bluuebunny/crossref_metadata_2025_split huggingface dataset:
Conceptualising the context and mechanisms for tackling loneliness in older adults through interventions: A Critical Interpretive Synthesis
Authors: Ratcliffe John , Matcham Faith , Molteni Erika , Antonelli Michela , Rees Jessica , Shi Yu , Liu Jingqi , Ourselin Sebastian , Tinker Anthea , Zhou Yi , Liu Wei 
Published: January 2025

AbstractBackgroundLoneliness in later life has been widely associated with poor mental and physical health. However, despite many reviews, current evidence does not provide a clear picture of how to tackle loneliness in older adults through interventions. Research examining the contexts and mechanisms for reducing loneliness through interventions is required to identify how, why, and for who interventions work or do not work.MethodsA critical interpretive synthesis, a review method designed to rigorously and reflexively re-examine existing literature, was conducted to re-consider and identify what matters in interventions. This was enacted through a broad search strategy incorporating database searches, contacting experts, reference-chaining, and team discussions, enabling a flexible and iterative review able to generate new theory.Results274 papers were included in the analysis. We identified four dimensions to whether and how interventions worked.Intended outcomemirrored different theoretical perspectives on how to reduce loneliness. Four intended outcomes were identified: cognitive change; improved social connections; physiological change; and a more meaningful life. The second dimension was thelevelof an intervention - whether it intended to intervene at a micro, meso, or macro level. Thirdly, 13positive featuresof interventions were noted to have been evidenced to lead to or constitute more effective interventions. These were interventions that are organised, adaptable, have good staff/volunteers, provide support to attend, routinised, built on shared interests/identities, personalised, culturally aware, co-produced, involve active participation, strengths-based, lasting, and targeted at the appropriate people. Lastly, nineemotions that represent less lonelinesswere identified: a feeling of reciprocated interactions; emotional and social support; belonging; perspective; self-efficacy; mattering; pride; purpose; and empowerment.ConclusionsInterventions and evaluations should look beyond comparing activities to see which are best and recognise that multidimensionality and variation is vital for individuals and communities with different needs. Identifying what the intended outcome of an intervention is, what level of society it intends to impact, and whether it actions the positive features identified in this study, can be employed to better target the variety of emotions that represent less loneliness.
Retinal vascularization rate predicts retinopathy of prematurity and remains unaffected by low-dose bevacizumab treatment
Authors: Chang Emer , Josan Amandeep , Purohit Ravi , Aslam Sher A , Hartley Caroline , Patel Chetan K , Xue Kanmin 
Published: January 2025

ABSTRACTPurposeTo assess the rate of retinal vascularisation derived from ultra-widefield (UWF) imaging-based retinopathy of prematurity (ROP) screening as predictor of type 1 ROP and characterise the effect of anti-VEGF therapy on vascularisation rate.DesignRetrospective, consecutive cohort study.Subjects132 eyes of 76 premature infants with mean gestational age (GA) of 26.0(±2.0SD) weeks and birth weight (BW) of 815(±264) g, who underwent longitudinal UWF imaging for ROP screening.Setting/VenueLevel 3 neonatal unit in Oxford, United KingdomMethodsThe extent of retinal vascularisation on each UWF image was measured as the ratio between ‘disc-to-temporal vascular front’ and ‘disc-to-fovea’ distance along a straight line bisecting the vascular arcades. Measurements from ≥3 timepoints plotted against post-menstrual age (PMA) enabled calculation of temporal vascularisation rate (TVR) for each eye. Using TVR, GA and BW as predictors, a machine learning model was created to classify eyes as either Group AB (no ROP and type 2 ROP) or Group C (type 1 ROP). The model was validated in a withheld cohort of 32 eyes (19 infants) of which 8 eyes (5 infants) required treatment. TVR in 37 eyes (20 infants) was compared before and after ultra-low-dose (0.16 mg) intravitreal bevacizumab treatment.Main Outcome MeasuresRate of retinal vascularisation.ResultsSlower retinal vascularisation correlated with increasing ROP severity, with TVR being 29% slower in Group C eyes (n=50) than Group AB eyes (n=33 no ROP and n=49 type 2 ROP) (p=0.04). Our model correctly predicted ROP outcomes of 30/32 eyes, achieving a balanced accuracy of 95.8%. No significant change in TVR was found before and after bevacizumab treatment with mean post-treatment imaging follow-up of 7.7(±7.9) weeks (p=0.60 right eyes, p=0.71 left eyes).ConclusionsUWF imaging-based ROP screening enables quantification of retinal vascularisation rate, which can provide early prediction of type 1 ROP independent of BW and GA. Rate of physiological retinal vascularisation does not appear to be significantly affected by ultra-low-dose anti-VEGF treatment, which has significant implications for the development of peripheral avascular retina and timing of anti-VEGF intervention to prevent disease progression in high risk infants.
Mixtures of multiple air pollutants from specific industrial or residential sources and mortality from ischemic heart disease, cardiovascular disease, and non-accidental causes: A large general population Canadian cohort study
Authors: Zhao Naizhuo , Olaniyan Toyib , Mitchell Kimberly , Rouleau Mathieu , Popadic Ivana , Anastasopolos Angelos , Tjepkema Michael , Cakmak Sabit 
Published: January 2025

AbstractBackgroundPrevious studies on ambient air pollution and mortality typically focus on individual pollutants rather than their mixtures, and overall pollution rather than air pollution from specific sources. We aimed to assess the associations between ambient mixtures of fine particulate matter (PM2.5), sulfur dioxide (SO2), nitrogen dioxide (NO2), and ozone (O3) from various industrial and residential sources, and deaths from ischemic heart disease (IHD), cardiovascular disease (CVD) and non-accidental causes.MethodsWe linked the 2006 Canadian Census Health and Environment Cohort (CanCHEC) with the Canadian Vital Statistics Database, identifying 56190, 98185, and 381050 deaths between 2006 and 2019 from IHD, CVD, and non-accidental causes, respectively. Annual average concentrations of PM2.5, SO2, NO2, and O3from upstream petroleum, downstream petroleum, non-ferrous smelting, chemical industry and residential fuel combustion were estimated using the Global Environmental Multiscale-Modelling Air Quality and Chemistry (GEM-MACH) model. These concentrations were assigned to CanCHEC participants based on their annual residential postal codes. Quantile g-computation models were used to calculate hazard ratios (HRs) for deaths from IHD, CVD, and non-accidental causes per quartile increase in all four air pollutants from each specific sector.ResultsWe observed significant associations between the mixture of air pollutants and deaths from IHD, CVD, and non-accidental causes for emissions from upstream petroleum [HR: 1.18 (95% CI: 1.12-1.24), 1.12 (1.08-1.16), and 1.05 (1.04-1.05)], downstream petroleum [1.06 (1.05-, 1.04 (1.03-1.05), and 1.03 (1.02-1.03)], the chemical industry [1.10 (1.08-1.13), 1.07 (1.06-1.09), and 1.10 (1.08-1.13)], and residential fuel combustion [1.18 (1.12-1.23), 1.12 (1.08-1.16), and 1.07 (1.05-1.09)]. PM2.5and SO2contributed more to the increased risk of death than NO2and O3. Mortality from CVD or non-accidental causes was not associated with the mixtures of air pollutants from non-ferrous smelting.ConclusionsAmbient PM2.5and SO2from certain sectors, but not all, greatly contribute to the increased risk of non-accidental, IHD, and CVD deaths.
Markers of mitochondrial function and oxidative metabolism in female skeletal muscle do not display intrinsic circadian regulation
Authors: Fitzgerald Liam S. , Reynoso Spurrier Connor S. , Lau Nathan J. , Melamed Miles D. , Burnett Lindsey A. , Meyer Gretchen A. , Gui Chang , Hevener Andrea L. , Sanford James A. , Schenk Simon 
Published: January 2025

AbstractMitochondria are key regulators of metabolism and ATP supply in skeletal muscle, while circadian rhythms influence many physiological processes. However, whether mitochondrial function is intrinsically regulated in a circadian manner in mouse skeletal muscle is inadequately understood. Accordingly, we measured post-absorptive transcript abundance of markers of mitochondrial biogenesis, dynamics, and metabolism (extensor digitorum longus [EDL], soleus, gastrocnemius), protein abundance of electron transport chain complexes (EDL and soleus), enzymatic activity of SDH (tibialis anterior and plantaris), and maximum uncoupled respiration (tibialis anterior) in different skeletal muscles from female C57BL/6NJ mice at four zeitgeber times (ZT), ZT 1, 7, 13, and 19. Our findings demonstrate that markers of mitochondrial function and oxidative metabolism do not display intrinsic time-of-day regulation at the gene, protein, enzymatic, or functional level. The core-clock genesBmal1andDbpexhibited intrinsic circadian rhythmicity in skeletal muscle (i.e., EDL, soleus, gastrocnemius) and circadian amplitude varied by muscle type. These findings demonstrate that female mouse skeletal muscle does not display circadian regulation of markers of mitochondrial function or oxidative metabolism over 24 hours.
BASTA, a simple whole blood assay for measuring β-cell antigen specific CD4+T-cell responses in type 1 diabetes
Authors: Lacorcia Matthew , Bhattercharjee Pushpak , Foster Abby , Hardy Melinda Y. , Tye-Din Jason , Karas John , Wentworth John M , Cameron Fergus , Mannering Stuart I. 
Published: January 2025

AbstractType 1 diabetes (T1D) is an autoimmune disease where T-cells mediate the destruction of the insulin-producing β-cells found within the Islets of Langerhans in the pancreas. Currently, autoantibodies to β-cell antigens are the only tests available to detect β-cell autoimmunity. T-cell responses to β-cell antigens, which are known to cause T1D, can only be measured in research settings due to the complexity of assays and the large blood volumes required. Here we describe theβ-cellantigenspecificT-cellassay – BASTA. BASTA is a simple whole blood assay that can detect human CD4+T-cell responses to β-cell antigens by measuring antigen-stimulated IL-2 production. BASTA is both more sensitive and specific than the CFSE-based Proliferation Assay. We used BASTA to identify the regions of preproinsulin which stimulated T-cell responses specifically in blood from people with T1D. BASTA can be done with as little as 2-3 mL of blood. We found that effector memory CD4+T cells are the primary producers of IL-2 in response to preproinsulin peptides. We then evaluated responses to individual and pooled preproinsulin peptides in a cross-sectional study of pediatric subjects: without T1D, without T1D but with a first-degree relative with T1D, or diagnosed with T1D. In contrast to other preproinsulin peptides, full-length C-peptide (PI33-63) showed excellent specificity for T1D (AUC = 0.86). We suggest that BASTA will be a useful tool for monitoring changes in β-cell specific CD4+T-cell responses both in research and clinical settings.One Sentence Summaryβ-cell antigen specific CD4+T-cell responses in children with T1D can be measured using a simple whole blood assay.
Effective prediction of IL-17 inducing peptides using hybrid approach: iIL17pred
Authors: Arora Pooja , Periwal Neha , Aggarwal Lakshay , Sood Vikas , Kaur Baljeet 
Published: January 2025

AbstractBackgroundInterleukin 17 (IL-17) plays a crucial role in regulating the immune system and is associated with numerous diseases. Modulating IL-17 levels has demonstrated potential in mitigating disease symptoms, positioning it as a compelling target for drug development. Therefore, identifying and characterizing novel drug molecules capable of influencing IL-17 levels is critical. Recent advances in therapeutic peptides underscore their promise as attractive drug candidates, inspiring the development of IL-17 modulating peptides.ResultsThis study aimed to enhance existing methods for efficiently classifying IL-17 inducing peptides. Positive and negative datasets were obtained from the Immune Epitope Database, and peptide features were extracted using the pfeature algorithm. A three-stage hybrid approach combining BLAST, MERCI, and machine learning techniques was employed to accurately classify IL-17-inducing peptides.ConclusionsExtensive benchmarking experiments revealed that our proposed method outperforms existing techniques i.e IL17eScan, across key performance metrics, including sensitivity, accuracy, and area under the curve-receiver operating characteristics (AUC-ROC). Our algorithm achieved an accuracy of 88.08% and a Matthews Correlation Coefficient (MCC) of 0.68 on an external dataset, significantly surpassing the accuracy of 78.57% and MCC of 0.57 achieved by existing methods under comparable conditions. This demonstrates a substantial improvement in IL-17 peptide classification. The results are accessible via a user-friendly web server (http://www.soodlab.com/iil17pred/). These findings hold significant potential for predicting IL-17-inducing peptides, which can be further validated experimentally.
PHYSICAL EXERCISE RESTORES NEUROCOGNITIVE HOMEOSTASIS DISRUPTED BY NON-SEVERE MURINE MALARIA
Authors: de Sousa Luciana Pereira , de Oliveira Lavigne Ingrid , da Silva Nogueira Mônica , Daniel-Ribeiro Cláudio Tadeu 
Published: January 2025

AbstractMalaria disrupts neurocognitive homeostasis in humans, including in the non-severe manifestation of the disease - which is the most prevalent form of malaria in the world. This disruption is classically observed in human and experimental models of cerebral malaria. More recently, we demonstrated that this can also be observed in an experimental model of non-severe malaria and that Th2-immune response improves cognition and attenuates anxiety-like behavior associated to malaria. Complementarily, we have been studying the effect of physical exercise in restoring the neurocognitive homeostasis lost after non-severe murine malaria.
Single-nuclei transcriptomics revealed auxin-driven mechanisms of wood plasticity and severe drought tolerance in poplar
Authors: Gómez-Soto Daniela , Pereira Wendell J. , Piedrabuena-Díaz Alejandro , Dervinis Christopher , Kirst Matias , Allona Isabel , Perales Mariano , Conde Daniel 
Published: January 2025

ABSTRACTDrought significantly affects forests and woody crops by limiting their growth, increasing their susceptibility to diseases, and reducing productivity. Wood anatomical plasticity is a crucial adaptive mechanism that enables trees to cope with fluctuations in water availability. During severe drought, trees develop more and narrower vessels, enhancing hydraulic safety and reducing the risk of embolism. However, the molecular regulation of vessel formation is still not well understood. Using single-nucleus transcriptomics, we generated a cell type-specific gene expression map of the mature poplar stem under well-watered and drought conditions. Our findings revealed extensive gene expression reprogramming in xylem-forming cells, with changes in auxin homeostasis identified as a key mechanism for anatomical adaptation. Specifically, we showed that poplarWAT1-like genes control vessel spatial patterning. Additionally, the downregulation ofWAT1-like gene expression in the dividing cells of the vascular cambium and the upregulation ofMP-like gene in cells undergoing early vessel differentiation facilitate the formation of secondary xylem with narrower and more numerous vessels. Furthermore, thewat2mutant exhibited greater drought tolerance than wild-type trees, underscoring its potential for developing drought-resilient tree varieties. These insights enhance our understanding of xylem plasticity and provide valuable targets for improving drought tolerance in woody plants.
Regenerative failure of sympathetic axons contributes to deficits in functional recovery after nerve injury
Authors: Tian Tina , Kim David , Yu Kuai , Hartzell Criss , Ward Patricia J. 
Published: January 2025

ABSTRACTRenewed scientific interest in sympathetic modulation of muscle and neuromuscular junctions has spurred a flurry of new discoveries with major implications for motor diseases. However, the role sympathetic axons play in the persistent dysfunction that occurs after nerve injuries remains to be explored. Peripheral nerve injuries are common and lead to motor, sensory, and autonomic deficits that result in lifelong disabilities. Given the importance of sympathetic signaling in muscle metabolic health and maintaining bodily homeostasis, it is imperative to understand the regenerative capacity of sympathetic axons after injury. Therefore, we tested sympathetic axon regeneration and functional reinnervation of skin and muscle, both acute and long-term, using a battery of anatomical, pharmacological, chemogenetic, cell culture, analytical chemistry, and electrophysiological techniques. We employed several established growth-enhancing interventions, including electrical stimulation and conditioning lesion, as well as an innovative tool called bioluminescent optogenetics. Our results indicate that sympathetic regeneration is not enhanced by any of these treatments and may even be detrimental to sympathetic regeneration. Despite the complete return of motor reinnervation after sciatic nerve injury, gastrocnemius muscle atrophy and deficits in muscle cellular energy charge, as measured by relative ATP, ADP, and AMP concentrations, persisted long after injury, even with electrical stimulation. We suggest that these long-term deficits in muscle energy charge and atrophy are related to the deficiency in sympathetic axon regeneration. New studies are needed to better understand the mechanisms underlying sympathetic regeneration to develop therapeutics that can enhance the regeneration of all axon types.
AUTO-SP: automated sample preparation for analyzing proteins and protein modifications
Authors: Lih T. Mamie , Jiao Liyuan , Chen Lijun , Woo Jongmin , Wang Yuefan , Zhang Hui 
Published: January 2025

ABSTRACTLiquid chromatography (LC) tandem mass spectrometry (MS/MS) is one of the widely used proteomic techniques to study the alterations occurred at protein expression level as well as post-translation modifications (PTMs) of proteins that are relevant to different physiological or pathological statuses. The mass spectrometric analysis of peptides fragmented from proteins (bottom-up proteomics) has emerged as one of the major approaches for proteomics. In this approach, proteins are first cleaved into peptides for mass spectrometric analysis and peptides with PTMs are further enriched followed by the LC-MS/MS analysis. To achieve a reproducible and quantitative proteomic characterization, a well-established protease digestion and PTM peptide enrichment protocol is critical. In this study, we developed an automated sample preparation (AUTO-SP) for analyzing proteins and protein modifications utilizing Patient-Derived Xenograft (PDX) breast cancer tumors (basal-like and luminal subtypes). The protein amount was quantified and proteins were further digested by using AUTO-SP for each PDX sample. Based on the data-independent acquisition (DIA)-MS data, we observed samples of the same breast cancer subtypes were highly correlated (>0.98). Additionally, >14,000 ubiquitinated peptides were identified in the PDX samples when using AUTO-SP for ubiquitin enrichment, while unique pathways were enriched from the basal-like and luminal subtypes. AUTO-SP demonstrated its efficacy to provide reliable and reproducible sample preparation procedure for MS-based proteomic and PTM analyses.
A cationic liposome-formulated Toll Like Receptor (TLR)7/8 agonist enhances the efficacy of a vaccine against fentanyl toxicity
Authors: Hamid Fatima A , Le Nguyet-Minh Nguyen , Song Daihyun , Amin Hardik , Hicks Linda , Bird Sophia , Siram Karthik , Hoppe Brooke , Demeler Borries , Evans Jay T. , Burkhart David , Pravetoni Marco 
Published: January 2025

AbstractThe U.S. opioid epidemic is an extraordinary public health crisis that started in 1990 and significantly accelerated in the last decade. Since 2020, over 100,000 fatal drug overdoses have been reported annually, and 75% of those involved fentanyl and its analogs (F/FA). Accelerating the translation of innovative, effective, and safe treatments is needed to augment existing measures to counteract such a crisis. Active immunization against F/FA and other opioids represents a promising therapeutic and prophylactic strategy for opioid use disorder (OUD) and opioid-induced overdose toxicity. Previously we demonstrated that the anti-fentanyl vaccine comprising a fentanyl-based hapten (F) conjugated to the diphtheria cross-reactive material (CRM), admixed with the novel lipidated toll-like receptor 7/8 (TLR7/8) agonist INI-4001 adsorbed on Alhydrogel®(alum) induced high-affinity fentanyl-specific polyclonal antibodies that protected against fentanyl-induced pharmacological effects in mice, rats, and mini-pigs. Here, INI-4001 was formulated into liposomes with different surface charges, and their impact on F-CRM adsorption, INI-4001 adjuvanticity, and vaccine efficacy were explored. Additionally, as the role of innate immunity in mediating the efficacy of addiction vaccines is largely unknown, we tested these formulations on the activation of innate immunityin vitro. Cationic INI-4001 liposomes surpassed other liposomal and aluminum-based formulations of INI-4001 by enhancing the efficacy of fentanyl vaccines and protecting rats against bradycardia and respiratory depression by blocking the distribution of fentanyl to the brain. Fentanyl vaccines adjuvanted with either cationic INI-4001 liposomes or the aqueous INI-4001 adsorbed to alum induced significant surface expression of co-stimulatory molecules and maturation markers in a murine dendritic cell line (JAWS II), while the former was superior in enhancing the macrophages surface expression of CD40, CD86 and inducible nitric oxide synthase (iNOS), indicative of maturation and activation. These results warrant further investigation of liposome-based formulations of TLR7/8 agonists for improving the efficacy of vaccines targeting F/FA and other opioids of public health interest.Graphical abstract
PRESENCE OF A LARGE DASYPODIDAE GRAY, 1821 FROM THE CUVIERI CAVE, EASTERN BRAZIL
Authors: Chahud Artur 
Published: January 2025

AbstractCingulata represent a group of Xenarthra characterized by the presence of a carapace composed of bony plates (osteoderms). The Cuvieri Cave, located in the Lagoa Santa karst complex, presents a relevant quantity of vertebrate fossils, including extinct and extant species. Although several paleontological studies have been carried out, the material was reviewed from a taxonomic point of view, including Xenarthra material. Two osteoderms, initially attributed to the genusEuphractus, were found in Pleistocene deposits, but it was observed that the specimens did not belong to this genus. The aim of this study is to present the revision of these two specimens, now recognized as the first evidence of a large member of the family Dasypodidae in the Cuvieri Cave. The specimens were found in levels where both extant and extinct species from the Lagoa Santa region were found, but due to the paleoenvironmental changes of the Pleistocene-Holocene transition in Lagoa, it was not possible to determine the environment in which the specimen lived.