S.
Published: January 2025

Stuart Hall stated “the university is a critical institution or it is nothing.” When it comes to the historical study of sexual abuse in Canadian sport, until very recently, it has been very much the latter. Nothing. As part of a larger project on studies of sexual abuse in sport, we reviewed articles across the four leading sport history journals – Sport History Review, Sport in History, Journal of Sport History, and International Journal of the History of Sport – to consider what methods, sports, and demographics received the most analysis. Such an effort proved impossible. There was scholarly silence on the matter. But this raised another question. So what? Would publishing in pay-walled academic journals about so pressing a societal issue make any difference at all? Furthermore, can a PhD-touting academic – including the lead author of this paper – ever enact change via the field of history if their sole purpose is to churn out studies for the ivory tower? We think not. It requires boots on the ground. Engagement and collaboration with those Antonio Gramsci called “organic intellectuals,” so we can tend the flames of knowledge and fuel a movement. History can be the tool one wields. Public, digital history.
In Defence of the Best Interest Standard: A Fiduciary Duty
Authors: Pringle Schuyler
Published: January 2025

Looking at Canadian provincial pediatric health care policies and laws, the best interest standard (BIS) enjoys support. Within philosophy, however, the BIS faces serious opposition. Granted, there remain a few fervent defenders of the BIS in the contemporary literature; however, I argue that while some authors nominally defend the BIS, my analysis reveals that what they really defend is at best a watered down version of it. In this article, I argue that not only must the BIS be understood narrowly, but a substitute decision-maker (SDM) must satisfy the BIS — for an SDM is her patient's fiduciary.
MacIntyrean Ethics and Lessons About Teleological Ethical Theories
Authors: Wall Edmund
Published: January 2025

Alasdair MacIntyre’s moral approach is ranked among the very important formulations in contemporary philosophical ethics. Yet, MacIntyre and his commentators have overlooked basic requirements of teleological ethical theories (end- or goal-oriented ethical theories). In the article, we will see just where MacIntyre has erred in constructing his Aristotelian-Thomist teleological moral approach, the most fundamental error being his failure to pursue and develop ultimate ends. MacIntyre’s moral approach, which heroically attempts to combine basic ancient and medieval foundational elements while assigning social practices a prominent role in shaping moral thinking, fails to provide a determinate teleological justificatory foundation.
Pierre d'Auriol et la théorie des deux sujets de l'intellection. Une lecture d'Averroès
Authors: Moaté Laura
Published: January 2025

La noétique de Pierre d'Auriol présente une théorie originale de l'intention, en partie fondée sur une relecture de la thèse des deux sujets de l'intellection prônée par Averroès. Auriol pose que l'intention possède deux sujets, mais varie dans le schéma qu'il produit en se confrontant aux difficultés qu'entraîne son affirmation. Cet article propose de tracer la genèse, les développements et les conséquences de cette théorie.
Are tropical oceanic islands overlooked? Knowledge gaps regarding the vulnerability of amphibians to global anthropogenic threats
Authors: Auguste Renoir J. , Deacon Amy E. , Hulme Mark F.
Published: January 2025

Climate and land-use changes are major threats to amphibian conservation. However, amphibians on tropical oceanic islands appear to have been overlooked with regards to their vulnerability to global anthropogenic threats. Here we examine whether there are gaps in research evaluating the vulnerability of tropical oceanic island amphibians to climate and land-use changes. We carried out a systematic review of the literature on experimental studies published during 1 July 1998–30 June 2022, to evaluate whether there are knowledge gaps in relation to geographical scope, taxonomic representation, life stage assessment, the factors affecting amphibians and how species and populations respond to these factors. Of 327 articles on climate change and 451 on land-use change, the research of only 18 was carried out on tropical oceanic islands, only on anurans, and < 20% of the authors were affiliated with an oceanic island institution. These 18 studies were on only five islands, and the range of families and life stages assessed was limited. We also found uneven research into the factors affecting oceanic island amphibians and their responses; analyses involving the effect of temperature on amphibian range expansion or contraction were the most common, with few studies of the effects of salinity. The scarcity and unevenness of research from oceanic islands limit our understanding of the effects of climate and land-use changes on amphibians. We discuss potential reasons for these knowledge gaps and recommend ways to address them, such as more equitable distribution of resources and provision of training and research opportunities for island-based biologists.
Climate Migration and the Right to Exclude
Authors: Boscov-Ellen Dan
Published: January 2025

Much mainstream political philosophy assumes that states have a broad right to decide who is granted entry and membership into their political community. On this conventional view, admission of migrants and refugees is understood as mostly a matter of general humanitarian duty or voluntary beneficence rather than as a specific obligation of justice. Through an analysis of climate-related migration from Central America's Dry Corridor to the United States, I argue that many such migrants may in fact be owed admission as reparation for injustice, and that the character of this injustice raises broader challenges for the conventional view.
Ukraine's Challenge to Europe: The EU as an Ethical and Powerful Geopolitical Actor
Authors: Vachudova Milada Anna , Koval Nadiia
Published: January 2025

In this essay, we bridge the gap between two understandings of the power of the European Union (EU): as a normative actor, guided by ethical principles and empowered by the internal market, and as a geopolitical actor, building its own military capabilities and ready to defend its interests through deterrence and defense. In view of Russia's invasion of Ukraine, we challenge the established “values vs. interests” dichotomy and argue that defending liberal democratic values is an essential foundation of the EU's existing and potential geopolitical power. We show how, over the last decade, opting for short-term expediency and capitulating to a kind of realpolitik “regime indifference” in dealings with authoritarian regimes at home and abroad have severely weakened the EU and also diminished Ukraine's capacities to defend itself as it fights for these shared values on the battlefield. We argue that it is in the EU's strategic interest to strengthen its commitment to values-based foreign and defense policies, revive a meritocratic and credible enlargement process, and work with the United States to provide more effective military assistance to Ukraine in its fight for liberal democratic values and a rules-based European security order.
SARS-CoV-2 infection and vaccination status in six ethnic groups in Amsterdam, The Netherlands, May to November 2022
Authors: Campman Sophie L. , Boyd Anders , Schinkel Janke , Coyer Liza , Agyemang Charles , Galenkamp Henrike , Koopman Anitra D.M. , Chilunga Felix P. , Koopsen Jelle , Zwinderman Aeilko H. , Jurriaans Suzanne , Stronks Karien , Prins Maria
Published: January 2025

We studied severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and vaccination status among six ethnic groups in Amsterdam, the Netherlands. We analysed participants of the Healthy Life in an Urban Setting cohort who were tested for SARS-CoV-2 spike protein antibodies between 17 May and 21 November 2022. We categorized participants with antibodies as only infected, only vaccinated (≥1 dose), or both infected and vaccinated, based on self-reported prior infection and vaccination status and previous seroprevalence data. We compared infection and vaccination status between ethnic groups using multivariable, multinomial logistic regression. Of the 1,482 included participants, 98.5% had SARS-CoV-2 antibodies (P between ethnic groups = 0.899). Being previously infected and vaccinated ranged from 41.5% (95% confidence interval (CI) = 35.0–47.9%) in the African Surinamese to 67.1% (95% CI = 59.1–75.0%) in the Turkish group. Compared to participants of Dutch origin, participants of South-Asian Surinamese (adjusted odds ratio (aOR) = 3.31, 95% CI = 1.50–7.31)), African Surinamese (aOR = 10.41, 95% CI = 5.17–20.94), Turkish (aOR = 3.74, 95% CI = 1.52–9.20), or Moroccan (aOR = 15.24, 95% CI = 6.70–34.65) origin were more likely to be only infected than infected and vaccinated, after adjusting for age, sex, household size, trust in the government’s response to the pandemic, and month of study visit. SARS-CoV-2 infection and vaccination status varied across ethnic groups, particularly regarding non-vaccination. As hybrid immunity is most protective against coronavirus disease 2019, future vaccination campaigns should encourage vaccination uptake in specific demographic groups with only infection.
From Contextualism to Contrastivism in Moral Theory
Authors: Sinnott-Armstrong Walter
Published: January 2025

In Morality by Degrees, Alastair Norcross presents contextualist accounts of good and right acts as well as harm and free will. All of his analyses compare what is assessed with “the appropriate alternative,” which is supposed to vary with context. This paper clarifies Norcross's approach, distinguishes it from previous versions of moral contextualism and contrastivism, and reveals difficulties in adequately specifying the context and the appropriate alternative. It also shows how these difficulties can be avoided by moving from contextualism to a kind of contrastivism that does not claim that any alternative is or is not appropriate or relevant.
Technological Innovations in the Context of Ukraine’s National Security Before a Full-scale Invasion
Authors: Zhelibo Ievgen , Sahaidak Iryna , Chorna Tetiana , Demianchuk Galyna , Bykhovchenko Valentyna
Published: January 2025

This article presents the critical importance of technological progress in strengthening Ukraine’s national security. It examines the intersection of technology, economic growth, and societal wellbeing, highlighting the role of innovation and investment in this context. The main objective is to analyse how technological modernization and a shift towards an innovative economic model can strengthen national security. The study uses a mixed-methods approach, combining qualitative and quantitative analyses, historical, and comparative methods to evaluate the impact of factors such as governance, economic systems, and emerging threats, including extremism, on national security. This multifaceted strategy offers a comprehensive understanding of internal and external influences on security dynamics. The findings suggest that national resilience against security threats is dependent on technological innovation. Additionally, it is important to effectively address non-conventional threats and adapt to global trends. This article argues that national security in the modern era is multifaceted and requires a comprehensive strategy that integrates technological innovation with economic and social policies. It suggests that a proactive approach towards innovation and investment can significantly contribute to safeguarding national interests in a rapidly changing global landscape.
Family and carer experiences of advanced care planning processes and outcomes
Authors: Whiteford Gail , Curley Dan , Mooney Graeme , Kinsman Leigh , Lower Tony , Hobbs Megan
Published: January 2025

Objectives

Despite practice development in the area of advanced care planning (ACP) and systems wide changes implemented to support ACP processes, there has been a paucity of research which has addressed the experiences of a key stakeholder group – family and carers – as they navigate their way through these often very challenging processes. The study described in this article focussed on this key group.

Methods

In-depth qualitative interviews were undertaken with family members and carers in a regional area of Australia in order to illuminate their lived experiences of ACP processes.

Results

Thematic analysis of the narrative data yielded 4 key themes: Being overwhelmed on the ACP journey; unifying effects of completing and using an advanced care directive (ACD); experiencing the highlights and lowlights of care; and paying it forward in advice to staff, carers and families.

Significance of Results

The ACP journey is unique for each carer/family and can be overwhelming. Whilst he lived experiences of families/carers indicated that the quality of care received was of a high standard, feedback to staff suggested their communications be timelier and more empathic. All participants in this study reported benefitting from engaging in ACP early and appreciated support to do so. All benefitted from the preparation of an ACD and found the outcomes (in terms of concordance) gratifying.
Granville Sharp’s Ancient Constitution: Legal Argument and Antislavery Thought
Authors: Connolly Jonathan
Published: January 2025

This article examines the role of legal argument in late eighteenth-century antislavery thought by subjecting Granville Sharp’s legal writing to detailed scrutiny. Much scholarship on law and antislavery in the British context justifiably focuses on the meaning of Lord Mansfield’s 1772 ruling in Somerset’s Case. Adopting a different approach, this article reads Sharp’s antislavery jurisprudence expansively, as an effort to fashion legal and political ideals. In so doing, it shows that Sharp’s legal writing was part of a broader project aimed at associating antislavery with a particular conception of national identity. Examining Sharp’s wide-ranging analysis of statute and common law, the article further argues that Sharp developed a form of natural-rights constitutionalism, melding the radical cause of abolition with the notion of tradition. Finally, the article explains how Sharp’s jurisprudence promoted an ideologically important vision of abolitionism as a distinctively modern form of progress. In short, the article argues that Sharp’s legal writing should be read not only in relation to Somerset but also as a means of understanding the character of antislavery thought and its relation to wider currents in eighteenth-century radicalism.
Vision and method in global historical sociology
Authors: Go Julian , Lawson George
Published: January 2025

Recent years have seen the development of a range of approaches concerned with theorizing and empirically demonstrating the significance of “transboundary entanglements” – patterns of connections between and across social sites. This work, spanning disciplines from sociology to international relations, and including subfields from postcolonial scholarship to global history, seeks to transcend the methodological nationalism associated with much preexisting historical social science by examining how, and with what effect, transboundary entanglements are formed and transformed over time. To date, however, the rich theoretical and substantive contributions made by these approaches have not been matched by comparable attention to the methodological principles and transposable procedures that can be used to analyze transboundary entanglements. This article contributes to this task. We make the case for a principle we call “global methodological relationalism” and explore how this principle can be operationalized through a three-step procedure: first, track relations across a boundary; second, follow these relations over time and across cases to establish variation; and third, provide an explanation of this variation. We highlight sites of overlap and contrast with existing methods for case selection, tracing historical processes, and making causal claims in small-N research, and establish the ways in which a “global historical sociology” oriented around “global methodological relationalism” can assess the significance of “transboundary entanglements.”
A feasibility study on using soft insoles for estimating 3D ground reaction forces with incorporated 3D-printed foam-like sensors
Authors: Willemstein Nick , Sridar Saivimal , van der Kooij Herman , Sadeghi Ali
Published: January 2025

Sensorized insoles provide a tool for gait studies and health monitoring during daily life. For users to accept such insoles, they need to be comfortable and lightweight. Previous research has demonstrated that sensorized insoles can estimate ground reaction forces (GRFs). However, these insoles often assemble commercial components restricting design freedom and customization. Within this work, we incorporated four 3D-printed soft foam-like sensors to sensorize an insole. To test the insoles, we had nine participants walk on an instrumented treadmill. The four sensors behaved in line with the expected change in pressure distribution during the gait cycle. A subset of this data was used to identify personalized Hammerstein–Wiener (HW) models to estimate the 3D GRFs while the others were used for validation. In addition, the identified HW models showed the best estimation performance (on average root mean squared (RMS) error 9.3%,

$ {R}^2 $

=0.85 and mean absolute error (MAE) 7%) of the vertical, mediolateral, and anteroposterior GRFs, thereby showing that these sensors can estimate the resulting 3D force reasonably well. These results were comparable to or outperformed other works that used commercial force-sensing resistors with machine learning. Four participants participated in three trials over a week, which showed a decrease in estimation performance over time but stayed on average 11.35% RMS and 8.6% MAE after a week with the performance seeming consistent between days two and seven. These results show promise for using 3D-printed soft piezoresistive foam-like sensors with system identification regarding the viability for applications that require softness, lightweight, and customization such as wearable (force) sensors.
Partizipation in der Klinik für Kinder- und Jugendpsychiatrie und -psychotherapie
Authors: Nolkemper Daria , Doering Bettina K. , Schroth Jennifer , Hausmann Tom , Zerbe Paul-Simon , Kölch Michael , Bienioschek Stefanie
Published: January 2025

Zusammenfassung: Fragestellung: Partizipation und Mitbestimmung sind ein wichtiges Recht von Kindern und Jugendlichen. Die vorliegende Studie untersuchte Diskrepanzen zwischen Wunsch und Erleben von Partizipation in der kinder- und jugendpsychiatrischen und -psychotherapeutischen Behandlung, ihren Zusammenhang mit der Behandlungszufriedenheit und die Frage, welche patient_innenbezogenen Variablen mit den berichteten Diskrepanzen in Zusammenhang stehen. Methode: Insgesamt 40 Kinder und Jugendliche aus teil- und vollstationären Gruppen berichteten anhand eines standardisierten Fragebogens zu ihrem Erleben von Partizipation und ihrem Wunsch nach Mitbestimmung. Weiterhin wurden soziodemographische und krankheitsbezogene Variablen sowie Persönlichkeitsstile erhoben. Ergebnisse: Die Befragten erlebten in allen Bereichen weniger Partizipation als sie sich wünschten. Die höchste Differenz fand sich in der Skala der persönlichen Freiheiten, welche inhaltlich die Kommunikation mit Familie und Freund_innen abbildet. Die Persönlichkeitsmerkmale „ahnungsvoll-schizotypisch“ und „loyal-abhängig“ hingen signifikant positiv mit der Differenzvariable zusammen. Je größer die Differenz zwischen Wunsch und Erleben von Partizipation, desto geringer war die Behandlungszufriedenheit. Schlussfolgerung: Kinder und Jugendliche wünschen sich mehr Partizipation als sie erleben. Flexible Konzepte erscheinen sinnvoll, um insbesondere im Bereich der persönlichen Freiheiten die Differenz zwischen Wunsch und Erleben von Partizipation zu verringern. Insbesondere bei Patient_innen mit den Persönlichkeitsmerkmalen „ahnungsvoll-schizotypisch“ und „loyal-abhängig“ sollte auf eine stärkere Einbindung geachtet werden.
Do Responsibility Attributions Mediate the Relationship Between Narcissism and Unforgiveness in Intimate Relationships?
Authors: Ryan Kathryn M. , Sprechini Gene , Beery Susan H. , Watsula Amanda
Published: January 2025

Abstract: Three studies explored the influence of grandiose and vulnerable narcissism on negative responsibility attributions and unforgiveness following a conflict in an intimate relationship. We tested Morf and Rhodewalt’s (2001a , 2001b ) Dynamic Self-Regulatory Processing Model of Narcissism. In the first two studies, participants were primarily heterosexual college students in a serious dating relationship and both types of narcissism were examined. The first study involved participants’ self-nominated biggest conflict. The second study involved an agreed-upon conflict. The third study attempted a conceptual replication of the actor effects found in the first two studies by testing mediation models with narcissism, negative responsibility attributions, and unforgiveness in a larger, convenience sample of MTurk workers. The first two studies showed gender differences suggesting that responsibility attributions either partially or fully mediated the relationship between grandiose narcissism and unforgiveness in males. The pattern of results for females was different in the first two studies. The third study showed that responsibility attributions partially mediated the relationship between all three forms of narcissism (grandiose narcissism, vulnerable narcissism, and entitlement) and unforgiveness in males and females supporting the Dynamic Self-Regulatory Processing Model of Narcissism.
Exploring Causal Relationships and Adjustment Timescales of Aerosol‐Cloud Interactions in Geostationary Satellite Observations and CAM6 Using Wavelet Phase Coherence Analysis
Authors: Zhou Xiaoli , Painemal David , Gettleman Andrew , Feingold Graham
Published: January 2025

We present for the first time within the cloud physics context, the application of wavelet phase coherence analysis to disentangle counteracting physical processes associated with the lead‐lag phase difference between cloud‐proxy liquid water path (LWP) and aerosol‐proxy cloud droplet number concentration (Nd) in an Eulerian framework using satellite‐based observations and climate model outputs. This approach allows us to identify the causality and dominant adjustment timescales governing the correlation between LWP and Nd. Satellite observations indicate a more prevalent positive correlation between daytime LWP and Nd regardless of whether LWP leads or lags Nd. The positive cloud water response, associated with precipitation processes, typically occurs within 1 hr, while the negative response resulting from entrainment drying, usually takes 2–4 hr. CAM6 displays excessively rapid negative responses along with overly strong negative cloud water response and insufficient positive response, leading to a more negative correlation between LWP and Nd compared to observations.
Ice‐kNN‐South: A Lightweight Machine Learning Model for Antarctic Sea Ice Prediction
Authors: Lin Yongcheng , Yang Qinghua , Li Xuewei , Dong Xiaoran , Luo Hao , Nie Yafei , Wang Jiuke , Wang Yiguo , Min Chao
Published: January 2025

Accurately predicting Antarctic sea ice on a subseasonal‐to‐seasonal scale remains a challenge for current numerical models, partly due to imperfect model parameterizations and the extensive computational resources required. Here, we have developed a lightweight machine learning model, Ice‐k‐nearest neighbor (kNN)‐South, to predict Antarctic sea ice concentration anomaly (SICA) up to 90 days in advance. The lightweight sea ice prediction model can be executed efficiently with limited computational resources. Compared with anomaly persistence, climatology, and the European Centre for Medium‐Range Weather Forecasts predictions, the Ice‐kNN‐South exhibits improved performance for almost 90 lead days, as evaluated by the mean absolute error (MAE), anomaly correlation coefficient (ACC), and integrated ice edge error (IIEE). Besides, the improvements of Ice‐kNN‐South are more pronounced in regions with high SICA variability by implementing a multi‐scale structure that combines field‐to‐field and grid‐to‐grid predictions. Furthermore, Ice‐kNN‐South shows the most significant enhancement in predictive skill during the summer and autumn seasons, particularly in summer. In contrast, relatively smaller enhancements are observed in the West Pacific Ocean and the Ross Sea during winter and spring. Even during the years of minimum sea ice areas (SIAs) in 2017, 2022, 2023, and 2024, Ice‐kNN‐South accurately captures sea ice variations, maintaining monthly averaged SIA errors below 8.5% compared to satellite observations within a 30‐day lead time. These findings suggest a potential approach to improve the accuracy of Antarctic sea ice predictions, particularly for the use of data‐driven models.
VCP downstream metabolite glycerol-3-phosphate (G3P) inhibits CD8+T cells function in the HCC microenvironment
Authors: Cheng Cheng , Zha Qingrui , Sun Linmao , Cui Tianming , Guo Xinyu , Xing Changjian , Chen Zhengxiang , Ji Changyong , Liang Shuhang , Tao Shengwei , Chu Junhui , Wu Chenghui , Chu Qi , Gu Xuetian , Zhang Ning , Fu Yumin , Deng Shumin , Zhu Yitong , Wang Jiabei , Liu Yao , Liu Lianxin
Published: January 2025

CD8+T cells within the tumor microenvironment (TME) are often functionally impaired, which limits their ability to mount effective anti-tumor responses. However, the molecular mechanisms behind this dysfunction remain incompletely understood. Here, we identified valosin-containing protein (VCP) as a key regulator of CD8+T cells suppression in hepatocellular carcinoma (HCC). Our findings reveal that VCP suppresses the activation, expansion, and cytotoxic capacity of CD8+T cells both in vitro and in vivo, significantly contributing to the immunosuppressive nature of the TME. Mechanistically, VCP stabilizes the expression of glycerol-3-phosphate dehydrogenase 1-like protein (GPD1L), leading to the accumulation of glycerol-3-phosphate (G3P), a downstream metabolite of GPD1L. The accumulated G3P diffuses into the TME and directly interacts with SRC-family tyrosine kinase LCK, a critical component of the T-cell receptor (TCR) signaling pathway in CD8+T cells. This interaction heightens the phosphorylation of Tyr505, a key inhibitory residue, ultimately reducing LCK activity and impairing downstream TCR signaling. Consequently, CD8+T cells lose their functional capacity, diminishing their ability to fight against HCC. Importantly, we demonstrated that targeting VCP in combination with anti-PD1 therapy significantly suppresses HCC tumor growth and restores the anti-tumor function of CD8+T cells, suggesting synergistic therapeutic potential. These findings highlight a previously unrecognized mechanism involving VCP and G3P in suppressing T-cell-mediated immunity in the TME, positioning VCP as a promising upstream target for enhancing immunotherapy in HCC.
Skeletal abnormalities caused by a Connexin43R239Q mutation in a mouse model for autosomal recessive craniometaphyseal dysplasia
Authors: Fujii Yasuyuki , Okabe Iichiro , Hatori Ayano , Sah Shyam Kishor , Kanaujiya Jitendra , Fisher Melanie , Norris Rachael , Terasaki Mark , Reichenberger Ernst J. , Chen I-Ping
Published: January 2025

Craniometaphyseal dysplasia (CMD), a rare craniotubular disorder, occurs in an autosomal dominant (AD) or autosomal recessive (AR) form. CMD is characterized by hyperostosis of craniofacial bones and metaphyseal flaring of long bones. Many patients with CMD suffer from neurological symptoms. The pathogenesis of CMD is not fully understood. Treatment is limited to craniofacial surgery. Here, we report a knock in (KI) mouse model for AR CMD carrying a Cx43R239Q mutation. Cx43

KI/KI
mice replicate typical features of AR CMD, including thickening of craniofacial bones, club-shaped femurs, and widened diaphyseal cortical bones. Female Cx43

KI/KI
mice display remarkably more bone overgrowth than male Cx43

KI/KI
mice as they age. In contrast to Cx43

+/+
littermates, Cx43

KI/KI
mice exhibit periosteal bone deposition and increased osteoclast (OC) numbers in the endosteum of long bones. Although formation of resting OCs in Cx43

+/+
and Cx43

KI/KI
mice is comparable, the actively resorbing Cx43

KI/KI
OCs have reduced resorption on bone chips. Cx43

KI/KI
mice display reduced osteocyte dendrites. RNA from Cx43

KI/KI
femoral cortical bones show reduced expression levels of Sost, Tnf-α, IL-1β, Esr1, Esr2, and a lower Rankl/Opg ratio. Moreover, the Cx43R239Q mutation results in altered spatial expression of Cx43 protein and mild reduction of gap junction and hemichannel activity. The distinct phenotype seen in Cx43

KI/KI
mice but not in Cx43 ablation models suggests that Cx43 loss-of-function is unlikely the main cause of AR CMD. Additional studies are required to investigate new roles of CMD-mutant Cx43.
Computational design of highly signalling-active membrane receptors through solvent-mediated allosteric networks
Authors: Chen K.-Y. M. , Lai J. K. , Rudden L. S. P. , Wang J. , Russell A. M. , Conners K. , Rutter M. E. , Condon B. , Tung F. , Kodandapani L. , Chau B. , Zhao X. , Benach J. , Baker K. , Hembre E. J. , Barth P.
Published: January 2025

Protein catalysis and allostery require the atomic-level orchestration and motion of residues and ligand, solvent and protein effector molecules. However, the ability to design protein activity through precise protein–solvent cooperative interactions has not yet been demonstrated. Here we report the design of 14 membrane receptors that catalyse G protein nucleotide exchange through diverse engineered allosteric pathways mediated by cooperative networks of intraprotein, protein–ligand and –solvent molecule interactions. Consistent with predictions, the designed protein activities correlated well with the level of plasticity of the networks at flexible transmembrane helical interfaces. Several designs displayed considerably enhanced thermostability and activity compared with related natural receptors. The most stable and active variant crystallized in an unforeseen signalling-active conformation, in excellent agreement with the design models. The allosteric network topologies of the best designs bear limited similarity to those of natural receptors and reveal an allosteric interaction space larger than previously inferred from natural proteins. The approach should prove useful for engineering proteins with novel complex protein binding, catalytic and signalling activities.
Efficient and accurate determination of the degree of substitution of cellulose acetate using ATR-FTIR spectroscopy and machine learning
Authors: Rhein Frank , Sehn Timo , Meier Michael A. R.
Published: January 2025

Multiple linear regression models were trained to predict the degree of substitution (DS) of cellulose acetate based on raw infrared (IR) spectroscopic data. A repeated k-fold cross validation ensured unbiased assessment of model accuracy. Using the DS obtained from 1H NMR data as reference, the machine learning model achieved a mean absolute error (MAE) of 0.069 in DS on test data, demonstrating higher accuracy compared to the manual evaluation based on peak integration. Limiting the model to physically relevant areas unexpectedly showed the
$${\hbox {C}{-}\hbox {H}}$$
peak to be the strongest predictor of DS. By applying a n-best feature selection algorithm based on the F-statistic of the Pearson correlation coefficient, several relevant areas were identified and the optimized model achieved an improved MAE of 0.052. Predicting the DS of other cellulose acetate data sets yielded similar accuracy, demonstrating that the developed models are robust and suitable for efficient and accurate routine evaluations. The model solely trained on cellulose acetate was further able to predict the DS of other cellulose esters with an accuracy of
$$\approx 0.1-0.2$$
in DS and model architectures for a more general analysis of cellulose esters were proposed.
Classifying tumour infiltrating lymphocytes in oral squamous cell carcinoma histopathology using joint learning framework
Authors: Barua Barun , Chyrmang Genevieve , Bora Kangkana , Ahmed Gazi N. , Kakoti Lopamudra , Saikia Manob Jyoti
Published: January 2025

Oral squamous cell carcinoma (OSCC) is the most common form of oral cancer, with increasing global incidence and have poor prognosis. Tumour-infiltrating lymphocytes (TILs) are recognized as a key prognostic indicator and play a vital role in OSCC grading. However, current methods for TILs quantification are based on subjective visual assessments, leading to inter-observer variability and inconsistent diagnostic reproducibility. Only a few studies have been conducted in automating TILs quantification for OSCC, existing methods use score-based systems that focus only on tissue-level spatial analysis, overlooking essential cellular-level information and do not provide TILs infiltration subcategories required for determining OSCC grading. To address these limitations, we propose OralTILs-ViT, a novel joint representation learning framework that integrates cellular and tissue-level information. Our model employs two parallel encoders: one extracts cellular features from cellular density maps, while the other processes tissue features from H&E-stained tissue images. This dual-encoder approach enables OralTILs-ViT to capture complex tissue-cellular interactions, classifying TILs infiltration categories consistent with Broders’ grading system-“Moderate to Marked”, “Slight” and “None to Very Less.” This approach reflects pathology practices and increases TILs classification accuracy. To generate cellular density maps, we introduce TILSeg-MobileViT, a multiclass segmentation model trained using a weakly supervised method, minimizing the need for manual annotation of cellular masks and overcoming the limitations of previous TILs assessment techniques. An extensive evaluation of our methodology demonstrates that OralTILs-ViT with the configuration (Adam,

$$\alpha$$

α

= 0.001) outperforms existing approaches, achieving 96.37% accuracy, 96.34% precision, 96.37% recall, and a 96.35% F1 score. Furthermore, TOPSIS analysis confirms that our method ranks first across all TILs infiltration categories. In summary, our proposed methodology outperforms single modality-representation learning approaches for accurate and automated TILs classification.
Functional genomic insights into Floricoccus penangensis ML061-4 isolated from leaf surface of Assam tea
Authors: Rungsirivanich Patthanasak , Parlindungan Elvina , Mahony Jennifer , Supandee Witsanu , Thongwai Narumol , van Sinderen Douwe
Published: January 2025

Floricoccus penangensis ML061-4 was originally isolated from the leaf surface of an Assam tea plant (Camellia sinensis var. assamica) from Northern Thailand. To assess the functions encoded by the F. penangensis ML061-4 genome, gene identification and annotation were undertaken by in silico analysis. The complete genome of F. penangensis ML061-4 consists of single chromosome of 2,159,127 base pairs, containing a GC content of 33.2% and encompassing 2049 predicted protein-encoding genes. A total of 1195 genes (58.0%) in the F. penangensis ML061-4 genome have assignable functions based on BlastKOALA analysis. Furthermore, 1235 genes (59.9%) were classified into six KEGG functional categories with 187 associated pathways, while 1419 genes (68.8%) were assigned a putative function by the Clusters of Orthologous Groups (COGs) database. The ML061-4 genome was evaluated for genes associated with complex carbohydrate metabolism, bacterial adhesion, virulence factors, pathogenicity, bacteriophages, antiviral defence systems as well as toxin- and antibiotic-resistance associated genes, and genes involved in toxin production, secondary metabolite biosynthesis and xenobiotics biodegradation. The obtained results support the notion of F. penangensis ML061-4 being safe for biotechnological and food industry purposes. This is the first report outlining functional genomic insights regarding a member of the genus Floricoccus.
Novel relatives of Mecsek Mountains mammarenavirus (family Arenaviridae) in hedgehogs living in different sampling areas in Hungary
Authors: Takáts Károly , Pankovics Péter , Balázs Benigna , Boros Ákos , Mátics Róbert , Reuter Gábor
Published: January 2025

Mammarenaviruses (genus Mammarenavirus, family Arenaviridae) are rodent-borne zoonotic viruses consisting of 52 viral species, including ten that are pathogenic to humans. Currently, only two endemic mammarenavirus species are known in Europe: the human pathogenic Mammarenavirus choriomeningitidis (LCMV) and the recently discovered hedgehog-origin Mammarenavirus mecsekense (MEMV). In this study, 59 faecal specimens from Northern white-breasted hedgehogs (Erinaceus roumanicus) from different geographic regions in Hungary were investigated for mammarenavirus presence and complete genome characterization using newly designed screening primers by RT-semi-nested PCR and sequencing methods. Five (8.5%) of the 59 samples tested positive for mammarenavirus RNA (ER8, ER15, ER27, ER33, and ER39, GenBank accession numbers PQ441959-PQ441968). The L- and S-segments of these strains showed 66–93% and 73–92% nt identity to the closest known mammarenavirus, MEMV, respectively. The NP protein exhibited 86–97% aa sequence identity compared to the corresponding protein of MEMV. Notably, the S-segment intergenic region (S-IGR) of strains ER8, ER15, ER27 and ER33 exceeded the average nt length among known mammarenaviruses and contained two, highly similar stem-loop structures with conserved self-complementary nucleotide motifs. Based on the sequence- and phylogenetic analysis these strains (ER8, ER15, ER27 and ER33) potentially represent a novel mammarenavirus species, tentatively named Pannonia mammarenavirus (PANV).
AHNAK2: a potential diagnostic biomarker for pancreatic cancer related to cellular motility
Authors: Zardab Mohamed ,   Barts Pancreas Tissue Bank, Roberts Rhiannon , Hughes Christine , Imrali Ahmet , Saad Amina , Chelala Claude , Grose Richard P. , Kocher Hemant M.
Published: January 2025

Pancreatic ductal adenocarcinoma lacks suitable biomarkers for early diagnosis of disease. In gene panels developed for early diagnosis of pancreatic cancer, high AHNAK2 mRNA expression was one possible biomarker. In silico analysis of published human sample datasets (n = 177) and ex vivo analysis of human plasma samples (n = 30 PDAC with matched 30 healthy control) suggested AHNAK2 could be a diagnostic biomarker. At a plasma level of 421.47 ng/ml, AHNAK2 could potentially diagnose PDAC with a specificity and sensitivity of 83.33% and 86.67%. In vitro analysis suggests that in cell lines with diffuse cytoplasmic distribution of AHNAK2, there was colocalization of AHNAK2 with Cortactin in filipodia. This colocalization increased when cells were cultured on substrates such as Fibronectin and Collagen, as well as in hypoxia, and resulted in an augmented invasion of cancer cells. However, in cell lines with a vesicular AHNAK2 staining, such changes were not observed. Our study posits AHNAK2 as a valuable diagnostic biomarker in PDAC, now demanding prospective validation. Determination of mechanisms regulating AHNAK2 subcellular localisation may help explain its biological role.
Novel euthanasia technique for zebrafish using electric shock in standard group housing aquaria
Authors: Saarinen Ulla , Sundell Erika , Sneddon Lynne , Gräns Albin
Published: January 2025

Zebrafish are widely used in research, accounting for approximately 50% of all laboratory fish across Europe. Due to their rapid reproduction and aging, effective and practical euthanasia methods are necessary for managing large stocks. This study investigated whether adult zebrafish can be euthanised by delivering an electrical current directly via the water in their housing aquaria. For this, portable plate electrodes were developed for 3.5 and 8.0 L Tecniplast™ housing aquaria. Our results show that adult zebrafish can be euthanised in groups (5 fish per litre) with electrical fields and current densities of at least 6 or 7 VRMS cm−1, and 0.7 or 0.8 ARMS dm−2 in 3.5–8 L aquaria, respectively, when delivered for 30 s in water at 28 °C with a conductivity of 800 µS cm−1 at 50 Hz. If widely implemented, this technique could improve the welfare of the vast number of zebrafish used across the world.
Analytical protocol for measuring micro-molar quantities of sulfur volatile species in experimental high pressure and temperature fluids
Authors: Secchiari Arianna , Toffolo Luca , Recchia Sandro , Tumiati Simone
Published: January 2025

Validating thermodynamic models is essential in experimental geosciences for exploring increasingly complex systems and developing analytical protocols. However, investigating solid–fluid equilibria in mm3-sized experimental capsules poses several challenges, particularly in sulfur-bearing chemical systems. These include maintaining bulk fluid composition and performing quantitative analysis with extremely low amounts of synthesized fluid. We present an innovative methodology for measuring ultra-low amounts of sulfur volatiles (H2S and SO2) generated during experimental runs at high pressure and temperature conditions of 3 GPa and 700 °C. Using solid sulfides (FeS + FeS2) and water as reactants, we performed redox-controlled syntheses employing a piston cylinder apparatus. We demonstrate that ex-situ measurements of these fluids by quadrupole mass spectrometry ensure accurate and precise analysis, confirming predicted thermodynamic compositions. This methodology allows in-depht investigation of sulfide solid–fluid equilibria, shedding light on sulfur volatiles behavior and geochemical cycles under high P–T conditions characteristic of the Earth’s interior.
Analytical nuclear gradient and derivative coupling theories for multireference perturbation methods
Authors: Park Jae Woo
Published: January 2025

This perspective aims to provide an easy-to-follow review of analytical gradient theories. We also briefly review the practical applications of these methods.
Synthesis of robust yet flexible and transparent CPA hydrogels inspired by molting crab shells
Authors: Zao Yamei , You Muqiu , Ma Jieru , Du Xiaoyu , Jin Yongcan , Li Dagang , Xu Zhaoyang , Chen Chuchu
Published: January 2025

Robust yet flexible and transparent CPA hydrogels, which mimic the structure and composition of molting crab shells and have great properties, are obtained by constructing a 3D ChMNF network with the incorporation of stable ACC and protein-like PAA.
The rise of mRNA therapeutic vaccines
Authors: Du Jinlu , Fan Ziling , Huang Jiangming , Li Zhengyuan , Hu Hongguo , Li Yanxia
Published: January 2025

The development of mRNA therapeutic vaccine products is reviewed.
Synthesis and applications of conjugated main-chain charged polyelectrolytes
Authors: Huang Hai-Yan , Fan Dongyang , Wang Dong , Han Ting , Tang Ben Zhong
Published: January 2025

The synthetic methods and applications of conjugated main-chain charged polyelectrolytes (CMCPs) with different cationic structures are summarized in this review to facilitate the development of more diversified CMCPs with advanced functionalities.
Carbon dots with red emission as nanoprobe for sensing of heparin in biofluids and pharmaceutical samples
Authors: Safarpoor Mohammad , Dinarvand Rassoul , Ghaedi Mehrorang , Asfaram Arash
Published: January 2025

Schematic presentation for selective detection of HEP by R-CDs.
First-principles predictions of two-dimensional Ce-based ferromagnetic semiconductors: CeF2 and CeFCl monolayers
Authors: Hu Y. , Song Y. L. , Huang Y. H. , Cao S. Y. , Yang Y.
Published: January 2025

The CeFCl monolayer is a ferromagnetic bipolar semiconductor with stable semiconducting features and high Curie temperature.
Study on the Brill transition of polyamide 6 with different crystal forms using low- and high-frequency Raman spectroscopy
Authors: Gao Jiacheng , Sato Harumi
Published: January 2025

A newly identified band at approximately 60 cm−1 for α-form PA6 is investigated using Raman spectroscopy and attributed to backbone rotational motion through QCC. This rotational motion serves as a driving force for the Brill transition.