bluuebunny/crossref_metadata_2025 huggingface dataset:
Points to Consider on the Use of Medicines in Pregnancy Throughout the Product Lifecycle Based on Global Regulatory Guidance
Authors: Alexe Amalia , Wurst Keele , Balramsingh-Harry Leesha , Apara Olatayo , Abramova Nadezda , Eisele Osa , Fernandes Maria Fernanda Scantamburlo , Garg Anju , Kovacs Birgit , Lewis David
Published: February 2025

The thalidomide tragedy of the 1960s led to restrictions and limitations in the participation of pregnant women in clinical trials. Despite the paucity of information on the safe and effective use of medicines in this population, most pregnant women are prescribed medications. A landscape assessment review of guidelines and legislation governing the use of medicines in pregnancy and during breastfeeding was conducted by the TransCelerate Pharmacovigilance Pregnancy and Breastfeeding Team. Insights from the landscape assessment review were compiled to identify important points to consider concerning the use of medicines in pregnancy throughout a product lifecycle. Four main areas were identified for consideration for use of medicines in pregnancy: (1) Product development considerations: Key points on the disease itself, the medicine characteristics, non-clinical and clinical development. (2) Interventional study considerations: Key aspects in enrollment of pregnant women in clinical trials and the follow-up requirements for such women. (3) Post-marketing considerations: Key elements in spontaneous case reporting of medicines exposure during pregnancy, implementation of appropriate risk management plans for medicines likely to be used in pregnancy. (4) Full lifecycle considerations: Activities required by regulators to ensure safety surveillance and maintenance throughout product lifecycle. There is a need for harmonized guidance on how to study the use of medicine in pregnancy. This paper addresses regulatory considerations, to aid in the planning and execution of research programs focused on developing medicines for use in pregnancy when permissible under established regulatory framework.
A Critical Analysis of How Victims of Sexual Assault Face Violence in the Medical Process of Bangladesh Through Foucault’s Concept of Medical Gaze
Authors: Banarjee Subrata
Published: February 2025

Research continues to demonstrate that the women in Bangladesh are facing harassment during the medical process after being victims of rape. The current medical process is discriminatory and does not protect victims’ safety, confidentiality, and ethical issues. This paper identifies the challenges that victims of rape face during the medical procedure. I employed Foucault’s concept of medical gaze as the theoretical lens to uncover how the gaze is imposed upon the victims in the medical process. Discussion also show that the current medical process has significant gaps and limitations in treating women after victimization.
Striving for Peace through Personal Narratives of Genocide and War
Authors: Chaitin Julia , Avlagon Elad
Published: February 2025

Personal narratives of genocide and intractable war can provide valuable insights around notions of collective identity, perceptions of the 'enemy,' intergenerational coping with massive social trauma, and sustainable peace and reconciliation. Written in an accessible and narrative style, this book demonstrates how the sharing of and listening to personal experiences deepens understandings of the long-term psychosocial impacts of genocide and war on direct victims and their descendants in general, and of the Holocaust and the Jewish–Arab/Palestinian–Israeli context, in particular. It provides a new theoretical model concerning the relationship between different kinds of personal narratives of genocide and war and peacebuilding or peace obstruction. Through its presentation and analysis of personal narratives connected to the Holocaust and the Palestinian–Israeli conflict, it provides a deep exploration into how such narratives have the potential to promote peace and offers concrete ideas for further research of the topic and for peacebuilding on the ground.
Deciphering the Intermodel Spread in Projections of the Impacts of Indian Summer Monsoon on ENSO Under Global Warming
Authors: Lin Shuheng , Yang Song , Dong Buwen , Deng Kaiqiang , Fang Keyan
Published: February 2025

The Indian summer monsoon (ISM) is intricately linked to the El Niño‐Southern Oscillation (ENSO) on interannual timescale. Although previous studies have explored ENSO's effects on the ISM, the reverse influence, particularly under global warming, remains unclear. This study examines the projected changes in the ISM's impacts on ENSO under the SSP5‐8.5 emission scenario using 34 climate models from the Coupled Model Intercomparison Project Phase 6 (CMIP6) that reasonably simulate the monsoon's effects on ENSO. A significant spread is found in the projections across the models, with approximately half of the models projecting an enhancing influence of ISM on ENSO, whereas the other half indicates a weakening effect. The intermodel spread is primarily associated with the projected changes in the strength of the feedback between precipitation and low‐level circulation over the tropical northwest Pacific, which is crucial for generating ISM‐induced anomalous circulation over the region. Models projecting an enhanced precipitation‐circulation feedback simulate larger ISM‐driven rainfall and circulation anomalies over the tropical northwest Pacific in a warmer climate, leading to more pronounced zonal wind anomalies near the equator along the southern side of the anomalous circulation and vice versa. As a result, the larger zonal wind anomalies caused by abnormal monsoons exert intensified effects on the subsequent ENSO evolution by significantly suppressing or amplifying the atmosphere‐ocean coupling processes related to ENSO development.
Mercury's Field‐Aligned Currents: Perspectives From Hybrid Simulations
Authors: Shi Z. , Rong Z. J. , Fatemi S. , Dong C. F. , Klinger Lucy , Gao J. W. , Slavin J. A. , He F. , Wei Y. , Holmström M. , Barabash S.
Published: February 2025

Previous studies suggested that Mercury's magnetosphere could possess Earth‐like field‐aligned currents (FACs) despite the absence of an ionosphere. However, due to the limited coverage of spacecraft observations, our understanding of Mercury's FACs is scarce. Here, we employed Amitis, a hybrid‐kinetic plasma model, to investigate the establishment and global pattern of Mercury's FACs. The responses of Mercury's FACs to various interior conductivity profiles and different orientations of the upstream interplanetary magnetic field (IMF) were simulated. It has been shown that the profile of a less resistive upper layer and a conducting core favors the establishment of FACs. Three types of large‐scale FACs (Region 1‐like, Region 2‐like and NBZ‐like FACs) are shown in simulations. Comparison with previous observations suggests that Mercury's effective conductance for closing R1‐like FACs is ∼2.4–3.4 S. The influence of IMF orientation on FACs is similar to that observed in Earth's magnetosphere, but the response of the R2‐like FACs to the IMF orientation is different.
WindSightNet: The Inter‐Annual Variability of Martian Winds Retrieved From InSight's Seismic Data With Machine Learning
Authors: Stott Alexander E. , Garcia Raphael F. , Murdoch Naomi , Mimoun David , Drilleau Mélanie , Newman Claire , Spiga Aymeric , Banfield Don , Lemmon Mark , Navarro Sara , Mora‐Sotomayor Luis , Charalambous Constantinos , Pike William T. , Lognonné Philippe , Banerdt William B.
Published: February 2025

Wind measurements from landed missions on Mars are vital to characterize the near surface atmospheric behavior on Mars and improve atmospheric models. These winds are responsible for aeolian change and the mixing of dust in and out of the atmosphere, which has a significant effect on global circulation. The NASA InSight mission recorded wind data for around 750 sols. The seismometer, however, recorded data for around 1400 sols. The dominant source of energy in the seismic data is in fact due to winds. To this end, we propose a machine learning model, dubbed WindSightNet, to map the seismic data to wind speed and direction. The trained network achieves wind speed and direction measurements with errors of 0.932 m/s and 32.6°. We use WindSightNet to retrieve winds from the entire time the seismometer was recording to compare year‐to‐year wind variations at InSight. The continuous nature of the data set enables the extraction of periodic behavior. We observe a pattern of waves due to baroclinic activity with periods of 2–3, 4, 5–7 and 9–20 sols occurring 180–360°. We also observe periodicity during the day due to convective cells. This is used to estimate the boundary layer height, yielding values between 2.3 and 7.7 km. A data‐science based metric is proposed to provide a quantification of the year‐to‐year differences in the wind speeds. This highlights variations linked to dust activity as well as other transient differences. On the whole, the seismic‐derived winds confirm the dominance of the global circulation leading to repeatable weather patterns.
U.S. Power Grids are Vulnerable to Extreme Weather
Authors: Scharping Nathaniel
Published: February 2025

Different kinds of severe weather, including multiple kinds at once, have different impacts on the grid in different places.
Dynamic water vapor sorption: a helpful tool for preventive conservation of salt contaminated built heritage
Authors: Stahlbuhk Amelie , Godts Sebastiaan , Steiger Michael
Published: February 2025

The presence of salts and related salt-induced damage represent one of the major threats to the preservation of our built heritage. Identifying critical relative humidity values that facilitate crystallization cycles is essential for understanding damage risks and extents. This knowledge helps in developing recommendations for favorable, damage-avoiding climates, particularly in controllable indoor environments. While for single salts their deliquescence humidity is known, for multi-ion mixtures relevant for the built heritage multiple transitions happen over a range of relative humidity. Modeling of equilibrium crystallization pathways is possible, e.g. using the Pitzer formalism. However, for complex mixtures, only predictions can be given, which need to be validated through experimental results. This work focuses on the use of dynamic water vapor sorption measurements to investigate phase transitions in salt mixtures, demonstrating its applicability, scrutinizing different influencing factors and an appropriate interpretation of results. Additionally, presenting an experimental design that delivers reliable results for the conservation of cultural heritage is crucial. In addition to single salts, mixtures from the common hygroscopic system Na+–K+–Mg2+–Ca2+–Cl––NO3
––H2O are investigated, including their behavior in a stone material. The identified transitions are compared to the calculated behavior using the ECOS–Runsalt model. The presented results are accurate and reproducible. They show the ability to determine the critical relative humidity ranges (in bulk and in porous materials) and validate thermodynamic models.
Acylcarnitines metabolism in depression: association with diagnostic status, depression severity and symptom profile in the NESDA cohort
Authors: Montanari Silvia , Jansen Rick , Schranner Daniela , Kastenmüller Gabi , Arnold Matthias , Janiri Delfina , Sani Gabriele , Bhattacharyya Sudeepa , Mahmoudian Dehkordi Siamak , Dunlop Boadie W. , Rush A. John , Penninx Brenda W. H. J. , Kaddurah-Daouk Rima , Milaneschi Yuri
Published: February 2025

Acylcarnitines (ACs) are involved in bioenergetics processes that may play a role in the pathophysiology of depression. Previous genomic evidence identified four ACs potentially linked to depression risk. We carried forward these ACs and tested the association of their circulating levels with Major Depressive Disorder (MDD) diagnosis, overall depression severity and specific symptom profiles. The sample from the Netherlands Study of Depression and Anxiety included participants with current (n = 1035) or remitted (n = 739) MDD and healthy controls (n = 800). Plasma levels of four ACs (short-chain: acetylcarnitine C2 and propionylcarnitine C3; medium-chain: octanoylcarnitine C8 and decanoylcarnitine C10) were measured. Overall depression severity as well as atypical/energy-related (AES), anhedonic and melancholic symptom profiles were derived from the Inventory of Depressive Symptomatology. As compared to healthy controls, subjects with current or remitted MDD presented similarly lower mean C2 levels (Cohen’s d = 0.2, p ≤ 1e-4). Higher overall depression severity was significantly associated with higher C3 levels (ß = 0.06, SE = 0.02, p = 1.21e-3). No associations were found for C8 and C10. Focusing on symptom profiles, only higher AES scores were linked to lower C2 (ß = −0.05, SE = 0.02, p = 1.85e-2) and higher C3 (ß = 0.08, SE = 0.02, p = 3.41e-5) levels. Results were confirmed in analyses pooling data with an additional internal replication sample from the same subjects measured at 6-year follow-up (totaling 4141 observations). Small alterations in levels of short-chain acylcarnitine levels were related to the presence and severity of depression, especially for symptoms reflecting altered energy homeostasis. Cellular metabolic dysfunctions may represent a key pathway in depression pathophysiology potentially accessible through AC metabolism.
Glycolysis reprogramming in CAFs promotes oxaliplatin resistance in pancreatic cancer through circABCC4 mediated PKM2 nuclear translocation
Authors: He Rihua , Hu Chonghui , Yuan Yuan , Li Tingting , Tian Qing , Huang Tianhao , Lin Qing , Zheng Shangyou , Chen Chujie , Fu Zhiqiang , Chen Rufu
Published: February 2025

Cancer-associated fibroblasts (CAFs) play a key role in oxaliplatin resistance in pancreatic ductal adenocarcinoma (PDAC). However, the potential mechanisms by which CAFs promote chemotherapy resistance have not yet been explored. In this study, we found that circABCC4 (hsa_circ_0030582) was positively correlated with poor platinum-chemotherapeutic response and a shorter progression-free survival (PFS) time in late-stage PDAC patients. CircABCC4 enhanced the ability of CAFs to induce oxaliplatin resistance in pancreatic cancer cells through glycolysis reprogramming. Mechanistically, circABCC4 enhanced the interaction between PKM2 and KPNA2 to promote PKM2 nuclear translocation in CAFs, leading to the transcription of glycolysis-related genes. The glycolytic reprogramming of CAFs promoted the secretion of IL-8, which in turn enhanced DNA damage repair in pancreatic cancer. Blocking PKM2 nuclear translocation abolished circABCC4-driven oxaliplatin resistance of pancreatic cancer in vivo. Collectively, our study reveals a circRNA-mediated glycolysis reprogramming of CAFs to induce oxaliplatin resistance and highlights circABCC4 as a potential therapeutic target.
STX17-DT facilitates axitinib resistance in renal cell carcinoma by inhibiting mitochondrial ROS accumulation and ferroptosis
Authors: Pan Yihui , Liu Shuang , Shu Guannan , Chen Minyu , Fu Liangmin , Chen Cheng , Chen Yimeng , Zhuang Qianfeng , Xue Dong , He Xiaozhou
Published: February 2025

Axitinib resistance remains a serious challenge in the treatment of advanced renal cell carcinoma (RCC), and the underlying mechanisms are not fully understood. Here, we constructed an in vivo axitinib-resistant RCC model and identified the long non-coding RNA STX17-DT as a driver of therapy resistance in RCC. The expression of STX17-DT was significantly elevated in axitinib-resistant RCC cells and correlated with poorer prognosis in RCC patients. Elevated levels of STX17-DT contributed to the development of resistance to axitinib both in vitro and in vivo. Mechanistically, STX17-DT modulated the stability of IFI6 mRNA by recruiting and binding to hnRNPA1, leading to decreased accumulation of mitochondrial reactive oxygen species (ROS) and attenuated ferroptosis. Meanwhile, STX17-DT was packaged into extracellular vesicles through hnRNPA1, thus transmitting axitinib resistance to other cells. Compared with axitinib monotherapy, combined treatment of axitinib and STX17-DT-targeted in vivo siRNA demonstrated enhanced therapeutic efficacy. These findings indicate a novel molecular mechanism of axitinib resistance in RCC and suggest that STX17-DT may serve as a prognostic indicator and potential therapeutic target to overcome resistance to targeted therapy.
SREBF1-based metabolic reprogramming in prostate cancer promotes tumor ferroptosis resistance
Authors: Wei Guojiang , Huang Ying , Li Wenya , Xie Yuxin , Zhang Deyi , Niu Yuanjie , Zhao Yang
Published: February 2025

Metabolic reprogramming in prostate cancer has been widely recognized as a promoter of tumor progression and treatment resistance. This study investigated its association with ferroptosis resistance in prostate cancer and explored its therapeutic potential. In this study, we identified differences in the epithelial characteristics between normal prostate tissue and tissues of various types of prostate cancer using single-cell sequencing. Through transcription factor regulatory network analysis, we focused on the candidate transcription factor, SREBF1. We identified the differences in SREBF1 transcriptional activity and its association with ferroptosis, and further verified this association using hdWGCNA. We constructed a risk score based on SREBF1 target genes associated with the biochemical recurrence of prostate cancer by combining bulk RNA analysis. Finally, we verified the effects of the SREBPs inhibitor Betulin on the treatment of prostate cancer and its chemosensitization effect. We observed characteristic differences in fatty acid and cholesterol metabolism between normal prostate tissue and prostate cancer tissue, identifying high transcriptional activity of SREBF1 in prostate cancer tissue. This indicates that SREBF1 is crucial for the metabolic reprogramming of prostate cancer, and that its mediated metabolic changes promoted ferroptosis resistance in prostate cancer in multiple ways. SREBF1 target genes are associated with biochemical recurrence of prostate cancer. Finally, our experiments verified that SREBF1 inhibitors can significantly promote an increase in ROS, the decrease in GSH, and the decrease in mitochondrial membrane potential in prostate cancer cells and confirmed their chemosensitization effect in vivo. Our findings highlighted a close association between SREBF1 and ferroptosis resistance in prostate cancer. SREBF1 significantly influences metabolic reprogramming in prostate cancer cells, leading to ferroptosis resistance. Importantly, our results demonstrated that SREBF1 inhibitors can significantly enhance the therapeutic effect and chemosensitization of prostate cancer, suggesting a promising therapeutic potential for the treatment of prostate cancer.
Macrocarpal I induces immunogenic cell death and synergizes with immune checkpoint inhibition by targeting tubulin and PARP1 in colorectal cancer
Authors: Zhang Yaxin , Li Huali , Zhao Yali , Liu Lingtao , Zhou Yi , Pan Xingyan , Ding Yanqing , Liao Wenting , Qi Lu , Huang Chengmei , Tang Na
Published: February 2025

Colorectal cancer (CRC) presents an obstacle to immunotherapy, primarily because most cases are microsatellite stable (MSS) tumors, which are often described as “cold tumors” with limited immunogenicity. Recent studies have indicated that several therapeutic approaches, such as chemotherapy and targeted therapies, can elicit immunogenic cell death (ICD) and stimulate immune responses. However, challenges such as target affinity and in vivo pharmacokinetics limit the efficacy and immune response of current targeted therapies. In this study, we demonstrate that Macrocarpal I is a potent inducer of ICD by activating the PERK/eIF2A/ATF4/CHOP signaling pathway. Furthermore, Macrocarpal I induces apoptosis and ferroptosis, both of which act as triggers for ICD. Mechanistically, Macrocarpal I directly targets TUBB2B and PARP1, disrupting microtubule polymerization and DNA repair processes. Importantly, treatment with Macrocarpal I enhances the anti-tumor immune response and augments responsiveness to anti-PD-1 therapy in an MC38 syngeneic mouse model of CRC.
Chromobox protein homolog 7 suppresses the stem-like phenotype of glioblastoma cells by regulating the myosin heavy chain 9-NF-κB signaling pathway
Authors: Ni Kaixiang , Liu Yuankun , DI Pinggang , Wang Lu , Huang Hui , Holsinger R. M. Damian , Kiang Karrie Mei-Yee , Jiao Jiantong
Published: February 2025

Cancer stem cells (CSCs) are significant factors in the treatment resistance and recurrence of glioblastoma. Chromobox protein homolog 7 (CBX7) can inhibit the progression of various tumors, but its impact on the stem cell-like properties of glioblastoma cells remains unclear. Clinically, low levels of CBX7 are associated with poor prognosis and increased distant metastasis in glioblastoma patients, and this low expression is caused by methylation of the CBX7 promoter. Our current research indicates that CBX7 plays a key role in suppressing the stem-like phenotype of glioblastoma. In this study, through bioinformatics analysis, we found that CBX7 is the most significantly downregulated member of the CBX family in glioblastoma and is closely associated with the stem-like phenotype of glioblastoma cells. We show that CBX7 promotes the degradation of myosin heavy chain 9 (MYH9) protein through the ubiquitin-proteasome pathway via the polycomb repressive complex 1 (PRC1) and suppresses the stem-like phenotype of glioblastoma cells by inhibiting the nuclear factor kappa-B (NF-κB) signaling pathway. Furthermore, overexpression of MYH9 in glioblastoma cells reverses the inhibitory effects of CBX7 on migration, proliferation, invasion, and stemness of glioblastoma cells. In summary, CBX7 acts as a tumor suppressor by inhibiting the stem cell-like characteristics of glioblastoma. The CBX7-MYH9-NF-κB signaling axis may serve as a potential therapeutic target for glioblastoma.
Anomalous δ15N values in the Neoarchean associated with an abundant supply of hydrothermal ammonium
Authors: Martin Ashley N. , Stüeken Eva E. , Gehringer Michelle M. , Markowska Monika , Vonhof Hubert , Weyer Stefan , Hofmann Axel
Published: February 2025

Unusually high δ15N values in the Neoarchean sedimentary record in the time period from 2.8 to 2.6 Ga, termed the Nitrogen Isotope Event (NIE), might be explained by aerobic N cycling prior to the Great Oxidation Event (GOE). Here we report strongly positive δ15N values up to +42.5 ‰ in ~2.75 – 2.73 Ga shallow-marine carbonates from Zimbabwe. As the corresponding deeper-marine shales exhibit negative δ15N values that are explained by partial biological uptake from a large ammonium reservoir, we interpret our data to have resulted from hydrothermal upwelling of 15N-rich ammonium into shallow, partially oxic waters, consistent with uranium isotope variations. This work shows that anomalous N isotope signatures at the onset of the NIE temporally correlate with extensive volcanic and hydrothermal activity both locally and globally, which may have stimulated primary production and spurred biological innovation in the lead-up to the GOE.
The utility of animal models to inform the next generation of human space exploration
Authors: Duporge Isla , Pereira Talmo , de Obeso Santiago Castiello , Ross Julius G. Bright , J. Lee Stephen , G. Hindle Allyson
Published: February 2025

Animals have played a vital role in every stage of space exploration, from early sub-orbital flights to contemporary missions. New physiological and psychological challenges arise with plans to venture deeper into the solar system. Advances in chimeric and knockout animal models, along with genetic modification techniques have enhanced our ability to study the effects of microgravity in greater detail. However, increased investment in the purposeful design of habitats and payloads, as well as in AI-enhanced behavioral monitoring in orbit can better support the ethical and effective use of animals in deep space research.
Clinical and functional evidence for the pathogenicity of the LRRK2 p.Arg1067Gln variant
Authors: Lim Shen-Yang , Toh Tzi Shin , Hor Jia Wei , Lim Jia Lun , Lit Lei Cheng , Ahmad-Annuar Azlina , Tay Yi Wen , Foo Jia Nee , Ng Ebonne Yulin , Muthusamy Kalai Arasu , Mohamed Ibrahim Norlinah , Ibrahim Khairul Azmi , Tan Louis Chew Seng , Zulkefli Jannah , Khairul Anuar Anis Nadhirah , Black Kirsten , Lis Pawel , Xie Fei , Cen Zhidong , Lim Kai Shi , Lohmann Katja , Padmanabhan Shalini , Alessi Dario R. , Luo Wei , Tan Eng King , Sammler Esther , Tan Ai Huey
Published: February 2025

LRRK2-related Parkinson’s disease (LRRK2-PD) is the most frequent form of monogenic PD worldwide, with important therapeutic opportunities, exemplified by the advancement in LRRK2 kinase inhibition studies/trials. However, many LRRK2 variants, especially those found in underrepresented populations, remain classified as variants of uncertain significance (VUS). Leveraging on Malaysian, Singaporean, and mainland Chinese PD datasets (n = 4901), we describe 12 Chinese-ancestry patients harboring the LRRK2 p.Arg1067Gln variant, more than doubling the number of previously reported cases (total n = 23, 87% East Asian, mean age of onset: 53.9 years). We determine that this variant is enriched in East Asian PD patients compared to population controls (OR = 8.0, 95% CI: 3.0–20.9), and provide supportive data for its co-segregation with PD, albeit with incomplete penetrance. Utilizing established experimental workflows, this variant showed increased LRRK2 kinase activity, by ~2-fold compared to wildtype and higher than the p.Gly2019Ser variant. Taken together, p.Arg1067Gln should be reclassified from a VUS to pathogenic for causing LRRK2-PD.
A standardized lexicon of body odor words crafted from 17 countries
Authors: Bierling Antonie L. , Croy Alexander , Bilem Fatma , Bloy Leah , HO Fiona Yan-Yee , Jimenez Andres F. , Kyjaková Pavlína , Mastinu Mariano , Power Guerra Nicole , Sailer Uta , Schirmer Annett , Silva Edgardo C. , Surakka Veikko , Takau Lana , Thunell Evelina , Verma Kedarmal , Żyżelewicz Barbara R. , Majid Asifa , Croy Ilona
Published: February 2025

Body odors offer a unique window into the physiological and psychological profile of the emitter. This information, broadcast in nonverbal communication, significantly shapes social interactions. However, effectively digitizing body odors requires a precise framework for perceptual operationalization. Previous research has used a very limited number of verbal terms, such as pleasant, intense, or attractive, which fails to adequately capture qualitative differences. To address this gap, we elicited body odor descriptions from 2,607 participants across 17 countries and 13 languages. All these descriptions are presented here in one dataset, together with a condensed list of 25 body odor words (BOW). Those terms reliably differentiated between body states, and were validated in a separate study with a different group of 155 perceivers. The dataset, available as a web application, provides a novel operationalization of body odor impressions, which is a precondition for studying olfaction in human nonverbal communication, for perception-based digitization of body odors and for comparative studies.
Canopy height model and NAIP imagery pairs across CONUS
Authors: Allred Brady W. , McCord Sarah E. , Morford Scott L.
Published: February 2025

Canopy height models (CHM) provide detailed environmental vertical structure information and are an important indicator and input for ecological and geospatial applications. These models are often spatiotemporally inconsistent, necessitating additional modeling to scale them in space and time. Yet, such scaling is hindered by a lack of spatially diverse data. To address this, we use United States Geological Survey 3D Elevation Program lidar data to produce 22,796,764 one meter resolution CHM chips, stratified across the dominant land covers of the conterminous United States. For each CHM, we pair a matching time-aligned aerial image from the United States Department of Agriculture National Agriculture Imagery Program. This dataset can be used to train models for large scale CHM production.
Spatial recognition and semi-quantification of epigenetic events in pancreatic cancer subtypes with multiplexed molecular imaging and machine learning
Authors: Szymoński Krzysztof , Janiszewska Natalia , Sofińska Kamila , Skirlińska-Nosek Katarzyna , Lupa Dawid , Czaja Michał , Urbańska Marta , Jurkowska Katarzyna , Konik Kamila , Olszewska Marta , Adamek Dariusz , Awsiuk Kamil , Lipiec Ewelina
Published: February 2025

Genomic alterations are the driving force behind pancreatic cancer (PC) tumorigenesis, but they do not fully account for its diverse phenotypes. Investigating the epigenetic landscapes of PC offers a more comprehensive understanding and could identify targeted therapies that enhance patient survival. In this study, we have developed a new promising methodology of spatial epigenomics that integrates multiplexed molecular imaging with convolutional neural networks. Then, we used it to map epigenetic modification levels in the six most prevalent PC subtypes. We analyzed and semi-quantified the resulting molecular data, revealing significant variability in their epigenomes. DNA and histone modifications, specifically methylation and acetylation, were investigated. Using the same technique, we examined DNA conformational changes to further elucidate the transcriptional regulatory mechanisms involved in PC differentiation. Our results revealed that the foamy-gland and squamous-differentiated subtypes exhibited significantly increased global levels of epigenetic modifications and elevated Z-DNA ratios. Overall, our findings may suggest a potentially reduced efficacy of therapeutics targeting epigenetic regulators for these subtypes. Conversely, the conventional ductal PC subtype has emerged as a promising candidate for treatment with epigenetic modulators.
Multimodal machine learning to predict surgical site infection with healthcare workload impact assessment
Authors: McLean Kenneth A. , Sgrò Alessandro , Brown Leo R. , Buijs Louis F. , Mountain Katie E. , Shaw Catherine A. , Drake Thomas M. , Pius Riinu , Knight Stephen R. , Fairfield Cameron J. , Skipworth Richard J. E. , Tsaftaris Sotirios A. , Wigmore Stephen J. , Potter Mark A. , Bouamrane Matt-Mouley , Harrison Ewen M. ,   TWIST Collaborators, Baweja K. , Cambridge W. A. , Chauhan V. , Czyzykowska K. , Edirisooriya M. , Forsyth A. , Fox B. , Fretwell J. , Gent C. , Gherman A. , Green L. , Grewar J. , Heelan S. , Henshall D. , Iiuoma C. , Jayasangaran S. , Johnston C. , Kennedy E. , Kremel D. , Kung J. , Kwong J. , Leavy C. , Liu J. , Mackay S. , MacNamara A. , Mowitt S. , Musenga E. , Ng N. , Ng Z. H. , O’Neill S. , Ramage M. , Reed J. , Riad A. , Scott C. , Sehgal V. , Sgrò A. , Steven L. , Stutchfield B. , Tominey S. , Wilson W. , Wojtowicz M. , Yang J.
Published: February 2025

Remote monitoring is essential for healthcare digital transformation, however, this poses greater burdens on healthcare providers to review and respond as the data collected expands. This study developed a multimodal neural network to automate assessments of patient-generated data from remote postoperative wound monitoring. Two interventional studies including adult gastrointestinal surgery patients collected wound images and patient-reported outcome measures (PROMs) for 30-days postoperatively. Neural networks for PROMs and images were combined to predict surgical site infection (SSI) diagnosis within 48 h. The multimodal neural network model to predict confirmed SSI within 48 h remained comparable to clinician triage (0.762 [0.690–0.835] vs 0.777 [0.721–0.832]), with an excellent performance on external validation. Simulated usage indicated an 80% reduction in staff time (51.5 to 9.1 h) without compromising diagnostic accuracy. This multimodal approach can effectively support remote monitoring, alleviating provider burden while ensuring high-quality postoperative care.
Mechanisms of electrochemical hydrogenation of aromatic compound mixtures over a bimetallic PtRu catalyst
Authors: Catizane Cesar , Jiang Ying , Sumner Joy
Published: February 2025

Efficient electrochemical hydrogenation (ECH) of organic compounds is essential for sustainability, promoting chemical feedstock circularity and synthetic fuel production. This study investigates the ECH of benzoic acid, phenol, guaiacol, and their mixtures, key components in upgradeable oils, using a carbon-supported PtRu catalyst under varying initial concentrations, temperatures, and current densities. Phenol achieved the highest conversion (83.17%) with a 60% Faradaic efficiency (FE). In mixtures, benzoic acid + phenol yielded the best performance (64.19% conversion, 74% FE), indicating a synergistic effect. Notably, BA consistently exhibited 100% selectivity for cyclohexane carboxylic acid (CCA) across all conditions. Density functional theory (DFT) calculations revealed that parallel adsorption of BA on the cathode (−1.12 eV) is more stable than perpendicular positioning (-0.58 eV), explaining the high selectivity for CCA. These findings provide a foundation for future developments in ECH of real pyrolysis oil.
Ice core evidence for the Los Chocoyos supereruption disputes millennial-scale climate impact
Authors: Innes Helen M. , Hutchison William , Sigl Michael , Crick Laura , Abbott Peter M. , Bigler Matthias , Chellman Nathan J. , Davies Siwan M. , Kutterolf Steffen , McConnell Joseph R. , Severi Mirko , Sparks R. Stephen J. , Svensson Anders , Wolff Eric W. , Rae James W. B. , Burke Andrea
Published: February 2025

Volcanic supereruptions are considered among the few drivers of global and existential catastrophes, with recent hypotheses suggesting massive volcanic stratospheric sulfate injection could instigate major shifts in global climate. The absence of supereruptions during recent history as well as large uncertainties on eruption ages limits understanding of the climatic risk they impose. Polar ice cores have well-resolved continuous age models, record past temperature, and contain volcanic sulfate and cryptotephra deposits which can be geochemically fingerprinted to determine eruption timing and improve stratospheric sulfur loading estimates. Here, we provide an age of 79,500 years for the Atitlán Los Chocoyos supereruption, one of the largest Quaternary eruptions, by identifying tephra shards in ice cores from both Greenland and Antarctica. This ice core age is supported by a revised marine sediment core stratigraphy age for the Los Chocoyos ash layer. Through comparison with well-dated ice-core temperature proxy records, our study suggests that despite being one of the largest sulfur emissions recorded in ice cores, the Los Chocoyos supereruption did not trigger a millennial-scale cold period.
Application of decision analytic modelling to cardiovascular disease prevention in Sub-Saharan Africa: a systematic review
Authors: Oguta James Odhiambo , Breeze Penny , Wambiya Elvis , Kibe Peter , Akoth Catherine , Otieno Peter , Dodd Peter J.
Published: February 2025

Background

This systematic review sought to examine the application of decision analytic models (DAMs) to evaluate cardiovascular disease (CVD) prevention interventions in sub-Saharan Africa (SSA), a region that has experienced an increasing CVD burden in the last two decades.

Methods

We searched seven databases and identified model-based economic evaluations of interventions targeting CVD prevention among adult populations in SSA. All articles were screened by two reviewers, data was extracted, and narrative synthesis was performed. Quality assessment was performed using the Philips checklist.

Results

The review included 27 articles from eight SSA countries. The majority of the studies evaluated interventions for primary CVD prevention, with primordial prevention interventions being the least evaluated. Markov models were the most commonly used modelling method. Seven studies incorporated equity dimensions in the modelling, which were assessed mainly through subgroup analysis. The mean quality score of the papers was 68.9% and most studies reported data challenges while only three studies conducted model validation.

Conclusions

The review finds few studies modelling the impact of interventions targeting primordial prevention and those evaluating equitable strategies for improving access to CVD prevention. There is a need for increased transparency in model building, validation and documentation.
Post-discharge suicide prediction among US veterans using natural language processing-enriched social and behavioral determinants of health
Authors: Mitra Avijit , Chen Kun , Liu Weisong , Kessler Ronald C. , Yu Hong
Published: February 2025

Despite the established association between social and behavioral determinants of health (SBDH) and suicide risk, SBDHs from unstructured electronic health record notes for suicide prediction remain underutilized. This study investigates the impact of SBDH identified from both structured and unstructured data utilizing a natural language processing (NLP) system on suicide prediction at 7, 30, 90, and 180 days post-discharge. Using data from 2,987,006 US Veterans between 1 October 2009, and 30 September 2015, we designed a case-control study demonstrating that structured and NLP-extracted SBDH significantly enhance distinct prediction models’ performance. For example, the random forest model improved its 180-day post-discharge prediction with an area under the receiver operating characteristic curve increase from 83.57% to 84.25% (95% CI = 0.63%–0.98%, p val < 0.001) and area under the precision-recall curve increase from 57.38% to 59.87% (95% CI = 3.86%–4.82%, p val < 0.001) after integrating NLP-extracted SBDH. These findings underscore the potential of NLP-extracted SBDH in advancing suicide prediction.
Mimicking women’s endocrine milieu in mice for women’s health-related studies
Authors: Constantin Céline , Matvienko Daria , László Csaba , Scabia Valentina , Battista Laura , Binz Pierre-Alain , Bruce Stephen J. , Brisken Cathrin
Published: February 2025

To improve preclinical studies and their translation, patient-derived xenografts (PDXs) are increasingly used. They have human-specific tumor characteristics and reflect intra and inter-tumor heterogeneity. However, the endocrine milieu differs between humans and host mice. In light of sex-specific cancer biology and a rise in endocrine-related cancers there is an urgent need to correctly reflect the hormonal milieu in PDX models. We show that female mice of NOD.Cg-Prkdc

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/SzJ (NSG) strain widely used for PDXs has 17-β-estradiol (E2) and testosterone (T) levels comparable to C57Bl6 females but higher progesterone (P4) levels. E2 levels are comparable, T levels are lower and P4 levels higher than those observed in postmenopausal women. Ovariectomy increases T to levels observed in postmenopausal women. Subcutaneous E2 and combined E2/P4 silicon pellets provide NSG females with premenopausal ovarian hormone levels. These procedures humanize the endocrine environment of experimental animals, improving PDX relevance in women’s health-related research.
Recruitment of apolipoprotein E facilitates Herpes simplex virus 1 attachment and release
Authors: Liu Lifeng , Bano Fouzia , Conca Dario Valter , Thorsteinsson Konrad , Jayaweera Sanduni Wasana , Avinens Damien , Pace Hudson , Lövheim Hugo , Olofsson Anders , Bally Marta
Published: February 2025

Human apolipoprotein E (ApoE) has been shown to play important roles during primary infection and pathogenesis of several viruses. Furthermore, epidemiological studies suggest that interactions between ApoE 4 and herpes simplex virus type-1 (HSV1) could associate with higher risk of Alzheimer’s disease. Nevertheless, little is known about the ApoE-HSV1 interactions at molecular levels. Here, we investigate the effects of ApoE on HSV1 infection in vitro. Our results show that ApoE promotes HSV1 growth, which is attributed to the incorporation of ApoE into HSV1 particles. Using both biological and biophysical approaches, we conclude that ApoE-coated HSV1 demonstrates a more efficient attachment to and faster release from the cell surface. Mechanistic studies reveal that ApoE modifies HSV1 interactions with heparan sulfate, thereby modulating interactions between HSV1 and the cell surface. Overall, our results provide new insights into the roles of ApoE during HSV1 infections which may inspire future studies on Alzheimer’s disease etiology.
Gold(i)-catalysed [2+4] cycloaddition of 1,1-difluoroallenes with conjugated enones: synthesis of ring-difluorinated dihydro-2H-pyrans
Authors: Miyazaki Daisuke , Eto Reo , Ichikawa Junji , Fuchibe Kohei
Published: February 2025

1,1-Difluoroallenes underwent regioselective [2+4] cycloaddition with α,β-unsaturated ketones (enones) in the presence of an AuCl(IPr)–AgSbF6 catalyst.
Effect of molar ratios on formation, dissolution and physical stability of naringenin-meglumine co-amorphous by integrating theoretical-modeling-experimental techniques
Authors: Han Jiawei , Sun Wen , Chen Jiaxin , Yue Zhimin , Fang Weitao , Liu Xiaoqian , Wang Jue , Wu Gao-Rong
Published: February 2025

Although the molar ratio is a crucial parameter for co-amorphous formulations, the selection of molar ratio on their formation and important physicochemical properties is rarely studied during development process. Herein,...
Molecular Dynamics of Synergistic Behavior at the Air-Water Interface: Mixed Cationic-anionic Fluorocarbon-Hydrocarbon Surfactants
Authors: Quan Xiaolong , Xiong Jing , Tong Tong , Jiao Jinqing , Zou Jian-Ping , Wei Yuechang
Published: February 2025

Ecological concerns surrounding conventional aqueous film-forming foam extinguishing agents, predominantly composed of long-chain fluorocarbon surfactants, have spurred the need for innovation in eco-compatible substitutes, such as short-chain fluorocarbon surfactants. Molecular...
Tuning the Li-Sn alloy dispersity to improve the lithiophilicity of lithium metal anode towards stable lithium metal batteries
Authors: Du Junmou , Li Guocheng , Tan Yuchen , Duan Xiangrui , Fan Tianchi , Du Changhong , Zhou Anjian , Wang Yu
Published: February 2025

The pursuit of high-energy-density batteries has generated significant interest in lithium metal anodes due to their high specific capacity and low redox potential. However, challenges such as the formation of...
Enhancing the stability of Cs3Bi2Br9 quantum dots for anti-counterfeiting applications in leather through polyacrylate coating
Authors: Gao Dang-Ge , Bao Xin , Lyu Bin , Chen Zhixin , Zhang Ailin , Ma Jianzhong
Published: February 2025

The growing demand for anti-counterfeiting technology has drawn attention to the emerging perovskite quantum dots (QDs). However, the poor stability of such materials is the main obstacles to the application...
Categorization Method of Power Supply Quality Events Using Rule‐Based Decision Trees, Combining Traditional Indices With Higher‐Order Statistics
Authors: Remigio‐Carmona Paula , Florencias‐Oliveros Olivia , González‐de‐la‐Rosa Juan‐José
Published: February 2025

This letter presents a novel method for power quality event detection using higher‐order statistical indicators and rule‐based decision trees. The method achieves up to 90% efficiency in the most challenging cases and excels in hybrid event classification, increasingly common in modern grids. Its simplicity enables fast execution and real‐time applicability, making it a robust complement to traditional visualization tools.
Leitlinien-Update: phänotypbasiertes Management der Kardiomyopathie
Authors: Amr Ali , Frey Norbert , Meder Benjamin
Published: February 2025

Was ist neu?

Die Leitlinien bieten aktualisierte Klassifikationen für die dilatierte und nicht dilatierte linksventrikuläre (LV) Kardiomyopathie, wobei besonderer Wert auf die Bedeutung der kardialen Magnetresonanztomografie (CMR: Cardiovascular Magnetic Resonance) zur Beurteilung des Myokards gelegt wird.

Es wird ein besonderer Fokus auf den klinischen Verlauf gelegt, von der Erstvorstellung über die Diagnose, bis hin zum Management, wobei die Notwendigkeit eines systematischen, multiparametrischen Ansatzes zur Identifizierung der zugrundeliegenden Ursache der Kardiomyopathie betont wird. Neue Empfehlungen heben die Bedeutung des klinischen und genetischen Kaskaden-Screenings für Familienmitglieder von Personen mit Kardiomyopathie hervor.

Die Leitlinien betonen die Notwendigkeit einer kontinuierlichen Versorgung – beginnend in der Kindheit bis ins Erwachsenenalter, insbesondere während wichtiger Übergangsphasen – und behandeln die verschiedenen klinischen Stadien der Kardiomyopathien (z.B. subklinisch, symptomatisch erkrankt, Endstadium).

Die Leitlinien betonen die Bedeutung eines multidisziplinären Ansatzes, der die Einbeziehung verschiedener Fachrichtungen und die Einbindung der Familie in den Behandlungsprozess vorsieht.

Es werden neue Richtlinien zur Risikobewertung für SCD bei verschiedenen Kardiomyopathie-Phänotypen gegeben, einschließlich Empfehlungen für pädiatrische Populationen, mit einem Schwerpunkt bezüglich genetischer Faktoren bei der Risikobewertung.

Aktualisierte Empfehlungen zum Management von LVOTO, einer häufigen Manifestation der HCM.

Die Taskforce empfiehlt, den Begriff „Hypertrabekularisierung“ statt LVNC zu verwenden und das Takotsubo-Syndrom nicht als Kardiomyopathie zu klassifizieren, da es sich dabei meist um vorübergehende Phänomene handelt.
Pneumokokkensepsis 2015–2022: Überlegungen zu Impfstrategien
Authors: Hof Herbert , Singer Sabine , Steiner Ika , Bertsch Daniela , Kirstahler Maria , Oberdorfer Klaus , Imöhl Matthias , van der Linden Mark
Published: February 2025

Obwohl Impfstoffe zur Verfügung stehen, ist die Häufigkeit von Sepsisfällen mit Streptococcus pneumoniae immer noch recht hoch.

In den Jahren von 2015–2022 wurden bei 925 in unserem Labor untersuchten Blutkulturen Streptococcus pneumoniae nachgewiesen. Von einem Großteil, nämlich von 754 Stämmen, wurde der Serotyp bestimmt. Außerdem wurde deren in-vitro-Empfindlichkeit gegen einige Antibiotika getestet.

Die Isolate stammten überwiegend von älteren Menschen (>60 Jahre), und zwar häufiger von Männern als von Frauen. In den Jahren 2020 und 2021 wurden deutlich weniger Fälle von Pneumokokken-Sepsis verzeichnet, was vermutlich auf den nicht pharmazeutischen Maßnahmen zur Prävention aerogen übertragener Infektionen während der Coronapandemie (Schutzmasken, Abstand halten) beruht. Kinder im Alter bis zu einem Jahr waren auch relativ anfällig. Die Serotypen 3 und 8 dominierten. In dem 20-valenten Konjugat-Impfstoff waren 67% der gefundenen Serotypen enthalten und 75% in dem reinen Polysaccharid-Impfstoff. Die überwiegende Mehrzahl der Isolate war gegen Penicillin, Erythromycin und auch gegen Doxycyclin empfindlich. Multi-drug-resistente Stämme wurden nicht beobachtet.

Eine Impfung hätte einen Großteil der Infektionen vermutlich verhindern können. Zu beachten ist jedoch, dass immerhin 27% der gefundenen Serotypen in keinem der angebotenen Impfstoffe enthalten sind.