bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of Early Intervention for Early Psychosis on Suicidal Behavior—A Meta‐Analysis
Authors: Tahmazov Elkhan , Bosse Jordan , Glemain Benjamin , Nabbe Patrice , Guillou Morgane , Blachier Athéna , Walter Michel , Lemey Christophe 
Published: November 2024

ABSTRACTIntroductionEarly‐onset psychotic disorders include the prodromal phase and the first‐episode psychosis (FEP). They constitute a high‐risk period for suicidal behavior. Early intervention for psychosis (EIP) consists of intervening as early as possible. The effectiveness of early intervention on overall prognosis has been reported in numerous studies, and EIP services are emerging worldwide. Several authors report an improvement in suicidal behavior, but no study has looked at all the data.Aims of the StudyThe aim of work is to study whether early intervention for psychosis has an impact on deaths by suicide and suicide attempts, and study which intervention methods have an impact on suicidal behavior.MethodologyBy respecting the PRISMA criteria, previously declared on PROSPERO, by exploring 5 medical databases (PubMed, Cochrane, PsycINFO, Scopus, Embase), from their creation dates, published until 20/02/2023, in English, we carried out a meta‐analysis. The articles selected had to deal with the EIP and deaths by suicide or suicide attempts. Our primary outcome is the deaths by suicide and the secondary outcome the suicide attempt.ResultsThe exhaustive search identified a total of 2310 references. Nine articles were included. Their intervention modalities were pharmacotherapy, psychotherapy, case‐management, or related services, and psycho‐social therapies. Our meta‐analysis shows that early intervention for early‐onset psychotic disorders is associated with a statistically significant reduction by a third in deaths by suicide (ORa = 0.66 (0.49–0.88), p = 0.005) and by a third in suicide attempts (ORa = 0.66 (0.50–0.86), p = 0.002), with non‐significant heterogeneity. Sensitivity analyses excluding the study with statistical difficulties due to the absence of an event and studies with a high risk of bias point in the same direction, that is a statistically significant reduction and non‐significant heterogeneity.ConclusionThe literature shows that early intervention programs are associated with positive impact on deaths by suicide and suicide attempt. This is the first meta‐analysis of early intervention in early psychotic disorders and its impact on suicidal risk. The deployment of EIP should be supported worldwide in order to intervene as early as possible and prevent the risk of suicide.
Trial Registration: PROSPERO CRD42022366976
Quantifying the impacts of stoat and cat incursions on reintroduced bird populations in a predator‐fenced wildlife sanctuary
Authors: Parker K.A. , Lovegrove T.G. , Maitland M. , Parlato E. , Stone Z. , Armstrong D.P. 
Published: November 2024

AbstractControl of introduced predators is essential for conserving many threatened species, but species range in vulnerability. Therefore, efficient conservation management requires estimating the vulnerabilities of different threatened species to introduced predators. Here, we quantify population responses of reintroduced toutouwai (Petroica longipes), popokatea (Mohoua albicilla) and tīeke (Philesturnus rufusater) to incursions of stoats (Mustela erminea) and cats (Felis catus) to a 588‐ha predator‐fenced sanctuary in Aotearoa New Zealand. There were fewer than 0.5 detections per year for both predator species from 2004 to 2016, but stoat detections increased >10‐fold from 2017 to 2019 and cats >30‐fold from 2020 to 2021. We estimated the growth and persistence of each bird population pre‐ and post‐2017. This involved fitting integrated population models to survival, reproduction and count data for toutouwai and tīeke, and fitting a variation of the Moran–Ricker model to 5‐min point counts for popokatea. We used these models to derive λmax, the finite rate of increase at zero density, which must be >1 for a population to persist. Popokatea showed no sign of impacts, with λmax estimated to be 1.68 (95% CRI 1.49–1.97) up to 2017 and 1.87 (1.42–2.62) after 2017. Toutouwai had tentative decreases in survival and reproduction, dropping the estimated λmax from 1.28 (1.10–1.51) to 1.06 (0.83–1.41). Tīeke survival dropped dramatically from 2017 to 2019, but returned to pre‐2017 levels when stoats were reduced, but recruitment was reduced and remained low, presumably due to cats. λmax was estimated to be 1.74 (1.04–2.70) on pre‐2017 rates; 1.14 (0.80–1.71) if only recruitment were predator‐affected; and 0.79 (0.36–1.36) if both adult survival and recruitment were predator‐affected. Our results therefore indicated that this level of stoat and cat incursion was inconsequential for popokatea, tentatively reduced toutouwai persistence from safe to marginal, and would have driven tīeke to extinction.
Alternatives to Injectable Adrenaline for Treating Anaphylaxis
Authors: Pouessel Guillaume , Neukirch Catherine 
Published: November 2024

ABSTRACTAdrenaline is the first line treatment for anaphylaxis and adrenaline auto‐injectors (AAI) allow reliable, safe and ergonomic administration in the community. However, AAIs have significant limitations and adrenaline is often not used in anaphylaxis. Innovations to administer adrenaline via alternative routes may potentially improve usage rates and treatment effectiveness. Here, we describe the known limitations and barriers to AAI use in anaphylaxis. We then summarise current data for adrenaline devices which use alternative routes of administration for treating anaphylaxis. Several novel devices are in development, which deliver adrenaline via nasal, sublingual or transcutaneous routes. Pharmacokinetic, pharmacodynamic and safety studies have compared these treatments with AAI or intramuscular adrenaline via needle and syringe. The first non‐injectable adrenaline delivery device for emergency treatment of anaphylaxis was approved in Europe and the United States. Neffy, an adrenaline nasal spray, is licensed for use in adult and paediatric patients who weigh at least 30 kg. In the near future, multiple alternatives to injectable adrenaline may be available for managing anaphylaxis, overcoming some, but not all of the limitations of AAIs.
Deconvoluting zavegepant drug–drug interactions: A phase I study to evaluate the effects of rifampin and itraconazole on zavegepant pharmacokinetics
Authors: Bhardwaj Rajinder , Malatesta Jo Ann , Madonia Jennifer , Anderson Matt S. , Morris Beth , Matschke Kyle T. , Croop Robert , Bertz Richard , Liu Jing 
Published: November 2024

AbstractZavegepant is a calcitonin gene‐related peptide receptor antagonist for acute migraine treatment. This Phase I, open‐label, fixed‐sequence study evaluated the effects of itraconazole (a strong cytochrome P450 3A4 [CYP3A4] and P‐glycoprotein [P‐gp] inhibitor) on the pharmacokinetics of intranasal/oral zavegepant and the effects of rifampin (a strong inducer of CYP3A4 and P‐gp; and an inhibitor of organic anion transporting polypeptide 1B3 [OATP1B3]) on oral zavegepant in healthy participants. In the intranasal/oral zavegepant–itraconazole cohort, participants received a single 10‐mg dose of zavegepant nasal spray on Day 1, followed by oral zavegepant (50 mg) on Day 3. Itraconazole 200 mg once daily was administered from Days 4 to 12. On Day 7 zavegepant nasal spray and on Day 11 oral zavegepant were coadministered with itraconazole. In the oral zavegepant–rifampin cohort, participants received oral zavegepant (100 mg) on Day 1, rifampin 600 mg once daily on Days 2–10, and rifampin with zavegepant on Day 11. No significant change in zavegepant exposure was observed following coadministration of itraconazole with zavegepant nasal spray. For oral zavegepant coadministered with itraconazole, the area under the curve from 0 to infinity (AUC0−inf) and the maximum observed concentration (Cmax) of oral zavegepant increased by 59% and 77%, respectively. For oral zavegepant coadministered with rifampin, the AUC0−inf and Cmax of oral zavegepant increased by approximately 2.3‐ and 2.2‐fold, respectively. These results suggest that OATP1B3 and intestinal P‐gp are the more prominent pathways, as opposed to CYP3A4, for a zavegepant drug–drug interaction. Coadministration of OATP1B3 inhibitors with zavegepant nasal spray should be avoided.
Assessment of pharmacokinetics and tolerability following single‐dose administration of molnupiravir in participants with hepatic or renal impairment
Authors: Duncan Kelly E. , Carstens Russ P. , Butterfield Kristin L. , Jin Yoon , Inbody Laura R. , Schaeffer Andrea K. , Matthews Catherine Z. , Zhao Tian , Patel Shruti , Maas Brian M. , Cheng Mickie H. , Stoch S. Aubrey 
Published: November 2024

AbstractIndividuals with chronic liver or kidney disease are at increased risk of severe COVID‐19. Molnupiravir is an orally administered antiviral authorized for the treatment of mild‐to‐moderate COVID‐19 in adults at risk of progression to severe disease. Two nonrandomized, open‐label, single‐dose, multicenter, phase 1 trials were conducted to investigate the effects of hepatic and renal impairment on the tolerability and pharmacokinetics of molnupiravir (800 mg) and its metabolite β‐D‐N4‐hydroxycytidine (NHC; NCT05386589/NCT05386758). The impact of renal impairment on urinary excretion of NHC was also assessed. The 90% CI for the geometric mean ratio of the plasma NHC area under the concentration–time curve (AUC) from zero to infinity was <2.0 for participants with moderate hepatic or severe renal impairment versus healthy mean‐matched controls. Comparable geometric mean values were observed for other pharmacokinetic parameters—including AUC from 0 to 12 h, AUC from zero to the last measurable concentration, and peak plasma concentration—in participants with moderate hepatic or severe renal impairment and in healthy mean‐matched controls. Urinary excretion of NHC was low in healthy participants and participants with severe renal impairment; renal clearance was numerically lower in those with renal impairment. In both trials, all adverse events were of mild or moderate intensity and resolved by study completion. There were no clinically relevant treatment‐related effects on other safety evaluations. Overall, molnupiravir was generally well‐tolerated, with similar pharmacokinetic profiles in participants with hepatic or renal impairment and healthy participants, supporting its use for treating COVID‐19 in these individuals without the need for dose adjustment.
Combining Real‐Time Neuroimaging With Machine Learning to Study Attention to Familiar Faces During Infancy: A Proof of Principle Study
Authors: Throm Elena , Gui Anna , Haartsen Rianne , da Costa Pedro F. , Leech Robert , Mason Luke , Jones Emily J. H. 
Published: November 2024

ABSTRACTLooking at caregivers’ faces is important for early social development, and there is a concomitant increase in neural correlates of attention to familiar versus novel faces in the first 6 months. However, by 12 months of age brain responses may not differentiate between familiar and unfamiliar faces. Traditional group‐based analyses do not examine whether these ‘null’ findings stem from a true lack of preference within individual infants, or whether groups of infants show individually strong but heterogeneous preferences for familiar versus unfamiliar faces. In a preregistered proof‐of‐principle study, we applied Neuroadaptive Bayesian Optimisation (NBO) to test how individual infants’ neural responses vary across faces differing in familiarity. Sixty‐one 5–12‐month‐olds viewed faces resulting from gradually morphing a familiar (primary caregiver) into an unfamiliar face. Electroencephalography (EEG) data from fronto‐central channels were analysed in real‐time. After the presentation of each face, the Negative central (Nc) event‐related potential (ERP) amplitude was calculated. A Bayesian Optimisation algorithm iteratively selected the next stimulus until it identified the stimulus eliciting the strongest Nc for that infant. Attrition (15%) was lower than in traditional studies (22%). Although there was no group‐level Nc‐difference between familiar versus unfamiliar faces, an optimum was predicted in 85% of the children, indicating individual‐level attentional preferences. Traditional analyses based on infants’ predicted optimum confirmed NBO can identify subgroups based on brain activation. Optima were not related to age and social behaviour. NBO suggests the lack of overall familiar/unfamiliar‐face attentional preference in middle infancy is explained by heterogeneous preferences, rather than a lack of preference within individual infants.
Coding‐Sequence Evolution Does Not Explain Divergence in Petal Anthocyanin Pigmentation Between Mimulus luteus Var luteus and M. l. variegatus
Authors: Orr Walker E. , Kim Ji Yang , Márquez Iker J. Sánchez , Ryan Caine J. , Raj Tejas , Hom Ellen K. , Person Ashley E. , Vonada Anne , Stratton John A. , Cooley Arielle M. 
Published: November 2024

ABSTRACTBiologists have long been interested in understanding genetic constraints on the evolution of development. For example, noncoding changes in a gene might be favored over coding changes if they are less constrained by pleiotropic effects. Here, we evaluate the importance of coding‐sequence changes to the recent evolution of a novel anthocyanin pigmentation trait in the monkeyflower genus Mimulus. The magenta‐flowered Mimulus luteus var. variegatus recently gained petal lobe anthocyanin pigmentation via a single‐locus Mendelian difference from its sister taxon, the yellow‐flowered M. l. luteus. Previous work showed that the differentially expressed transcription factor gene MYB5a/NEGAN is the single causal gene. However, it was not clear whether MYB5a coding‐sequence evolution (in addition to the observed patterns of differential expression) might also have contributed to increased anthocyanin production in M. l. variegatus. Quantitative image analysis of tobacco leaves, transfected with MYB5a coding sequence from each taxon, revealed robust anthocyanin production driven by both alleles. Counter to expectations, significantly higher anthocyanin production was driven by the allele from the low‐anthocyanin M. l. luteus, a result that was confirmed through both a replication of the initial study and analysis by an alternative method of spectrophotometry on extracted leaf anthocyanins. Together with previously published expression studies, our findings support the hypothesis that petal pigment in M. l. variegatus was not gained by protein‐coding changes, but instead solely via noncoding cis‐regulatory evolution. Finally, while constructing the transgenes needed for this experiment, we unexpectedly discovered two sites in MYB5a that appear to be post‐transcriptionally edited—a phenomenon that has been rarely reported, and even less often explored, for nuclear‐encoded plant mRNAs.
Giant miniature endplate potentials at vertebrate neuromuscular junctions: A review
Authors: Alkadhi Karim A. 
Published: November 2024

AbstractAn unusually large amplitude spontaneous miniature endplate potentials (gMEPPs) occur naturally at low frequency at the vertebrate neuromuscular junction. Unlike the normal miniature endplate potentials (nMEPPs), these gMEPPs have long duration and long time to peak. More strikingly, gMEPPs seem to be independent of extracellular and intracellular Ca+2. and have a greater temperature sensitivity than nMEPPs. They are potentiated by tetrodotoxin but inhibited by acetylcholine (ACh) receptor blockers indicating ACh is the neurotransmitter responsible for gMEPPs. The frequency of gMEPPs is greatly increased in muscles weakened by various drugs, toxins or disease conditions suggesting that gMEPPs may be a part of possible neurotrophic mechanism to preserve effective neuromuscular transmission when the normal function is compromised.
The future of scientific labs: how we are making our research more sustainable
Authors: Monson Ebony A , Rutter Stephanie , Reimann Christopher C , Bueno‐Pedraz Andrea , Vella Caitlin , Pearce Xavier G , Wood Jennifer L , Fanson Kerry V 
Published: November 2024

AbstractThe need for climate action is becoming increasingly urgent, and research labs need to be part of the solution. Scientific labs consume large amounts of energy and water and produce significant waste. Globally, scientific research generates over 5.5 million tons of plastic waste annually, which is ~2% of the world's plastic waste. Recognizing the need for sustainability in research, the La Trobe Green Labs program leads this effort in Australia. Since receiving Australia's first “MyGreenLab” certification in 2021, a dedicated steering committee of volunteers has driven successful green initiatives at La Trobe University. The program ensures proper implementation of sustainable practices, enhanced safety and integration with existing operations. More importantly, these small changes will initiate wide‐scale and long‐term transformations that will improve research into more sustainable options for the future.
iPSCs‐derived iMSCs prevent osteoporotic bone loss and affect bone metabolites in ovariectomized mice
Authors: Wang Wei‐Zhou , Wang Yang‐Hao , Bao Sha‐Sha , He Fei , Li Guoyu , Yang Guang , Chen Jing , Yang Xin‐Yu , Xiao Ya , Tong Ya‐Shuang , Zhao Xue‐Ting , Hu Jun , You Ding‐You 
Published: November 2024

AbstractOsteoporosis is a metabolic bone disease that seriously jeopardizes the health of middle‐aged and elderly people. Mesenchymal stem cell‐based transplantation for osteoporosis is a promising new therapeutic strategy. Induced mesenchymal stem cells (iMSCs) are a new option for stem cell transplantation therapy. Acquired mouse skin fibroblasts were transduced and reprogrammed into induced pluripotent cells and further induced to differentiate into iMSCs. The iMSCs were tested for pluripotency markers, trilineage differentiation ability, cell surface molecular marker tests, and gene expression patterns. The iMSCs were injected into the tail vein of mice by tail vein injection, and the distribution of cells in various organs was observed. The effect of iMSCs on the bone mass of mice was detected after injection into the mouse osteoporosis model. The effects of iMSCs infusion on metabolites in femoral tissue and peripheral blood plasma were detected based on LC–MS untargeted metabolomics. iMSCs have similar morphology, immunophenotype, in vitro differentiation potential, and gene expression patterns as mesenchymal stem cells. The iMSCs were heavily distributed in the lungs after infusion and gradually decreased over time. The iMSCs in the femoral bone marrow cavity gradually increased with time. iMSCs infusion significantly avoided bone loss due to oophorectomy. The results of untargeted metabolomics suggest that amino acid and lipid metabolic pathways are key factors involved in iMSCs bone protection and prevention of osteoporosis formation. iMSCs obtained by reprogramming‐induced differentiation had cellular properties similar to those of bone marrow mesenchymal stem cells. The iMSCs could promote the remodelling of bone structure in ovariectomy‐induced osteoporotic mice and affect the changes of several key metabolites in bone and peripheral blood. Some of these metabolites can serve as potential biomarkers and therapeutic targets for iMSCs intervention in osteoporosis. Investigating the effects of iMSCs on osteoporosis and the influence of metabolic pathways will provide new ideas and methods for the clinical treatment of osteoporosis.
Effect of Propionate on Citrobacter rodentium Infection in Mice by Regulating NleH Expression
Authors: Li Yingying , Mei Wenjie , Zhang Qinhan , Li Li , Ji Qiaorong 
Published: November 2024

ABSTRACTPropionate is one of the main short chain fatty acids in the gut. Previously, we found that propionate significantly down‐regulated the expression of NleH. NleH is a virulence effector secreted by Citrobacter rodentium (C. rodentium, C.r.) and is essential for its intestinal colonisation and infection. Therefore, this study intends to explore the effect and mechanism of propionate on C.r. infection by regulating the expression of NleH. Wild‐type C.r. and its NleH mutant (C.r.△NleH), E.coli and its NleH1 mutant (E.coli△NleH1) were co‐cultured with propionate separately, changes in strain growth and invasion adhesion were detected. Meanwhile, C57BL/6J mice were infected with C.r. and C.r.△NleH to establish animal model, and propionate intervention was given. Through detecting the invasive and infectious ability of strains in mice and the changes related to colon inflammation, to analyse the effect of propionate on C.r. infection by regulating NleH expression. The results showed that propionate can reduce the adhesion of C.r. and intestinal damage by down‐regulating NleH expression, meanwhile changes of microbial functional metabolism enhance the resistance to C.r. infection in mice.
Role of m6A Methylation Regulators in the Diagnosis and Subtype Classification of COPD Based on the GEO Database
Authors: Zhang Pingan , Gao Na , Li Xiaoning , Zheng Xudong , Kong Deyu , Wu Jianjun 
Published: November 2024

ABSTRACTN6‐methyladenosine (m6A) is a prevalent mRNA modifier, yet its role in chronic obstructive pulmonary disease (COPD) remains unexplored. We sourced expression levels of m6A methylation regulators from the GSE76925 dataset. These regulators' differential expression (DEMs) predicted COPD risk via random forest and support vector machine models. Additionally, a nomogram model using DEMs estimated COPD prevalence. We employed consistent cluster analysis of m6A methylation regulators to categorise COPD samples into distinct subtypes. Analyses of immune cell infiltration in these subtypes and differential gene expression (DEGs) across m6A methylation subtypes were conducted. A cell model validated several m6A regulators and their associated pathways. Fifteen m6A methylation regulators showed differential expression and were used in random forest and support vector machine models. Eleven were selected for a nomogram model, which decision curve analysis suggested could benefit patients. Consensus cluster analysis divided the COPD samples into two subtypes: Cluster A and Cluster B. Cluster B was associated with neutrophil and eosinophil‐dominated immunity, while Cluster A was linked with monocyte‐dominated immunity. Validation of some research findings was achieved through cell experiments. m6A methylation regulators appear instrumental in diagnosing and classifying subtypes of COPD.