bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prolactin levels and chronic kidney disease and the subsequent risk of cardiovascular events: A long term population based cohort study
Authors: Rojhani Ehsan , Rahmati Maryam , Firouzi Faegheh , Ziaeefar Pardis , Soudmand Saber Amanollahi , Azizi Fereidoun , Tehrani Fahimeh Ramezani , Behboudi-Gandevani Samira 
Published: February 2025

Abstract
Both the clearance and secretion of prolactin are disrupted in chronic kidney disease (CKD). Evidence indicates that prolactin may play a role in cardiovascular (CV) disturbances. Considering the increased cardiovascular risk associated with CKD, this study investigates the relationship between prolactin levels, CKD, and the risk of CV events in both women and men, with an average follow-up period of 20 years. The study included 2,005 participants from the Tehran Lipid and Glucose Study (TLGS) who met the inclusion criteria. They were reassessed approximately every three years for a median follow-up of 19.0 years (Interquartile range (IQR):16.4–20.2), during which occurrences of CKD and CV events were recorded. A pooled logistic regression model examined the influence of Prolactin on CV events and its interaction with CKD. During follow-up, we identified 156 incident cases of CV events among men and 73 among women. Median (95%CI) PRL levels were 7.4 (5.5–10.5) ng/mL for men and 15.2 (10.3–23) ng/mL for women. The results of analyses showed that a history of CKD was associated with significantly higher odds of CV events for both men 4.2 (95% CI: 2.6–6.8) and women 5.5 (95% CI: 2.6–11.5). Results remained unchanged after adjustment for confounders including age, waist circumference, smoking, education, history of diabetes and hypertension, and family history of CV events. Interaction analyses revealed no statistically significant interaction between CKD and PRL on the odds of CV events in unadjusted and adjusted models. This consistent pattern was observed regardless of gender. Results of population-based data with over a median follow-up period of 20 years showed that CKD independently increases the risk of CV events in both men and women. However, our findings suggest that this elevated risk may not be substantially influenced by prolactin levels. Further investigation may be warranted to confirm these findings.
3D quantification of metal-induced geometric distortions in MRI
Authors: Li Hao , Özen Ali C. , Juerchott Alexander , Breckwoldt Michael , Jesser Jessica , Vollherbst Dominik F. , Schwarz Daniel , Bendszus Martin , Heiland Sabine , Hilgenfeld Tim 
Published: February 2025

Abstract
The increasing number of patients with metal implants raises concerns about metal-induced geometric distortions (MD) in MR-guided treatments. This study proposes a method for three-dimensional quantification of MD and evaluates its accuracy and reliability. A 3D lattice phantom was designed and measured with two sequences (VIBE and SPACE) and two implants (crown-supported-dental-implant and stainless-steel-bracket). Automated detection of displacement of 9360 crossing points caused by MD was performed. Distortion-quantification accuracy was improved by correcting for noise-induced error (NE), related to different signal-to-noise ratios (SNR), and implant-related signal loss and pile-up artifact volumes (SLPUA). The method’s accuracy was validated against computed tomography. Results showed high reliability, with an excellent intraclass correlation coefficient (≥ 0.99) and low mean residual errors in all directions (2.6%/1.6%/1.8% of voxel size in X/Y/Z direction). SNR/SLPUA volumes were significant confounders (p-value ≤ 0.001) when comparing different sequences/implants, but corrections significantly reduced their impacts (p-value ≤ 0.001). This method enables accurate 3D MD quantification and fair comparison across different sequences/implants. By optimizing MRI protocols for MD minimization and defining implant-specific MD profiles for patient data correction, it may help improve spatial accuracy in MRI-guided treatments in the future.
AgRP neurons shape the sperm small RNA payload
Authors: Tahiri Iasim , Llana Sergio R. , Díaz-Castro Francisco , Claret Marc , Obri Arnaud 
Published: February 2025

Abstract
Paternal dietary patterns and obesity can affect offspring through epigenetic signals in sperm RNA. By activating hypothalamic Agouti-related peptide (AgRP) neurons in mice to simulate obesity’s effects, we observed changes in the small noncoding RNA payload of sperm. These alterations, particularly in transfer RNA-derived small RNAs (tsRNAs), are similar to those induced by short-term high-fat diets, suggesting a common upstream regulatory mechanism involving AgRP neurons that affects metabolic epigenetic inheritance.
Use of HSALR female mice as a model for the study of myotonic dystrophy type I
Authors: Carrascosa-Sàez Marc , Colom-Rodrigo Anna , González-Martínez Irene , Pérez-Gómez Raquel , García-Rey Andrea , Piqueras-Losilla Diego , Ballestar Ana , Llamusí Beatriz , Cerro-Herreros Estefanía , Artero Ruben 
Published: February 2025

Abstract
HSALR mice are the most broadly used animal model for studying myotonic dystrophy type I (DM1). However, so far, HSALR preclinical studies have often excluded female mice or failed to document the biological sex of the animals. This leaves an unwanted knowledge gap concerning the differential development of DM1 in males and females, particularly considering that the disease has a different clinical presentation in men and women. Here we compared typical functional measurements, histological features, molecular phenotypes and biochemical plasma profiles in the muscles of male and female HSALR mice in search of any significant between-sex differences that could justify this exclusion of female mice in HSALR studies and, critically, in candidate therapy assays performed with this model. We found no fundamental differences between HSALR males and females during disease development. Both sexes presented comparable functional and tissue phenotypes, with similar molecular muscle profiles. The only sex differences and significant interactions observed were in plasma biochemical parameters, which are also intrinsically variable in patients with DM1. In addition, we tested the influence of age on these measurements. We therefore suggest including female HSALR mice in regular DM1 studies, and recommend documenting the sex of animals, especially in studies focusing on metabolic alterations. This will allow researchers to detect and report any potential differences between male and female HSALR mice, especially regarding the efficacy of experimental treatments that could be relevant to patients with DM1.
A combination of measures limits demand for critical materials in Sweden’s electric car transition
Authors: Morfeldt Johannes , Johansson Daniel J. A. , Davidsson Kurland Simon 
Published: February 2025

Abstract
Electrification of passenger cars will result in an increased demand for critical raw materials. Here we estimate the quantities of nickel, manganese, cobalt, lithium, and graphite that could be required for a transition to electric cars in Sweden and how different measures can limit material demand. We find notable reduction potentials for shorter battery range—enabled by improved charging infrastructure, increased vehicle energy efficiency, and reduced travel demand compared to a reference scenario. The reduction potentials for downsizing and more lightweight cars, and car sharing are more modest. The combined impact of these measures would be 50–75% reduction in cumulative demand and 72–87% reduction in in-use stock in 2050, depending on the material and battery chemistry pathway. Generally, the reduction potentials are larger than the potential contributions from recycling, suggesting that these complementary measures may be more effective in reducing material demand.
Sediment resuspension in muddy sediments enhances pyrite oxidation and carbon dioxide emissions in Kiel Bight
Authors: Kalapurakkal Habeeb Thanveer , Dale Andrew W. , Schmidt Mark , Taubner Heidi , Scholz Florian , Spiegel Timo , Fuhr Michael , Wallmann Klaus 
Published: February 2025

Abstract
Sediment resuspension of blue carbon ecosystems (e.g., seagrass beds) and muddy sediments exposes buried particulate organic carbon to oxygenated waters and remineralization, potentially enhancing carbon dioxide fluxes. However, the kinetics of carbon degradation under oxic and anoxic conditions are poorly constrained. We report the results of incubation experiments with sediments from Kiel Bight to simulate sediment resuspension events induced by natural and anthropogenic resuspension in this area. A numerical model determined that oxic carbon remineralization rates were up to two-fold higher than those under anoxic conditions. A coupled sediment-water column model demonstrated that pyrite oxidation, rather than carbon oxidation, has the potential to induce large carbon dioxide emissions to the atmosphere following anthropogenic sediment disturbance by trawling. Upscaling to muddy areas of Kiel Bight suggests an annual emission of up to ~14 k tonnes of carbon dioxide per year. Pyrite oxidation may contribute to a weakening of the carbon shelf pump and a reduction of anthropogenic carbon dioxide uptake.
CITRINO: phase 1 dose escalation study of anti-LAG-3 antibody encelimab alone or in combination with anti-PD-1 dostarlimab in patients with advanced/metastatic solid tumours
Authors: Hecht J. Randolph , Michot Jean-Marie , Bajor David , Patnaik Amita , Chung Ki Y. , Wang Judy , Falchook Gerald , Cleary James M. , Kim Richard , Krishnamurthy Anuradha , Marathe Omkar , Youssoufian Hagop , Ellis Catherine , Waszak Angela , Ghosh Srimoyee , Zhang Hailei , Yablonski Kaitlin , Shah Shruti D. , Diaz-Padilla Ivan , Ulahannan Susanna 
Published: February 2025

Abstract

Background
Dual programmed cell death protein (ligand)-1 (PD-[L]1) and lymphocyte-activation gene-3 (LAG-3) blockade has demonstrated improved anti-tumour response in some advanced solid tumours. CITRINO, a two-part, Phase 1 dose-escalation study, evaluated encelimab (TSR-033; novel anti-LAG-3) monotherapy and in combination in patients with advanced/metastatic solid tumours.

Methods
Part 1 (P1) involved dose escalation (20–720 mg Q2W) of encelimab as monotherapy (P1A/B) and with dostarlimab (500 mg Q3W) in patients with previously treated advanced/metastatic solid tumours (P1C). P2 involved cohort expansion in patients with anti-PD-(L)1-naïve microsatellite stable advanced/metastatic colorectal cancer with recommended phase 2 dose (RP2D) of encelimab with dostarlimab as third/fourth-line therapy (P2A), or with dostarlimab, bevacizumab and mFOLFOX6/FOLFIRI as second-line therapy (P2B). Objectives included RP2D, safety/tolerability, efficacy, pharmacokinetics/pharmacodynamics, and exploratory biomarkers.

Results
Maximum tolerated encelimab dose was not reached; 720 mg Q2W was used for P2 plus dostarlimab 1000 mg Q6W. One dose-limiting toxicity occurred (Grade 2 myasthenia gravis; P1A). No clinical responses were observed in P1; 1 (3%) and 4 (17%) patients achieved partial response in P2A and 2B, respectively.

Conclusions
Encelimab has a manageable safety profile as a monotherapy and in tested combinations; however, anti-tumour activity was limited.

Clinical trial registration
NCT03250832.
Breaking barriers: we need a multidisciplinary approach to tackle cancer drug resistance
Authors: Ingham James , Ruan Jia-Ling , Coelho Matthew A. 
Published: February 2025

Abstract
Most cancer-related deaths result from drug-resistant disease(1,2). However, cancer drug resistance is not a primary focus in drug development. Effectively mitigating and treating drug-resistant cancer will require advancements in multiple fields, including early detection, drug discovery, and our fundamental understanding of cancer biology. Therefore, successfully tackling drug resistance requires an increasingly multidisciplinary approach. A recent workshop on cancer drug resistance, jointly organised by Cancer Research UK, the Rosetrees Trust, and the UKRI-funded Physics of Life Network, brought together experts in cell biology, physical sciences, computational biology, drug discovery, and clinicians to focus on these key challenges and devise interdisciplinary approaches to address them. In this perspective, we review the outcomes of the workshop and highlight unanswered research questions. We outline the emerging hallmarks of drug resistance and discuss lessons from the COVID-19 pandemic and antimicrobial resistance that could help accelerate information sharing and timely adoption of research discoveries into the clinic. We envisage that initiatives that drive greater interdisciplinarity will yield rich dividends in developing new ways to better detect, monitor, and treat drug resistance, thereby improving treatment outcomes for cancer patients.
Plasmids are anchored to inactive regions of eukaryotic chromosomes through a nucleosome signal
Authors: Girard Fabien , Even Antoine , Thierry Agnès , Ruault Myriam , Meneu Léa , Larrous Pauline , Garnier Mickaël , Adiba Sandrine , Taddei Angela , Koszul Romain , Cournac Axel 
Published: February 2025

Abstract
Natural plasmids are common in prokaryotes, but few have been documented in eukaryotes. The natural 2µ plasmid present in the yeast Saccharomyces cerevisiae is one of these best-characterized exceptions. This highly stable genetic element has coexisted with its host for millions of years, faithfully segregating at each cell division through a mechanism that remains unclear. Using proximity ligation methods (such as Hi-C, Micro-C) to map the contacts between 2µ plasmid and yeast chromosomes under dozens of different biological conditions, we found that the plasmid is tethered preferentially to regions with low transcriptional activity, often corresponding to long, inactive genes. These contacts do not depend on common chromosome-structuring factors, such as members of the structural maintenance of chromosome complexes (SMC) but depend on a nucleosome-encoded signal associated with RNA Pol II depletion. They appear stable throughout the cell cycle and can be established within minutes. This chromosome hitchhiking strategy may extend beyond the 2µ plasmid/S. cerevisiae pair, as suggested by the binding pattern of the natural eukaryotic plasmid Ddp5 along silent chromosome regions of the amoeba Dictyostelium discoideum.
Proton conductance by human uncoupling protein 1 is inhibited by purine and pyrimidine nucleotides
Authors: Jones Scott A , Sowton Alice P , Lacabanne Denis , King Martin S , Palmer Shane M , Zögg Thomas , Pardon Els , Steyaert Jan , Ruprecht Jonathan J , Kunji Edmund R S 
Published: February 2025

Abstract
Uncoupling protein 1 (UCP1, SLC25A7) is responsible for the thermogenic properties of brown adipose tissue. Upon fatty acid activation, UCP1 facilitates proton leakage, dissipating the mitochondrial proton motive force to release energy as heat. Purine nucleotides are considered to be the only inhibitors of UCP1 activity, binding to its central cavity to lock UCP1 in a proton-impermeable conformation. Here we show that pyrimidine nucleotides can also bind and inhibit its proton-conducting activity. All nucleotides bound in a pH-dependent manner, with the highest binding affinity observed for ATP, followed by dTTP, UTP, GTP and CTP. We also determined the structural basis of UTP binding to UCP1, showing that binding of purine and pyrimidine nucleotides follows the same molecular principles. We find that the closely related mitochondrial dicarboxylate carrier (SLC25A10) and oxoglutarate carrier (SLC25A11) have many cavity residues in common, but do not bind nucleotides. Thus, while UCP1 has evolved from dicarboxylate carriers, no selection for nucleobase specificity has occurred, highlighting the importance of the pH-dependent nucleotide binding mechanism mediated via the phosphate moieties.
An epitranscriptomic program maintains skeletal stem cell quiescence via a METTL3-FEM1B-GLI1 axis
Authors: Wang Jing , Liu Weidong , Zhang Tiantian , Cui Manman , Gao Kexin , Lu Pengbo , Yao Shuxin , Cao Ziyan , Zheng Yanbing , Tian Wen , Li Yan , Yin Rong , Hu Jin , Han Guoqiang , Liang Jianfei , Zhou Fuling , Chai Jihua , Zhang Haojian 
Published: February 2025

Abstract
Skeletal stem cells (SSCs) maintain the skeletal system via pluripotency and differentiation capacity. However, it remains largely unknown how these cells precisely regulate their function to maintain skeletal organization. Here, we delineate the RNA m6A modification landscape across skeletal cell populations in the mouse epiphysis. Our findings show that m6A modifications are prevalent in skeletal stem cell and progenitor populations and play critical roles in cell fate determination. Genetic deletion of Mettl3, the core catalytic subunit of the m6A-methyltransferase complex, in murine skeletal stem and progenitors impaired bone development, leading to shortened limbs, disrupted growth plate zonation, and decreased bone mass. Moreover, Mettl3 deficiency induced quiescence exit in SSCs, together with compromised self-renewal capacity and differentiation potential. Mechanistically, Mettl3-mediated m6A modification reduced mRNA stability of the Cul2-RING E3 ligase complex subunit Fem1b, which subsequently stabilizes Gli1 protein, a key transcription factor of Hedgehog pathway for maintaining SSC identity and function. Thus, we present a comprehensive RNA m6A modification landscape of skeletal cell hierarchy and uncover the essential function of epitranscriptomically-regulated proteostasis in maintaining SSCs quiescence and potency.
Kontakteinschränkende Maßnahmen in Pflegeeinrichtungen im Rahmen der
COVID-19 Pandemie und ihre Auswirkungen auf die Bewohner – ein
Plädoyer
Authors: Heudorf Ursel , Stalla Kristin 
Published: February 2025

ZusammenfassungIn der COVID-19 Pandemie hatten Bewohner* von
Altenpflegeeinrichtungen ein besonders hohes Risiko, an diesem Virus sehr
schwer zu erkranken und auch daran zu versterben. Deswegen wurden strenge
Schutzmaßnahmen bis hin zu Besuchsverboten ergriffen. Sehr bald zeigten sich
jedoch die negativen Auswirkungen dieser kontakteinschränkenden Maßnahmen
auf die psychische und physische Gesundheit, die Lebensqualität das
Selbstbestimmungsrecht und letztendlich die Würde der Bewohner und es wurde
die Frage aufgeworfen, ob die Isolierung (Confinement disease) nicht
gesundheitsschädlicher sei als die Erkrankung selbst. Es wurden Stellungnahmen zu Infektionsschutz-Maßnahmen in den
Pflegeeinrichtungen, Studien mit Stimmen von Betroffenen (Bewohnern,
Angehörigen, Mitarbeitern in Pflegeeinrichtungen) und Interviews mit
Bewohnern von Pflegeeinrichtungen sowie Reviews zu unerwünschten Wirkungen
der Schutzmaßnahmen recherchiert. Die Suche umfasste sowohl sog. „graue
Literatur“ als auch Publikationen aus PubMed. Die Bewohner litten stark unter der Isolation und darunter, dass über sie
entschieden wurde, ohne sie zu fragen. Sie beklagten den Verlust ihrer
Autonomie und fühlten sich in ihrer Würde verletzt. Die Reviews zeigten bei
den Bewohnern generell häufiger Einsamkeit, Angst, Traurigkeit und
Depressivität, teilweise auch einen körperlichen Abbau. In Zukunft muss darauf geachtet werden, eine unter rechtlichen und
gesundheitlichen Aspekten gute Balance zwischen Infektionsschutz und Schutz
der psychischen und physischen Gesundheit, des Wohlbefindens und der
Lebensqualität der Bewohner, der Achtung der Autonomie, des Rechts auf
Selbstbestimmung und der Würde der Bewohner zu erreichen. Hierzu bedarf es
einer breiten gesellschaftlichen Diskussion, in der nicht nur Fachleute aus
den Bereichen der Infektiologie sondern auch aus den Bereichen der
Geriatrie, der Pflege, der öffentlichen Gesundheit, der Ethik und des Rechts
sondern insbesondere auch die Betroffenen selbst oder ihre Vertreter, ihre
Angehörigen gehört und ihre Argumente berücksichtigt werden.
Adipositas und Gewichtsverluste bei Pflegeheimbewohner*innen und
deren Einfluss auf die Mortalität. Eine retrospektive Analyse von
Routinedaten
Authors: Graeb Fabian , Wolke Reinhold , Berger Bianca , Marx Julian , Alf Frank , Reiber Petra , Essig Gundula 
Published: February 2025

ZusammenfassungIn der Langzeitpflege wird oft auf Untergewicht
fokussiert, wenig ist jedoch über Gewichtsveränderungen bei initialer
Adipositas bekannt. Diese Studie untersucht Gewichtsveränderungen bei
Pflegeheimbewohner*innen mit Adipositas (AG) im Vergleich zu Unter- (UG) und
Normalgewicht (NG).Sekundäranalyse eines Routinedatensatzes aus sechs
Langzeitpflegeeinrichtungen, retrospektive Auswertung von Daten von 495
Bewohner*innen.Bewohner*innen mit Adipositas sind signifikant jünger (UG
88,0; NG 84,0; AG 78,5 Jahre) und haben einen geringeren Frauenanteil (UG
86,0%; NG 68,9%; AG 55,3%). Sie haben ein höheres Risiko für
medikationsbedingte Probleme (UG 9,4; NG 10,8; AG 15,0). Der
Morbiditätsindex, die Prävalenz chronischer Erkrankungen und
Gewichtsveränderungen nach 3, 6 und 12 Monaten unterscheiden sich nicht
signifikant. Die Mortalität ist in der AG nach 36 Monaten am geringsten (UG
68,0%; NG 56,7%; AG 42,6%). Auch nach Risikoadjustierung um die Variablen um
die Variablen Alter, Geschlecht, Morbiditätsindex und MERIS zeigt sich ein
Überlebensvorteil bei Adipositas (HR 0,63) und positiveren
Gewichtsveränderungen in den ersten 6 Monaten (HR 0,94).Pflegeheimbewohner*innen mit Adipositas verlieren
ähnlich viel Gewicht wie andere Gruppen, wobei Übergewicht einen protektiven
Effekt gegen Versterben haben könnte.
Characterizing Negative Online Reviews in Hand Surgery
Authors: Lin Lawrence J. , Mai Eric , Lan Rae , Jacobi Sophia , Abola Matthew V. , Ayalon Omri 
Published: February 2025

Abstract
Background Physician review websites are easily accessible resources for patients seeking care. The purpose of our study is to characterize the negative reviews of hand surgeons found on popular review sites using a random sample of members from the American Academy of Orthopaedic Surgeons (AAOS) directory.
Materials and Methods We randomly selected 500 hand surgeons from the AAOS Find an Orthopaedist database and searched for reviews on three websites: Healthgrades.com, Vitals.com, and RateMDs.com. All one-star written reviews were categorized based on the primary complaint in the review. These complaints were analyzed to determine the factors most frequently associated with negative reviews.
Results A total of 1,848 written one-star reviews were included in the analysis. Of all included reviews, 18.1% directly referenced having surgery with the reviewed surgeon while 81.9% did not. Nonclinical complaints comprised the majority of reviews (73.6%). Of the nonclinical complaints, bedside manner was the most frequently cited complaint (53.8%), while wait time (11.0%), time spent with the provider (10.4%), and staff complaints (8.5%) were the next most common. Among the clinical complaints, unfavorable surgical outcomes (40.4%) were most common, while disagreement with or unclear treatment plans (23.6%), misdiagnosis (12.3%), and uncontrolled pain (11.9%) were next.
Conclusion While there are several potential sources of patient dissatisfaction, we have demonstrated that nonclinical aspects of care, such as surgeon bedside manner and office wait times, are disproportionately cited as reasons for negative ratings on physician review websites. It is essential for hand surgeons to understand the motivations behind the reviews that they receive.