bluuebunny/crossref_metadata_2025_split huggingface dataset:
Significant Reduction in Manual Annotation Costs in Ultrasound Medical Image Database Construction Through Step by Step Artificial Intelligence Pre-annotation
Authors: Zheng Fu , XingMing Liu , JuYing Xu , MengYing Tao , BaoJian Yang , Yan Shan , KeWei Ye , ZhiKai Lu , Cheng Huang , KeLan Qi , XiHao Chen , WenFei Du , Ping He , RunYu Wang , Ying Ying , XiaoHui Bu 
Published: January 2025

AbstractThis study investigates the feasibility of reducing manual image annotation costs in medical image database construction by utilizing a step by step approach where the Artificial Intelligence model(AI model) trained on a previous batch of data automatically pre-annotates the next batch of image data, taking ultrasound image of thyroid nodule annotation as an example. The study used yolov8 as the AI model. During the AI model training, in addition to conventional image augmentation techniques, augmentation methods specifically tailored for ultrasound images were employed to balance the quantity differences between thyroid nodule classes and enhance model training effectiveness. The study found that training the model with augmented data significantly outperformed training with raw images data. When the number of original images number was only 1,360, with 7 thyroid nodule classifications, pre-annotation using the AI model trained on augmented data could save at least 30% of the manual annotation workload for junior physicians. When the scale of original images number reached 6,800, the classification accuracy of the AI model trained on augmented data was consistent with that of junior physicians, eliminating the need for manual preliminary annotation.
Characteristics of individuals who received a complete, 2-dose mpox vaccine regimen as part of the public health response to the mpox epidemic in Ontario, Canada: A CIRN study
Authors: Grewal Ramandip , Lau Cindy , Kwong Jeffrey C , Burchell Ann N , Friedman Lindsay , Navarro Christine , Okpokoro Evaezi , Tan Darrell H S , Zygmunt Austin , Mishra Sharmistha , Buchan Sarah A 
Published: January 2025

ABSTRACTBackgroundIn May 2022, an outbreak of mpox emerged in Canada. In June 2022, the province of Ontario began offering first doses of a 2-dose regimen of Modified Vaccinia Ankara–Bavaria Nordic (MVA-BN) to those at high risk of exposure. Second doses became available in September 2022. To help increase dose 2 access and uptake, we sought to understand how individuals who received 2 doses differed from those who received only 1 dose.MethodsWe linked provincial health administrative data of individuals who received ≥1 dose of MVA-BN between June 6, 2022 and October 31, 2023 in Ontario. We used age-adjusted Poisson regression to examine the association between demographic, social, and economic characteristics; co-morbidities; and proxies for sexual exposure (e.g., bacterial sexually transmitted infection [STI] diagnoses) and proxies for healthcare engagement (e.g., syphilis testing, past receipt of other vaccines) with MVA-BN dose 2 receipt.ResultsAmong 33,012 individuals with ≥1 MVA-BN dose, 38.2% (12,620) received 2 doses. Receipt of dose 2 versus only dose 1 was associated with region (e.g., Ottawa versus Toronto [prevalence ratio, PR=1.08, 95% confidence interval, CI 1.06-1.09]); syphilis testing (≥4 tests PR=1.12, 95%CI 1.11-1.14) or receiving a COVID-19, influenza, or other vaccine (PR=1.12, 95%CI 1.11-1.14) in the year before dose 1; and syphilis testing (≥4 tests PR=1.19, 95%CI 1.18- 1.20) or bacterial STI diagnoses >3 months after dose 1 (≥4 diagnoses PR=1.07, 95% CI 1.05- 1.08). Refugees were less likely to get dose 2 versus Canadian-born individuals or long-term immigrants (PR=0.93, 95%CI 0.91-0.95).ConclusionsOur findings suggest lower healthcare access and/or engagement may play a role in limiting dose 2 receipt in Ontario. Public messaging around availability and eligibility of second doses, tailored strategies for eligible refugees, increased access outside healthcare venues, and adopting promotion strategies from regions with high uptake, may help increase dose 2 coverage.
A Randomised Controlled Trial of the effects of Galacto-Oligosaccharides on the gut brain-axis of young females
Authors: Johnstone Nicola , Kadosh Kathrin Cohen 
Published: January 2025

AbstractBackgroundGalacto-oligosaccharides (GOS) are prebiotics linked to gut microbiota modulation and potential gut-brain axis effects on neurochemistry, mental health and cognition. This study evaluated the influence of GOS along the gut-brain axis, integrating assessments of mental health, neurochemistry, gut microbiome composition, cognition, and nutrition in healthy females.MethodsIn a randomised, double-blind, placebo-controlled trial, 83 females (17–25 years) received GOS or placebo for 28 days. Assessments occurred at baseline, endline, and 28 days post-supplementation. The primary outcome was trait anxiety, with secondary outcomes including neurochemical measures of GABA and glutamate via 1H-MRS in the dorsolateral prefrontal cortex (dlPFC), anterior cingulate cortex (ACC), and inferior occipital gyrus (IOG) of the brain, and gut microbiome composition. Tertiary outcomes included social anxiety, depression, emotion behaviour, reaction times, and nutritional intake. Analyses included intention-to-treat, per-protocol, and sensitivity approaches.ResultsTrait anxiety did not differ significantly between groups at endline (p = .443), though trends favoured lower anxiety in the GOS group at follow-up (p = .069). GOS reduced GABA at trend significance in the inferior occipital gyrus (p = .053) and dorsolateral prefrontal cortex (p = .088) in high-anxious participants, with effects persisting at follow-up. GOS increased Bifidobacterium abundance (p = .001) but did not affect overall microbiome diversity. Tertiary outcomes showed no significant changes in social anxiety or depression but faster reaction rates in high-anxious participants for simple (p = .036) and choice tasks (p < .001). Nutritional intake was unaffected.ConclusionWhile GOS supplementation did not significantly reduce trait anxiety, it produced neurochemical changes and transient modulations of the gut microbiome in Bifidobacterium abundance. These findings suggest GOS-induced changes can be traced along the gut-brain axis, with implications for mental health and cognitive function that warrant further investigation.
White matter tracts associated with iTBS-induced heart rate deceleration and treatment response in major depressive disorder
Authors: Wilkening Jonas , Goya-Maldonado Roberto 
Published: January 2025

AbstractIntermittent theta burst stimulation (iTBS) is a well-established treatment for major depressive disorder (MDD), but predicting clinical outcomes remains challenging. Heart rate modulation induced by iTBS has emerged as a potential biomarker for treatment response, yet the role of white matter (WM) properties in mediating these effects is largely unexplored. In this quadruple-blind, crossover study, we investigated the relationship between WM microstructure, iTBS-driven heart rate deceleration, and antidepressant effects. Using correlational tractography, we analyzed four major WM tracts—the cingulum, fornix, superior longitudinal fasciculus, and uncinate fasciculus—and examined short-term WM microstructural changes to assess their predictive value for therapeutic outcomes. Baseline WM findings revealed that in the fornix and right dorsal cingulum fractional anisotropy (FA) negatively correlated with heart rate deceleration. Radial and mean diffusivity (MD, RD) in the fornix positively correlated with heart rate deceleration. FA in the right ventral cingulum positively correlated while MD and RD negatively correlated with symptom improvement. Longitudinally, FA increases in the left cingulum were significantly associated with greater symptom alleviation after treatment. Notably, iTBS-induced heart rate modulations correlated with clinical improvement after six weeks, while WM microstructural properties in the fornix and cingulum demonstrated predictive value for both heart rate modulation and treatment response. WM changes in the cingulum, evident as early as four weeks, highlight its unique neuroplasticity potential along iTBS intervention. Together, these findings provide novel insights into the structural connectivity patterns influencing iTBS outcomes, offering a novel foundation for more personalized therapeutic strategies in MDD.
Inequalities in access to health care: an exploration of the cascade of care for in-transit migrants and asylum seekers, and the general population in Mexico
Authors: Banerjee Arjun , Rodríguez-Chavez César , Sepúlveda Jaime , Strathdee Steffanie , Bojorquez Ietza 
Published: January 2025

ABSTRACTBACKGROUNDAll over the world, migrants experience inequalities in access to health care. While this issue has been amply explored among immigrants and refugees in high-income countries, there is a dart of information on the situation of in-transit migrants and asylum seekers (IMAS) in low- or middle-income countries. Since these are the main recipient countries for this population, it is important to document inequalities in access to care in this context, especially for countries such as Mexico, in which IMAS are entitled to health care in par with the general population.OBJECTIVEto assess the inequalities in access to health care experienced by in-transit migrants in Mexico, as compared to the general population of Mexico, employing a cascade of care approach.METHODSWe analyzed data from a cross-sectional survey of IMAS in shelters in Tijuana (November 2020-April 2021, n=481), and from ENSANUT-COVID 2020, a representative survey of the general population in Mexico conducted at about the same time (unweighted n=25,959). We compared the cascade of care – the self-reported presence of health needs, whether participants sought care given the need, and whether they received care – of the two samples.RESULTSA higher percentage of IMAS had experienced a health need in the past three months, as compared to the general population of Mexico (43.0% vs 21.9%). IMAS were less likely to seek care given the need (58.9% vs 81.8%), to receive care when they sought it (86.9% vs 97.7%), and to receive care in the public health system (19.7% vs 43.3%).CONCLUSIONSInequalities in access to care were apparent, even in a health system that normatively should provide care regardless of migration status. Understanding why this occurs is important, and our results represent a baseline from which to evaluate future improvements in universal health coverage in Mexico.
A Rational Information Gathering Account of Infant Habituation
Authors: Karni Gili , Mattar Marcelo G. , Emberson Lauren , Daw Nathaniel D. 
Published: January 2025

AbstractGaze is one of the primary experimental measures for studying cognitive development, especially in preverbal infants. However, the field is only beginning to develop a principled explanatory framework for making sense of the various factors affecting gaze. We approach this issue by addressing infant gaze from first principles, using rational information gathering. In particular, we revisit the influential descriptive account of Hunter and Ames (1988) (H&A), which posits a set of regularities argued to govern how gaze preference for a stimulus changes with experience and other factors. When H&A’s model is reconsidered from the perspective of rational information gathering (as recently also proposed by other authors), one feature of the model emerges as surprising: that preference for a stimulus is not monotonic with exposure. This claim, which has at least some empirical support, is in contrast to most statistical measures of informativeness, which strictly decline with experience. We present a normative, computational theory of visual exploration that rationalizes this and other features of the classic account. Our account suggests that H&A’s signature nonmonotonic pattern is a direct manifestation of a ubiquitous principle of the value of information in sequential tasks, other consequences of which have recently been observed in a range of settings including deliberation, exploration, curiosity, and boredom. This is that the value of information gathering, putatively driving gaze, depends on the interplay of a stimulus’ informativeness (calledGain, the focus of other rationally motivated accounts) with a second factor (calledNeed) reflecting the estimated chance that information will be used in the future. This computational decomposition draws new connections between infant gaze and other cases of exploration, and offers novel, quantitative interpretations and predictions about the factors that may impact infant exploratory attention.
Alpha and beta desynchronization during consolidation of newly learned words
Authors: Zappa A. , León-Cabrera P. , Ramos-Escobar N. , Laine M. , Rodriguez-Fornells A. , François C. 
Published: January 2025

AbstractWhile a growing body of literature exists on initial word-to-meaning mapping and retrieval of fully lexicalized words, our understanding on the learning of semantic knowledge that occurs between these two stages remains limited. The current study investigated the neural correlates of retrieving newly learned word meanings using oscillatory brain dynamics. Participants learned to associate new words with unknown objects and performed overt and covert naming tasks during the first and last days of a five-day training period. Behavioral results showed improved overt naming on Day 5 compared to Day 1. Selecting only words that were successfully produced in the overt naming task, we examined alpha (8-12 Hz) and beta (13-25 Hz) band oscillatory activity associated with lexical-semantic retrieval while participants produced new words covertly, both pre-(Day 1) and post (Day 5) lexicalization. The results showed a robust alpha and lower beta power decrease during covert naming after learning. We hypothesize that this alpha-beta power decrease indexes successful word retrieval following lexical-semantic integration and consolidation.
Design of novel synthetic promoters to tune gene expression in T cells
Authors: Bonfá Giuliano , Martino Giovanna , Sellitto Assunta , Rinaldi Antonio , Tedeschi Fabiana , Caliendo Fabio , Melchiorri Loris , Perna Daniela , Starkey Freddie , Nikolados Evangelos , Menolascina Filippo , Siciliano Velia 
Published: January 2025

ABSTRACTTranscriptional control of transgene expression can be linked to dynamic changes in cellular states if this is accompanied by differential expression of transcription factors (TFs). Synthetic promoters (SPs) designed to respond to the desired TFs can provide this regulation with compactness, specificity, and orthogonality. T cells display differentially expressed TFs according to the functional state. In solid tumors, the highly immunosuppressive TME and the chronic exposure to antigens lead to a progression of T cells from a functional to a dysfunctional state known as exhaustion (Tex), in which their power against cancer cells is strongly compromised. Importantly, this transition is accompanied by a marked increase of several TFs, among other factors, that drive targeted genetic programs. Strategies to detect and mitigate Tex are extremely needed. Here, we design SPs that respond to TFs differentially expressed in activated and exhausted T cells to enable new classifiers of the functional/dysfunctional states. We developed a library of over 80 SPs responsive to 7 TFs. The SPs showed broad strength of activation of reporter genes or immunomodulatory molecules in HEK293 and Jurkat T cell lines. Moreover, using a transfer learning strategy we show SPs strength predictability. By combining SPs responding to different TFs, we created Boolean logic gates and implemented a feed-forward design that was previously shown to reduce noise in the OFF-state. Finally, as proof of principle, we demonstrate the dynamic activation of the NR4A2-responsive SP according to the T cell state in primary human CD8+ T cells. Collectively we present a sensing platform that provides a versatile tool to study and monitor the dynamic changes occurring in T cells. In perspective the biosensors coupled to therapeutic genes can be used to reprogram the TME and reinvigorate the T cell anti-tumoral functionality, preventing or reverting the exhausted phenotype.Graphical AbstractCreated withBioRender.com.
Dipeptidase 1 is a functional receptor for coronavirus PHEV
Authors: Dufloo Jérémy , Fernández Ignacio , Arbabian Atousa , Haouz Ahmed , Gimenez-Lirola Luis G. , Rey Félix A. , Sanjuán Rafael 
Published: January 2025

AbstractCoronaviruses of the subgenusEmbecovirusinclude several relevant pathogens such as the human seasonal coronaviruses HKU1 and OC43, bovine coronavirus, and porcine hemagglutinating encephalomyelitis virus (PHEV), among others. While sialic acid is thought to be required for embecovirus entry, protein receptors are unknown in most cases. Here we show that PHEV does not require sialic acid for entry and uses dipeptidase 1 (DPEP1) as a receptor. Cryo-electron microscopy revealed that PHEV, unlike other embecoviruses, samples open and closed conformations of its spike trimer at steady state. We found that the receptor binding domain (RBD) of the PHEV spike shares no detectable sequence homology or receptor usage with those of closely related viruses. In contrast, the X-ray structure of the RBD/DPEP1 complex showed that the elements involved in receptor binding are conserved across embecoviruses, revealing a striking versatility of the RBD to accommodate highly variable sequences that confer novel receptor specificities.
Foxi2 and Sox3 are master regulators controlling ectoderm germ layer specification
Authors: Hendrickson Clark L. , Blitz Ira L. , Hussein Amina , Paraiso Kitt D. , Cho Jin , Klymkowsky Michael W. , Kofron Matthew J. , Cho Ken W.Y. 
Published: January 2025

AbstractIn vertebrates, germ layer specification represents a critical transition where pluripotent cells acquire lineage-specific identities. We identify the maternal transcription factors Foxi2 and Sox3 to be pivotal master regulators of ectodermal germ layer specification inXenopus. Ectopic co-expression of Foxi2 and Sox3 in prospective endodermal tissue induces the expression of ectodermal markers while suppressing mesendodermal markers. Transcriptomics analyses reveal that Foxi2 and Sox3 jointly and independently regulate hundreds of ectodermal target genes. During early cleavage stages, Foxi2 and Sox3 pre-bind to key cis-regulatory modules (CRMs), marking sites that later recruit Ep300 and facilitate H3K27ac deposition, thereby shaping the epigenetic landscape of the ectodermal genome. These CRMs are highly enriched within ectoderm-specific super-enhancers (SEs). Our findings highlight the pivotal role of ectodermal SE-associated CRMs in precise and robust ectodermal gene activation, establishing Foxi2 and Sox3 as central architects of ectodermal lineage specification.HighlightsFoxi2 and Sox3 are master regulators for the ectodermal germ layer and sub-lineagesFive ectodermal cell states of early gastrulae are regulated by Foxi2 and Sox3Foxi2 and Sox3 binding sites in the genome are enriched in ectoderm super-enhancersSE-associated genes show high expression levels, low noise, stabilizing ectodermal regulation
Serotonin inhibits sexual receptivity in female cichlid fish
Authors: Lee Paige , Joyce Domino 
Published: January 2025

AbstractSerotonin is involved in multiple diverse and complex biological processes. Selective serotonin reuptake inhibitors (SSRIs) are often used to test this, and fluoxetine, a commonly detected SSRI in aquatic ecosystems from pharmaceutical pollution, has been found to disrupt important behaviours and functions in organisms exposed to the antidepressant. Increased serotonin generally has an inhibitory effect on sexual behaviour and decreased serotonin has a facilitatory effect, however in the few existing studies on fish, either no effect or the opposite effect have been reported in females, with most studies focusing on male behaviour. The present research aims to examine the role of the serotonin pathway in female sexual receptivity in the cichlid fishNyassachromiscf.microcephalus. The sexual dimorphism and lekking system of this species, where male-male competition is aggressive and female choice is important, make them an important and interesting evolutionary system. Serotonin levels were modulated using fluoxetine and after a three-week exposure to their respective treatments (control - 0µg/L, low ecologically relevant dose - 0.54µg/L, high dose - 5.4µg/L), female sexual receptivity to male courtship was measured in a simulated lek mating arena where multiple males were presented simultaneously. Sexual receptivity was inhibited in females exposed to a high dose of fluoxetine. This behaviour change due to a disruption of the serotonin pathway could affect sexual selection in the long term, and in the short term highlights the potential for pollution to affect aquatic life by directly altering mating behaviour.Highlights-Disrupting the serotonin pathway reduces sexual receptivity in female cichlid fish-The inhibitory effect of fluoxetine on female receptivity is dose-dependent-The serotonin pathway could be important in the evolution of male mating strategies-SSRI pollution could cause behaviour changes that amplify freshwater biodiversity loss
Context-dependent translation inhibition as a novel oncology therapeutic modality
Authors: Diamond Paige D. , Sauer Paul V. , Holm Mikael , Swanson-Swett Canessa J. , Ferguson Lucas , Bratset Natalie M. , Wienker Grant W. , Sim Justin Seiwert , Adams Hailey K. , Kenner Lillian , Meyers Margot , Gygi David , Könst Zef A. , Bahmanyar Sogole Sami , Hamann Lawrence G. , Schuller Anthony P. 
Published: January 2025

AbstractInhibitors of protein synthesis, including anisomycin, homoharringtonine, and other natural products bind in the peptidyl-transferase center (PTC) of the eukaryotic ribosome to inhibit translation. Recent work has demonstrated that some PTC-binding antibiotics act in a sequence-selective manner, inhibiting translation elongation at specific amino acids while the polypeptide is engaged in the PTC. However, this phenomenon has yet to be documented for compounds that inhibit translation by the human ribosome. Here we use structure-based design to guide synthesis of molecules called interdictors that bind to the human ribosome PTC and act in a context-selective manner to inhibit translation elongation. Using ribosome profiling, in combination within vitrobiochemistry and cryo-electron microscopy, we characterize the context selectivity of unique analogues and observe their preferred interactions with nascent chain residues with complementary properties. Furthermore, we present a structure for an interdictor bound to a portion of the MYC protein at ∼ 1.9 Å resolution and identify resulting structural rearrangements in both the nascent chain and ribosomal RNA. In cells, we document how these compounds differentially impact the ribotoxic stress response pathway which monitors ribosome collisions and can trigger apoptosis. Finally, we confirm their tumor growth inhibition activity after oral dosing in cell line derived xenografts in mice using the MDA-MB-231 model for triple-negative breast cancer. Together, our data establish sequence-selective inhibition of translation as a novel small-molecule therapeutic modality for historically difficult to address cancers by targeting translation of oncogenic dependency factors in the human ribosome PTC.