bluuebunny/crossref_metadata_2025_split huggingface dataset:
G-quadruplex stabilization provokes DNA breaks in human PKD1, revealing a second hit mechanism for ADPKD
Authors: Parsons Agata M. , Byrne Seth , Kooistra Jesse , Dewey John , Zebolsky Aaron L. , Alvarado Gloria , Bouma Gerrit J. , Vanden Heuvel Gregory B. , Larson Erik D. 
Published: January 2025

AbstractThe “secondhit” pathway is responsible for biallelic inactivation of many tumor suppressors, where a pathogenic germline allele is joined by somatic mutation of the remaining functional allele. The mechanisms are unresolved, but the human PKD1 tumor suppressor is a good experimental model for identifying the molecular determinants. Inactivation of PKD1 results in autosomal dominant polycystic kidney disease, a very common disorder characterized by the accumulation of fluid-filled cysts and end-stage renal disease. Since human PKD1 follows second hit and mouse Pkd1 heterozygotes do not, we reasoned that there is likely a molecular difference that explains the elevated mutagenesis of the human gene. Here we demonstrate that guanine quadruplex DNA structures are abundant throughout human, but not mouse, PKD1 where they activate the DNA damage response. Our results suggest that guanine quadruplex DNAs provoke DNA breaks in PKD1, providing a potential mechanism for cystogenesis in autosomal dominant polycystic kidney disease specifically and for the inactivation of guanine quadruplex-rich tumor suppressors generally.
Structures of Saccharolobus solfataricus initiation complexes with leaderless mRNAs highlight archaeal features and eukaryotic proximity
Authors: Bourgeois Gabrielle , Coureux Pierre-Damien , Lazennec-Schurdevin Christine , Madru Clément , Gaillard Thomas , Duchateau Magalie , Chamot-Rooke Julia , Bourcier Sophie , Mechulam Yves , Schmitt Emmanuelle 
Published: January 2025

AbstractThe archaeal ribosome is of the eukaryotic type. TACK and Asgard superphyla, the closest relatives of eukaryotes, have ribosomes containing eukaryotic ribosomal proteins not found in other archaea, eS25, eS26 and eS30. Here, we investigate the case of Saccharolobus solfataricus, a TACK crenarchaeon, using mainly leaderless mRNAs. We characterize the small ribosomal subunit of S. solfataricus bound to SD-leadered or leaderless mRNAs. Cryo-EM structures show eS25, eS26 and eS30 bound to the small subunit. We identify two ribosomal proteins, aS33 and aS34, and an additional domain of eS6. Leaderless mRNAs are bound to the small subunit with contribution of their 5’-triphosphate group. Archaeal eS26 binds to the mRNA exit channel wrapped around the 3’ end of rRNA, as in eukaryotes. Its position is not compatible with an SD:antiSD duplex. Our results suggest a positive role of eS26 in leaderless mRNAs translation and possible evolutionary routes from archaeal to eukaryotic translation.
The hybrid lipoplex induces cytoskeletal rearrangement via autophagy/RhoA signaling pathway for enhanced anticancer gene therapy
Authors: Hu Xueyi , Wang Yichun , Wang Ruohan , Pu Yiyao , Jin Rongrong , Nie Yu , Shuai Xintao 
Published: January 2025

AbstractDelivering plasmid DNA (pDNA) to solid tumors remains a significant challenge due to the requirement for multiple transport steps and the need to promote delivery efficiency. Herein, we present a virus-mimicking hybrid lipoplex, composed of an arginine-rich cationic lipid, hyaluronic acid derivatives coated gold nanoparticles, and pDNA. This system induces cytoskeletal rearrangements through “outside-in” mechanical and “inside-out” biochemical signaling, overcoming intra- and intercellular barriers to enhance pDNA delivery. By modulating autophagy, RhoA signaling, and cytoskeletal dynamics, we achieve a 20-fold increase in gene expression with high tissue specificity in solid tumors. Furthermore, the system is applied to co-deliver a p53 plasmid and an MDM2 inhibitor, demonstrating significant synergistic antitumor effects in hepatocellular and lung carcinomas.
Effect of titanium and vanadium nano-carbide size on hydrogen embrittlement of ferritic steels
Authors: Boot Tim , Kömmelt Pascal , Brouwer Hans J. C. , Böttger Amarante , Popovich Vera 
Published: January 2025

AbstractThe effect of TiC and VC nano-precipitate size on the hydrogen embrittlement of ferritic steels was studied in this work. Steels containing two size distributions (10 nm or less and 10 - 100 nm) of TiC and VC carbides are subjected to tensile tests in-situ in an electrochemical hydrogen charging environment. Hydrogen is found to be trapped in interstitial matrix sites on the precipitate/matrix interface with activation energies of 14 - 20 kJ/mol and inside misfit dislocation cores with energies of 27 - 37 kJ/mol. All steels are embrittled by 15 to 20%, except the TiC steel with semi-coherent carbides up to 100 nm, which is embrittled by 37%. This is caused by accelerated intergranular fracture as a result of hydrogen trapped in dislocation pile-ups around grain boundary precipitates. The steel with coherent VC nano-carbides retained the highest strength and ductility during in-situ testing. This is therefore the optimal carbide configuration for use in hydrogen environments.
Plasma proteomic signatures of social isolation and loneliness associated with morbidity and mortality
Authors: Shen Chun , Zhang Ruohan , Yu Jintai , Sahakian Barbara J. , Cheng Wei , Feng Jianfeng 
Published: January 2025

Abstract
The biology underlying the connection between social relationships and health is largely unknown. Here, leveraging data from 42,062 participants across 2,920 plasma proteins in the UK Biobank, we characterized the proteomic signatures of social isolation and loneliness through proteome-wide association study and protein co-expression network analysis. Proteins linked to these constructs were implicated in inflammation, antiviral responses and complement systems. More than half of these proteins were prospectively linked to cardiovascular disease, type 2 diabetes, stroke and mortality during a 14 year follow-up. Moreover, Mendelian randomization (MR) analysis suggested causal relationships from loneliness to five proteins, with two proteins (ADM and ASGR1) further supported by colocalization. These MR-identified proteins (GFRA1, ADM, FABP4, TNFRSF10A and ASGR1) exhibited broad associations with other blood biomarkers, as well as volumes in brain regions involved in interoception and emotional and social processes. Finally, the MR-identified proteins partly mediated the relationship between loneliness and cardiovascular diseases, stroke and mortality. The exploration of the peripheral physiology through which social relationships influence morbidity and mortality is timely and has potential implications for public health.
A magneto-thermoelectric with a high figure of merit in topological insulator Bi88Sb12
Authors: Pan Yu , He Bin , Feng Xiaolong , Li Fan , Chen Dong , Burkhardt Ulrich , Felser Claudia 
Published: January 2025

AbstractHigh thermoelectric performance is generally achieved by synergistically optimizing two or even three of the contradictorily coupled thermoelectric parameters. Here we demonstrate magneto-thermoelectric correlation as a strategy to achieve simultaneous gain in an enhanced Seebeck coefficient and reduced thermal conductivity in topological materials. We report a large magneto-Seebeck effect and high magneto-thermoelectric figure of merit of 1.7 ± 0.2 at 180 K and 0.7 T in a single-crystalline Bi88Sb12 topological insulator. This result fills a gap of a high performance below 300 K and is promising for low-temperature thermoelectric applications. The large magneto-Seebeck response is attributed to the ultrahigh mobility and the Dirac band dispersion. The application of a low magnetic field to achieve a high thermoelectric performance can be extended to topological materials with similar features that are rapidly emerging because it synergistically optimizes the thermoelectric parameters.
Phenotypic evolution of SARS-CoV-2 spike during the COVID-19 pandemic
Authors: Furnon Wilhelm , Cowton Vanessa M. , De Lorenzo Giuditta , Orton Richard , Herder Vanessa , Cantoni Diego , Ilia Georgios , Mendonca Diogo Correa , Kerr Karen , Allan Jay , Upfold Nicole , Meehan Gavin R. , Bakshi Siddharth , Das Udeet Ranjan , Molina Arias Sergi , McElwee Marion , Little Sarah , Logan Nicola , Kwok Kirsty , Smollett Katherine , Willett Brian J. , Da Silva Filipe Ana , Robertson David L. , Grove Joe , Patel Arvind H. , Palmarini Massimo 
Published: January 2025

Abstract
SARS-CoV-2 variants are mainly defined by mutations in their spike. It is therefore critical to understand how the evolutionary trajectories of spike affect virus phenotypes. So far, it has been challenging to comprehensively compare the many spikes that emerged during the pandemic in a single experimental platform. Here we generated a panel of recombinant viruses carrying different spike proteins from 27 variants circulating between 2020 and 2024 in the same genomic background. We then assessed several of their phenotypic traits both in vitro and in vivo. We found distinct phenotypic trajectories of spike among and between variants circulating before and after the emergence of Omicron variants. Spike of post-Omicron variants maintained enhanced tropism for the nasal epithelium and large airways but displayed, over time, several phenotypic traits typical of the pre-Omicron variants. Hence, spike with phenotypic features of both pre- and post-Omicron variants may continue to emerge in the future.
Proteomic changes upon treatment with semaglutide in individuals with obesity
Authors: Maretty Lasse , Gill Dipender , Simonsen Lotte , Soh Keng , Zagkos Loukas , Galanakis Michael , Sibbesen Jonas , Iglesias Miquel Triana , Secher Anna , Valkenborg Dirk , Purnell Jonathan Q. , Knudsen Lotte Bjerre , Tahrani Abd A. , Geybels Milan 
Published: January 2025

Abstract
Obesity and type 2 diabetes are prevalent chronic diseases effectively managed by semaglutide. Here we studied the effects of semaglutide on the circulating proteome using baseline and end-of-treatment serum samples from two phase 3 trials in participants with overweight or obesity, with or without diabetes: STEP 1 (n = 1,311) and STEP 2 (n = 645). We identified evidence supporting broad effects of semaglutide, implicating processes related to body weight regulation, glycemic control, lipid metabolism and inflammatory pathways. Several proteins were regulated with semaglutide, after accounting for changes in body weight and HbA1c at end of trial, suggesting effects of semaglutide on the proteome beyond weight loss and glucose lowering. A comparison of semaglutide with real-world proteomic profiles revealed potential benefits on disease-specific proteomic signatures including the downregulation of specific proteins associated with cardiovascular disease risk, supporting its reported effects of lowering cardiovascular disease risk and potential drug repurposing opportunities. This study showcases the potential of proteomics data gathered from randomized trials for providing insights into disease mechanisms and drug repurposing opportunities. These data also highlight the unmet need for, and importance of, examining proteomic changes in response to weight loss pharmacotherapy in future trials.
ApisTox: a new benchmark dataset for the classification of small molecules toxicity on honey bees
Authors: Adamczyk Jakub , Poziemski Jakub , Siedlecki Pawel 
Published: January 2025

AbstractThe global decline in bee populations poses significant risks to agriculture, biodiversity, and environmental stability. To bridge the gap in existing data, we introduce ApisTox, a comprehensive dataset focusing on the toxicity of pesticides to honey bees (Apis mellifera). This dataset combines and leverages data from existing sources such as ECOTOX and PPDB, providing an extensive, consistent, and curated collection that surpasses the previous datasets. ApisTox incorporates a wide array of data, including toxicity levels for chemicals, details such as time of their publication in literature, and identifiers linking them to external chemical databases. This dataset may serve as an important tool for environmental and agricultural research, but also can support the development of policies and practices aimed at minimizing harm to bee populations. Finally, ApisTox offers a unique resource for benchmarking molecular property prediction methods on agrochemical compounds, facilitating advancements in both environmental science and chemoinformatics. This makes it a valuable tool for both academic research and practical applications in bee conservation.
Effectiveness of tacrolimus therapy in refractory ulcerative colitis compared to infliximab with propensity score matching
Authors: Yoshihara Takeo , Amano Takahiro , Shinzaki Shinichiro , Tsujii Yuri , Asakura Akiko , Tashiro Taku , Tani Mizuki , Otake-Kasamoto Yuriko , Yamada Takuya , Sakakibara Yuko , Osugi Naoto , Ishii Shuji , Egawa Satoshi , Araki Manabu , Arimoto Yuki , Nakahara Masanori , Murayama Yoko , Kobayashi Ichizo , Kinoshita Kazuo , Ogawa Hiroyuki , Hiyama Satoshi , Shibukawa Narihiro , Komori Masato , Okuda Yorihide , Kizu Takashi , Kitamura Tetsuhisa , Kato Minoru , Tsujii Yoshiki , Inoue Takahiro , Iijima Hideki , Hayashi Yoshito , Takehara Tetsuo 
Published: January 2025

AbstractThere is insufficient evidence comparing the outcomes of tacrolimus-based remission induction therapy with infliximab in refractory ulcerative colitis (UC) and evidence regarding optimal strategies after tacrolimus-based remission induction therapy. We conducted a multi-institutional retrospective study of patients with UC treated with tacrolimus or infliximab between January 2010 and March 2019. The proportion of clinical remission at week 8 and cumulative colectomy-free rate were examined using propensity score matching analysis. The predictors for colectomy after tacrolimus induction were also investigated. Ninety patients in the tacrolimus group and 151 in the infliximab group were enrolled. The proportion of patients in clinical remission at week 8 was 65.2% in the matched tacrolimus group and 37.3% in the matched infliximab group (P = 0.0016), and the long-term colectomy-free rate was lower in the matched tacrolimus group than in the matched infliximab group (P = 0.0003). After clinical remission with tacrolimus, a serum albumin level of ≤ 3.5 g/dL at week 8 was extracted as a factor predicting colectomy (area under the curve: 0.94). Tacrolimus showed a higher remission induction effect for UC compared to infliximab. However, a high rate of colectomy after transition to maintenance treatment was found to be a concern for tacrolimus therapy.
Annual migrations, vertical habitat use and fidelity of Atlantic bluefin tuna tracked from waters off the United Kingdom
Authors: Horton Thomas W. , Binney Francis C. T. , Birch Samantha , Block Barbara A. , Exeter Owen M. , Garzon Francesco , Plaster Alex , Righton David , van der Kooij Jeroen , Witt Matthew J. , Hawkes Lucy A. 
Published: January 2025

Abstract
Understanding the spatial ecology of commercially exploited species is vital for their conservation. Atlantic bluefin tuna (Thunnus thynnus, ABT) are increasingly observed in northeast Atlantic waters, yet knowledge of these individuals’ spatial ecology remains limited. We investigate the horizontal and vertical habitat use of ABT (158 to 241 cm curved fork length; CFL) tracked from waters off the United Kingdom (UK) using pop-up satellite archival tags (n = 63). Analyses reveal distinctive movements from the UK to the Bay of Biscay (BoB) and Central North Atlantic between September and December, and size-specific habitat preferences in May and July—all ABT < 175 cm CFL inhabiting the BoB and 73% of ABT ≥ 175 the Mediterranean Sea. All ABT tracked for more than 300 days (n = 25) returned to waters off the UK the following year, where most stayed (n = 22; 88%) and three continuing north with deployments ending off northwest Ireland. ABT mostly occupied waters between 0 and 20 m (daytime 49 ± 6% of time; nighttime 71 ± 6%). Vertical habitat use was coupled with illumination, mean depth occupied, maximum depth reached, and vertical movement rate increased during the daytime and when moons were brightest. These data provide valuable insights into the spatial ecology of ABT reoccupying northerly foraging areas following decades of absence.
Mechanistic modelling of allergen-induced airways disease in early life
Authors: Pybus Hannah J. , Dangarh Prakrati , Ng Man Yin Melanie , Lloyd Clare M. , Saglani Sejal , Tanaka Reiko J. 
Published: January 2025

AbstractAsthma affects approximately 300 million individuals worldwide and the onset predominantly arises in childhood. Children are exposed to multiple environmental irritants, such as viruses and allergens, that are common triggers for asthma onset, whilst their immune systems are developing in early life. Understanding the impact of allergen exposures on the developing immune system and resulting alterations in lung function in early life will help prevent the onset and progression of allergic asthma in children. In this study, we developed an in silico model describing the pulmonary immune response to a common allergen, house dust mite, to investigate its downstream impact on the pathophysiology of asthma, including airway eosinophilic inflammation, remodelling, and lung function. We hypothesised that altered epithelial function following allergen exposure determines the onset of airway remodelling and abnormal lung function, which are irreversible with current asthma therapies. We calibrated the in silico model using age appropriate in vivo data from neonatal and adult mice. We validated the in silico model using in vivo data from mice on the effects of current treatment strategies. The in silico model recapitulates experimental observations and provides an interpretable in silico tool to assess airway pathology and the underlying immune responses upon allergen exposure. The in silico model simulations predict the extent of bronchial epithelial barrier damage observed when allergen sensitisation occurs and demonstrate that epithelial barrier damage and impaired immune maturation are critical determinants of reduced lung function and asthma development. The in silico model demonstrates that both epithelial barrier repair and immune maturation are potential targets for therapeutic intervention to achieve successful asthma prevention.
Ironing out differences in attenuation and blooming artifact in acute stroke thrombi
Authors: Velasco Gonzalez Aglae , Görlich Dennis , Buerke Boris , Sauerland Cristina , Meier Norbert , Fobker Manfred , McCarthy Ray , Jeibmann Astrid , Heindel Walter , Faldum Andreas , Kugel Harald 
Published: January 2025

AbstractThis study aims to improve our understanding of acute ischemic stroke clot imaging by integrating CT attenuation information with MRI susceptibility signal of thrombi. For this proof-of-principle experimental study, fifty-seven clot analogs were produced using ovine venous blood with a broad histological spectrum. Each clot analog was analyzed to determine its RBC content and chemical composition, including water, Fe III, sodium, pH, and pO2. Non-contrast CT and a susceptibility-weighted MRI sequence were used for imaging. The study found that RBC content correlated more accurately than iron content with clot attenuation on CT. There was a strong correlation between Fe III content and RBC percentage in clots. Specifically, changes in RBC content accounted for 64% of the variance in Fe III content (R2 = 0.640; p < .0001). Thrombi with blooming artifacts (BA) displayed higher attenuation on non-contrast CT than those without (73.4 vs. 40 HU, p < .0001) and had the highest RBC and iron contents. The cut-off value of 1242 µg/g of iron predicted blooming artifacts with high sensitivity and specificity. The pH level strongly affected the appearance of blooming artifacts, particularly for negative clots with high RBC content. These findings provide significant insights into the imaging behavior of acute ischemic stroke clots across both imaging modalities and could potentially improve the diagnosis and treatment of acute stroke patients. Furthermore, these results open the possibility for future research aimed at developing pH-modulated therapeutic strategies based on the acid-base state of thrombi.
AI-based visualization of loose connective tissue as a dissectable layer in gastrointestinal surgery
Authors: Kumazu Yuta , Kobayashi Nao , Senya Seigo , Negishi Yuya , Kinoshita Kazuya , Fukui Yudai , Mita Kazuhito , Osaragi Tomohiko , Misumi Toshihiro , Shinohara Hisashi 
Published: January 2025

AbstractWe aimed to develop an AI model that recognizes and displays loose connective tissue as a dissectable layer in real-time during gastrointestinal surgery and to evaluate its performance, including feasibility for clinical application. Training data were created under the supervision of gastrointestinal surgeons. Test images and videos were randomly sampled and model performance was evaluated visually by 10 external gastrointestinal surgeons. The mean Dice coefficient of the 50 images was 0.46. The AI model could detect at least 75% of the loose connective tissue in 91.8% of the images (459/500 responses). False positives were found for 52.6% of the images, but most were not judged significant enough to affect surgical judgment. When comparing the surgeon’s annotation with the AI prediction image, 5 surgeons judged the AI image was closer to their own recognition. When viewing the AI video and raw video side-by-side, surgeons judged that in 99% of the AI videos, visualization was improved and stress levels were acceptable when viewing the AI prediction display. The AI model developed demonstrated performance at a level approaching that of a gastrointestinal surgeon. Such visualization of a safe dissectable layer may help to reduce intraoperative recognition errors and surgical complications.
Healthcare workers safety: a cohort study using healthcare utilisation databases on vaccination and vaccine timeliness impact against SARS-CoV-2 infection
Authors: Skrami Edlira , Faragalli Andrea , Iommi Marica , Morbidoni Marco , Mancini Cristina , Guidi Antonella , Cardone Annalisa , Pompili Marco , Serafini Pietro , Appignanesi Remo , Ferrante Luigi , Carle Flavia 
Published: January 2025

AbstractHealthcare Workers (HCWs) are at ongoing risk of SARS-CoV-2 infection, potentially contributing to its transmission. This study assessed full vaccination and vaccination timeliness impact on SARS-CoV-2 infections among HCWs in Italy’s Marche Region, using Healthcare Utilization Databases. We evaluated vaccination coverage and its associated factors. The cohort comprised 21,118 HCWs aged 18–70 from the region’s five Local Health Authorities (LHA), enrolled between February 2020 - May 2021. Factors associated with full vaccination were assessed using multiple logistic regression. The impact of vaccination status, time to vaccination, occupational role, age, gender, and health status on infection risk was analysed with a multiple Cox regression model, adjusting for vaccination coverage velocity, swabbing probability, and monthly intensive care unit admissions rate in each LHA. Of the cohort, 81.2% were fully vaccinated. Factors associated with full vaccination included age, role, LHA, prior infection, and health status. Vaccination reduced infection risk by 77% (95% CI: 70–82). Infection risk was higher among healthcare assistants, nurses/physiotherapists/technicians compared to physicians, among male HCWs, and it decreased as vaccination timeliness increased. Vaccination timeliness is crucial for reducing SARS-CoV-2 infection risk among HCWs, regardless of their characteristics. This underscores the importance of efficiently organizing vaccination administration across different territories and for all HCW categories.