bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cardiovascular outcomes and mortality in diabetic multiple myeloma patients initiated on proteasome inhibitors according to prior use of glucagon-like peptide 1 agonists
Authors: Chang Yu-Cheng , Peng Chun-Yu , Chi Kuan-Yu , Song Junmin , Chang Yu , Chiang Cho-Hung , Gao Wenli , Chiang Cho-Han 
Published: January 2025

Lay Summary
Glucagon-like peptide 1 agonists may reduce the risk of major adverse cardiovascular events, heart failure, and all-cause mortality among patients with multiple myeloma and Type 2 diabetes mellitus receiving proteasome inhibitors. The use of glucagon-like peptide 1 agonist is associated with a reduction in cardiovascular events and mortality among patients with multiple myeloma and Type 2 diabetes mellitus receiving proteasome inhibitors. The use of glucagon-like peptide 1 agonist is not associated with an increased risk of adverse events among patients with multiple myeloma and Type 2 diabetes mellitus receiving proteasome inhibitors.
Nicotinamide Prevents The Plasticity Impairments And The Cognitive Dysfunction Caused By Bone Fracture In Older Mice
Authors: Guncay Tatiana , Concha Jorge , Lobos Pedro , More Jamileth , Bruna Barbara , Sansores Daniel , Contreras Pamela , Ponce Daniela P , Brañez Julian , Quiroz Gabriel , Barrientos Genaro , Hidalgo Cecilia , Salech Felipe 
Published: January 2025

Abstract
Postoperative delirium (POD), an acute cognitive dysfunction linked to morbidity and mortality, is characterized by memory impairments and disturbances in consciousness, particularly in patients aged 65 and older. Neuroinflammation and NAD+ imbalance are key mechanisms behind POD, leading to synaptic and cognitive deterioration. However, how surgery contributes to POD and neuroinflammation remains unclear, and effective treatments are lacking. Here we used a rodent model of bone fracture to examine the impact of surgery on synaptic plasticity, inflammation, and cognition. Additionally, we explored whether treatment with Nicotinamide (NAM), a NAD+ precursor, reduced the neuroinflammation and metabolic imbalance caused by surgery.
Female C57BL/6J mice aged 20-22 months underwent tibial fracture surgery and received pre- and post-surgery NAM treatment. Neuroinflammation, synaptic plasticity, and cognition were assessed 72 hours post-surgery via long-term potentiation (LTP) assays, dendritic spine counting, and behavioral tests (open field maze and Y-maze).
Tibial fracture surgery decreased LTP, dendritic spine density, and hippocampal-dependent memory function, and increased hippocampal inflammatory markers (IL-1 beta mRNA, CD38, and SIRT1 protein content); NAM pretreatment prevented these changes. Given surgery adverse effects on LTP and dendritic spine density, we assessed cellular oxidative state and BDNF protein levels. We found that surgery increased the oxidation of ryanodine receptor calcium channels (cellular redox sensors), and decreased BDNF protein levels; NAM supplementation mitigated both effects and prevented the cognitive decline and synaptic plasticity deficits while reducing inflammation post-surgery by lowering IL-1 beta and CD38 protein levels. We propose that the CD38 signaling pathway mediates these NAM protective effects.
The Cotangent Bundle of G/U
P and Kostant–Whittaker Descent
Authors: Gannon Tom 
Published: January 2025

Abstract
We prove that the algebra of functions on the cotangent bundle $T^{*}(G/U_{P})$ of the parabolic base affine space for a reductive group $G$ and a parabolic subgroup $P$ is isomorphic to the subalgebra of the functions on $G \times L \times \mathfrak{l}\ /\!\!/\ L$ which are invariant under a certain action of the group scheme of universal centralizers on $G$, where $L$ is a Levi subgroup of $P$ and $\mathfrak{l}$ is its Lie algebra, upgrading an isomorphism of Ginzburg and Kazhdan simultaneously to the parabolic and the modular setting. We also derive a related isomorphism for the partial Whittaker cotangent bundle of G, which proves a conjecture of Devalapurkar.
Fourier Restriction for Schatten Class Operators and Functions on Phase Space
Authors: Luef Franz , Samuelsen Helge J 
Published: January 2025

Abstract
We formulate a variant of Fourier restriction for operators in Schatten classes, where the Fourier–Wigner transform of a bounded operator replaces the Fourier transform of a function. The Fourier–Wigner transform is closely related to the group Fourier transform of the Heisenberg group. The first result shows that Fourier–Wigner restriction for Schatten class operators is equivalent to the restriction of the symplectic Fourier transform of functions on phase space. We deduce various Schatten class results for the quantum Fourier extension operator and answer a conjecture by Mishra and Vemuri concerning the Weyl transform of measures in the affirmative.
Cytokine storm in a massively burned pediatric patient
Authors: Sharma Mala , Roach Lauren , Bull Ashleigh , Flygt LeeAnne , Ballas Zuhair , Kurjatko Alex , Chegondi Madhuradhar , Wibbenmeyer Lucy 
Published: January 2025

Abstract
Cytokine storm can occur in many different clinical conditions and lack of recognition can lead to death. While cytokines have been measured and trended in burn patients, cytokine storm has not been widely discussed or its treatment reported. We present herein the diagnosis and the treatment of a 5-year-old, 91% burn patient, who developed cytokine storm three times during his hospital course. Aggressive treatment led to successful resolution. Cytokine storm should be entertained in patients who develop classic storm signs and symptoms, along with supporting laboratory. Treatment should be tailored to the patients’ clinical picture. More study is warranted to define cytokine storm as well as its treatment in burn patients.
A narrative review of occupational solar ultraviolet radiation in Britain and skin cancer
Authors: Cherrie J W 
Published: January 2025

Abstract

Background
Occupational exposure to solar ultraviolet (UV) is known to cause malignant melanoma (MM) and non-melanoma skin cancer (NMSC). However, knowledge of the causal associations has developed erratically.

Aims
This review aims to identify when it was accepted that workplace solar UV exposure could cause skin cancer and when it was recognized that there was a risk for outdoor workers in Britain, identifying the steps employers should have taken to protect their workers.

Methods
Informative reviews, published since 1974, were located through a systematic literature search. These were used to chart changes in summative knowledge of the role of occupational solar UV exposure in causing skin cancer. An assessment was made of the identified hazards of skin cancer and the recognition of risks for outdoor workers in Britain.

Results
From at least 1975, it has been accepted that occupational solar UV exposure could cause squamous cell carcinoma, and from around 2011 for MM and basal cell carcinoma. From 2004, repeated sunburn at work was identified as a likely cause of MM. From 1999, it was accepted that occupational solar UV exposure causes NMSC amongst British workers, and from 2012 there was limited evidence for an MM risk for outdoor workers in northern European countries.

Conclusions
Skin cancer risks for British outdoor workers should be actively managed and they should have health surveillance. Outdoor workers who have skin cancer should be eligible for compensation.
The potential role of N-acetylcysteine as an adjuvant therapy in acute aluminum phosphide poisoning: a randomized clinical trial
Authors: Abd El-khalek Soha H , Amin Safaa A , El-Ebiary Ahmad A , Elfeky Ahmed , Kandeel Fatma 
Published: January 2025

Abstract

Objective
Aluminum phosphide (AP) intoxication is a life-threatening emergency with no available effective antidote. This study evaluated the efficacy and safety of N-acetylcysteine (NAC) infusion in cases of acute AP poisoning.

Methods
This randomized, single-blinded, parallel-group, controlled, clinical trial enrolled 96 patients with acute AP poisoning. The patients were allocated to two groups and received either conventional treatment (control group) or conventional treatment plus NAC infusion (NAC group). The patients were subjected to full clinical evaluation, routine laboratory investigations, silver nitrate test, and evaluation of the oxidative markers, malondialdehyde (MDA) and total antioxidant capacity (TAC), at admission and after 24 h treatment. The primary outcome was mortality, and the secondary outcomes were the arterial blood pressure, the length of hospital stay, and the need for intubation or mechanical ventilation.

Results
Compared to the control group, the NAC group showed significantly lower MDA (median [interquartile range (IQR)]: 4.6 [1.9–10.6] vs. 6.8 [3.5–17.4] nmol/mL, P = 0.014) and higher TAC levels (median [IQR]: 0.7 [0.6–0.7] vs. 0.6 [0.6–06] mM/L, P &lt; 0.001). The mortality rate and the need for mechanical ventilation were comparable in both groups (P = 0.601 and 0.505, respectively). However, the NAC group showed significant improvements of both systolic and diastolic blood pressure values (both P = 0.030). The duration of hospitalization was significantly shorter in the NAC group (P = 0.017). No adverse events were reported in patients who received NAC infusion.

Conclusion
In patients with acute AP poisoning, the use of NAC mitigates oxidative stress and partially enhances clinical manifestations without inducing noticeable adverse effects.
Investigating the link between microplastic exposure (benzyl butyl phthalate) and neurodegenerative diseases using high-performance computational toxicology
Authors: Abdulrahman Alhamyani 
Published: January 2025

Abstract

Background
Microplastics are tiny plastic particles, typically less than 5 mm in size, formed from the breakdown of larger plastic products. This breakdown releases additives, including benzyl butyl phthalate (BBP), into the environment. Humans can be exposed to BBP through contaminated food and water, inhalation, and dermal contact.

Aim
Research suggests that BBP, like other phthalates, may have neurotoxic effects, potentially contributing to neurodevelopmental disorders, though its specific toxic targets are not yet clear.

Methodology
In this study, high-performance computational methods were used to identify potential neurotoxic targets of BBP. The findings indicate that BBP has a strong potential to interact with Parkin (PRKN) and Pyruvate dehydrogenase lipoamide kinase isozyme 1 (PDK1), with binding scores of −5.35 kcal/mol, −5.56 kcal/mol, respectively. The PRKN and PDK1 BBP complexes were stable throughout the simulation period, as evidenced by the system's backbone exhibiting slight fluctuations and binding energies confirmed by molecular dynamics (MD) simulation trajectories.

Results
The MMPBSA analysis revealed free binding energies of −21.29 kcal/mol and − 27.06 kcal/mol for the PRKN and PDK1 BBP complexes, respectively. The interaction energies of BBP with PRKN and PDK1 were also within an acceptable range, at −113.68 ± 3.1 kJ/mol and − 117.54 ± 6.2 kJ/mol, respectively. Additionally, density-functional theory (DFT) based optimization showed negative values for the highest occupied molecular orbital (HOMO) -6.934 eV and lowest unoccupied molecular orbital (LUMO) -1.562 eV, indicating that BBP is energetically stable, which is crucial for forming a stable ligand-protein complex.

Conclusion
Overall, the computational investigation reveals that BBP has the potential to interact with PRKN and PDK1, leading to neurodegeneration.
Tissue-specific effects of dietary protein on cellular senescence are mediated by branched-chain amino acids
Authors: Calubag Mariah F. , Ademi Ismail , Grunow Isaac , Breuer Lucia , Babygirija Reji , Lialios Penelope , Le Sandra , Minton Dennis , Sonsalla Michelle M. , Illiano Julia , Knopf Bailey A. , Xiao Fan , Konopka Adam R. , Harris David A. , Lamming Dudley W. 
Published: January 2025

AbstractDietary protein is a key regulator of healthy aging in both mice and humans. In mice, reducing dietary levels of the branched-chain amino acids (BCAAs) recapitulates many of the benefits of a low protein diet; BCAA-restricted diets extend lifespan, reduce frailty, and improve metabolic health, while BCAA supplementation shortens lifespan, promotes obesity, and impairs glycemic control. Recently, high protein diets have been shown to promote cellular senescence, a hallmark of aging implicated in many age-related diseases, in the liver of mice. Here, we test the hypothesis that the effects of high protein diets on metabolic health and on cell senescence are mediated by BCAAs. We find that reducing dietary levels of BCAAs protects male and female mice from the negative metabolic consequences of both normal and high protein diets. Further, we identify tissue-specific effects of BCAAs on cellular senescence, with restriction of all three BCAAs – but not individual BCAAs – protecting from hepatic cellular senescence while potentiating cell senescence in white adipose tissue. We find that the effects of BCAAs on hepatic cellular senescence are cell-autonomous, with lower levels of BCAAs protecting cultured cells from antimycin-A induced senescence. Our results demonstrate a direct effect of a specific dietary component on a hallmark of aging and suggest that cellular senescence may be highly susceptible to dietary interventions.
Site-specific immunogenicity and anti-PD1 response in mismatch repair deficient lung adenocarcinoma models
Authors: Abad Etna , Zadra Ivan , Krasko Anastasia , Subirana-Granés Marc , Reyes Diana , Borredat Pablo , Pasquali Lorenzo , Aramburu Jose , López-Rodríguez Cristina , Janic Ana 
Published: January 2025

AbstractImmunotherapy has revolutionized cancer treatment, yet responses vary significantly based on tumour characteristics and microenvironment. Here, we developed and analysed subcutaneous and orthotopic immunocompetent mice models of mismatch repair-deficient (dMMR) lung adenocarcinoma (LUAD) by selectively ablating Mlh1. Subcutaneous tumours demonstrated partial sensitivity to anti-PD1 therapy, characterized by tumour volume reduction without significant changes in immune infiltration. In contrast, orthotopic tumours exhibited robust responses, with substantial reductions in tumour burden, enhanced immune infiltration, and increased CD4+memory T cells, highlighting the critical role of anatomical site and tumour microenvironment in shaping immunotherapy outcomes. Our findings emphasise the relevance of orthotopic models for preclinical evaluation and suggest that they more accurately reflect clinical responses to immune checkpoint blockade in dMMR LUAD.
Endothelial tPA-dependent recruitment of microglia to vessels protects the blood-brain barrier after stroke in mice
Authors: Etuzé Tamara , Fosset Louis , Vivien Denis , Roussel Benoit D , Lemarchand Eloise 
Published: January 2025

AbstractThrombolysis with tissue-type plasminogen activator (tPA) remains the only pharmacological treatment for the acute phase of ischemic stroke. In this study, we hypothesize that endothelial tPA plays a key role in modulating the microglial response and maintaining blood brain barrier (BBB) integrity after stroke. Using a mouse model with conditional deletion for endothelial tPA (VeCadCre– tPAFlox) combined with a thrombotic stroke model and high-resolution imaging, we investigated the effects of endothelial tPA on vascular inflammation and microglia activation during the acute phase of stroke. Our results demonstrate that microglia-vessel contacts increase post-stroke. Notably, endothelial tPA deletion reduces vascular VCAM1 expression associated with decreased microglial activation and fewer microglia-vessel contacts. Following stroke, endothelial tPA deletion is associated with increased BBB permeability and heightened risk of haemorrhagic transformation. Collectively, these findings indicate that endothelial tPA mediates microglial recruitment to blood vessels, thereby exerting a protective effect on BBB integrity following ischemic stroke.
Mechanism of RPA phosphocode priming and tuning by Cdk1/Wee1 signaling circuit
Authors: Roshan Poonam , Kaushik Vikas , Mistry Ayush , Vayyeti Abhinav , Antony Aidan , Luebbers Riley , Deveryshetty Jaigeeth , Antony Edwin , Origanti Sofia 
Published: January 2025

ABSTRACTReplication protein A (RPA) is a heterotrimeric single-strand DNA binding protein that is integral to DNA metabolism. Segregation of RPA functions in response to DNA damage is fine-tuned by hyperphosphorylation of the RPA32 subunit that is dependent on Cyclin-dependent kinase (Cdk)-mediated priming phosphorylation at the Ser-23 and Ser-29 sites. However, the mechanism of priming-driven hyperphosphorylation of RPA remains unresolved. Furthermore, the modulation of cell cycle progression by the RPA-Cdk axis is not clearly understood. Here, we uncover that the RPA70 subunit is also phosphorylated by Cdk1 at Thr-191. This modification is crucial for the G2 to M phase transition. This function is enacted through reciprocal regulation of Cdk1 activity through a feedback circuit espoused by stabilization of Wee1 kinase. The Thr-191 phosphosite on RPA70 is also crucial for priming hyperphosphorylation of RPA32 in response to DNA damage. Structurally, phosphorylation by Cdk1 primes RPA by reconfiguring the domains to release the N-terminus of RPA32 and the two protein-interaction domains that markedly enhances the efficiency of multisite phosphorylation by other kinases. Our findings establish a unique phosphocode-dependent feedback mechanism between RPA and RPA-regulating kinases that is fine-tuned to enact bipartite functions in cell cycle progression and DNA damage response.
Risk factors for fluoroquinolone- and macrolide-resistance among swineCampylobacter coliusing multi-layered chain graphs
Authors: Wang C. Annie , Love William J. , Jara Manuel , van Vliet Arnoud H.M. , Thakur Siddhartha , Lanzas Cristina 
Published: January 2025

AbstractCampylobacter spp. resistant to fluoroquinolones and macrolides are serious public health threats. Studies aiming to identify risk factors for drug-resistantCampylobacterhave narrowly focused on antimicrobial use at the farm level. Using chain graphs, we quantified risk factors for fluoroquinolones- and macrolide-resistance inCampylobacter coliisolated from two distinctive swine production systems, conventional and antibiotic-free (ABF). The chain graphs were learned using genotypic and phenotypic resistance data from 1082 isolates and host exposures obtained through surveys for 18 cohorts of pigs. The gyrA T86I point mutation alone explained at least 58 % of the variance in ciprofloxacin minimum inhibitory concentration (MIC) for ABF and 79 % in conventional farms. For macrolides, genotype and host exposures explained similar variance in azithromycin and erythromycin MIC. Among host exposures, heavy metal exposures were identified as risk factors in both conventional and ABF. Chain graph models can generate insights into the complex epidemiology of antimicrobial resistance by characterizing context-specific risk factors and facilitating causal discovery.Author summaryAntimicrobial resistance is influenced by multiple factors, including exposures to selecting agents, such as antibiotics, antiseptics, or heavy metals, and factors affecting the transmission of resistant pathogens, such as biosecurity and hygiene measures. Understanding what specific factors are associated with resistance in a given context is challenging. We developed an approach based on probabilistic graphical models to investigate context-specific antimicrobial resistance risk factors. We applied the approach to Campylobacter coli isolated from pigs in antibiotic-free and conventional farms. We demonstrated how for fluoroquinolones, risk factors were similar across both types of farms, but risk factors for macrolides were different across settings.
When will hybridization bring long-term benefits?
Authors: Schneemann Hilde , Welch John J. 
Published: January 2025

AbstractHybridization between distinct populations injects genetic variation, which can bring fitness benefits. However, these benefits often appear as F1 heterosis, and might not persist into later generations; especially since, as emphasized by classical theories, heterosis can be caused in several different ways. Here, we study the long-term outcomes of hybridization, using a model that allows us to tune several properties of the genetic variation, including the strength and architecture of heterosis, thereby unifying the classical theories. Results suggest that long-term outcomes depend mainly on the variance in epistasis, which determines the ruggedness of the fitness landscape, but without affecting the heterosis. Together, results suggest that the study of heterosis may tell us relatively little about the long-term outcomes of hybridization, and that hybridization might bring benefits more often than has been assumed.
Linking Expression and Function ofDrosophilaType-I TGF-β Receptor Baboon Isoforms: Multiple Roles of BaboA Isoform in Shaping of the Adult Central Nervous System
Authors: Lee Gyunghee G. , Peterson Aidan J. , Kim Myung-Jun , Shimell MaryJane , O’Connor Michael B. , Park Jae H. 
Published: January 2025

AbstractEvolutionarily conserved transforming growth factor β (TGF-β) signaling is used in both vertebrates and invertebrates to regulate a variety of developmental and cellular processes. Thebaboon(babo) gene encoding aDrosophilatype-I TGF-β receptor produces three isoforms via alternative splicing: BaboA, BaboB, and BaboC. In this study, we generated three fly lines, each carrying an isoform-specific GFP tag, and another line with a GFP conjugated at the C-terminus common to all isoforms. Using these lines, we assessed (1) whether the tagged proteins function properly in rescue assays and (2) how the isoform expression is regulated in various tissues including the central nervous system (CNS). AGal4knock-in line in thebabolocus was also characterized for reporter expression, mutant phenotypes, and isoform-specific knockdown phenotypes. We found that the C-terminal tag does not interrupt the subcellular targeting and functions of the tagged isoforms, but the internal isoform tags do so in a cell- and isoform-specific fashion. Nevertheless, our results demonstrated that these tags faithfully reflect endogenous expression of individual isoforms. Certain cell types express single or multiple isoforms at different levels, suggesting that alternative splicing could determine the isoform types and their levels depending on cell (or tissue) type. The larval CNS displays distinct patterns of two isoforms, BaboA and BaboC. BaboC is mostly expressed in neural cells originating during embryogenesis, while BaboA is broadly expressed in neural cells produced from both embryonic and postembryonic stages. Assays of both isoform-specific mutants and cell-specific knockdown of individual isoforms revealed broad roles played by BaboA in postembryonic neurogenesis and differentiation of precursor neurons, remodeling processes of persisting larval neurons, and metamorphic CNS reorganization, which are essential for establishing of the adult CNS. Taken together, this study demonstrates that the GFP-tagged lines permit visualization of endogenous expression of individual isoforms, which further provides clues about cell- and stage-specific functions played by each isoform.