bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessing genomic diversity and signatures of selection in Qingyuan Wapiti
Authors: Pi Te , Yi Wenfeng , Hu Mingyue , Quan Xinjiao , Tian Laiming , Sun Hao , Yan Shouqing 
Published: January 2025

AbstractRed deer is a species of family Cervidae that is widely distributed in the world and is often raised to provide antlers, as a trophy or traditional medicine materials, and meat. Currently, the whole genomic data for red deer are very limited. Qingyuan Wapiti (QYW), China's first breed of red deer by artificial breeding, is well known for its high yield of antlers and large body size. The phylogenetic tree showed that QYW had a closer genetic relationship with Tarim red deer than European red deer. To explore the genetic diversity and selection signatures, the whole genome of 28 QYW individuals was sequenced, and 19 401 749 biallelic SNPs and 1 849 784 indels were obtained. The value of observed heterozygosity, expected heterozygosity, and nucleotide diversity were 0.258598, 0.268844, and 0.002193, respectively. Based on Tajima's D and integrated haplotype score analyses, the candidate regions containing 187 genes were detected, including PLD1, ANTXR1, PLCL1, CPE, and CTNNA3, which have been reported to be correlated with osteogenesis and mineralization, growth, and body size by previous studies. The results obtained in this study will contribute to elucidating the genetic mechanisms underlying the formation of excellent traits in QYW and provide the whole genome data for future exploration of genomic diversity and adaptation evolution of red deer worldwide.
Lactams Exhibit Potent Antifungal Activity Against Monospecies and Multispecies Interkingdom Biofilms on a Novel Hydrogel Skin Model
Authors: Abduljalil Hafsa , Alshanta Om Alkhir , Chougule Safa , Butcher Mark , Short Bryn , McLean William , Parry Neil , O'Keeffe Joanne , Ramage Gordon 
Published: January 2025

ABSTRACTInfections of intact and damaged skin barriers and keratin are frequently associated with complex biofilm communities containing bacteria and fungi, yet there are limited options for successful management. This study intended to focus on the utility of some novel proprietary lactam molecules, quorum sensing (QS)–derived halogenated furanones, which act to block the QS pathway, against key fungal pathogens of the skin (Candida albicans, Malassezia furfur and Microsporum gypseum). Moreover, we aimed to assess how these actives performed against complex interkingdom biofilms in a clinically relevant model. Two lactam derivatives were tested against a panel of important fungal pathogens and then quantitatively assessed against simple and increasingly complex interkingdom biofilm models on polystyrene coverslips and a novel keratin hydrogel system. The lactams were shown to be effective against a wide range of fungal species in the planktonic and biofilm forms, with no ability to regrow. The fungal component of the multispecies biofilm models was significantly reduced with lactam treatment. Lactam treatment was also comparably effective compared to the non‐prescription topical antifungal ‘Lamisil’ against C. albicans early and late biofilms. This study highlights the effectiveness of lactams as a novel antimicrobial for the management of the polymicrobial and interkingdom multispecies biofilms.
Exploring weight management beliefs during the menopausal transition (ME‐WEL project): A qualitative comparative study based on Health Belief Model
Authors: Leitão Mafalda , Pérez‐López Faustino R. , Marôco João , Pimenta Filipa 
Published: January 2025

AbstractObjectivesWhile most women experience weight gain during the menopausal transition, a subset successfully maintains a healthy weight. This study explores the determinants influencing different weight experiences during the menopausal transition, using the Health Belief Model (HBM).DesignQualitative design.MethodsSemi‐structured individual interviews with 62 Portuguese post‐menopausal women were performed. Among them, 31 women maintained a normal weight from pre‐menopause to post‐menopause, with a variation not exceeding 5% of pre‐menopausal weight, while another 31 women transitioned from normal weight in pre‐menopause to overweight or obesity in post‐menopause, with an increase above 7% of pre‐menopausal weight. Deductive‐dominant content analysis and multiple correspondence analysis were performed.ResultsProminent differences exist between the Unhealthy Weight Gain Group (UWG‐G) and the Healthy Weight Maintenance Group (HWM‐G). The UWG‐G lacks perceived susceptibility in pre‐menopause and perceives obesity as stigmatizing. They prioritize immediate changes as benefits, while the HWM‐G focuses on self‐concept. Both groups face barriers like food cravings and weight loss challenges in middle‐aged. For cues to action, the UWG‐G emphasizes social support and self‐care resources, while the HWM‐G emphasizes age progression and healthy behaviour adherence. The HWM‐G presents higher self‐efficacy.ConclusionThis study confirms the suitability of the HBM in understanding weight management beliefs among post‐menopausal women, highlighting differences between women who maintain a healthy weight and those who experience weight gain during this life phase. This facilitates identifying key determinants (perceived susceptibility, perceived severity, perceived benefits, perceived barriers, cues to action and self‐efficacy) crucial for future interventions in weight management.
Evaluation of Larger Side‐Group Functionalities and the Side/End‐Group Interplay in Ritonavir‐Like Inhibitors of CYP3A4
Authors: Samuels Eric R. , Sevrioukova Irina F. 
Published: January 2025

ABSTRACTA new series of 13 ritonavir‐like inhibitors of human drug‐metabolizing CYP3A4 was rationally designed to study the R2 side‐group and R3 end‐group interplay when the R1 side‐group is represented by phenyl. Spectral, functional, and structural characterization showed no improvement in the binding affinity and inhibitory potency of R1/R2‐phenyl inhibitors upon elongation and/or fluorination of R3‐Boc (tert‐butyloxycarbonyl) or its replacement with benzenesulfonyl. When R3 is pyridine, the impact of R2‐phenyl‐to‐indole/naphthalene substitution was multidirectional and highly dependent on side‐group stereo configuration. Overall, the R2‐naphthalene/R3‐pyridine containing 2f (R/S) was the series lead compound and one of the strongest binders/inhibitors designed thus far (Ks = 0.009 μM; IC50 = 0.10 μM). Introduction of a larger biphenyl or fluorene as R2 did not lead to any improvements. Contrarily, fluorene‐containing 13 was the series weakest binder and inhibitor (Ks = 0.734 μM; IC50 = 1.32 μM), implying that the fluorene moiety is too large to allow unrestricted access to the active site. The R2‐biphenyl, however, can switch positions with R3‐Boc to enable heme ligation. Thus, for small and chemically simple end‐groups such as Boc and pyridine, the R2/R3 interplay could lead to conformational rearrangement that would be difficult to foresee without structural information.
Protective Effects of Mdivi‐1 on Cognition Disturbance Following Sepsis in Mice via Alleviating Microglia Activation and Polarization
Authors: Hong Chen , Wang Li , Zhou Xiaowei , Zou Liyong , Xiang Xinming , Deng Haoyue , Li Qinghui , Wu Yue , Liu Liangming , Li Tao 
Published: January 2025

ABSTRACTBackgroundNeuroinflammation is one of the essential pathogeneses of cognitive damage suffering from sepsis‐associated encephalopathy (SAE). Lots of evidences showed the microglia presented mitochondrial fragmentation during SAE. This study investigated the protective effects and novel mechanisms of inhibiting microglia mitochondrial fragmentation via mitochondrial division inhibitor 1 (Mdivi‐1) on cognitive damage in SAE.MethodsThe SAE model was performed by cecal ligation and puncture (CLP), and Mdivi‐1 was administrated via intraperitoneal injection. Morris water maze was performed to assess cognitive function. Mitochondrial morphology was observed by electron microscope or MitoTracker staining. The qRT‐PCR, immunofluorescence staining, and western blots were used to detect the inflammatory factors and protein content, respectively. Flow cytometry was used to detect the polarization of hippocampal microglia. Bioinformatics analysis was used to verify hypotheses.ResultsMdivi‐1 administration alleviated sepsis‐induced mitochondrial fragmentation, microglia activation, polarization, and cognitive damage. The mechanisms study showed neuroinflammation and oxidative stress were suppressed via NF‐κB and Keap1/Nrf2/HO‐1 pathways following Mdivi‐1 administration; meanwhile, pyroptosis in microglia was reduced, which was associated with enhanced autophagosome formation via p62 elevation following Mdivi‐1 administration.ConclusionInhibition of microglia mitochondrial fragmentation is beneficial to SAE cognitive disturbance, the mechanisms are related to alleviating neuroinflammation, oxidative stress, and pyroptosis.
Tailoring Kidney Transplant Strategies: Unraveling the Impact of Acute Kidney Injury and Preservation Methods Across Different Strata of Kidney Risk
Authors: Kaufman Daniel M. , Perkins James D. , Leca Nicolae , Bakthavatsalam Ramasamy , Sibulesky Lena 
Published: January 2025

ABSTRACTBackgroundThe use of donor kidneys with acute kidney injury (AKI) aims to expand the organ pool, but uncertainty remains regarding their outcomes across different Kidney Donor Profile Index (KDPI) groups and preservation methods.MethodsWe retrospectively analyzed 108 160 deceased donor kidney transplants from the OPTN database, focusing on adult recipients of kidneys from donors with or without AKI between December 2014 and December 2022. Propensity matching was used for each KDPI group (1–20, 21–59, 60–84, and 85–100), comparing donors with AKIN stages 0–1 to AKIN stages 2–3. Cox proportional hazards analysis assessed graft survival by AKIN stages and preservation type.ResultsThe use of AKIN stage 2–3 kidneys significantly increased over the study period. AKIN does not negatively impact graft survival in the KDPI 1–20 group and is linked to improved survival in KDPI 21–59 and 60–84. In the KDPI 85–100 group, AKIN stage 2–3 shows a trend toward increased graft failure. Pump preservation reduces delayed graft function (DGF) across most KDPI groups but does not consistently improve long‐term survival, except in KDPI 85–100.ConclusionTransplantation with AKIN stage 2–3 kidneys is viable, but outcomes vary by KDPI group. Tailored guidelines should consider transplant center capabilities.
Early development of the calcified exoskeleton of the polyplacophoran mollusk, with insight into the evolutionary history of shell plates and spicules
Authors: Yoshikawa Hiroki , Morino Yoshiaki , Wada Hiroshi 
Published: January 2025

AbstractRecent molecular phylogenetic studies have raised two questions about the evolutionary history of the calcified exoskeleton of mollusks. The first question concerns the homology of the two types of skeleton: whether spicules and shell plates share an evolutionary origin. The second question is the homology of the shell plates between chitons and other mollusks, including gastropods and bivalves. To gain insight into these questions, we examined the early development of shell plates and spicules in chitons. We identified several developmental genes that are involved in both shell plates and spicules, suggesting that spicules and shell plates share a common evolutionary origin. We also found that subpopulations of the dorsal shell field (the ridge and the plate field) have specific gene expression profiles. The differential gene expression of the ridge and plate field is not identical to the profiles of the zones of the gastropod shell field. This observation may suggest an independent evolutionary origin of the shell plates in chitons and gastropods.
Favourable Outcome of Relapsed PCNSL Among Transplant Eligble Patients
Authors: Pellonperä Eetu , Puhakka Inka , Kuitunen Hanne , Rönkä Aino , Sunela Kaisa , Kuusisto Milla E. L. , Klaavuniemi Tuula , Jäkälä Pekka , Rajamäki Aino , Arkko Ulla‐Mari , Kuittinen Outi 
Published: January 2025

ABSTRACTPurposeThe prognosis of relapsed primary central nervous system lymphoma remains a concern. This study aimed to compare the effects of various patient‐ and disease‐related factors on the prognosis of relapsed primary central nervous system lymphoma (PCNSL).MethodsWe retrospectively collected real‐world data from eight Finnish hospitals on 198 patients diagnosed with PCNSL between 2003 and 2020. Characteristics of the patients were available. At total of 63 patients with relapses were included after excluding seven isolated ocular relapses.ResultsThe median progression‐free survival after relapse was 3 months. The median overall survival after the first relapse (OS2) was 4 months. Patients aged 70 or younger with good performance status who received autologous stem cell transplantation (ASCT) consolidation as second‐line treatment had significantly better OS2 of 39 months (p = 0.002). OS2 for patients without ASCT consolidation remained at 3 months. Age over 70 years, poor performance status, and a first‐line progression‐free survival of less than 6 months negatively impacted the prognosis.ConclusionThis study confirms previous findings of poor outcomes in patients with relapsed PCNSL. Some subgroups, particularly those receiving ASCT consolidation, can achieve long‐term remission with current treatment options. New treatment strategies are needed for patients ineligible for ASCT or those who do not respond to salvage induction therapies.
Vital for Sustainable Agriculture: Pedological Knowledge and Mapping
Authors: Demattê José A. M. , Minasny Budiman , Hartemink Alfred E. 
Published: January 2025

ABSTRACTOver the past 60 years, efforts to enhance agricultural productivity have mainly focussed on optimising strategies such as the use of inorganic fertilisers, advancements in microbiology and improved water management practices. Here, we emphasise the critical role of pedology as a foundation in soil management and long‐term sustainability. We will demonstrate how overlooking the intrinsic properties of soils can result in detrimental effects on soil and overall sustainability. Communication between academia, extension experts, consultants and farmers often results in an overemphasis on the surface layer, for example, 20 to 40 cm, neglecting the functions that occur at depth. Soil health and regenerative agriculture must be coupled with an understanding of how soil functions as a dynamic system. We find that pedological knowledge and digital soil mapping technologies are underused for achieving sustainable agriculture. By bridging the gap between pedology and emerging agricultural technologies, we can provide land users with the tools needed to make informed decisions, ensuring that their practices not only increase production but also preserve the health of the soil for future generations.
BLOSOM: A Plant Growth Facility Optimised for Continuous 13C Labelling and Measurement of Soil Organic Matter Dynamics
Authors: Friggens Nina L. , England Neville , Murton Julian B. , Phoenix Gareth K. , Hartley Iain P. 
Published: January 2025

ABSTRACTChanges in soil carbon (C) stocks are largely driven by rhizosphere processes forming new soil organic matter (SOM) or stimulating SOM decomposition by rhizosphere priming effects (RPEs). Quantifying these changes is challenging and requires high spatial sampling densities or plant–soil experiments with highly distinct C isotopic signatures for plants and soils. Current methods for quantifying new SOM formation and RPEs rely on low labelling intensities, which introduces high levels of uncertainty. Here, we describe the design and operation of an experimental laboratory facility—BLOSOM (Botanical Labelling Observatory for Soil Organic Matter)—optimised for continuous 13C labelling of plants at high labelling intensities (> 500‰) to quantify new SOM formation and RPEs in temperature‐controlled soils from 216 experimental units. Throughout a > 6‐month experimental period, independent control of soil and air temperature was achieved across diurnal cycles averaging at 5.24°C ± 0.05°C and 21.4°C ± 1.2°C, respectively. BLOSOM can maintain stable CO2 concentrations and δ13C isotopic composition within 5% of setpoints (CO2: 440 ppm, δ13C: 515‰) across a > 6‐month period. This high‐precision control on atmospheric enrichment enables the detection of new SOM formation with a total uncertainty of ±39% to ±3% for a theoretical range of 0.5%–10% new SOM formation, respectively. BLOSOM has the potential improve quantification and mechanistic understanding of new SOM formation and RPEs across many different combinations of plants, soils and simulated climatic conditions to mimic a wide range of ecosystems and climate scenarios.
Opicapone as adjunct to levodopa in treated Parkinson's disease without motor complications: A randomized clinical trial
Authors: Ferreira Joaquim J. , Rascol Olivier , Stocchi Fabrizio , Antonini Angelo , Moreira Joana , Castilla‐Fernández Guillermo , Rocha José‐Francisco , Holenz Joerg , Poewe Werner ,   the Epsilon Study investigators
Published: January 2025

AbstractBackgroundCatechol‐O‐methyl transferase (COMT) inhibitors are routinely used to manage motor fluctuations in Parkinson's disease (PD). We assessed the effect of opicapone on motor symptom severity in levodopa‐treated patients without motor complications.MethodsThis was a randomized, double‐blind, 24‐week, placebo‐controlled study of opicapone 50 mg as adjunct to levodopa (NCT04978597). Levodopa‐treated patients without motor complications were randomized to 24 weeks of double‐blind treatment with adjunct opicapone 50 mg or matching placebo. The primary efficacy endpoint was the mean change from baseline to week 24 in Movement Disorder Society‐Unified Parkinson's Disease Rating Scale Part III (MDS‐UPDRS‐III) total score.ResultsA total of 355 patients were randomized (opicapone 50 mg n = 177, placebo n = 178) and 322 (91%) completed the double‐blind period. The adjusted mean [95% CI] change from baseline to week 24 in MDS‐UPDRS‐III subscore was −6.5 [−7.9, −5.2] in the opicapone group versus −4.3 [−5.7, 3.0] in the placebo group resulting in a significant difference of −2.2 [−3.9, −0.5] favoring opicapone (p = 0.010). There was no difference in the incidence of patients who developed motor complications (5.5% with opicapone vs. 9.8% with placebo) and the incidence of adverse events considered related to study medication was similar between groups (opicapone 10.2% vs. placebo 13.5%).ConclusionsTreatment with once‐daily adjunct opicapone was well tolerated, improved motor severity, and did not induce the development of motor complications. These results support the clinical usefulness of opicapone in the management of PD patients without motor complications.
Hyperreflective retinal foci are associated with retinal degeneration after optic neuritis in neuromyelitis optica spectrum disorders and multiple sclerosis
Authors: Klyscz Philipp , Vigiser Ifat , Solorza Buenrostro Gilberto , Motamedi Seyedamirhosein , Leutloff Carla Johanna , Schindler Patrick , Schmitz‐Hübsch Tanja , Paul Friedemann , Zimmermann Hanna Gwendolyn , Oertel Frederike Cosima 
Published: January 2025

AbstractBackgroundHyperreflective retinal foci (HRF) visualized by optical coherence tomography (OCT) potentially represent clusters of microglia. We compared HRF frequencies and their association with retinal neurodegeneration between people with clinically isolated syndrome (pwCIS), multiple sclerosis (pwMS), aquaporin 4‐IgG positive neuromyelitis optica spectrum disorder (pwNMOSD), and healthy controls (HC)—as well as between eyes with (ON+eyes) and without a history of optic neuritis (ON−eyes).MethodsCross‐sectional data of pwCIS, pwMS, and pwNMOSD with previous ON and HC were acquired at Charité—Universitätsmedizin Berlin. HRF analysis was performed manually on the central macular OCT scan. Semi‐manual OCT segmentation was performed to acquire the combined ganglion cell and inner plexiform layer (GCIPL), inner nuclear layer (INL), and peripapillary retinal nerve fiber layer (pRNFL) thickness. Group comparisons were performed by linear mixed models.ResultsIn total, 227 eyes from 88 patients (21 pwCIS, 32 pwMS, and 35 pwNMOSD) and 35 HCs were included. HRF in GCIPL and INL were more frequently detected in pwCIS, pwMS, and pwNMOSD than HCs (p < 0.001 for all comparisons) with pwCIS exhibiting the greatest numbers. ON+eyes of pwMS had less HRF in GCIPL than ON−eyes (p = 0.036), but no difference was seen in pwCIS and pwNMOSD. HRF GCIPL were correlated to GCIPL thickness in ON+eyes in pwMS (p = 0.040) and pwNMOSD (p = 0.031).ConclusionHRF occur in ON+eyes and ON−eyes across neuroinflammatory diseases. In pwMS and pwNMOSD, HRF frequency was positively associated with GCIPL thickness indicating that HRF formation might be dependent on retinal ganglion cells.
A genome‐wide association study for recurrent laryngeal neuropathy in the Thoroughbred horse identifies a candidate gene that regulates myelin structure
Authors: McGivney Charlotte L. , McGivney Beatrice A. , Farries Gabriella , Gough Katie F. , Han Haige , Holtby Amy R. , MacHugh David E. , Katz Lisa Michelle , Hill Emmeline W. 
Published: January 2025

AbstractBackgroundEquine recurrent laryngeal neuropathy (RLN) is an economically important upper respiratory tract (URT) disease with a genetic contribution to risk, but genetic variants independent of height have not been identified for Thoroughbreds. The method of clinical assessment for RLN is critical to accurately phenotype groups for genetic studies.ObjectivesTo identify genetic risk loci for RLN in Thoroughbreds in a genome‐wide association study (GWAS) following high‐resolution phenotyping.Study designCase–control.MethodsThoroughbred horses were characterised as RLN cases and controls using resting and exercising URT endoscopic examinations and laryngeal ultrasonography, with the case‐cohort supplemented using a questionnaire. Genotypes for 43 831 autosomal single‐nucleotide polymorphisms (SNPs) from n = 235 horses (n = 110 cases; n = 125 controls) were used to estimate trait heritability and identify significantly associated SNPs in a GWAS. Haplotypes were examined in cases and controls and risk allele frequencies were examined in a population cohort (n = 3126).ResultsHeritability was h2 = 0.30 including sex and 5PCs as covariates. A SNP on ECA20 located between candidate genes, DAAM2 and LRFN2, was significantly associated with RLN. Six index SNPs with allelic effect sizes OR = 1.5–2.9 were identified on ECA1, ECA14, and ECA20 close to candidate genes ATPA10, KCNN2, and TFAP2A. Eleven ECA20 SNPs defined seven haplotypes with homozygous H2/H2 horses having a 3.1× higher risk of RLN. Risk alleles segregate in the population, and stallions are carriers.Main limitationsThe main study population was young. Horses in the control group had no evidence of RLN as 2‐ or 3‐year olds but may have developed RLN later.ConclusionsGenetic markers for RLN were identified which may be useful for the development of a polygenic risk score. Candidate genes with functions in neuropathies may further the understanding of RLN pathobiology.