bluuebunny/crossref_metadata_2025 huggingface dataset:
Long-Term Changes in Parameters of Bone Quality in Kidney Transplant Recipients Treated with Denosumab
Authors: Pollastri Francesco , Fassio Angelo , Ferraro Pietro Manuel , Andreola Stefano , Gambaro Giovanni , Spasiano Andrea , Caletti Chiara , Stefani Lisa , Gatti Matteo , Fabbrini Paolo , Rossini Maurizio , Galvagni Isotta , Gatti Davide , Adami Giovanni , Viapiana Ombretta
Published: February 2025

Kidney transplant recipients (KTRs) have an elevated fracture risk. While dual-energy X-ray absorptiometry (DXA) is commonly used to assess areal bone mineral density (aBMD), it does not capture all aspects of bone quality. We investigated the long-term effects on bone DXA-derived indices of bone quality in KTRs treated with denosumab and untreated with denosumab. This is a retrospective study, including KTRs treated with denosumab and untreated age and sex-matched KTR controls. DXA-derived parameters, including trabecular bone score (TBS) and 3D-DXA parameters, were measured at the lumbar spine and femur at baseline and after four years. Hierarchical linear models were used to assess the between-group effect of treatment over time, also adjusting for site-specific aBMDs. We enrolled 23 KTRs treated with denosumab and 23 KTR denosumab-untreated KTRs. Significant between-group differences over time in favor of the denosumab group were observed for TBS (0.843, 95%CI 0.439; 1.248,p < 0.001), trabecular volumetric BMD at the total hip (Tb.vBMD TH) (13.492, 95%CI 1.707; 25.278, p = 0.003), cortical volumetric BMD at the femoral neck (Ct.vBMD FN) (28.766, 95%CI 8.373; 49.158, p = 0.008), cortical surface BMD at the total hip (c.sBMD TH) (10.507, 95%CI 4.140; 16.873,p = 0.002), cortical surface at the femoral neck (c.sBMD FN) (8.795, 95%CI 2.818; 14.771, p = 0.006), and cortical thickness at the total hip (Ct.th.TH) (0.075, 95%CI 0.020; 0.130, p = 0.010). After adjusting for BMD, the differences on TBS and Ct.vBMD FN and c.sBMD FN remained significant. Denosumab treatment in KTRs was associated with better outcomes in terms of bone quality and geometry parameters, independent of changes in aBMD.
Defining a minimum nodal yield for neck dissection in mucosal head and neck squamous cell carcinoma, a systematic review
Authors: Bassani Sara , Tesauro Paolo , Monzani Daniele , Molteni Gabriele
Published: February 2025

Background

Analysis of existing literature on lymph node yield (LNY) in neck dissection (ND) for head and neck squamous cell carcinomas (HNSCC) used as a prognostic factor and an indication of treatment adequacy.

Methods

PubMed, EMBASE and Web of Science databases were systematically searched from January 2010 to June 2023. Inclusion criteria encompassed studies on mucosal HNSCC patients undergoing ND with data on LNY and its association with survival outcomes. The quality assessment followed the REMARK guidelines.

Results

Among 29 included studies, minimum LNY tresholds associated with improved survival outcomes ranged from 10 to 36.5 nodes. The heterogeneity in subsite involvement and cN0/cN + status constituted a challenge in establishing a consensus cutoff. The review highlights the need for standardized surgical techniques and pathological assessments to ensure data comparability.

Conclusions

LNY is a prognostic indicator and could reflect ND quality in HNSCC.
Synthesis and Electron Spin Resonance Study of Zn0.7Ni0.3RE0.1Fe1.9O4 (RE = Gd, Sm, Dy) Nanostructured Ferrites
Authors: Masuku S. J. C. , Msomi J. Z. , Mahule T. S. , Srinivasu V. V.
Published: February 2025

The glycol-thermal technique synthesized Zn0.7Ni0.3RE0.1Fe1.9O4 (RE = 0, Gd, Sm, Dy) nanostructured ferrites with fine particles in the 8–13 nm range. X-ray diffraction (XRD) data confirmed a single-phase cubic spinel structure with no impurity peaks for the samples investigated. High-resolution transmission electron microscopy (HrTEM) showed nearly spherical particle images for the pure Zn0.7Ni0.3Fe2O4. HrTEM images for Zn0.7Ni0.3RE0.1Fe1.9O4 (RE = Gd, Sm, or Dy) rare-earth-substituted fine particles revealed agglomerated particles with irregular shapes. Reduced particle sizes of rare-earth-substituted Zn-Ni compared to undoped compounds have been explained based on electron–electron repulsion of 4f electrons. Electron spin dynamics were investigated by electron spin resonance (ESR) measurements. A broad ESR signal with the highest intensity has been observed for the Sm-doped compound (Zn0.7Ni0.3Sm0.1Fe1.9O4) with a particle size of about 8 nm. Broadening of the signal revealed stronger magnetic dipole interactions and narrower signals for Gd- and Dy-doped compounds indicate stronger superexchange interactions. The slightest ESR signal observed for the Gd-based (Zn0.7Ni0.3Gd0.1Fe1.9O4) compound has been attributed to high spin–orbit coupling and the paramagnetic nature of Gd ions disrupting magnetic resonance. The evolution of the magnetic parameters, such as signal line width, intensities, and g-factors, as a function of the type of rare-earth ions, has been presented and correlated with the outer 4f electron number of rare-earth ions and particle size. Rare-earth-doped Zn0.7Ni0.3RE0.1Fe1.9O4 (RE = Gd, Sm, Dy) nanostructured ferrites exhibit enhanced magnetic and structural properties, critical for advanced applications such as magnetic separation and biomedical imaging. This study demonstrates the influence of rare-earth doping on ESR parameters, particle size, and magnetization, providing insights into the role of 4f electron configurations.
Beyond the BRCA1/2 genes in ovarian cancer: the role of germline pathogenic variants in the ATM gene
Authors: Guadagnolo Daniele , Minucci Angelo , Chiavassa Antonella , Gentile Gabriella , Salvatori Francesca , Khaleghi Hashemian Nader , Maneri Giulia , Piane Maria , Grotta Simona , Grammatico Paola , Pizzuti Antonio , Santini Daniele , De Marchis Laura
Published: February 2025

Background

Ovarian Cancer (OC) prevention and early-stage detection represents a challenge due to the lack of effective surveillance. The identification of high-risk women is crucial as it provides access to prophylactic oophorectomy and reduces disease burden. Next-Generation Sequencing approaches enable the investigation of several genes associated with monogenic hereditary cancer predisposition, including ovarian cancer. For family members of patients affected by ovarian cancer without identification of a germline pathogenic variant, despite the increased empirical risk (3 times) of ovarian cancer incidence, prophylactic surgery is not indicated but may be suggested as the only efficient strategy.

Methods and Results

We hereby present 2 cases of OC in which a germline heterozygous pathogenic variant in the ATM gene was identified: the first in the contest of Hereditary Breast and Ovarian Cancer (HBOC) family history and, in the other one, a late onset of neoplasms, to underline the importance of defining guidelines and management of moderate penetrance genes variants also for ovarian cancer prevention.

Conclusions

Carriers of heterozygous pathogenic variants in the ATM gene have an increased risk of neoplasms incidence, mostly breast but also of OC with an absolute estimated risk of 2–3 times greater than the general population. For these patients there is not well-established evidence of benefit in risk reducing bilateral Salpingo-oophorectomy.
Moral certainty, deep disagreement, and disruption
Authors: Hermann Julia
Published: February 2025

Wittgenstein’s On Certainty has been a source of inspiration for philosophers concerned with the notion of deep disagreement (see Fogelin in Informal Logic 25(1):3–11, 2005; Pritchard in Topoi 40:1117–1125, 2021. https://doi.org/10.1007/s11245-018-9612-y). While Wittgenstein’s examples of certainties do not include moral certainties, some philosophers have argued that an analogy can be drawn between certainty regarding the empirical world and moral certainty (Goodman in Metaphilosophy 13:138–148,1982; Hermann in On moral certainty, justification, and practice: A Wittgensteinian perspective, Palgrave Macmillan, Basingstoke, 2015; Pleasants in Inquiry 51(3):241–267, 2008. https://doi.org/10.1080/00201740802120673). Moral certainty manifests itself in our fundamental ways of feeling, thinking, and acting morally. It is closely related to an “agreement in form of life” (Wittgenstein in Philosophical investigations, Translated by G.E.M. Anscombe. Third ed., Basil Blackwell, Oxford, 1968, § 241.), which makes moral disagreements possible in the first place. In this paper, I aim to shed light on the phenomenon of moral deep disagreement by relating it not only to the notion of moral certainty but also to the concept of deep disruption as it is currently developed and discussed in the philosophy of technology. I argue that certainty, deep disagreement, and deep disruption are all located at the level of “bedrock practices” (Williams in Wittgenstein, mind and meaning, Routledge, Milton Park, 1999, p. 198), and that the fundamentality of their objects should be understood in terms of relationality and interconnectedness. Deep disagreements can occur through deep technology-induced disruption and can take the form of a disruption of deep conceptual agreement. Conceptual common ground can be re-established by continuous interaction and a collective process of moral articulation. Deep disruption and moral deep disagreement can lead to moral progress, for instance in the form of recognising and correcting an epistemic injustice.
Retheorizing Archaeological “Artefacts” as “Belongings”
Authors: Pitblado Bonnie L. , Thomas Suzie , Wessman Anna , Woodward Sophie
Published: February 2025

In this article, we suggest that archaeologists should recognise the limitations of the term “artefact”, because it does not capture the many ways that diverse groups think about and interact with such objects. There are two important reasons for doing this. First, as we show through numerous examples, archaeologists’ conception of portable material objects as “artefacts” is narrow and unlikely to align with the conceptions by the people who left them behind. Second, like the terms “prehistory” and “human remains”, “artefact” is a settler-colonialist construct that elevates Western scientific jargon above terminology that other stakeholders may see as more respectful or appropriate. As an alternative to the term “artefact”, this article explores “belongings” as a way to open up understandings of the many different meanings associated with archaeological objects and to refer more inclusively to them in diverse contexts.
Informationsschatz aus Umweltproben
Authors: Wyler Emanuel , Landthaler Markus
Published: February 2025

Our environment is a treasure trove of genetic information. High-throughput sequencing enables a spectrum of investigations, from observing human pathogens to assessing the constitution of an ecosystem. Here, we summarize our work on longitudinal total RNA/DNA sequencing from wastewater samples combined with in-depth data analysis. We explore the wealth of data from known virus detection to discovery of novel biotechnological enzyme sequences, showcasing the potential of such systematic approaches.
(t)RNA-Seq: mehr als nur Sequenzierung
Authors: Kolberg Tim , Hoffmann Anne , Mörl Mario , Stadler Peter F.
Published: February 2025

With Next Generation Sequencing, technical advances in the field of nucleic acid sequencing enabled access to the entire transcriptome of organisms. However, the variety of information available in RNA-seq data exceeds mere sequence information. Specific RNA molecules, as well as their modification patterns or their spatial structure, can be addressed using customized biochemical and bioinformatic methods, providing deep insights into regulatory processes at transcriptome level.
Illegal reintroductions of lynx are irresponsible and the wrong path forward for rewilding in Scotland
Authors: Whitehead Toryn
Published: February 2025

In January 2025 four Eurasian lynx (Lynx lynx) were illegally released into the Cairngorms National Park in the Scottish Highlands. All four animals were subsequently captured but unfortunately one lynx died overnight. While the conservation community has widely condemned the unknown perpetrators, possibly guerrilla rewilders, little attention has been given to why illegal releases are damaging. Here I outline the three main social-cultural reasons as to why an illegal reintroduction is irresponsible - 1) a breakdown in dialogue and trust; 2) the negative implications for conflict and coexistence; and 3) the spread of misinformation and politicisation – and the disproportionate benefits of a legal reintroduction. Scotland’s history is already littered with illicit releases which have damaged trust and sparked human-wildlife conflicts which otherwise may have been avoided or mitigated. Without patience, empathy, and dialogue to co-produce a reintroduction plan and coexistence strategies, any legal reintroduction of lynx is doomed to fail – let alone an illegal release.
Spatio-temporal exposure risk estimation for COVID-19 using social network analysis and mobile phone data
Authors: Pedro Cumbane Silvino , Gidófalvi Győző
Published: February 2025

The COVID-19 pandemic highlighted the critical role of human mobility in disease transmission. Understanding and anticipating spatio-temporal exposure risk is crucial for effective public health interventions. Although various mobility datasets have been explored, the potential of anonymized Call Detail Records (CDRs), combined with social network analysis, remains largely untapped for exposure risk estimation. This study investigates the use of social network analysis for estimating spatio-temporal exposure risk, using anonymized Call Detail Records (CDRs) from Mozambique to model human mobility patterns. The study focuses on three centrality measures: weighted in-degree centrality, improved in-degree centrality, and weighted PageRank. Daily origin–destination matrices constructed from CDRs are used to build directed-weighted networks representing human flow between provinces and districts. The exposure risk scores derived from these measures are compared against a risk score calculated from daily COVID-19 case data and the time-varying reproduction number. Results at the province level show that while all three centrality measures reveal similar trends in spatio-temporal exposure risk, weighted PageRank demonstrates the highest correlation with the COVID-19-based risk score. Poisson regression models, built to predict COVID-19 cases using the three centrality measures, further support the strong influence of exposure risk on the number of cases, with the weighted PageRank model showing the best predictive performance. The district-level analysis, focusing on the Greater Maputo area, used the distribution of Points of Interest (POIs) for validation. The results indicate that education, financial, and transport POIs correlate with exposure risk across all three centrality measures. In general, weighted PageRank consistently outperforms the other two measures in capturing exposure risk across most POI categories. The study concludes that CDRs, in conjunction with weighted PageRank, can effectively estimate spatio-temporal exposure risk, aiding decision-makers in implementing informed interventions to mitigate disease spread.
Beyond stable alliances: uncertainty at the dawn of Trump’s second act
Authors: Wiedekind Jakob , Böller Florian
Published: February 2025

Donald Trump’s successful bid for the White House in 2024, combined with the Republican Party’s unified control of Congress and a solid conservative majority on the Supreme Court, underscores a stark reality: the second coming of “Trumpism” may be more relentless than the first. While Trump’s initial presidency from 2017 to 2021 introduced a disruptive “America First” paradigm that already led to far-spread uncertainty in International Relations, his return now carries the force of unrestrained partisan alignment across all branches of the federal government. His return also buries any hopes in Europe for the US to pursue its traditional foreign policy role any time soon. This configuration has far-reaching implications for the global stage, sowing a profound sense of uncertainty among allies and partners, especially in Europe.
F-t joint distributions on real Siegel domains
Authors: Inoue Hiroto
Published: February 2025

In statistics, the homogeneous cones are considered as the general parameter spaces for variance matrices related with the graphical models. For the argument of probability distributions, the Wishart distributions are defined based on the analysis of homogeneous cones, as the image of the normal distributions by quadratic maps. Now, the parameter space of pairs of variance matrix and mean vector is identified with more general homogeneous domain, called the real Siegel domain. In the present work, we consider random variables valued in the real Siegel domain associated with the quadratic map of homogeneous cone, and derive their probability density functions via the transformation group. This derivation is also based on the analysis on homogeneous cones including the gamma and beta functions due to Gindikin. We call our result the F-t joint distribution on the real Siegel domain, since its marginal distributions give an extension of the F and t-distributions in 1-dimensional case. Especially, it enables us to describe a joint estimation and a simultaneous hypothesis testing for the pair of parameters of normal distribution.
The effect of combined oral contraceptive pills on angiogenesis in endometriotic lesions
Authors: Antonis Siampalis , Efthymia Papakonstantinou , Maria Keramida , Eleftherios Panteris , Sotiris Kalogeropoulos , Neoklis Georgopoulos , Fuminori Taniguchi , George Adonakis , Tasuku Harada , Apostolos Kaponis
Published: February 2025

Purpose

Neoangiogenesis is necessary for adhesion and invasion of endometriotic lesions. We hypothesize that by blocking angiogenetic pathways we can suppress endometriosis. Oral contraceptive pills (OCs) are routinely used in endometriosis to suppress symptoms of the disease. In the current study, we attempt to evaluate the effects of OCs on various angiogenetic factors in women with endometriosis.

Methods

Sixty women with endometriosis were randomly divided into two groups. Group A consisted of 30 women who received OCs in a cyclical manner for 3 months before surgery and group B of 30 women who did not. Biopsy specimens of ovarian endometrioma were collected. We used qRT-PCR to study the mRNA expression levels of VEGF, TF, PAR-2, SP1, and FGF1.

Results

The levels of mRNA of all angiogenic factors were found to be elevated in women who received OCs compared with women who did not. This difference was statistically significant for VEGF, TF, FGF1, SP1 (p < 0.001), and PAR-2 (p = 0.046).

Conclusion

OC administration does not inhibit neoangiogenesis in endometriotic lesions; on the contrary, angiogenetic pathways might be upregulated.
Machine learning approach for predicting the compressive strength of biomedical waste ash in concrete: a sustainability approach
Authors: Kumar Rakesh , Karthik S. , Kumar Abhishek , Tantri Adithya , Shahaji  , Sathvik S.
Published: February 2025

This study investigates the effects of strength and durability of concrete for different water-cement ratios, aggregate contents, and partial replacement of biomedical waste ash at 5%, 10%, 15%, 20%, and 25% by weight of cement. At 7, 14, and 28 days, the control mix showed inferior mechanical properties, particularly compressive strength, compared to concrete mixtures containing Biomedical Waste Ash (BWA). The replacement of cement by 5% and 10% increased the compressive strength but it is decreasing from 15%. Additionally, BWA modified concrete demonstrated a slower water absorption rate and minimal weight loss under acid test curing conditions, indicating enhanced durability. The economic and environmental benefits of incorporating biomedical waste into concrete promote sustainable construction practices. Using three machine learning approaches—K-Nearest Neighbors (KNN), Random Forest (RF), and CatBoost—the compressive strength of concrete with biomedical waste ash was simulated. Cement, biomedical waste, water absorption, slump, and the water-to-cement ratio were key input variables. Among the models tested, the RF model emerged as the most accurate, with a predictive performance of R2 = 0.9945 and RMSE = 0.7080. Its unparalleled reliability, consistency, and accuracy in predicting compressive strength make it a top choice for this task.
Decoding urban heritage: a multi-dimensional analysis framework applied to Assiut’s historic core
Authors: Refaat Ahmed Mohamed
Published: February 2025

One of the challenges confronting urban conservation is the inclusion of heritage areas in the development process. While often seen as constraints, heritage areas represent promising opportunities to enhance city character and quality. Nevertheless, the inclusion of heritage areas in the development process is intricate, requiring an extensive analysis of the urban form of heritage areas to facilitate the inclusion process. From this stance, this paper proposes a comprehensive analytical framework for identifying the features and characteristics of heritage areas, using Assiut City in Egypt as a case study. The proposed framework addresses four interrelated dimensions of urban design: the morphological, the functional, the perceptual, and the social. Space syntax methodology, mainly axial mapping, is employed to analyze the urban pattern of Assiut’s Historic Core to disclose its spatial configuration and morphological features. The author will use Survey and field observation to address the heritage area’s functional, perceptual, and social features (33 respondents and five interviewees). Thus, this paper utilizes a mixed-methods approach, combining quantitative and qualitative techniques to provide a holistic understanding of the urban heritage area. Implications of the study are discussed in terms of the importance of including heritage areas in the development process and how the proposed analytical framework can contribute to revealing the features of urban areas in general and heritage areas in particular. Thus, policymakers and urban planners can map out the areas of improvement and development fostering inclusive, well-integrated urban regeneration and urban development of our cities.
The relationship between commodity diversification and the adoption of technological innovations for Southeast beef cattle producers
Authors: Berg Nikolas L. , Thayer Anastasia W. , De Figueiredo Silva Felipe , Vassalos Michael , Wang Zuyi , Smith Nathan B.
Published: February 2025

For almost eight decades, productivity in the United States agricultural sector has substantially increased, in large extent due to the adoption of technological innovations. Despite the increased utilization of technology, questions remain regarding which producers are more likely to adopt a greater number of technological innovations. This research seeks to understand how commodity diversification strategies, farm characteristics, producer perceptions of risk, conservation, information sources, climate adaptation, and producer demographic characteristics are associated with technology adoption among beef cattle producers in the Southeast United States. Utilizing data from an online survey and an Ordered Probit model, we show that beef cattle producers who also produce fruit have an increased probability of adopting a greater number of technologies. The opposite effect is found for other commodities such as vegetables, row crops, and other livestock. Policy recommendations are also discussed.
Zhongjiang Chinese
Authors: Rao Dongmei , Shaw Jason A.
Published: February 2025

Zhongjiang Chinese (中江话) is a variety of Mandarin Chinese, one of the ten language families in China (Mandarin, Cantonese, Xiang, Min, Gan, etc.,). Sometimes the term “Mandarin” is also used to refer to the national lingua franca “Putonghua”. We refer to the national lingua franca as “Standard Mandarin” and reserve the term Mandarin (官话) to refer to the language family, as distinct from other families, e.g., Cantonese, Xiang, Min, Gan, etc. Within Mandarin, Zhongjiang is a member of the Southwestern dialects (西南官话) (Language Atlas of China 1988). It is spoken in the urban areas of Zhongjiang county (中江县) in Sichuan province (四川省 ) of China. Zhongjiang county belongs to the Deyang (德阳) region, which is located in the middle of Sichuan province, about 100 kilometers northeast from the provincial capital of Chengdu (成都). Zhongjiang is just beyond the Chengdu Plain (成都平原), so the terrain is mostly hilly, with little flat land. It has a population of 1.37 million residents and an area of 2,200km2 (data from Zhongjiang official website, updated July 7, 2021).
Situations in which caregivers and patients are likely to collude: Perspectives from caregivers of advanced cancer patients in Bangladesh
Authors: Biswas Jheelam , Khanam Salma Ahsan , Tauhid Md. Shamsudduha , Sarker Shima Rani , Afsar Nahid , Islam Nashid
Published: February 2025

Objectives

This study aimed to explore situations where caregivers and patients are likely to collude, from the perspective of caregivers of advanced cancer patients in Bangladesh.

Methods

This study took place in 2 different tertiary care hospitals in Bangladesh. The study design included both quantitative and qualitative components. In this study, we focused on situations in which caregivers choose not to disclose the truth, regardless of their patients’ desire to know it. This may include instances of mutual withholding or cases of deliberate withholding by caregivers, even when patients express a desire to know the truth. While collusion may occur in some instances, not all situations qualify as collusion; nonetheless, all of these situations were broadly considered as collusion-prone. The intensity of enactment was assessed using the “Caregiver Collusion Questionnaire,” and in-depth exploration of collusion-prone situations was conducted through key person interviews with the caregivers.

Results

The intensity of enactment was medium to high among two-thirds (83.1%) of caregivers. This intensity was significantly associated with the caregivers’ relationship with the patients and their intention to disclose the truth (p < 0.01). Higher intensity of enactment has been observed among the children who are tending to their terminally ill parents. Four major themes regarding collusion-prone situation were generated by the qualitative analysis: (1) Reasons for nondisclosure; (2) Time of disclosure; (3) Selective disclosure; and (4) Discloser of truth.

Significance of Results

The nature of collusion-prone situations is shaped by culture and social values. By gradually and indirectly addressing these situations, healthcare professionals can assist families in navigating through difficult conversations and ensure that the patient’s wishes and values are respected.
Quantifying Biodiversity's Present and Future: Current Potentials and SSP‐RCP‐Driven Land Use Impacts
Authors: Cheng Yilin , Liu Hongxi , Du Jizeng , Yi Yujun
Published: February 2025

Biodiversity, vital for ecosystem stability and human well‐being, faces threats from land use and climate change. Accurately predicting these effects is crucial for effective conservation. High emission development scenario is commonly viewed as the most detrimental to biodiversity. However, recent researches suggest a more complex relationship between development paths and biodiversity outcomes. Our study addresses this by using an emergy‐based approach to estimate current provincial‐level biodiversity potential and project future species richness losses (amphibians, mammals, and birds) across climate zones and provincial divisions under various SSP‐RCP scenarios for 2030, 2050, 2070, and 2090. The results revealed significant regional variations in China's biodiversity potential, with the highest in southwestern provinces. Future land use trends indicate increased construction land and barren alongside a decline in grasslands, leading to considerable habitat loss and fragmentation under various scenarios, stressing conservation needs. Future biodiversity loss follows the Hu line and climate zones, with significant decreases in the south and humid regions. Land‐use changes could reduce species richness by 1–6 per 10 km grid cell. High‐emission scenario SSP585 do not necessarily have the most detrimental effects on biodiversity and different scenarios require targeted focus on specific climatic zones and provinces. These findings underscore that different scenarios require targeted conservation efforts in specific regions sensitive to biodiversity loss. Our study provides a scientific foundation for these targeted efforts, ensuring that regions are prioritized under various future scenarios. This approach aids in developing effective conservation strategies amidst the complex interplay of land use dynamics and climate change.
Impact of Mid‐Pliocene Boundary Conditions on the Atlantic Meridional Overturning Circulation (AMOC)
Authors: Weiffenbach Julia E. , Chan Wing‐Le , Abe‐Ouchi Ayako , von der Heydt Anna S.
Published: February 2025

We use the coupled atmosphere‐ocean model MIROC4m to investigate the effect of mid‐Pliocene boundary conditions on the Atlantic Meridional Overturning Circulation (AMOC), studying the impact of increased , reduced ice sheets and altered orography and vegetation. We find that a higher concentration and smaller ice sheets both weaken the AMOC with respect to the pre‐industrial. The stronger mid‐Pliocene AMOC is therefore a consequence of mid‐Pliocene orography and vegetation, where the closed Arctic gateways are responsible for approximately 80% of the AMOC strengthening. The main mechanism for mid‐Pliocene AMOC strengthening is reduced transport of freshwater from the Arctic into the North Atlantic, enhanced by a decrease of surface freshwater flux into the high‐latitude North Atlantic.
Constraining 2.0 Ga Volcanism on the Moon via 40Ar/39Ar Dating of Chang'e‐5 Basalts
Authors: Su Fei , Zhang Xuhang , Li Youjuan , Jicha Brian R. , Joy Katherin H. , Li Qiuli , Chen Yi , Cai Shuhui , Liu Runchuan , Zhou Qin , Yang Saihong , Li Xianhua , Yang Liekun , Chen Wen , Li Junjie , Zhang Wanfeng , Qiu Huaning , He Huaiyu
Published: February 2025

The Chang'e‐5 landing site provides an important window into the Moon's late Eratosthenian period of volcanism at ∼2 Ga. Clarifying the Moon's history of volcanic activity using radioisotopic dating assists investigations of the evolution of the lunar surface as well as the Moon's internal dynamics. Recent chronological investigations of Chang'e‐5 basalts produced ages spanning ∼100 Ma, thereby inhibiting interpretation of the duration of volcanism recorded in the returned samples. We used microcomputed tomography and Back‐Scatter Electron imaging to characterize the structure and morphology of nine Chang'e‐5 basalt clasts. Several basalt clasts lack shock features and are interpreted to have not been significantly thermally disturbed. 40Ar/39Ar incremental heating produced well defined plateaus for four sub‐split samples that give a weighted mean age of 2,021 ± 17 Ma (2σ). These are among the youngest mare basalts to be dated thus far by the 40Ar/39Ar method and, when combined with most of the published Pb‐Pb ages for Chang'e‐5 basalts, define a single episode of mare volcanism at ∼2,021 Ma.
Investigating the Characteristics and Drivers of Slow Droughts and Flash Droughts: A Multi‐Temporal Scale Drought Identification Framework
Authors: Qi Zixuan , Ye Yuchen , Cai Yanpeng , Yuan Chaoxia , Xie Yulei , Cheng Guanhui , Zhang Pingping , Sun Lian , Wan Hang
Published: February 2025

Global climate change has altered the characteristics of conventional drought events, with an increasing number of Slow droughts (SD) rapidly transitioning into Flash droughts (FD). This study introduces a novel multi‐temporal scale drought identification framework (MTSDIF) that classifies historical agricultural drought events into three types: SD, FD, and Slow‐to‐Flash Drought (SFD). Based on the MTSDIF, the GLDAS‐Noah root zone soil moisture dataset was used to analyze the spatiotemporal characteristics, evolution, and driving factors of multi‐temporal scale droughts in China. Our study confirms the effectiveness of the proposed MTSDIF in classifying droughts with different onset speeds (SD, FD, and SFD). The results indicate that, from 1980 to 2020, the three types of drought events in China exhibited short‐term, medium‐term, and long‐term periodic oscillations. Before 2000, SD events were the predominant type of agricultural drought in China, but post‐2000, the areas affected by FD and SFD have been continuously expanding. Compared to SD, key meteorological elements influencing FD and SFD show anomalies exceeding 0.5 times the standard deviation. In the southeastern regions of China, areas with human‐impacted soils, leached soils, and incept soils exhibit a higher response frequency to FD. Sea surface temperature indices, including the interannual El Niño‐Southern Oscillation in the Pacific and interdecadal variations such as the +PDO and −AMO, significantly influence the occurrence of FD in the monsoon regions of China (p < 0.01). Together, the results highlight the necessity of understanding the disparities and consistencies in land‐atmosphere‐ocean mechanisms behind drought events with varying onset speeds.
Inhibition of CDC27 O-GlcNAcylation coordinates the antitumor efficacy in multiple myeloma through the autophagy-lysosome pathway
Authors: Wu Hai-qi , Qin Ren-cai , Li Wei-jie , Liu Jie-na , Deng Chong , Zheng Zi-han , Zheng Jing-peng , Liu Yu , Meng Yan-fang , Tang Chun , Tan Hong-mei , Duan Fang-fang , Tang Yuan , Xiao Fan , Lu Li-wei , Dai Xiao-yan , Ma Kong-yang
Published: February 2025

Multiple myeloma (MM) is a prevalent hematologic malignancy characterized by abnormal proliferation of cloned plasma cells. Given the aggressive nature and drug resistance of MM cells, identification of novel genes could provide valuable insights for treatment. In this study we performed machine learning in the RNA microarray data of purified myeloma plasma cell samples from five independent MM cohorts with 957 MM patients, and identified O-GlcNAcylation transferase (OGT) and cell division cycle 27 (CDC27) as the key prognostic genes for MM. We demonstrated a close link between OGT and CDC27 in MM cells by knockdown of OGT with siOGT, pharmacological inhibition of O-GlcNAcylation with OSMI-1 and pharmacological accumulation of O-GlcNAcylation with Thiamet G. Using mass spectrometry and immunoprecipitation, we identified the O-GlcNAcylated CDC27 protein as a key target protein that may be directly downregulated by OSMI-1 in MM.1S cells. We further revealed that O-GlcNAcylation maintained CDC27 protein stability by blocking the autophagy-lysosome pathway (ALP). Moreover, we demonstrated the enhanced antitumor efficacy of combined OSMI-1 and bortezomib (BTZ) treatment in MM cells both in vivo and in vitro. Thus, this study identifies a novel function of O-GlcNAcylation-related ALP in regulating CDC27 protein stability and a potential therapeutic strategy for treating MM.
Nuclear localization of BRCA1-associated protein 1 is important in suppressing hepatocellular carcinoma metastasis via CTCF and NRF1/OGT axis
Authors: Xie Xiaoyu , Tsui Yu-Man , Zhang Vanilla Xin , Yu Tiffany Ching-Yun , Husain Abdullah , Chiu Yung-Tuen , Tian Lu , Lee Eva , Lee Joyce Man-Fong , Ma Hoi-Tang , Ho Daniel Wai-Hung , Sze Karen Man-Fong , Ng Irene Oi-Lin
Published: February 2025

Germline mutations of the deubiquitinase BRCA1-associated protein 1 (BAP1) lead to the “BAP1 cancer syndrome” characterized by development of cancers. However, the role of BAP1 in hepatocellular carcinoma (HCC) is unclear. We found that BAP1 was upregulated at mRNA level in human HCCs and significantly correlated with a more aggressive tumour behaviour. Intriguingly, we observed cytoplasmic but no or minimal nuclear BAP1 in human HCC samples by immunohistochemistry. We observed that, while BAP1 protein was found mainly in the cytoplasm and less in the nuclei of HCC cell lines, BAP1 expression was predominantly nuclear in HepG2 cells, by cell fractionation and immunofluorescence analyses. Functionally, in the orthotopic liver injection mouse model, silencing the BAP1 predominant nuclear expression of HepG2 cells promoted intrahepatic tumor metastasis, with more frequent tumor microsatellite formation and venous invasion. With transcriptomic profiling, we identified RHOJ amongst the downregulated targets in HepG2 cells upon BAP1 knockdown. Subsequent overexpression of RHOJ suppressed cell migration in HCC cells, suggesting that BAP1 might upregulate RHOJ resulting in reduced cell migratory ability of HCC cells. Furthermore, we identified two transcription factors, CTCF and NRF1, which activated BAP1 transcription by binding to BAP1 promoter region. On the other hand, we uncovered that O-linked N-acetylglucosamine (GlcNAc) transferase (OGT) physically bound to BAP1 in the nucleus, resulting in diminished stability of the nuclear BAP1. Intriguingly, OGT transcription was upregulated and was also under the control of CTCF and NRF1 in human HCC, acting as a negative regulator of BAP1. To summarize, this study uncovered the underlying mechanisms of the regulation of BAP1 and that loss of the nuclear localization of BAP1 protein contributed to enhanced cell migration in vitro and more aggressive tumor behavior in human HCCs.
Cyclic jetting enables microbubble-mediated drug delivery
Authors: Cattaneo Marco , Guerriero Giulia , Shakya Gazendra , Krattiger Lisa A. , G. Paganella Lorenza , Narciso Maria L. , Supponen Outi
Published: February 2025

The pursuit of targeted therapies capable of overcoming biological barriers, including the blood–brain barrier, has spurred the investigation of stimuli-responsive microagents that can improve therapeutic efficacy and reduce undesirable side effects. Intravenously administered, ultrasound-responsive microbubbles are promising agents with demonstrated potential in clinical trials, but the mechanism underlying drug absorption remains unclear. Here we show that ultrasound-driven single microbubbles puncture the cell membrane and induce drug uptake through stable cyclic microjets. Our theoretical models successfully reproduce the observed bubble and cell dynamic responses. We find that cyclic jets arise from shape instabilities, as opposed to classical inertial jets that are driven by pressure gradients, enabling microjet formation at mild ultrasound pressures below 100 kPa. We also establish a threshold for bubble radial expansion beyond which microjets form and facilitate cellular permeation and show that the stress generated by microjetting outperforms previously suggested mechanisms by at least an order of magnitude. Overall, this work elucidates the physics behind microbubble-mediated targeted drug delivery and provides the criteria for its effective and safe application.
A novel microfluidic approach to quantify pore-scale mineral dissolution in porous media
Authors: Musabbir Rahman Rafid , Niemur Elliott , Blois Gianluca , Kazemifar Farzan , Kim Myeongsub , Li Yaofa
Published: February 2025

Mineral dissolution in porous media coupled with single- and/or multi-phase flows is pervasive in natural and engineering systems. Dissolution modifies the physical, hydrological, and geochemical properties of the solid matrix, resulting in a complex coupling between local dissolution rate and pore-scale flow. The work reports a microfluidic approach that includes 2D reactive porous media and advanced pore flow diagnostics for the study of pore-scale dissolution in porous media with unprecedented details. The 2D microfluidic porous media, called micromodels, were fabricated in calcite by combining photolithography and wet etching, which not only offers precise control over the structural and chemical properties, but also facilitate unobstructed optical access to the pore flow, significantly improving over existing methods. We believe the work represents the first of its kind as it for the first time directly applies photolithography to calcite samples and demonstrates the use of particle image velocimetry to investigate chemical reactions in porous media. The preliminary results have revealed the crucial roles of local concentration gradients in mineral dissolution and call for reconsideration of many assumptions used in the current modeling tools, which paves the way for renewed fundamental understanding of reactive transport and improved modeling tools with better accuracy.
Genetic evidence identifies a causal relationship between EBV infection and multiple myeloma risk
Authors: Li Jian , Tan Rong , Yang Bing , Du Changpu , Tian Jie , Yang Zhu , Tang Dongxin
Published: February 2025

Background: Previous observational studies have suggested a potential association between Epstein-Barr virus (EBV) infection and the development of multiple myeloma (MM), but this relationship is not clear. Therefore, we conducted a systematic Mendelian randomization (MR) analysis to investigate the causal relationship between EBV infection and the risk of MM, while exploring the possible mediating role of immune cells in this association. Methods: The study first conducted a two-sample MR analysis using the MM R11 dataset from the FinnGen Consortium to evaluate the causal relationship between five EBV infection-related antibodies (AEB-IgG, EA-D, EBNA-1, VCA-p18, and ZEBRA) and MM, with validation in the MM R10 dataset. A reverse MR analysis was then performed. For significant results, multivariable MR (MVMR) was used to adjust for the effects of confounding risk factors. Next, a two-step MR mediation analysis was applied to investigate the potential mediating role of 731 immune cell types between positive exposure and MM. Multiple sensitivity analyses were conducted to assess the robustness of the findings. Results: A two-sample MR study found that EBNA-1 antibodies (OR = 1.36, 95% CI: 1.06–1.73; P = 0.015) were associated with an increased risk of MM, with similar results observed in the FinnGen Consortium R10 replication study. Although the association did not remain statistically significant after false discovery rate (FDR) adjustment (P_fdr = 0.075), further adjustment for relevant confounders using multivariable MR (MVMR) demonstrated that EBNA-1 antibodies (OR = 1.33, 95% CI: 1.01–1.75; P = 0.041) were still significantly associated with an increased risk of MM. Reverse MR analysis indicated no causal effect of MM on EBV-related antibodies. A two-sample MR analysis involving 731 immune cell phenotypes identified 27 potential mediating cell types. Ultimately, two-step MR confirmed that HLA-DR on myeloid dendritic cells (HLA-DR⁺ mDC) serves as a mediating factor, with EBNA-1 antibodies downregulating HLA-DR⁺ mDC, thereby increasing MM risk. Multiple sensitivity analyses supported the robustness of these findings. Conclusion: The findings of this study suggest that EBNA-1 antibodies may increase the risk of MM by downregulating HLA-DR⁺ mDC. This indicates that chronic EBV infection may contribute to an elevated risk of MM. We hope these results provide new insights for future research on the prevention and treatment of MM.
DNA-encoded Library Machine Learning Applications
Authors: Sigel Eric A.
Published: February 2025

Machine learning (ML) has begun to realize its promise in many domains in the last several years. While small molecule drug discovery has lagged in comparison to other areas, developments in computing capabilities, data generation, and algorithms have enabled significant progress in molecule prediction. DNA-encoded libraries (DELs) represent an efficient way to generate the quantity of data required for effective model building, providing a mechanism for protein-target specific prediction with economics that permit individual organizations to operate. DEL-based machine learning (DEL-ML) has been demonstrated to work for a variety of targets and continues to expand in its usage in the industry and in the approaches reported. With this initial success, a number of challenges and considerations faced by the DEL-ML practitioner have been identified including denoising of DEL data, choice of ML algorithm, hyperparameters and molecule representations, and the need for relevant metrics for assessment, particularly given the high resource and time costs of testing predictions. In order to fully realize the potential of DEL-ML, key improvements in drug discovery infrastructure and broad availability of DEL data are needed.
Solid-phase DNA-encoded Library Technology
Authors: Hu Juan , Burdick John P. , Paegel Brian M.
Published: February 2025

Solid-phase DNA-encoded library (DEL) technology introduces advanced activity-based screening capabilities by virtue of its “one-bead-one-compound” (OBOC) format. In this review, we first describe the design and construction of so-called “OBOC-DELs.” We then explore the engineering of a microfluidic screening platform that integrates and automates high-throughput bead-based screening, highlighting examples of fluorescence-based functional assay development and miniaturization to microfluidic droplets. Additionally, we detail the statistical framework of OBOC-DEL screening experimental design and data interpretation. Finally, we summarize the numerous applications that have spawned since OBOC-DEL technology’s inception, including screening by biochemical activity, dose-response, cellular activity, competition binding affinity, and pharmacokinetic properties. Looking forward, there are likely further opportunities to employ bead-based synthesis and screening strategies to other encoded library modalities.
MXenes in healthcare: synthesis, fundamentals and applications
Authors: Babar Zaheer Ud Din , Iannotti Vincenzo , Rosati Giulio , Zaheer Ayesha , Velotta Raffaele , Della Ventura Bartolomeo , Álvarez-Diduk Ruslan , Merkoçi Arben
Published: February 2025

This review serves as a tutorial on MXene synthesis, outlining laboratory practices and linking them to core scientific concepts. It also examines healthcare applications, computational aspects, and the role of AI technologies in advancing MXene research.
Site-specific photo-crosslinking in a double crossover DNA tile facilitated by squaraine dye aggregates: advancing thermally stable and uniform DNA nanostructures
Authors: Basu Shibani , Roy Simon K. , Sharma Mandeep , Barcenas German , Yurke Bernard , Knowlton William B. , Lee Jeunghoon
Published: February 2025

We investigated the role of dichloro-squaraine (SQ) dye aggregates in facilitating thymine–thymine interstrand photo-crosslinking of double crossover (DX) tiles to improve the thermal and structural stability of two-dimension DNA-based nanostructures.
Dual-Mode Molecular Photoswitches with Multi-Stimulus Response by Introducing Multifunctionality and Eliminating the Heavy Atom Effect
Authors: Han Zhengdong , Zhan Jiale  , Peng Xin , Wu Penglei , Li Tian , Liu Wei-Dong , Qian Zhaosheng , Feng Hui
Published: February 2025

The development of new multifunctional smart materials can be significantly advanced by the creation of multi-stimulus-responsive optical switches. However, the design of such switches that can operate in both absorption...
General component additivity, reaction engineering, and machine learning models for hydrothermal liquefaction
Authors: Guirguis Peter M. , Savage Phillip E.
Published: February 2025

State-of-the-art machine learning, reaction engineering, and component additivity models for biomass HTL, accurately predicting biocrude yields to optimize reaction conditions for biomass-to-oil yield across diverse feedstocks.
Rapid in situ bulk transformation of NiFe particle for highly efficient oxygen evolution in anion exchange membrane water electrolyzers
Authors: Chen Bin , Bai Fan , Feng Yingjie , Wang Sipu , Cao Xinyi , Li Wei , Wang Lianqin , Fu Xiaoyue , Jin Li , Zhang Junfeng , Yin Yan , Guiver Michael D.
Published: February 2025

The limited surface reconstruction of NiFe alloy-based catalysts in an anion exchange membrane water electrolysis (AEMWE) restricts the utilization of active sites in the MEA (membrane electrode assembly), which hinders...