bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Digital Game‐Based Learning on Student's Problem‐Solving Ability: A Three‐Level Meta‐Analysis
Authors: Cai Zhihui , Zhang Xin , Liu Caiyan , Zhan Jieni
Published: February 2025

Background

Problem‐solving ability is an important skill for students to develop in the 21st century. Many previous studies have focused on the impact of diverse digital educational games on problem‐solving ability. However, there is inconsistency in the findings, with some studies reporting positive effects of digital game‐based learning (DGBL) on problem‐solving ability, while others either found no significant improvement or reported negative effects.

Objectives

The objective of this study was to conduct a three‐level meta‐analysis to investigate the influence of DGBL on problem‐solving ability. Additionally, the study aimed to examine various moderating factors to explore the potential sources of inconsistency among the primary studies.

Methods

Through a systematic literature search, 21 primary studies were identified, encompassing a total of 60 effect sizes. The analysis involved assessing the effectiveness of DGBL in enhancing students' problem‐solving ability and examining heterogeneity among the studies. Moderator analysis was also conducted to explore the impact of different factors on the effectiveness of DGBL.

Results and Conclusions

The results indicated that DGBL could effectively enhance students' problem‐solving ability (g = 0.654), with significant heterogeneity observed among studies (Q = 858.358, p < 0.001). Furthermore, our findings suggested that studies focusing on the perception of problem‐solving ability (g = 1.498) yielded significantly larger effect size compared to studies focused on problem‐solving skill (g = 0.440). Moreover, combining relevant teaching strategies with DGBL (g = 1.246) resulted in a significantly better effect compared to using DGBL alone (g = 0.399). The analysis of moderating factors revealed that the effect size was significantly influenced by teaching strategy and problem‐solving construct. Other examined moderating factors did not show significant effects on the inconsistent findings.
Accuracy of CAD/CAM Technology in Fabricating Custom Post‐and‐Core Restorations: A Comparative Analysis
Authors: Mourouzis Petros , Dionysopoulos Dimitrios , Tolidis Kosmas
Published: February 2025

Objective

This study aims to compare the accuracy of various intraoral scanners and traditional analog impressions in scanning root canals for CAD/CAM post‐fabrication.

Methods

A dental mannequin with a factory‐made #21 tooth root canal was used to simulate clinical settings. Three intraoral scanners were tested: CEREC Primescan, TRIOS 3, and CEREC Omnicam. The inEos X5 desktop scanner provided high‐resolution control images. The analog impression polyvinyl siloxane (PVS) material was used with custom trays, following standard protocols. The surface areas were measured with CAD software and compared with the desktop scanner's reference.

Results

Primescan demonstrated the highest accuracy among the intraoral scanners, followed by Trios 3 and Omnicam. Significant differences were found between each scanner and the true surface area. The analog impression method demonstrated superior accuracy compared with intraoral scanners; however, this high precision is attributed to irregularities in the silicone material.

Conclusions

The analog impression method was more accurate in capturing the details of complex root canal anatomy; however, material irregularities can affect its clinical efficacy. Intraoral scanners showed high accuracy but had some limitations in capturing complex geometries. Further development of scanner technology will increase precision and, therefore, the clinical outcome.

Clinical Significance

The use of CAD/CAM technology and intraoral scanners offers potential for precise, custom‐fit post‐and‐core restorations.
Ultra‐Processed Foods and Dietetic Practice: Findings From a Survey and Focus Group With UK Dietitians
Authors: Moran Veronica , Moore Sally G. , Ho Peter
Published: February 2025

Background

Food processing converts fresh food into products and is of interest to nutrition professionals including dietitians given emerging evidence linking consumption of 'ultra‐processed' products with health.

Objective

To explore dietitians' professional practice around the topic of processed foods and health, including their perceptions of individual food products.

Methods

An online survey was developed to evaluate professional involvement, confidence and views using a 5‐point scale (i.e., 1 = never, 5 = daily). Respondents' perceptions of three products were also obtained, including level of processing (LoP) (from 1 = unprocessed to 5 = ultra‐processed) and recommended frequency of consumption (FoC) (from 1 = avoid to 5 = several times/day). Eligible survey respondents (UK dietitians) were recruited via the British Dietetic Association and social media. Data were analysed descriptively. A focus group was held with five dietitians to discuss current practice around this topic. Verbal data were thematically analysed.

Results

Survey respondents (n = 366) possessed an average of 13 ± 9.8 years practising across various specialisms. Most discussed (82%) and provided guidance on (77%) processed foods and health monthly or more frequently, with 'high' levels of confidence (61%–59%), and agreed that healthy diets may include processed (94%) or 'highly/ultra' processed (71%) foods. Perceptions of each individual food product varied, yet the largest proportion of respondents selected LoP and FoC options for Tinned tomatoes: 'minimally processed' (54%), 'several times/week' (69%); mycoprotein mince: 'highly/ultra‐processed' (57%), 'several times/month' (40%); and wholemeal bread: 'processed' (46%), 'several times/week' (58%). Focus group themes included uncertainties in definitions of ultra‐processed and negative consumer perceptions around processing.

Conclusion

This first survey of UK dietitians on processed foods suggests that dietetic practice frequently involves this topic and that views on the role of these foods in healthy diets are varied. Respondents also possessed a range of perceptions on the LoP of individual products, and further work is now warranted to support future development for dietetic practice.
Ganaxolone Reverses the Effect of Amyloid β‐Induced Neurotoxicity by Regulating the Liver X Receptor Expression in APP Transfected SH‐SY5Y Cells and Murine Model of Alzheimer's Disease
Authors: Divya  , Faruq Mohammed , Nazir Sheikh Sana , Kaushik Pooja , Parvez Suhel , Vohora Divya
Published: February 2025

Inhibiting β‐amyloid aggregation and enhancing its clearance are the key strategies in Alzheimer's disease (AD) treatment. Liver X receptors (LXRs) plays a crucial role in cholesterol homeostasis and inflammation, and their activation can clear Aβ aggregates in AD. Allopregnanolone, a neurosteroid, positively influences AD through LXR regulation, while ganaxolone, its synthetic analog, is known for its neuroprotective properties. This study explores the effect of ganaxolone on LXR activation and regulation of genes involved in mitigating Aβ toxicity and tauopathy in SH‐SY5Y cells transfected with APP695 Swe/Ind plasmid and an Aβ1–42 induced AD mouse model. Molecular docking stimulations indicated ganaxolone's binding and interaction with LXRβ. Subsequently, transfected neuronal cells exhibited increased mRNA levels of APP, TNF‐α and IL‐1β, decreased cell viability, reduced MMP and altered protein expression of Aβ, LXR, BCL‐2, APOE, ABCA1, along with increased levels of mROS, Bax, and caspase 3 activity. Ganaxolone treatment significantly abrogated Aβ‐induced effect in transfected neuronal cells by enhancing LXRβ expression, inducing LXR:RXR colocalization, thereby increasing APOE and ABCA1 expression. It also decreased tau mRNA levels in transfected cells. Importantly, in AD mice, ganaxolone ameliorated cognitive impairment, reduced Aβ toxicity, tau levels, and neuroinflammatory markers, restored mitochondrial function, and decreased neuronal apoptosis. Taken together, these novel results highlight the central role of LXR in mediating Aβ‐induced toxicity and provide preclinical evidence for ganaxolone as a potential agent to reduce toxicity in an LXR‐dependent manner. This may serve as a promising treatment strategy to slow or prevent neurodegeneration in AD patients.

image
Climate Change Adaptation: New Vistas for Management Research
Authors: Benischke Mirko H. , D'Ippolito Beatrice , Sharma Garima , Wickert Christopher
Published: February 2025

Climate change adaptation has for a long time been the neglected half of the climate equation, as most attention has been directed toward mitigation. Yet, the catastrophic effects of a changing climate are already occurring, unavoidable, and in many cases irreversible. Organizations need to identify ways of adapting to present and future climatic conditions. In this editorial, we make the case for climate change adaptation as a research topic on par with mitigation. We outline how and why management and organizational scholarship should work toward an integrated approach of mitigation and adaptation in responding to climate change, suggesting three key avenues of research for future inquiry. In so doing, we encourage more impactful and ecologically relevant management research that will make a difference to society at large.
A Study of Body Composition in Children Suffering From Infantile Vitamin B12 Deficiency
Authors: Vohra Viresh , Kaur Harvinder , Attri Savita Verma , Bharati Bhavneet , Kumar Pawan , Kesavan Shivan , Sankhyan Naveen
Published: February 2025

Background

Infantile tremor syndrome (ITS), or neurocutaneous infantile vitamin B12 deficiency syndrome (NIBS), is characterised by tremors, developmental delay, anaemia and skin hyperpigmentation. This study aimed to assess the body composition and serum lipids in children with ITS.

Methods

Children under 2 years of age with a clinical diagnosis of ITS were enrolled. Dietary history, developmental milestones and anthropometric data were recorded, along with blood tests for B12, homocysteine, lipid profile and blood counts.

Results

Of 50 children screened, 31 with a median age of 13 months were included. Most (80.6%) were from lower socio‐economic backgrounds. Limb tremors were observed in 51.6%, and all but one child had a developmental quotient (DQ) below 70, indicating significant developmental delays. Microcephaly was present in 35.4%, and moderate to severe anaemia was nearly universal. Growth parameters, including fat mass and fat‐free mass, were significantly lower in children with ITS compared to controls. Lipid profiles revealed consistently high triglycerides, low HDL and elevated LDL in most age groups, suggesting a pro‐atherogenic metabolic state.

Conclusion

Severe Infantile vitamin B12 deficiency significantly impairs head growth, overall development and body composition, with potential long‐term cardiovascular risks due to abnormal lipid profiles.
A Bottleneck Analysis of Iron and Folic Acid Supplementation Program in Pakistan
Authors: Ghur Anamta , Randhawa Soha , Shahid Namira , Ali Waffa , Ali Banafsha , Rashid Saroosh , Khan Ambreen , Babri Aman Akbar , Masood Khawaja , Shuja Saba , Fatima Maliha , Ali Noshad , Khan M. Imran , Turab Ali
Published: February 2025

Iron and folic acid deficiency is a significant public health concern, especially in low and middle‐income countries, particularly among women of reproductive age, leading to adverse maternal and child health outcomes. In Pakistan, approximately 41.7% of women of reproductive age have iron deficiency. For this research, we conducted 33 key informant interviews and 32 focus group discussions with stakeholders from all four provinces and the two federally administered regions of Pakistan for in‐depth and representative bottleneck assessment. The modified Tanahashi model was used to inform the determinant codes and for coding reliability thematic analysis using NVivo 14. On the supply side, barriers relate to effective forecasting, procurement, and distribution of Iron Folic Acid supplements to the recipients. The demand–supply gap widened due to the supply bottlenecks, impacting the community's trust in the frontline health worker. These factors were gravely impacted by the governance challenges of ensuring sustainable funds, minimizing bureaucratic and procedural delays, and eliminating political pressure. Affordability of Iron Folic Acid and conservative social norms influenced the demand and awareness of Iron Folic Acid and nutritional knowledge among the target population. The stakeholder recommendations emphasize the need for intersectoral collaboration, mass media campaigns, frequent capacity building and incentivizing of healthcare workers, engagement of key community stakeholders, digitizing the health system, improvement in supply chain mechanism, and investment in small‐scale innovative solutions.
Epigenomic Changes in Ostrinia Moths Under Elevated Pupal and Adult Temperature
Authors: Velikaneye Brittany A. , Kozak Genevieve M.
Published: February 2025

Epigenetic changes in the methylation of DNA may occur in response to environmental stressors, including warming climates. DNA methylation may also play an important role in regulating gene expression during both male and female reproduction in many insect species. However, it is currently unknown how DNA methylation shifts when individuals are reproducing under warmer temperatures. We exposed European corn borer moths (Ostrinia nubilalis) to heat during the pupal and adult life stages then investigated changes in DNA methylation across the genome using enzymatic methyl‐seq (EM‐seq). We compared methylation patterns in reproductive males and females exposed to heat (28°C) to those that experienced an ambient temperature (23°C). We found that heat exposure led to a small but significant increase in the percentage of methylated CpG sites throughout the genome in both sexes. However, DNA methylation rates were higher in females and differential methylation following heat exposure localised to unique regions in each sex. In males, methylation shifted within genes belonging to pathways including Hippo signalling, ubiquitin‐mediated proteolysis, DNA damage repair and spermatogenesis. In females, differential methylation occurred in genes related to histone modification and oogenesis. Our results suggest that DNA methylation patterns respond to moderate heat exposure in Lepidoptera and provide insight into epigenetic responses to heatwaves, suggesting novel pathways that may be involved in responding to heat stress during metamorphosis and reproduction.
REIMAGINE: A central nervous system basket trial showing safety and efficacy of vafidemstat on aggression in different psychiatric disorders
Authors: Ferrer Marc , Richarte Vanesa , Gisbert Laura , Xaus Jordi , Gutierrez Sonia , Arevalo Maria Isabel , Ropacki Michael , Bullock Roger , Buesa Carlos , Ramos‐Quiroga Josep Antoni
Published: February 2025

Aim

Vafidemstat is a brain‐penetrant, orally bioavailable, small molecule irreversible inhibitor of the histone lysine‐specific demethylase KDM1A (also known as LSD1), which corrects memory deficits and behavior alterations including aggression and social interaction deficits in preclinical models.

Methods

Here, we report the results of REIMAGINE, a phase IIa, single‐center, open‐label, one‐arm basket trial that evaluated the safety and efficacy of vafidemstat on aggression in adult patients with borderline personality disorder (BPD), attention‐deficit/hyperactivity disorder (ADHD), and autistic spectrum disorder (ASD). Participants received 1.2 mg/day of vafidemstat for 8 weeks.

Results

Vafidemstat was shown to be safe and well tolerated, and no drug‐related clinically significant adverse events were observed. Furthermore, all neuropsychiatric scales assessed showed notable efficacy signals, whether assessing agitation/aggression (Clinical Global Impression for Severity [CGI‐S] and Clinical Global Impression for Improvement [CGI‐I] and Neuropsychiatric Inventory [NPI] questionnaire for Agitation‐Aggression [NPI‐AA]), overall patient functioning (total NPI), or disease‐specific features (Attention‐Deficit/Hyperactivity Disorder Rating Scale [ADHD‐RS] and Borderline Personality Disorder Checklist [BPDCL]). Statistically significant improvements were observed in the aggregated data (all participants) and for each of the three disease groups independently. Changes were evident within the first 2 weeks of treatment.

Conclusion

In summary, the REIMAGINE study supports that vafidemstat is safe, well tolerated, and causes a significant and consistent reduction in agitation/aggression and nonaggression features in BPD, ADHD, and ASD. These data support continuing the development of vafidemstat as a new treatment option for these psychiatric disorders.
Evaluation of NANOG/HDAC1 Expression in Predicting Outcomes of BCG Therapy in Non‐Muscle Invasive Bladder Cancer
Authors: Yamashita Takahisa , Higashi Morihiro , Yamazaki Mami , Imada Hiroki , Takayanagi Natsuko , Shimizu Tomomi , Sawada Keisuke , Yamamoto Wataru , Murakami Chiaki , Nagata Marino , Kikuchi Yukina , Momose Shuji
Published: February 2025

Urinary bladder cancer includes non‐muscle invasive bladder cancer (NMIBC) and muscle invasive bladder cancer (MIBC). While patients with NMIBC have a better prognosis, NMIBC often recurs, requiring long‐term surveillance and repeated treatments. Intravesical Bacillus Calmette‐Guérin (BCG) therapy is standard for high‐grade or recurrent NMIBC; however, 30%–50% of patients failed to respond, and the mechanisms of resistance remain unclear. To identify predictive biomarkers for response to intravesical BCG therapy, we analyzed NANOG and Histone deacetylase 1 (HDAC1) expression in 90 bladder cancer specimens from NMIBC patients treated with BCG therapy using immunohistochemistry. The correlation between NANOG and HDAC1 expression and clinical outcomes, including response to BCG therapy, was assessed. High‐grade NMIBC cases showed significantly higher expression of NANOG and HDAC1 compared to low‐grade cases (p < 0.05). Additionally, elevated NANOG expression in combination with HDAC1, was associated with poor response to BCG therapy and decreased lymphocyte infiltration in the tumor‐microenvironment. NANOG is suggested to directly increases HDAC1 expression, which could suppress lymphocyte infiltration in the tumor microenvironment by altering immune‐related gene expression. These findings suggest that the NANOG/HDAC1 axis plays a key role in predicting resistance to intravesical BCG therapy in NMIBC.
Substitutability evaluation and resource utilization of non‐medicinal parts of Ardisia crenata Sims, a traditional ethnic medicine
Authors: Peng Jie , Liu Sha , Liu Fusong , Qin Lin , Wang Qian , He Yuqi , Zhang Delin , He Wenping , Ke Xinyue , Wu Faming , Wang Xiaoshuang
Published: February 2025

The severe scarcity of wild resources of Ardisia crenata Sims (AS) has greatly limited its current clinical and pharmaceutical applications. We aimed to demonstrate the substitutability of stems and leaves for AS roots. In this study, 28 local samples from the Guizhou Province of China were selected for a comprehensive comparison of quality markers, chemical composition and efficacy. HPLC analysis showed that both stems and leaves contained bergenin, the main active ingredient of AS. Metabolomics studies showed that the chemical composition of the three parts was 99% similar. Network pharmacology analysis showed that similar signalling targets including STAT3 and MAPK1, AKT1 and EP300, SRC and TP53, were targeted by three parts. Animal experiments further demonstrated that extracts from the three different parts of the plant relieved the pathological symptoms of acute pharyngitis, and decreased serum inflammatory factors, showing similar efficacy. In sum, these findings strongly proved that stems and leaves can be used as supplements or substitutes for roots, providing a powerful strategy to solve the problem of AS resource shortage and greatly promoting the optimal utilization of AS. The study also anticipated some additional benefits, including the expansion of natural sources of bergenin and the discovery of potential cancer‐related targets of AS.
Financial Inclusion, Digital Technology and Farmers' Well‐Being Nexus: Evidence From Rural of Xizang, China
Authors: Li Fanghua , Chandio Abbas Ali , Zang Dungang , Liu Haiyue
Published: February 2025

The paper examines the impact of financial inclusion on farmers' well‐being and the moderating role of digital technology in this relationship in rural areas of Xizang, China. It relies on transaction cost theory to equate utility with well‐being, using 2021 micro‐survey data from the region to address its objectives. The findings reveal a positive impact of financial inclusion on farmers' well‐being. To examine the moderating role of digital technology, the paper explores both internal and external embedding of digital technology. The findings indicate that the impact of external embedding is greater than that of internal embedding. Additionally, the paper provides evidence that financial inclusion significantly improves the well‐being of farmers in poverty‐eradicated and non‐elite rural groups, showing no indication of “favoring the rich over the poor” or “elite capture.” These findings provide new evidence for research on farmers' well‐being in underdeveloped regions.
Asymptotic Behavior of a Degenerate Forest Kinematic Model With a Perturbation
Authors: LI Lu , Cantin Guillaume
Published: February 2025

In this paper, we study the asymptotic behavior of the global solutions to a degenerate forest kinematic model, under the action of a perturbation modeling the impact of climate change. In the case where the main nonlinear term of the model is monotone, we prove that the global solutions converge to a stationary solution, by showing that the Lyapunov function derived from the system satisfies a Łojasiewicz–Simon gradient inequality. We also present an original algorithm, based on the Statistical Model Checking framework, to estimate the probability of convergence toward nonconstant equilibria. Furthermore, under suitable assumptions on the parameters, we prove the continuity of the flow and of the stationary solutions with respect to the perturbation parameter. Then, we succeed in proving the robustness of the weak attractors, by considering a weak topology phase space and establishing the existence of a family of positively invariant regions. At last, we present numerical simulations of the model and explore the behavior of the solutions under the effect of several types of perturbations. We also show that the forest kinematic model can lead to the emergence of chaotic patterns.
Holding It, Together: Beyond Bearing Witness and Burning Out
Authors: Sheese Kate
Published: February 2025

Concepts like vicarious trauma, burnout, compassion fatigue, and moral injury do important work in making suffering legible and enabling claims to recognition, acknowledgement, and care. Nonetheless, these conceptualizations have little to say about the nature of the suffering, the varied and ambiguous ways it is experienced, or the social, affective, political conditions that give rise to it. In this article I argue for taking up response‐ability as a lens for examining, understanding, and addressing the particular kinds of suffering experienced when registering and resisting violence, particularly in the face of complicity. Drawing on ethnographic work with activist volunteers in refugee camps, I explore what response‐ability, with its relational ontology, allows us to see, feel, understand about suffering that is otherwise out of view, obscured, or rendered unsayable, or even unfeelable. I discuss the ways in which response‐ability assumes complicity and requires grief/mourning and explore how these characteristics alter the possibilities and obligations for collective care and containment when intervening in crises and conflicts.
Characterisation of the Novel HLA‐DQB1*03:572 Allele by Next‐Generation Sequencing
Authors: Wanyan Zhang‐Xiang , Bian Cheng , Wang Xiao‐Hui , Zheng Zhong‐zheng , Yang Zhao‐Qing
Published: February 2025

HLA‐DQB1*03:572 differs from DQB1*03:01:01:01 by one nucleotide substitution at position 208G>T in exon 2.
Engaging Clinical Learners Asynchronously With Social Annotation for Case‐Based Discussions
Authors: Adamson Dylan T. , Kavalukas Sandra , Shaw M. Ann , Weingartner Laura A.
Published: February 2025

Background

Clinical educators are often challenged to sustain learner engagement beyond the clinical learning environment. A social annotation platform is an instructional tool typically used in bachelor's‐level and other nonmedical instructional settings to facilitate asynchronous discussions for reading assignments. This work aimed to promote asynchronous engagement among clinical learners by adapting a social annotation platform for case‐based learning.

Approach

We piloted a social annotation platform in a 4‐week surgical residency preparatory course with fourth‐year medical students. We designed four longitudinal clinical cases representing common scenarios that surgical interns may encounter. Students discussed each case section asynchronously on the platform by annotating case content and replying to peer discussion comments.

Evaluation

We measured engagement through activity on the platform and collected student perceptions through a postcourse evaluation survey. Nine students completed the residency preparatory course over 4 weeks in 2023. Engagement was high, with 95% of reading assignments completed. On average, students submitted nine discussion comments per assignment (three required) and spent 62 active minutes discussing each case section. Students engaged more overall with nonclinical topics. All students completed the postcourse survey and indicated that the platform was easy to navigate. Students appreciated being able to see peers' line of thinking through the case and reported feeling engaged with other students.

Implication

A social annotation platform may offer an effective tool for engaging clinical students asynchronously. This platform can be used in clinical education to provide instructional flexibility for faculty while helping students feel engaged with their peers and clinical curriculum.
The effects of resting time, centrifugation time, and technician training on plasma sample quantity and quality: Implications for the Dog Aging Project
Authors: Holland Sydney N. , Tinkle Amanda K. , Prescott Jena N. , Blattman Brianna L. ,   Dog Aging Project Consortium, Creevy Kate E. , Fajt Virginia R.
Published: February 2025

Background

The Dog Aging Project (DAP) is a large‐scale longitudinal study of aging in dogs. For some dogs in the DAP, blood samples for plasma isolation are collected by non‐DAP personnel. However, plasma samples are sometimes inadequate, which can lead to, for example, insufficient volume for assays.

Objective

We aimed to examine three factors that may affect plasma yield: resting time after sample collection, centrifugation time, and level of operator or technician training.

Methods

We designed three experiments using a convenience sample of five dogs. Each experiment varied one of the three factors and held the other two constant. Experiment 1 examined five different resting times: 10 min and 1, 4, 24, and 72 h. Experiment 2 compared centrifugation times of 7 and 14 min. Experiment 3 compared trained and untrained personnel. The sample resting was always under refrigeration. Experimental outcomes were total plasma volume, number of successful aliquots, hemolysis, and lipemia.

Results

A resting time of 72 h yielded statistically significantly lower plasma volume than resting times ≤4 h. Resting times of 24 and 72 h also had statistically significantly higher hemolysis scores compared with other resting time points. In addition, trained operators or technicians yielded an average of 0.5 more aliquots. Outcomes were similar by centrifugation time in Experiment 2.

Conclusion

To mitigate sample loss, we recommend shorter post‐collection resting times and ensuring technician proficiency. Additionally, increasing the requested whole blood volume may improve sample yield.
Underlying Mechanisms Controlling Wear of Ti6Al4V-SS316L Tribo-Pair at Varying Sliding Speed and Contact Area in Vacuum
Authors: Philip Jibin T. , Singh Kamini , Kailas Satish Vasu
Published: February 2025

In tribo-systems, tribological behavior is influenced by a combination of several mechanisms. Among them, plastic deformation mechanisms (PDMs) and tribo-chemical reactions (TCRs) are particularly significant. The article explores the role of these fundamental mechanisms during the dry sliding of a Ti6Al4V-pin against an SS316L disk. PDM was controlled by changing the sliding speed (0.01–1.5 ms−1). To explore the interdependence of TCR submechanisms, namely, the formation of a mechanically mixed layer (MML) and tribo-oxidation, the pin diameter was varied (2.1, 4.6, and 6.6 mm) while maintaining a constant vacuum environment and contact pressure. At low sliding speeds (0.01–0.3 ms−1), the high wear-rate and coefficient of friction (CoF) are due to the dominance of PDM, enabled by adiabatic shear banding (ASB). Within the sliding speed range of 0.3–0.7 ms−1, a durable and wear-resistant MML forms on the pin surface incorporating Fe transferred from the disk. As the MML attains its highest stable thickness (≈51 µm at 0.7 ms−1), the lowest values of wear-rate (18.15 × 10−4 mm3/Nm) and CoF (0.324) are observable. Above 0.7 ms−1, thermally induced phase transformation-assisted material softening leads to a substantial increase in wear-rate and CoF. The case is otherwise for the smallest pin (2.1 mm) sliding at 1.5 ms−1. As sliding speed increases, wear transitions from adhesion to mild abrasion and then to severe adhesion.
Experiencing the “Unpredictable Inevitables”: Creating Opportunities on a Taught Master’s Program for Structured One-to-One Physical Activity Behavior-Change Support for Adolescent Girls (The HERizon Project)
Authors: Wood Hannah Clare , Carey Laura , Cowley Emma S. , Cacciatore Isabella , Ballinger Jennifer , Glover Ellie , Gore Payal , Simpson Amelia , Wells Nicole , Mansfield Chiara , Whitcomb-Khan Gabriella , Watson Paula M.
Published: February 2025

This case study presents the experiences of MSc Sport Psychology students delivering a psychologically informed behavior-change intervention within the context of a PhD research project to develop their applied practice skills. We aimed to provide an example of how higher education providers can create such an opportunity for master’s students to conduct individualized support sessions in a safe and structured environment, while preserving the autonomy needed for professional growth. The placement was situated within the HERizon project (conducted between 2021 and 2022), an online physical activity behavior-change intervention for adolescent girls. MSc students worked as “Activity Mentors” and provided weekly one-to-one support for participants via video calls. In this case study, we reflect on what we learned as both students and supervisors responsible for the delivery of HERizon, both immediately after completing the project and 3 years after the experience, and offer recommendations for future practice.
Exploring the Path Between Life-Course Trajectories of Physical Activity Levels and Cardiometabolic Disease Incidence: Insights From the ATTICA Cohort Study (2002–2022)
Authors: Dimitriadis Nikos , Arnaoutis Giannis , Tambalis Konstantinos D. , Chrysohoou Christina , Barkas Fotios , Liberopoulos Evangelos , Sfikakis Petros P. , Pitsavos Christos , Tsioufis Costas , Panagiotakos Demosthenes
Published: February 2025

Objective: To evaluate the paths between lifelong physical activity levels and the development of cardiometabolic disease. Methods: The ATTICA is a population-based cohort study with a 20-year follow-up conducted in the Attica region, Greece and included, 3042 adult males and females (45 [11] y). Participants physical activity levels’ tracking together with data regarding cardiovascular disease, obesity, hypertension, hypercholesterolemia, and diabetes incidence, were available in 1988 participants (45 [12] y old, 987 males and 1001 females), at 20-year follow-up. Physical activity levels were evaluated using the validated International Physical Activity Questionnaire, in all examinations (2001–2002, 2006, 2012, and 2022). Four physical activity trajectories were defined, that is, consistently active/inactive and changed from active/inactive. Path analysis was applied using structure equation models. Results: 54% of participants were classified as always inactive, 5% classified as became inactive from physically active, 38% as became active and, only 3% sustained physical activity levels. Participants who reported being consistently physically active throughout the 20-year period were 6% (OR, 0.94, 95% CI, 0.89–0.99) less likely to develop cardiovascular disease as compared with those who remained consistently physically inactive, had 21% lower risk of developing hypercholesterolemia (OR, 0.79, 95% CI, 0.59–1.04), 33% lower risk of obesity (OR, 0.67, 95% CI, 0.44–1.02), and 30% lower risk of diabetes (OR, 0.70, 95% CI, 0.48–1.03). Conclusions: Lifelong physical activity was strongly associated with reduced fatal or nonfatal cardiovascular disease events, as well as reduced risk of developing other cardiometabolic disorders, hypercholesterolemia, obesity, and diabetes.
Listerin promotes α-synuclein degradation to alleviate Parkinson’s disease through the ESCRT pathway
Authors: Qin Fei , Cao Runyu , Cui Wenjing , Bai Xuemei , Yuan Jiahua , Zhang Yuling , Liu Yaxing , Cao Nan , Dong Na , Zhou Min , Chen Tian , Liu Feng , Sun Wanwei , Zheng Yi , Zhao Wei , Liu Bingyu , Gao Chengjiang
Published: February 2025

Parkinson’s disease (PD) is a neurodegenerative disorder characterized by the progressive accumulation of abnormal α-synuclein (α-syn) within dopaminergic neurons in the substantia nigra region of the brain. Despite excessive accumulation of α-syn being key to the pathogenesis of PD, the mechanisms governing its clearance remain elusive. In this study, we found that the endosomal sorting complex required for transport (ESCRT) system plays a crucial role in capturing and facilitating the degradation of ubiquitinated α-syn. The E3 ubiquitin ligase Listerin was found to promote K27-linked polyubiquitination of α-syn, directing it to the endosome for subsequent degradation. We showed that the deletion of the Listerin gene exacerbates the neurodegenerative progression in a mouse model of PD, whereas the overexpression of Listerin effectively mitigates disease progression in PD mice. Consequently, our study reveals a mechanism for α-syn degradation and identifies Listerin as a promising therapeutic target for the treatment of PD.
Targeted approach to determine the impact of cancer-associated protease variants
Authors: Bickenbach Kira , David Nele , Koudelka Tomas , Joos Corentin , Scharfenberg Franka , Rüffer Malina , Armbrust Fred , Georgiadis Dimitris , Beau Fabrice , Stahmer Lea , Rahn Sascha , Tholey Andreas , Pietrzik Claus , Becker-Pauly Christoph
Published: February 2025

Several steps of cancer progression, from tumor onset to metastasis, critically involve proteolytic activity. To elucidate the role of proteases in cancer, it is particularly important to consider single-nucleotide variants (SNVs) that affect the active site of proteases, thereby influencing cleavage specificity, substrate processing, and thus cancer cell behavior. To facilitate systematic studies, we here present a targeted approach to determine the impact of cancer-associated protease variants (TACAP). Starting with the semiautomated identification of potential specificity-modulating SNVs, our workflow comprises mass spectrometry–based cleavage specificity profiling and substrate identification, localization, and inhibitor studies, followed by functional analyses investigating cancer cell properties. To demonstrate the feasibility of TACAP, we analyzed the meprin β R238Q variant. This amino acid exchange R238Q leads to a loss of meprin β’s characteristic cleavage preference for acidic amino acids at P1′ position, accompanied with changes in substrate pool and inhibitor affinity compared to meprin β wild type.
Disentangling climate’s dual role in dengue dynamics: A multiregion causal analysis study
Authors: Cawiding Olive R. , Jeon Saebom , Tubera-Panes Donnabel , de los Reyes V Aurelio A. , Kim Jae Kyoung
Published: February 2025

Dengue fever poses major public health challenges, with climate change complicating control efforts. Yet, the full extent of climate change’s impact on dengue remains elusive. To investigate this, we used an advanced causal inference method to 16 diverse climatic regions in the Philippines. This method is capable of detecting nonlinear and joint effects of temperature and rainfall to dengue incidence. We found that temperature consistently increased dengue incidence throughout all the regions, while rainfall effects differed depending on the variation in dry season length, a factor previously overlooked. Specifically, our results showed that regions with low variation in dry season length experience a negative impact of rainfall on dengue incidence likely due to strong flushing effect on mosquito habitats, while regions with high variation in dry season length experience a positive impact, likely due to increased mosquito breeding sites. Our findings emphasize the need for tailored prevention strategies based on local climate conditions, rather than a one-size-fits-all approach.
Exogenous bacterial cellulose induces plant tissue regeneration through the regulation of cytokinin and defense networks
Authors: Ruiz-Solaní Nerea , Alonso-Díaz Alejandro , Capellades Montserrat , Serrano-Ron Laura , Ferro-Costa Miquel , Sanchez-Corrionero Álvaro , Rabissi Agnese , Argueso Cristiana T. , Rubio-Somoza Ignacio , Laromaine Anna , Moreno-Risueno Miguel A. , Coll Núria S.
Published: February 2025

Regeneration is a unique feature of postembryonic development extensively observed in plants. The capacity to induce regeneration exogenously is limited and usually confined to meristematic-like tissues. We show that bacterial cellulose (BC), but not other structurally similar matrixes, induces postwounding regeneration in nonmeristematic plant tissues via a distinctive route to callus-mediated regenerative programs. The BC-specific program involves cytokinin operating concurrently with strongly activated plant biotic response genes to induce plant regeneration. A reactive oxygen species (ROS) burst, normally associated with defense responses, is sustained upon BC application, involving a network of tightly interconnected transcription factors, where WRKY8, known for regulating stress responses, shows a clustering and hierarchical prevalence. WRKY8 regulates BC-mediated plant regeneration and ROS homeostasis, including superoxide anion accumulation, to potentially promote cell proliferation after wounding. Collectively, our results demonstrate that the cytokinin- and ROS-associated defense responses can be targeted by BC application to promote plant wound regeneration through alternative regenerative programs.
Self-supervised machine learning methods for protein design improve sampling but not the identification of high-fitness variants
Authors: Ertelt Moritz , Moretti Rocco , Meiler Jens , Schoeder Clara T.
Published: February 2025

Machine learning (ML) is changing the world of computational protein design, with data-driven methods surpassing biophysical-based methods in experimental success. However, they are most often reported as case studies, lack integration and standardization, and are therefore hard to objectively compare. In this study, we established a streamlined and diverse toolbox for methods that predict amino acid probabilities inside the Rosetta software framework that allows for the side-by-side comparison of these models. Subsequently, existing protein fitness landscapes were used to benchmark novel ML methods in realistic protein design settings. We focused on the traditional problems of protein design: sampling and scoring. A major finding of our study is that ML approaches are better at purging the sampling space from deleterious mutations. Nevertheless, scoring resulting mutations without model fine-tuning showed no clear improvement over scoring with Rosetta. We conclude that ML now complements, rather than replaces, biophysical methods in protein design.
Correlation-driven attosecond photoemission delay in the plasmonic excitation of C
60
fullerene
Authors: Biswas Shubhadeep , Trabattoni Andrea , Rupp Philipp , Magrakvelidze Maia , Madjet Mohamed El-Amine , De Giovannini Umberto , Castrovilli Mattea C. , Galli Mara , Liu Qingcao , Månsson Erik P. , Schötz Johannes , Wanie Vincent , Wnuk Pawel , Colaizzi Lorenzo , Mocci Daniele , Reduzzi Maurizio , Lucchini Matteo , Nisoli Mauro , Rubio Angel , Chakraborty Himadri S. , Kling Matthias F. , Calegari Francesca
Published: February 2025

Extreme light confinement in plasmonic nanosystems enables novel applications in photonics, sensor technology, energy harvesting, biology, and quantum information processing. Fullerenes represent an extreme case for nanoplasmonics: They are subnanometer carbon-based molecules showing high-energy and ultrabroad plasmon resonances; however, the fundamental mechanisms driving the plasmonic response and the corresponding collective electron dynamics are still elusive. Here, we uncover the dominant role of electron correlations in the dynamics of the giant plasmon resonance (GPR) of the subnanometer system C
60
by using attosecond photoemission chronoscopy. We find a characteristic photoemission delay of up to about 300 attoseconds that is purely induced by coherent large-scale electron correlations in the plasmonic potential. These results provide insights into the nature of the plasmon resonances in subnanometer systems and open perspectives for advancing nanoplasmonic applications.
MAGE-A4 induces non–small cell lung cancer and tumor-promoting plasma cell accumulation
Authors: Armstrong Dominique , Chang Cheng-Yen , Hong Monica J. , Green Linda , Shen Yichao , Hudson William , Mauk Kelsey E. , Song Li-Zhen , Jammi Sheetal , Casal Benjamin , Burns Brianna , Creighton Chad J. , Carisey Alexandre , Zhang Xiang H.-F. , McKenna Neil J. , Kang Sung Wook , Lee Hyun-Sung , Decker William , Corry David B. , Kheradmand Farrah
Published: February 2025

Adaptive immunity is critical in eliminating tumors, but cancer-intrinsic factors can subvert this function. Melanoma antigen-A4 (MAGE-A4), a cancer-testis antigen, is expressed in solid tumors and correlates with poor survival, but its role in tumorigenesis and antitumor immunity remains unclear. We found that expression of MAGE-A4 was highly associated with the loss of
PTEN
, a tumor suppressor, in human non–small cell lung cancers (NSCLC). Here, we show that constitutive expression of human
MAGE-A4
with
Pten
loss in mouse airway epithelia results in metastatic adenocarcinoma. Tumors showed distinct enrichment in IgA
+
CD138
+
CXCR4
+
plasma cells (PCs) and increased expression of CXCL12 in endothelial cells. Consistently, human NSCLC expressing MAGE-A4 showed increased CD138
+
IgA
+
PCs surrounding tumors. Abrogation of PCs decreased tumor burden, increased activated T cell infiltration, and reduced CD163
+
CD206
+
macrophages in the MAGE-A4–induced lung tumors. These findings suggest MAGE-A4 promotes NSCLC tumorigenesis, in part, through the recruitment and retention of IgA
+
PCs in the lungs.
Diffuse scattering from correlated electron systems
Authors: Osborn Raymond , Pelc Damjan , Krogstad Matthew J. , Rosenkranz Stephan , Greven Martin
Published: February 2025

The role of inhomegeneity in determining the properties of correlated electron systems is poorly understood because of the dearth of structural probes of disorder at the nanoscale. Advances in both neutron and x-ray scattering instrumentation now allow comprehensive measurements of diffuse scattering in single crystals over large volumes of reciprocal space, enabling structural correlations to be characterized over a range of length scales from 5 to 200 angstroms or more. When combined with new analysis tools, such as three-dimensional difference pair-distribution functions, these advanced capabilities have produced fresh insights into the interplay of structural fluctuations and electronic properties in a broad range of correlated electron materials. This review describes recent investigations that have demonstrated the importance of understanding structural inhomogeneity pertaining to phenomena as diverse as superconductivity, charge density wave modulations, metal-insulator transitions, and multipolar interactions.
Tumor extracellular vesicle–derived PD-L1 promotes T cell senescence through lipid metabolism reprogramming
Authors: Ma Feiya , Liu Xia , Zhang Yuanqin , Tao Yan , Zhao Lei , Abusalamah Hazar , Huffman Cody , Harbison R. Alex , Puram Sidharth V. , Wang Yuqi , Peng Guangyong
Published: February 2025

The limited success of cancer immunotherapy has posed challenges in treating patients with cancer. However, promising strides could be made with a deeper understanding of the factors that cause T cell dysfunction within the tumor microenvironment and by developing effective strategies to counteract tumor-induced immune suppression. Here, we report that tumor-derived extracellular vesicles (tEVs) can induce senescence and suppression in T cells. Programmed death ligand 1 (PD-L1), a key component within tEVs, induced DNA damage and hyperactive lipid metabolism in both human and mouse T cells. This caused an elevated expression of lipid metabolic enzymes and an increase in cholesterol and lipid droplet formation, leading to cellular senescence. At a molecular level, PD-L1 derived from tEVs activated the cAMP-response element binding protein (CREB) and signal transducer and activator of transcription (STAT) signaling, which promoted lipid metabolism and facilitated senescence in human and mouse T cells. Inhibiting EV synthesis in tumors or blocking CREB signaling, cholesterol synthesis, and lipid droplet formation in effector T cells averted the tEV-mediated T cell senescence in vitro and in vivo in cell adoptive transfer and melanoma mouse models. The same treatments also bolstered the antitumor efficacy of adoptive transfer T cell therapy and anti–PD-L1 checkpoint immunotherapy in both human and mouse melanoma models. These studies identified mechanistic links between tumor-mediated immune suppression and potential immunotherapy resistance, and they provide new strategies for cancer immunotherapy.