bluuebunny/crossref_metadata_2025 huggingface dataset:
Sailing to Calanais: Monument Complexes and the Sea in the Neolithic of Western Scotland and Beyond
Authors: BRADLEY RICHARD , WATSON AARON
Published: November 2024

Ever since Alexander Thom visited Calanais in the Outer Hebrides, groups of Neolithic monuments in western Scotland have been studied in relation to the land and the sky. Less attention has been paid to their close relationship with the sea. These places were secluded and could be difficult or dangerous to reach, yet details of their architecture suggest that there were close links between them. How important were long distance connections between 3000 and 2000 bc? Were some ceremonial centres visited by boat? And was the journey itself treated as a rite of passage? The case extends to structures in Orkney and Ireland.
Local regularity for nonlocal double phase equations in the Heisenberg group
Authors: Fang Yuzhou , Zhang Chao , Zhang Junli
Published: November 2024

We prove interior boundedness and Hölder continuity for the weak solutions of nonlocal double phase equations in the Heisenberg group

$\mathbb{H}^n$

. This solves a problem raised by Palatucci and Piccinini et al. in 2022 and 2023 for the nonlinear integro-differential problems in Heisenberg setting. Our proof of the a priori estimates bases on De Giorgi–Nash–Moser theory, where the important ingredients are Caccioppoli-type inequality and Logarithmic estimate. To achieve this goal, we establish a new and crucial Sobolev–Poincaré type inequality in local domain, which may be of independent interest and potential applications.
Sex-specific association between later circadian timing of food intake and adiposity among Chinese young adults living in real-world settings
Authors: Huang Yan , Xu Yu-xiang , Shen Yu-ting , Zhou Yi , Wan Yu-hui , Tao Fang-biao , Sun Ying
Published: November 2024

Timing of food intake is an emerging aspect of nutrition; however, there is a lack of research accurately assessing food timing in the context of the circadian system. The study aimed to investigate the relation between food timing relative to clock time and endogenous circadian timing with adiposity and further explore sex differences in these associations among 151 young adults aged 18–25 years. Participants wore wrist actigraphy and documented sleep and food schedules in real time for 7 consecutive days. Circadian timing was determined by dim-light melatonin onset (DLMO). The duration between last eating occasion and DLMO (last EO-DLMO) was used to calculate the circadian timing of food intake. Adiposity was assessed using bioelectrical impedance analysis. Of the 151 participants, 133 were included in the statistical analysis finally. The results demonstrated that associations of adiposity with food timing relative to circadian timing rather than clock time among young adults living in real-world settings. Sex-stratified analyses revealed that associations between last EO-DLMO and adiposity were significant in females but not males. For females, each hour increase in last EO-DLMO was associated with higher BMI by 0·51 kg/m2 (P = 0·01), higher percent body fat by 1·05 % (P = 0·007), higher fat mass by 0·99 kg (P = 0·01) and higher visceral fat area by 4·75 cm2 (P = 0·02), whereas non-significant associations were present among males. The findings highlight the importance of considering the timing of food intake relative to endogenous circadian timing instead of only as clock time.
Model structures, n-Gorenstein flat modules and PGF dimensions
Authors: El Maaouy Rachid
Published: November 2024

Given a non-negative integer n and a ring R with identity, we construct a hereditary abelian model structure on the category of left R-modules where the class of cofibrant objects coincides with $\mathcal{GF}_n(R)$ the class of left R-modules with Gorenstein flat dimension at most n, the class of fibrant objects coincides with $\mathcal{F}_n(R)^\perp$ the right ${\rm Ext}$-orthogonal class of left R-modules with flat dimension at most n, and the class of trivial objects coincides with $\mathcal{PGF}(R)^\perp$ the right ${\rm Ext}$-orthogonal class of PGF left R-modules recently introduced by Šaroch and . The homotopy category of this model structure is triangulated equivalent to the stable category $\underline{\mathcal{GF}(R)\cap\mathcal{C}(R)}$ modulo flat-cotorsion modules and it is compactly generated when R has finite global Gorenstein projective dimension.

The second part of this paper deals with the PGF dimension of modules and rings. Our results suggest that this dimension could serve as an alternative definition of the Gorenstein projective dimension. We show, among other things, that (n-)perfect rings can be characterized in terms of Gorenstein homological dimensions, similar to the classical ones, and the global Gorenstein projective dimension coincides with the global PGF dimension.
The line bundles on the moduli stack of principal bundles on families of curves
Authors: Fringuelli Roberto , Viviani Filippo
Published: November 2024

Given a connected reductive algebraic group G over an algebraically closed field, we investigate the Picard group of the moduli stack of principal G-bundles over an arbitrary family of smooth curves.
To revive India’s industries: The global and imperial roots of swadeshi in the nineteenth century
Authors: Patel Dinyar
Published: November 2024

This article explores the long roots of swadeshi (economic self-reliance) in nineteenth-century India, focusing on attempts at industrial revival through pedagogical institutions, exhibitions, and associations. These roots, which influenced the Swadeshi Movement and Gandhian swadeshi activity in the early twentieth century, demonstrate how it is impossible to understand swadeshi without taking an extensive global perspective. Indian thinkers engaged in contemporary global economic debates and with British imperial deliberations on free trade and protection; they fine-tuned comparative perspectives on the Indian economy through international travel and their readings of global history. In a similar spirit, Indians forged core swadeshi techniques through observing associational, institutional, and technological innovations across the British empire and the wider world. History was a powerful motivating force. Popular conceptions of deindustrialization under colonial rule fired Indians’ imaginations about a past when the country was a global powerhouse for manufactured exports—and directly stimulated specific swadeshi endeavours. Situated at the confluence of profit-making and patriotism, swadeshi enterprise in the nineteenth century created some unexpected alliances: between Britons and Indians, colonial officials and nationalists, and urban intellectuals and small-town entrepreneurs.
A meta-analysis of the reliability of second language reading comprehension assessment tools
Authors: Zhao Huijun , Aryadoust Vahid
Published: November 2024

The present study aims to meta-analyze the reliability of second language (L2) reading assessments and identify the potential moderators of reliability in L2 reading comprehension tests. We examined 3,247 individual studies for possible inclusion and assessed 353 studies as eligible for the inclusion criteria. Of these, we extracted 150 Cronbach’s alpha estimates from 113 eligible studies (years 1998–2024) that reported Cronbach’s alpha coefficients properly and coded 27 potential predictors comprising of the characteristics of the study, the test, and test takers. We subsequently conducted a reliability generalization (RG) meta-analysis to compute the average reliability coefficient of L2 reading comprehension tests and identify potential moderators from 27 coded predictor variables. The RG meta-analysis found an average reliability of 0.79 (95% CI [0.78, 0.81]). The number of test items, test piloting, test takers’ educational institution, study design, and testing mode were found to respectively explain 16.76%, 5.92%, 4.91%, 2.58%, and 1.36% of variance in reliability coefficients. The implications of this study and future directions are further discussed.
Quick-reference criteria for identifying multivariate cognitive change in older adults with mild cognitive impairment and dementia: An ADNI study
Authors: Grant Jeremy G. , Wisinger Amanda M. , Abel Hilary F. , Hunter Jennifer M. , Smith Glenn E. ,   the Alzheimer’s Disease Neuroimaging Initiative
Published: November 2024

Objective:

To establish quick-reference criteria regarding the frequency of statistically rare changes in seven neuropsychological measures administered to older adults.

Method:

Data from 935 older adults examined over a two-year interval were obtained from the Alzheimer’s Disease Neuroimaging Initiative. The sample included 401 cognitively normal older adults whose scores were used to determine the natural distribution of change scores for seven cognitive measures and to set change score thresholds corresponding to the 5th percentile. The number of test scores that exceeded these thresholds were counted for the cognitively normal group, as well as 381 individuals with mild cognitive impairment (MCI) and 153 individuals with dementia. Regression analyses examined whether the number of change scores predicted diagnostic group membership beyond demographic covariates.

Results:

Only 4.2% of cognitively normal participants obtained two or more change scores that fell below the 5th percentile of change scores, compared to 10.6% of the stable MCI participants and 38.6% of those who converted to dementia. After adjusting for age, gender, race/ethnicity, and premorbid estimates, the number of change scores below the 5th percentile significantly predicted diagnostic group membership.

Conclusions:

It was uncommon for older adults to have two or more change scores fall below the 5th percentile thresholds in a seven-test battery. Higher change counts may identify those showing atypical cognitive decline.
Associations of linear growth and weight gain in the first 2 years with bone mass at 4 years of age in children in Dhaka, Bangladesh
Authors: Gias Maimuna , Qamar Huma , Fariha Farzana , Mahmud Abdullah Al , Shah Prakesh , Abrams Steven A , Roth Daniel E , O’Callaghan Karen M
Published: November 2024

Objective:

Growth faltering is widespread in many low- and middle-income countries, but its effects on childhood bone mass accrual are unknown. The objective of this study was to estimate associations between length (conditional length-for-age z-scores, cLAZ) and weight (conditional weight-for-age z-scores, cWAZ) gain in three age intervals (ages 0–6, 6–12 and 12–24 months) with dual-energy X-ray absorptiometry-derived measures of bone mass (total body less head (TBLH) bone mineral content (BMC), areal bone mineral density (aBMD) and bone area) at 4 years of age.

Design:

Associations between interval-specific growth parameters (cLAZ and cWAZ) and bone outcomes were estimated using linear regression models, adjusted for maternal, child and household characteristics.

Setting:

Data collection occurred in Dhaka, Bangladesh.

Participants:

599 healthy children enrolled in the BONe and mUScle Health in Kids Study.

Results:

cLAZ in each age interval was positively associated with TBLH BMC, aBMD and bone area at 4 years; however, associations attenuated towards null upon adjustment for concurrent height-for-age z-scores (HAZ) at age 4 years and confounders. cWAZ from 0 to 6 and 6 to 12 months was not associated with bone mass, but every sd increase in cWAZ between 12 and 24 months was associated with greater BMC (7·6 g; 95 % CI: 3·2, 12·0) and aBMD (0·008 g/cm2; 95 % CI: 0·003, 0·014) after adjusting for concurrent WAZ, HAZ and confounders.

Conclusions:

Associations of linear growth (birth to 2 years) with bone mass at age 4 years were explained by concurrent HAZ. Weight gain in the second year of life may increase bone mass independently of linear growth in settings where growth faltering is common.
Bridging the gap: Integrating cutting-edge techniques into biological imaging with deepImageJ
Authors: Fuster-Barceló Caterina , García-López-de-Haro Carlos , Gómez-de-Mariscal Estibaliz , Ouyang Wei , Olivo-Marin Jean-Christophe , Sage Daniel , Muñoz-Barrutia Arrate
Published: November 2024

This manuscript showcases the latest advancements in deepImageJ, a pivotal Fiji/ImageJ plugin for bioimage analysis in life sciences. The plugin, known for its user-friendly interface, facilitates the application of diverse pre-trained convolutional neural networks to custom data. The manuscript demonstrates several deepImageJ capabilities, particularly in deploying complex pipelines, three-dimensional (3D) image analysis, and processing large images. A key development is the integration of the Java Deep Learning Library, expanding deepImageJ’s compatibility with various deep learning (DL) frameworks, including TensorFlow, PyTorch, and ONNX. This allows for running multiple engines within a single Fiji/ImageJ instance, streamlining complex bioimage analysis workflows. The manuscript details three case studies to demonstrate these capabilities. The first case study explores integrated image-to-image translation followed by nuclei segmentation. The second case study focuses on 3D nuclei segmentation. The third case study showcases large image volume segmentation and compatibility with the BioImage Model Zoo. These use cases underscore deepImageJ’s versatility and power to make advanced DLmore accessible and efficient for bioimage analysis. The new developments within deepImageJ seek to provide a more flexible and enriched user-friendly framework to enable next-generation image processing in life science.
Impact of polypharmacy on patients undergoing revascularisation for peripheral arterial disease
Authors: Franke Philipp , Katsogridakis Emmanuel , Bisdas Theodosios , Saratzis Athanasios , Torsello Giovanni , Tsilimparis Nikolaos , Stavroulakis Konstantinos
Published: November 2024

Summary: Background: To evaluate the impact of polypharmacy, defined as the concurrent use of five or more medications, on the clinical outcomes of patients undergoing revascularisation for symptomatic peripheral arterial disease (PAD). Patients and methods: This is a retrospective analysis of consecutive PAD patients treated by surgical, endovascular or hybrid therapy in a tertiary center between January 2017 and December 2017. The composite of amputation and/or death (amputation-free survival; AFS) was the primary endpoint. Mortality, major limb amputation, risk for Major Cardio-Cerobro-vascular Events (MACCE) and re-intervention during follow-up were additionally analyzed. Results: A total of 560 patients (369 male, 66%) were included. Mean age was 72.43 ± 38.67, while the main indication for treatment was lifestyle limiting claudication (330 patients, 59%). Most patients (434, 78%) were treated with endovascular means, and the commonest anatomical site of intervention was the femoropopliteal arterial segment (449 patients, 80%). A total of 409 (73%) met the criteria for polypharmacy. Cox regression analysis showed that polypharmacy was an independent predictor of death (exp: 4.72, p=0.008), MACCE (exp: 2.82, p=0.001), re-intervention (exp 1.51, p=0.0016) and of the composite outcome of AFS (exp: 3.46, p=0.021) but not of major amputation (exp: 1.26, p=0.686). Propensity-score matching analysis showed that even when controlling for comorbidity and procedural characteristics, polypharmacy is associated with a higher risk of cardiovascular death (p<0.001), MACCE (p<0.001), and re-intervention (p=0.001). Conclusions: In this study, polypharmacy was associated with unfavourable clinical outcomes for patients undergoing revascularisation for symptomatic PAD, without influencing the risk for major limb amputation.
Fossil Fuel CO2 Emission Signatures Over India Captured by OCO‐2 Satellite Measurements
Authors: Balamurugan Vigneshkumar , Chen Jia
Published: November 2024

Monitoring greenhouse gas (GHG) emissions is crucial for developing effective mitigation strategies. Recent advances in satellite remote‐sensing measurements allow us to track greenhouse gas emissions globally. This study assessed emissions from various point or local sources, particularly power plants in India, using 8 years of concurrent high‐spatial resolution OCO‐2 satellite measurements. A Gaussian plume (GP) model was used to evaluate the power plant emissions reported in the Carbon Brief (CB) database. In total (39 cases), 42 different power plant emissions were assessed, with 26 of them being assessed more than once. The estimated power plant emissions were within 25% of the emissions reported in the CB database in 11 out of 39 cases and within 50% in 18 cases. To evaluate the EDGAR and ODIAC emission inventories in terms of missing and highly underestimated sources, we estimated the cross‐sectional (CS) emission flux for 45 cases. We identified the possible omission of power plant emissions in three cases for both inventories. Furthermore, we also showed 17 cases in which emissions from unknown (non‐power plant) sources were highly underestimated in the EDGAR and ODIAC emission inventories. Due to the simplicity of the employed approaches and their lower computational requirements compared to other methods, they can be applied to large data sets over extended time periods. This enables the acquisition of initial emission estimates for various sources, including those that are unknown and underestimated.
Future Scenarios for River Exports of Multiple Pollutants by Sources and Sub‐Basins Worldwide: Rising Pollution for the Indian Ocean
Authors: Micella Ilaria , Kroeze Carolien , Bak Mirjam P. , Tang Ting , Wada Yoshihide , Strokal Maryna
Published: November 2024

In the future, rivers may export more pollutants to coastal waters, driven by socio‐economic development, increased material consumption, and climate change. However, existing scenarios often ignore multi‐pollutant problems. Here, we aim to explore future trends in annual river exports of nutrients (nitrogen and phosphorus), plastics (macro and micro), and emerging contaminants (triclosan and diclofenac) at the sub‐basin scale worldwide. For this, we implement into the process‐based MARINA‐Multi model (Model to Assess River Inputs of pollutaNts to the seAs) two new multi‐pollutant scenarios: “Sustainability‐driven Future” (SD) and “Economy‐driven Future” (ED). In ED, river exports of nutrients and microplastics will double by 2100, globally. In SD, a decrease of up to 83% is projected for river export of all studied pollutants by 2100, globally. Diffuse sources such as fertilizers are largely responsible for increasing nutrient pollution in the two scenarios. Point sources, namely sewage systems, are largely responsible for increasing microplastic pollution in the ED scenario. In both scenarios, the coastal waters of the Indian Ocean will receive up to 400% more pollutants from rivers by 2100 because of growing population, urbanization, and poor waste management in the African and Asian sub‐basins. The situation differs for sub‐basins draining into the Mediterranean Sea and the Pacific Ocean (mainly less future pollution) and the Atlantic Ocean and Arctic Ocean (more or less future pollution depending on sub‐basins and scenarios). From 56% to 78% of the global population are expected to live in more polluted river basins in the future, challenging sustainable development goals for clean waters.
Soil Moisture‐Cloud‐Precipitation Feedback in the Lower Atmosphere From Functional Decomposition of Satellite Observations
Authors: Gao Yifu , Guilloteau Clément , Foufoula‐Georgiou Efi , Xu Chonggang , Sun Xiaoming , Vrugt Jasper A.
Published: November 2024

The feedback of topsoil moisture (SM) content on convective clouds and precipitation is not well understood and represented in the current generation of weather and climate models. Here, we use functional decomposition of satellite‐derived SM and cloud vertical profiles (CVP) to quantify the relationship between SM and the vertical distribution of cloud water in the central US. High‐dimensional model representation is used to disentangle the contributions of SM and other land‐surface and atmospheric variables to the CVP. Results show that the sign and strength of the SM‐cloud‐precipitation feedback varies with cloud height and time lag and displays a large spatial variability. Positive anomalies in antecedent 7‐hr SM and land‐surface temperature enhance cloud reflectivity up to 4 dBZ in the lower atmosphere about 1–3 km above the surface. Our approach presents new insights into the SM‐cloud‐precipitation feedback and aids in the diagnosis of land‐atmosphere interactions simulated by weather and climate models.
Climate‐Induced Saltwater Intrusion in 2100: Recharge‐Driven Severity, Sea Level‐Driven Prevalence
Authors: Adams Kyra H. , Reager J. T. , Buzzanga Brett A. , David Cédric H. , Sawyer Audrey H. , Hamlington Benjamin D.
Published: November 2024

Saltwater intrusion is a critical concern for coastal communities due to its impacts on fresh ecosystems and civil infrastructure. Declining recharge and rising sea level are the two dominant drivers of saltwater intrusion along the land‐ocean continuum, but there are currently no global estimates of future saltwater intrusion that synthesize these two spatially variable processes. Here, for the first time, we provide a novel assessment of global saltwater intrusion risk by integrating future recharge and sea level rise while considering the unique geology and topography of coastal regions. We show that nearly 77% of global coastal areas below 60° north will undergo saltwater intrusion by 2100, with different dominant drivers. Climate‐driven changes in subsurface water replenishment (recharge) is responsible for the high‐magnitude cases of saltwater intrusion, whereas sea level rise and coastline migration are responsible for the global pervasiveness of saltwater intrusion and have a greater effect on low‐lying areas.
Inequity in Population Exposure to Accelerated Warming
Authors: Sengupta Aditya , King Andrew D. , Ryan Robert G.
Published: November 2024

Recent temperature records have triggered debate about whether global warming is accelerating. Here, we examine for acceleration and explore possible causes for regional differences using gridded surface temperature data. We find that global and regional warming is accelerating, and on average, regions with low Human Development Index (HDI) experienced much higher accelerated warming in comparison to regions with high HDI. However, some regions of low HDI with a large population experienced slow acceleration due to high local aerosol emissions. Since aerosol negative forcing impacts are short‐lived and localized, rapid future reduction of aerosol emissions without a concurrent reduction in GHG emissions could have major compounding impacts. Such a pathway, similar to most 21st century scenarios, could expose a large fraction of the world's most vulnerable people to sudden warming acceleration and heat stress associated impacts. These results call for targeted climate adaptation strategies directing attention to low‐socioeconomic aerosol masked regions.
The Dayside Ionosphere of Mars as Controlled by the Interplay Between Solar Wind Dynamic Pressure and Crustal Magnetic Field Strength
Authors: Qin JunFeng , Curry Shannon , Mitchell Dave , Xu Shaosui , Lillis Robert , Andersson Laila
Published: November 2024

We investigate how the Martian dayside ionospheric structure is modified by crustal magnetic field (CMF) strength and upstream solar wind pressure by analyzing electron density data from the Langmuir Probe and Waves instrument onboard the MAVEN (Mars Atmosphere and Volatile EvolutioN) spacecraft. We find that the electron density above the exobase is anticorrelated with the ratio of solar wind's normal dynamic pressure () to CMF magnetic pressure (). We also analyze the electron density behavior across different magnetic topologies as a function of . The extremely low electron density in the draped topology relates to ionopause‐like structures. The lower electron density in the closed and open topology under higher may be attributed to a downward force, potentially the J × B force in the case of closed topology. This study highlights the complex interplay between solar wind and CMF in influencing the Martian dayside upper ionosphere.
The Conditional Bias of Extreme Precipitation in Multi‐Source Merged Data Sets
Authors: Kang Xiaoqi , Dong Jianzhi , Crow Wade T. , Wei Lingna , Zhang Huiwen
Published: November 2024

Multi‐source data merging via weighted average (WA) is widely applied to enhance large‐scale precipitation estimates. However, these data sets usually contain substantial conditional biases with respect to extreme precipitation (EP) events—undermining their utility for extreme event analysis. Nevertheless, the main source of such EP biases remains unknown. Here, we demonstrate that WA algorithms are responsible for less than 1% of total EP biases. Instead, EP biases originate from the multi‐source precipitation inputs, which are not adequately adjusted prior to WA. Specifically, current data‐merging frameworks only correct the monthly means or statistical distributions of the remote sensing/reanalysis precipitation inputs prior to WA. Such procedures are insufficient for adjusting EP timing uncertainties, which eventually propagate into the WA‐based merged data set as an EP bias. Therefore, developing algorithms that iteratively adjust EP timing and intensity errors should be prioritized in future precipitation merging frameworks.
Elevated Phosphorus Concentrations in Shallow Oceans as a Trigger for the 1.57‐Ga Oxygenation Event
Authors: Xie Baozeng , Zhang Zihu , Li Chao , Dodd Matthew S. , Shi Xiaoying , Shi Qing , Li Chao , Sun Longfei , Xu Lei , Wang Xinqiang , Tang Dongjie
Published: November 2024

Enhanced continental phosphorus (P) input into the oceans has been proposed as a potential trigger for the 1.57 Ga oxygenation event; however, uncertainty remains due to the absence of direct evidence for seawater P concentrations. Here, we investigate shallow marine carbonate rocks of the Gaoyuzhuang Formation in the North China Platform, using the carbonate‐associated phosphate (CAP) proxy to directly reconstruct seawater P levels at that time. Two significant CAP/(Ca + Mg) increases correspond with rises in I/(Ca + Mg) during the oxygenation event suggesting that elevated seawater P concentrations were important in triggering the oxygenation event. Furthermore, a concurrent positive shift in εNd(t) values from −12.3 to −0.9 suggests that a transition in weathering source rocks from intermediate to mafic lithologies significantly contributed to the elevated P fluxes to the oceans during the oxygenation event. This study provides new insights into assessing seawater P levels and their role in the mid‐Proterozoic oxygenation events.
Distilling the Evolving Contributions of Anthropogenic Aerosols and Greenhouse Gases to Large‐Scale Low‐Frequency Surface Ocean Changes Over the Past Century
Authors: Dong Yue , Kay Jennifer E. , Deser Clara , Capotondi Antonietta , Sanchez Sara C.
Published: November 2024

Anthropogenic aerosols (AER) and greenhouse gases (GHG)—the leading drivers of the forced historical change—produce different large‐scale climate response patterns, with correlations trending from negative to positive over the past century. To understand what caused the time‐evolving comparison between GHG and AER response patterns, we apply a low‐frequency component analysis to historical surface ocean changes from CESM1 single‐forcing large‐ensemble simulations. While GHG response is characterized by its first leading mode, AER response consists of two distinct modes. The first one, featuring long‐term global AER increase and global cooling, opposes GHG response patterns up to the mid‐twentieth century. The second one, featuring multidecadal variations in AER distributions and interhemispheric asymmetric surface ocean changes, appears to reinforce the GHG warming effect over recent decades. AER thus can have both competing and synergistic effects with GHG as their emissions change temporally and spatially.
Polyploid cancer cells reveal signatures of chemotherapy resistance
Authors: Schmidt Michael J. , Naghdloo Amin , Prabakar Rishvanth K. , Kamal Mohamed , Cadaneanu Radu , Garraway Isla P. , Lewis Michael , Aparicio Ana , Zurita-Saavedra Amado , Corn Paul , Kuhn Peter , Pienta Kenneth J. , Amend Sarah R. , Hicks James
Published: November 2024

Therapeutic resistance in cancer significantly contributes to mortality, with many patients eventually experiencing recurrence after initial treatment responses. Recent studies have identified therapy-resistant large polyploid cancer cells in patient tissues, particularly in late-stage prostate cancer, linking them to advanced disease and relapse. Here, we analyzed bone marrow aspirates from 44 advanced prostate cancer patients and found the presence of circulating tumor cells with increased genomic content (CTC-IGC) was significantly associated with poorer progression-free survival. Single cell copy number profiling of CTC-IGC displayed clonal origins with typical CTCs, suggesting complete polyploidization. Induced polyploid cancer cells from PC3 and MDA-MB-231 cell lines treated with docetaxel or cisplatin were examined through single cell DNA sequencing, RNA sequencing, and protein immunofluorescence. Novel RNA and protein markers, including HOMER1, TNFRSF9, and LRP1, were identified as linked to chemotherapy resistance. These markers were also present in a subset of patient CTCs and are associated with recurrence in public gene expression data. This study highlights the prognostic significance of large polyploid tumor cells, their role in chemotherapy resistance, and the expression of markers tied to cancer relapse, offering new potential avenues for therapeutic development.
Complex IIa formation and ABC transporters determine sensitivity of OSCC to Smac mimetics
Authors: Wang Yuhan , Liu Zijian , Si Qian , Lu Wanqiu , Song Yuxian , Jin Wanyong , Yang Xihu , Li Zihui , Hu Xinyang , Ding Liang , Jing Yue , Weng Pei , Yu Qiuya , O’Reilly Lorraine A. , Silke John , Zhang Xiaoxin , Hu Qingang , Ni Yanhong
Published: November 2024

Small molecule inhibitors of apoptosis proteins (IAPs) antagonists, known as Smac mimetics (SMs), activate non-canonical NF-κB and sensitize cancer cells to TNF-induced cell death. SMs are currently in phase III clinical trials for head and neck squamous cell carcinoma (HNSCC) after promising phase II trials. To explore the utility of SMs in oral squamous cell carcinoma (OSCC), we tested nine human OSCC cell lines and correlated SM sensitivity with both IAP mutation and expression levels. cIAP1 protein expression was shown to be higher in OSCC and a predictor of poor prognosis. However, our in vitro and in vivo testing demonstrated differential sensitivity to SMs, which did not correlate with cIAP1 and cIAP2 expression in these OSCC cell lines. Exogenous TNF failed to effectively increase the sensitivity of SM-resistant OSCC cells to SM-induced cell death. SM resistance was associated with a deficiency in Complex IIa formation, but activation of non-canonical NF-κB was not a determinant of SM efficacy. Finally, metabolic analysis revealed that the ABC transporter pathway was activated in SM-resistant OSSC cells, and SMs combined with ABC transporter inhibitors improved cell death sensitivity to overcome SM resistance. These studies highlight the therapeutic potential of SMs in OSCC and support patient stratification to improve efficacy with the addition of adjuvant therapy.
CFAP43 variant in persistent respiratory symptoms after hematopoietic cell transplantation
Authors: Nagasawa Shun , Nishimura Toyoki , Yamada Ai , Kamimura Sachiyo , Ishimura Masataka , Moritake Hiroshi
Published: November 2024

We describe a case of RAS-associated autoimmune leukoproliferative disease with primary ciliary dyskinesia (PCD)-like symptoms, such as recurrent pneumonia, sinusitis, and otitis media, that occurred 7 years after hematopoietic cell transplantation. Whole-exome sequencing revealed a heterozygous CFAP43 nonsense variant. Environmental factors related to hematopoietic cell transplantation may have led to PCD symptoms in this patient with this variant. Genetic screening can help avoid subsequent complications during patient management.
Optical skyrmions from metafibers with subwavelength features
Authors: He Tiantian , Meng Yuan , Wang Lele , Zhong Hongkun , Mata-Cervera Nilo , Li Dan , Yan Ping , Liu Qiang , Shen Yijie , Xiao Qirong
Published: November 2024

Optical skyrmions are an emerging class of structured light with sophisticated particle-like topologies with great potential for revolutionizing modern informatics. However, the current generation of optical skyrmions involves complex or bulky systems, hindering the development of practical applications. Here, exploiting the emergent “lab-on-fiber” technology, we demonstrate the design of a metafiber-integrated photonic skyrmion generator. We not only successfully generate high-quality optical skyrmions from metafibers, but also verify their remarkable properties, such as topology switchability and topology stability with subwavelength polarization features beyond the diffraction limits. Our flexible fiber-integrated optical skyrmions platform paves the avenue for future applications of topologically-enhanced remote super-resolution microscopy and robust information transfer.
Microstructural asymmetry in the human cortex
Authors: Wan Bin , Saberi Amin , Paquola Casey , Schaare H. Lina , Hettwer Meike D. , Royer Jessica , John Alexandra , Dorfschmidt Lena , Bayrak Şeyma , Bethlehem Richard A. I. , Eickhoff Simon B. , Bernhardt Boris C. , Valk Sofie L.
Published: November 2024

The human cerebral cortex shows hemispheric asymmetry, yet the microstructural basis of this asymmetry remains incompletely understood. Here, we probe layer-specific microstructural asymmetry using one post-mortem male brain. Overall, anterior and posterior regions show leftward and rightward asymmetry respectively, but this pattern varies across cortical layers. A similar anterior-posterior pattern is observed using in vivo Human Connectome Project (N = 1101) T1w/T2w microstructural data, with average cortical asymmetry showing the strongest similarity with post-mortem-based asymmetry of layer III. Moreover, microstructural asymmetry is found to be heritable, varies as a function of age and sex, and corresponds to intrinsic functional asymmetry. We also observe a differential association of language and markers of mental health with microstructural asymmetry patterns at the individual level, illustrating a functional divergence between inferior-superior and anterior-posterior microstructural axes, possibly anchored in development. Last, we could show concordant evidence with alternative in vivo microstructural measures: magnetization transfer (N = 286) and quantitative T1 (N = 50). Together, our study highlights microstructural asymmetry in the human cortex and its functional and behavioral relevance.
Immunotherapy that improves response to chemotherapy in high-grade serous ovarian cancer
Authors: Elorbany Samar , Berlato Chiara , Carnevalli Larissa S. , Maniati Eleni , Barry Simon T. , Wang Jun , Manchanda Ranjit , Kzhyshkowska Julia , Balkwill Frances
Published: November 2024

Single-cell RNA sequencing (scRNAseq) of tumour-infiltrating immune cells in high-grade serous ovarian cancer (HGSOC) omental biopsies reveals potential targets that could enhance response to neo-adjuvant chemotherapy (NACT). Analysis of 64,097 cells identifies NACT-induced overexpression of stabilin-1 (clever-1) on macrophages and FOXP3 in Tregs that is confirmed at the protein level. STAB1 inhibition in vitro induces anti-tumour macrophages. FOXP3 anti-sense oligonucleotide (FOXP3-ASO), repolarises Tregs to an effector T cell phenotype. ScRNAseq on 69,781 cells from an HGSOC syngeneic mouse model recapitulates the patients’ data. Combining chemotherapy with anti-stabilin1 antibody and/or Foxp3-ASO significantly increases survival of mice with established peritoneal disease in two HGSOC syngeneic models and progression-free survival in a third model. Long-term survivors (300 days + ) are resistant to tumour rechallenge. Anti-stabilin1 antibody enriches the tumours with CXCL9+ macrophages and Foxp3-ASO increases TBET cell infiltration. Our results suggest that targeting these molecules in immune cells may improve chemotherapy response in patients.
Photoinduced hydrogen dissociation in thymine predicted by coupled cluster theory
Authors: Kjønstad Eirik F. , Fajen O. Jonathan , Paul Alexander C. , Angelico Sara , Mayer Dennis , Gühr Markus , Wolf Thomas J. A. , Martínez Todd J. , Koch Henrik
Published: November 2024

The fate of thymine upon excitation by ultraviolet radiation has been the subject of intense debate. Today, it is widely believed that its ultrafast excited state gas phase decay stems from a radiationless transition from the bright ππ* state to a dark nπ* state. However, conflicting theoretical predictions have made the experimental data difficult to interpret. Here we simulate the early gas phase ultrafast dynamics in thymine at the highest level of theory to date. This is made possible by performing wavepacket dynamics with a recently developed coupled cluster method. Our simulation confirms an ultrafast ππ* to nπ* transition (τ = 41 ± 14 fs). Furthermore, the predicted oxygen-edge X-ray absorption spectra agree quantitatively with experiment. We also predict an as-yet uncharacterized πσ* channel that leads to hydrogen dissociation at one of the two N-H bonds. Similar behavior has been identified in other heteroaromatic compounds, including adenine, and several authors have speculated that a similar pathway may exist in thymine. However, this was never confirmed theoretically or experimentally. This prediction calls for renewed efforts to experimentally identify or exclude the presence of this channel.
3T-VASP: fast ab-initio electrochemical reactor via multi-scale gradient energy minimization
Authors: Mailoa Jonathan P. , Li Xin , Zhang Shengyu
Published: November 2024

Ab-initio methods such as density functional theory (DFT) is useful for fundamental atomistic-level study and is widely used across many scientific fields, including for the discovery of electrochemical reaction byproducts. However, many DFT steps may be needed to discover rare electrochemical reaction byproducts, which limits DFT’s scalability. In this work, we demonstrate that it is possible to generate many elementary electrochemical reaction byproducts in-silico using just a small number of ab-initio energy minimization steps if it is done in a multi-scale manner, such as via previously reported tiered tensor transform (3T) method. We first demonstrate the algorithm through a simple example of a complex floppy organic molecule passivator binding onto perovskite solar cell surface defect site. We then demonstrate more complex examples by generating hundreds of electrochemical reaction byproducts in lithium-ion battery liquid electrolyte (many are verified in previous experimental studies), with most trajectories completed within 50–100 DFT steps as opposed to more than 10,000 steps typically utilized in an ab-initio molecular dynamics trajectory. This approach requires no machine learning training data generation and can be directly applied on any new chemistries, making it suitable for ab-initio elementary chemical reaction byproduct investigation when temperature dependence is not required.
Realization of a classical Ruddlesden Popper type bilayer nickelate in Sr3Ni2−xAlxO7−δ with unusual Ni4+
Authors: Yilmaz Hasan , Küster Kathrin , Starke Ulrich , Clemens Oliver , Isobe Masahiko , Puphal Pascal
Published: November 2024

The discovery of 80 K superconductivity in bilayer La3Ni2O7 at pressures greater than 14 GPa presents a unique opportunity to study a novel class of high-temperature superconductors. Therefore, other bilayer nickelates following the classical (T4+) Ruddlesden-Popper (RP) series of Sr3Ni2O7 would present an interesting new candidate. In this work, we study the stabilization of RP n = 2 phase in Sr3Ni2−xAlxO7−δ, via floating zone growth of crystals. With powder and single-crystal XRD, we study the stability range of the RP-type phase. Our Thermogravimetric Analysis (TGA), X-ray photoelectron spectroscopy (XPS) and gas extraction studies reveal a remarkably high oxidation state of Ni4+ stabilized by chemical strain from Al. The obtained black crystals are insulating in transport and show a magnetic transition around 12 K.
Single-cell multiomics analysis reveals dynamic clonal evolution and targetable phenotypes in acute myeloid leukemia with complex karyotype
Authors: Leppä Aino-Maija , Grimes Karen , Jeong Hyobin , Huang Frank Y. , Andrades Alvaro , Waclawiczek Alexander , Boch Tobias , Jauch Anna , Renders Simon , Stelmach Patrick , Müller-Tidow Carsten , Karpova Darja , Sohn Markus , Grünschläger Florian , Hasenfeld Patrick , Benito Garagorri Eva , Thiel Vera , Dolnik Anna , Rodriguez-Martin Bernardo , Bullinger Lars , Mrózek Krzysztof , Eisfeld Ann-Kathrin , Krämer Alwin , Sanders Ashley D. , Korbel Jan O. , Trumpp Andreas
Published: November 2024

Chromosomal instability is a major driver of intratumoral heterogeneity (ITH), promoting tumor progression. In the present study, we combined structural variant discovery and nucleosome occupancy profiling with transcriptomic and immunophenotypic changes in single cells to study ITH in complex karyotype acute myeloid leukemia (CK-AML). We observed complex structural variant landscapes within individual cells of patients with CK-AML characterized by linear and circular breakage–fusion–bridge cycles and chromothripsis. We identified three clonal evolution patterns in diagnosis or salvage CK-AML (monoclonal, linear and branched polyclonal), with 75% harboring multiple subclones that frequently displayed ongoing karyotype remodeling. Using patient-derived xenografts, we demonstrated varied clonal evolution of leukemic stem cells (LSCs) and further dissected subclone-specific drug–response profiles to identify LSC-targeting therapies, including BCL-xL inhibition. In paired longitudinal patient samples, we further revealed genetic evolution and cell-type plasticity as mechanisms of disease progression. By dissecting dynamic genomic, phenotypic and functional complexity of CK-AML, our findings offer clinically relevant avenues for characterizing and targeting disease-driving LSCs.
Two decades of body length measurements of larval and juvenile fish populations in English rivers
Authors: Ainsworth Rachel F. , Vickers Lauren H. , Bolland Jonathan D. , Taylor Marie J. , Harvey Jon P. , Noble Richard A. A. , Cowx Ian G. , Nunn Andy D.
Published: November 2024

Long-term datasets provide context and understanding of complex ecological processes, including temporal variations in species diversity and ecosystem dynamics. This dataset is comprised of body length measurements (mm) of more than 380,000 larval or juvenile fish of 30 species from five English river catchments collected almost monthly over two decades. Such information can be used to determine growth rates, future recruitment success, population structure and compliance with monitoring protocols and conservation objectives. The dataset provides a baseline for analysing the impacts of anthropogenic disturbances such as climate change, pollution and habitat degradation, and, given that many fish populations are size structured with a positive relationship between fish body length and various biological attributes such as swimming ability, survival and fecundity, it will be invaluable for investigating natural and human- induced disturbances.
Lymphocytic choriomeningitis arenavirus utilises intercellular connections for cell to cell spread
Authors: Byford Owen , Shaw Amelia B. , Tse Hiu Nam , Moon-Walker Alex , Saphire Erica Ollmann , Whelan Sean P. J. , Stacey Martin , Hewson Roger , Fontana Juan , Barr John N.
Published: November 2024

The Arenaviridae family of segmented RNA viruses contains nearly 70 species with several associated with fatal haemorrhagic fevers, including Lassa, Lujo and Junin viruses. Lymphocytic choriomeningitis arenavirus (LCMV) is associated with fatal neurologic disease in humans and additionally represents a tractable model for studying arenavirus biology. Within cultured cells, a high proportion of LCMV spread is between directly neighbouring cells, suggesting infectivity may pass through intercellular connections, bypassing the canonical extracellular route involving egress from the plasma membrane. Consistent with this, we visualized abundant actin- and tubulin-rich connections conjoining LCMV-infected and uninfected cells within cultures, resembling tunnelling nanotubes (TNTs). Within these TNT-like connections, confocal and STED microscopy identified puncta containing the major structural components of LCMV virions alongside genomic RNA, consistent with intercellular transit of assembled virions or ribonucleoprotein genome segments. Blocking the extracellular route of infection by adding potent LCMV neutralising antibody M28 to supernatants during infection revealed around 50% of LCMV transmission was via intercellular connections. These results show arenaviruses transmission is more complex than previously thought involving both extracellular and intercellular routes.
Volumetric efficiency in motor-driven two-dimensional piston pumps with leakage and reverse flow under high pressure
Authors: Chen Yong , Hua Congcong , Tong Chengwei , Zang Yiren , Ruan Jian
Published: November 2024

This paper presents a volumetric efficiency model for high-pressure motor-driven 2D piston pumps, incorporating key factors such as axial internal and external leakage, circumferential leakage, and reverse flow. The model integrates hydraulic fluid compressibility and variations in flow coefficients to improve simulation accuracy. Co-simulation using AMESim and Simulink, along with experimental validation, demonstrates the model’s reliability across various operating conditions. The results show that rotational speed enhances volumetric efficiency due to its minimal effect on leakage and reverse flow, while pressure significantly reduces efficiency, particularly through reverse flow and circumferential leakage. Reducing trapped volume proves to be an effective strategy for minimizing reverse flow and improving overall pump performance. Additionally, refining flow coefficients to improve the accuracy of the simulation model remains an important area for further development.