bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modelling the potential use of pre-exposure prophylaxis to reduce nosocomial SARS-CoV-2 transmission
Authors: Stewart Lauren , Evans Stephanie , Brevini Teresa , Sampaziotis Fotios , Illingworth Christopher J. R. 
Published: December 2024

AbstractThe nosocomial transmission of respiratory pathogens is an ongoing healthcare challenge, with consequences for the health of vulnerable individuals. Outbreaks in hospitals can require the closure of bays or entire wards, reducing hospital capacity and having a financial impact upon healthcare providers. Here we evaluate a novel strategy of pre-exposure prophylaxis as a means to reduce the nosocomial transmission of SARS-CoV-2. We model the effect of ursodeoxycholic acid (UDCA) upon levels of ACE2 expression, SARS-CoV-2 viral entry, and ultimately the probability of an infection. We then implement this model within simulations describing the spread of SARS-CoV-2 infections within a hospital context, simulating an intervention in which UDCA is given to patients on a ward for 10 days following the detection of a case of SARS-CoV-2 on that ward. Under default model parameters we infer a potential 16.5% reduction (95% C. I. 14% - 20%) in the nosocomial transmission of SARS-CoV-2 to patients, with increased importation of cases into the hospital increasing the effectiveness of the intervention. Our study provides preliminary evidence of the value of pre-exposure prophylaxis with UDCA as a strategy to reduce nosocomial SARS-CoV-2 transmission.
Testing the Safety of the Nature Based Microbial Exposure with Atopic Dermatitis Patients – A Randomized, Placebo Controlled, Double-Blinded Pilot Trial
Authors: Kalmari Johanna , Mäkelä Iida , Kummola Laura , Roslund Marja , Huhtala Heini , Puhakka Riikka , Autio Pekka , Hyöty Heikki , Hytönen Vesa P , Sinkkonen Aki , Laitinen Olli H 
Published: December 2024

SummaryBiodiversity hypothesis posits that it is beneficial for human health to be in contact to microbial biodiversity, and loss of this contact leads to immune-mediated diseases like atopy. Based on this hypothesis, we wanted to study if a lotion containing highly diverse natural microbes is a safe and feasible way to administer nature exposure to humans, and to study the effects of the exposure on the skin. We recruited two groups: 15 people with healthy skin and 12 people with atopic dermatitis. The healthy people were divided to the three groups that used twice daily a lotion containing: 1) 10 % of live microbial extract; 2) 10 % inactivated microbial extract; 3) placebo. The people with atopic dermatitis used a lotion containing 1 % of inactivated microbial extract in one side of their body and a placebo lotion in another side. The daily use of the lotion containing diverse microbial extract was well tolerated by both healthy and atopic people. Microbial extract in lotion did not change the relative abundance ofStaphylococcuson healthy skin in 14 day-trial and did not change atopic eczema severity, transepidermal water loss or erythema on atopic skin compared to placebo during 28-day trial. Atopic dermatitis patients can benefit from the overall effect of moisturizing lotion and the microbial extract, which together down-regulated pro-inflammatory IL-1β, IL-22, IL-33 cytokines, and antimicrobial peptide hBD-2 on atopic lesions indicating enhanced tolerance and mitigation of eczema. Nature exposure by microbial extract in lotion could complement current atopic dermatitis treatments.
A Novel Playbook for Pragmatic Trial Operations to Monitor and Evaluate Ambient Artificial Intelligence in Clinical Practice
Authors: Afshar Majid , Resnik Felice , Ryan Baumann Mary , Hintzke Josie , Sullivan Anne Gravel , Shah Tina , Stordalen Anthony , Oberst Michael , Dambach Jason , Mrotek Leigh Ann , Quinn Mariah , Abramson Kirsten , Kleinschmidt Peter , Brazelton Tom , Twedt Heidi , Kunstman David , Long John , Patterson Brian , Liao Frank , Rasmussen Stacy , Burnside Elizabeth , Goswami Cherodeep , Gordon Joel 
Published: December 2024

ABSTRACTBackgroundAmbient artificial intelligence offers promise for improving documentation efficiency and reducing provider burden through clinical note generation. However, challenges persist in workflow integration, compliance, and widespread adoption. This study leveraged a Learning Health System (LHS) framework to align research and operations using a hybrid effectiveness-implementation protocol, embedded as pragmatic trial operations within the electronic health record (EHR).MethodsAn alpha phase was conducted to pilot technical integration, refine workflows, and determine sample size in planning for a beta phase designed as a pragmatic randomized controlled trial with the Stanford Professional Fulfillment Index (PFI) as primary outcome. During alpha, bi-directional governance was established between IS operations and LHS team with multidisciplinary workgroups for analytics, technical, documentation, and user experience. Ambient AI was embedded into the EHR using Fast Healthcare Interoperability Resources (FHIR), with real-time data dashboards tracking utilization and documentation accuracy for operations and research. Performance metrics were monitored serially using a difference-in-differences (DiD) analysis to detect drift caused by software workflow changes.ResultsThe alpha phase, designed as Type 1 Hybrid, informed a 24-week beta phase stepped-wedge trial with 90% power to detect changes in PFI. Across the alpha phase, the weighted median of average provider Ambient AI utilization was 65.4% following Plan-Do-Study-Act cycles addressing organizational feasibility and task-dependent adoption. During initial implementation, a workflow issue caused discrepancies between ICD-10 diagnosis entries and note content, reducing accuracy from 79% to 35% (p < 0.01). After implementing a new note template and provider training, accuracy returned to pre-intervention levels. DiD did not detect significant drifts in work outside of work or time in notes two weeks before and after the new note template. Beta phase enrollment achieved its targeted 66 providers across eight specialties, initiating on schedule.Conclusions and RelevanceWe provide a novel playbook for integrating Generative AI platforms in healthcare, combining pragmatic trial operations, human-centered design, and real-time monitoring to advance evidence-based implementation.ClinicalTrials.gov IDNCT06517082
Accessing AI mammography reports impacts patient interest in pursuing a medical malpractice claim: The unintended consequences of including AI in patient portals
Authors: Song Elizabeth C. , Bernstein Michael H. , Lay Parker S. , Druart Leo , Dibble Elizabeth H. , Lourenco Ana P. , Baird Grayson L. 
Published: December 2024

ABSTRACTBackgroundArtificial intelligence (AI) tools are increasingly used in breast imaging and radiology more broadly. Patients express varying levels of trust and acceptance toward the incorporation of AI tools, although no research has examined how it can best be communicated in the patient portal setting.MethodsEnglish-speaking US women with 1+ prior mammogram were recruited via Prolific and randomized to one of thirteen conditions. All participants were shown a vignette asking them to imagine receiving a BI-RADS 1 (Negative) radiologist report from their patient portal. Participants in twelve conditions also received an AI report with one of four AI abnormality scores (not flagged: 0, 29; flagged: 31, 50) and 0-2 accompanying features (nothing; a only; a & b): (a) an abnormality cutoff threshold; (b) the AI tool’s False Discovery Rate (FDR) or False Omission Rate (FOR). As the primary outcome, participants indicated whether they would consider a lawsuit if a one-year follow-up found evidence of Stage 3 breast cancer. Secondary outcomes included hypothetical decisions regarding follow-up (e.g., second opinions), concern for breast cancer, and desire for additional imaging.ResultsParticipants (n=1,623) were more likely to consider a lawsuit when AI was (versus was not) provided, p=0.001. However, for most AI abnormality scores, providing the abnormality cutoff threshold and FDR/FOR reduced lawsuit consideration relative to the AI abnormality score alone. Concern for breast cancer, desire for additional imaging, and follow-up requests (same radiologist, different radiologist, and ordering physician) increased as the AI abnormality score increased, though this was also often mitigated by providing the FDR (and sometimes FOR).ConclusionDisclosing AI feedback used for medical decision-making will impact patients’ perceptions and behaviors pertaining to malpractice and follow-up. Best practices are needed to engage and inform patients about the application of AI tools in their care while minimizing its unintended negative consequences.
CD8 and vimentin were associated with overall survival in patients with ovarian cancer treated with intraperitoneal chemotherapy
Authors: Kim Hyojin , Lee Ji Eun , Lee Yong Jae , Kim Kidong 
Published: December 2024

AbstractObjectiveTo identify immunohistochemistry markers affecting the survival in patients with ovarian cancer receiving intraperitoneal (IP) chemotherapy.MethodsA retrospective review of medical records identified 24 patients with newly diagnosed stage III or IV high-grade serous ovarian carcinoma who underwent more than three cycles of IP chemotherapy at a tertiary hospital in Republic of Korea between 1990 and 2013. Immunohistochemical staining of tumor tissue for CD8, FOXP3, PDL1, E-cad and vimentin was performed. The level of expression was measured using established protocols of each marker and was dichotomized (high vs. low) using median value. The association of level of expression of each marker with progression-free survival (PFS) or overall survival (OS) were examined.ResultsThe mean age was 44 years (range 27 to 59) and 23 patients were stage III. The median PFS was 15.3 months (range 0.4 to 148.3) and that of OS was 63.3 months (range 0.4 to 163.0). None of 5 markers were associated with PFS. However, CD8 (p=0.2) and vimentin (p=0.1) were marginally associated with OS. Patients with high CD8 or vimentin expression demonstrated a numerically longer PFS compared to those with low expression of both markers (median 19.7 months vs. 13.0 months,p= 0.073). Furthermore, patients with high CD8 or vimentin expression showed significantly improved OS compared to those with low expression of both markers (median 94.5 months vs. 25.4 months,p= 0.008).ConclusionCD8 and vimentin expression were correlated with OS in patients with ovarian carcinoma treated with IP chemotherapy.
GDBIG: the first birth cohort genomic database and platform facilitating intergenerational genetic research
Authors: Huang Shujia , Wang Chengrui , Huang Mingxi , Lu Jinhua , He Jian-Rong , Lin Shanshan , Liu Siyang , Xia Huimin , Qiu Xiu 
Published: December 2024

AbstractHigh-quality genome databases derived from large-scale family-based birth cohorts are essential resources for investigating genetic determinants affecting early-life traits and the impact of early-life environments on the health of both parents and offspring. Here, we have established the genome database of Born in Guangzhou Cohort Study (BIGCS), name as GDBIG, which represents the first birth-cohort-based genomic database in China and is designed to facilitate generational genetic research, based on the Phase I results of BIGCS, that contains the low-coverage (∼6.63x) whole-genome sequencing (WGS) data and numerous pregnancy phenotypes of 4,053 Chinese participants. The participants were from 30 out of 34 administrative divisions of China, covering Han and 12 minority ethnic groups. Currently, GDBIG provides a comprehensive range of services, including allele frequency inquiries for 56.23 million variants across two generations, a genotype imputation server featuring a high-quality family-based reference panel, and a GWAS meta-analysis interface for various maternal and infant phenotypes. The GDBIG database addresses the dearth of Asian birth-cohort-based genomic resources and provides a valuable platform for conducting genetic analysis online or through application programming interfaces athttp://gdbig.bigcs.com.cn/.
Latrophilin-3conditional knockout in tyrosine hydroxylase neurons (Lphn3-Th- Cre) Compared withLphn3Global KO rats: Role ofLphn3in Tyrosine Hydroxylase Neurons on the Cognitive and Behavioral Effects of this ADHD Susceptibility Gene
Authors: Regan Samantha L. , Sugimoto Chiho , Lingo Aliyah N. , Tepe Erin A. , Williams Michael T. , Vorhees Charles V. 
Published: December 2024

AbstractLatrophilin-3 (LPHN3) is a brain specific adhesion G-protein coupled receptor associated with elevated risk of attention deficit hyperactivity disorder (ADHD). We developed a globalLphn3knock-out (gKO) rat using CRISPR/Cas9 to delete exon-3. Here we report the development of a floxedLphn3rat crossed with tyrosine hydroxylase (Th-Cre) rats to create a conditionalLphn3KO rat specific for catecholaminergic- positive cells. The gKO rats are hyperactive and have egocentric and allocentric navigation deficits but showed sparing of conditioned contextual and novel object recognition memory. Here we compared gKO and cKO rats controlling for litter effects. Both gKO and cKO rats were hyperactive and were impaired in egocentric navigation in the Cincinnati water maze (CWM) with deficits greater in gKO rats. The gKO rats were impaired in allocentric navigation in the Morris water maze (MWM) whereas cKO rats were only slightly affected compared with WT, cre, and floxed rats. Striatal tyrosine hydroxylase and dopamine D1 receptors were not significantly different in either model, nor were NMDA-NR1 or NMDA-NR2 in the hippocampus. We previously showed, however, that dopamine is released more rapidly in the striatum of gKO rats by fast- scan cyclic voltammetry. The cKO model shows an important role of catecholamines in the phenotype of LPHN3 disruption and add evidence that this synaptic protein plays a role in neuroplasticity that are consistent with ADHD.
Exploring natural allies: Survey and identification of larval parasitoids for sustainable grape berry moth management in vineyards
Authors: Gomez-Llano Jesus H. , Khanal Neetu , Acevedo Flor E. 
Published: December 2024

AbstractThe American grape berry moth (GBM),Paralobesia viteanaClemens (Lepidoptera: Tortricidae) is an economically important pest of grapes. The larvae of this insect burrow inside the fruit upon hatching, consuming, and contaminating grapes and clusters. Current GBM management relies on pesticide applications, which do not offer complete protection due to the cryptic behavior of the larvae and asynchrony in egg-laying, highlighting the need to develop new management strategies. In this study, we identified GBM larval parasitoids in commercial vineyards and quantified their parasitism rates. Parasitoid samplings were conducted biweekly in six conventionally managed Concord vineyards in Erie County, Pennsylvania, during the 2023 and 2024 growing seasons. GBM-infested samples were monitored daily to track the emergence of both parasitoids and GBM, enabling the calculation of parasitism rates. We identified eight parasitoid species:Enytus obliteratus,Campoplex tortricidae,Scambussp,Glypta depressacf,Glypta ohioensiscf, andGlypta ignotacf. (Hymenoptera: Ichneumonidae);Bracon variabilis(Hymenoptera: Braconidae), andGoniozus fratellus(Hymenoptera: Bethylidae) praying on GBM larvae. From these,B. variabilis,E. obliteratus, andG. fratelluswere the most abundant. We also designed a graphic taxonomic key to facilitate the identification of these species. The parasitoid abundance differed over the growing season but was greatest in early August, reaching parasitism rates of up to 39% and 52.1% in 2023 and 2024, respectively. Our results demonstrate that GBM has several larval parasitoids that help reduce its populations in commercial vineyards. This project represented a first step toward our understanding of the GBM native natural enemies present in the Lake Erie Region and their potential use in management programs.
Phenolic compounds inMedicago truncatularoots are under the influence ofAgrobacterium fabrumthrough its species specific-genes regions
Authors: Padilla Rosa , Vial Ludovic , Dechèvre Florence , Thi Huyen Thu Nguyen , Gaillard Vincent , Meiffren Guillaume , Comte Gilles , Nesme Xavier , Lavire Céline , Kerzaon Isabelle 
Published: December 2024

ABSTRACTThe impact of plant microbiota on the health and physiology of their host is increasingly studied and recognized. However, in the rhizosphere, the functions of most bacteria and the genetic determinants involved in the molecular dialogue between plant and bacteria are poorly understood. Agrobacteria are ubiquitous soil borne and rhizospheric bacteria able to establish commensal or even beneficial interactions with plant roots. The genomic speciesAgrobacterium fabrumharbor seven specific-regions (SpG8-1 to SpG8-7), whose annotation seems to indicate a close connection with the plant during plant-bacteria interactions. To evaluate the involvement ofA. fabrum-specific regions in the plant-bacteria interaction, deletion mutant strains of eachA. fabrum-specific region were inoculated onMedicago truncatularoots. Root metabolite profiles were compared by UHPLC-UV/DAD-ESI-MS QTOF analyses, and the highlighted discriminating metabolites were annotated by tandem mass spectrometry. Metabolomic analyses have shown thatA. fabruminoculation modulates the content of phenolic compounds inM. truncatularoots, in particular flavonoids. These root metabolite modulations observed with the wild-type strain often appear to be linked to at least one of theA. fabrum-specific genes, as almost allA. fabrum-specific regions showed an influence on one or more of these specialized root metabolites. In addition, our results underlined a putative cross-talk or coordinated effect of theA. fabrum-specific regions during the interaction ofA. fabrumwithM. truncatula, as all mutants except one induced similar modifications on flavonoids. These results contribute to a better understanding of the ecological niche construction ofA. fabrumhighlighting the importance of its specific genes in the establishment of this fine-tuned interaction.
AtKC1 inhibitsAtAKT1 activation via its amino-terminal inhibitory domain
Authors: Zheng Zijie , Qu Yannan , Chen Jiexin , Tang Yuyue , Liu Dongliang , Huang Zhuo , Shen Huaizong 
Published: December 2024

AbstractAKT1 is a plant Shaker-like, hyperpolarization-activated K+channel which plays a crucial role in K+absorption. Besides phosphorylation, AKT1 is subject to negative regulation byAtKC1, a silent channel of the same family. Previous structural studies unveiled that AKT1 andAtKC1 form 2:2 heterotetramer in purified samples. However, the structural analysis failed to offer more insight into the inhibition mechanism of AKT1 activation byAtKC1. Here, inspecting the complex structure of AKT1-AtKC1 reveals that a stable domain ofAtKC1 (residues 53 to 80), named inhibitory domain or I-domain, may inhibit AKT1 activation by stabilizing its depolarized, closed conformation. We confirmed this hypothesis with electrophysiological experiments. Interestingly, a single-point mutation (G315D) inAtKC1 has been reported to abolish its ability to inhibit AKT1. We solved the structure of AKT1-AtKC1(G315D) at a resolution of 2.8 Å which revealed an unexpected stoichiometry alteration between AKT1 andAtKC1 from 2:2 to 3:1. This stoichiometry change further supports the hypothesis as we reason that single I-domain ofAtKC1 in the channel complex is insufficient to effectively inhibit channel activation. Our findings reveal the inhibition mechanism ofAtKC1 on AKT1 and offer insight into the regulatory mechanisms of hyperpolarization-activated channels.
Ecological assembly dynamics of the seed-borne microbiome in cultivated and wild wheat
Authors: Özkurt Ezgi , Mariush Zaywa , Landermann-Habetha Doreen , Stukenbrock Eva H. 
Published: December 2024

AbstractBackgroundPlants host diverse microbial communities that can significantly impact plant health. A portion of these communities is vertically transmitted to the next generation through seeds, influencing early plant development. While seed microbiota composition is known to be shaped by environmental, genetic, and stochastic factors, detailed insights into the factors that govern variation within and between plants of the same species remain limited. Furthermore, the dynamic of the vertically-transmitted microbes and their mode of host colonization are poorly understood.ResultsIn this study, we characterized the bacterial communities of multiple seeds originating from the same spike of adult wheat plants and demonstrated a high extent of homogeneity in the composition of microorganisms. We propagated wheat seedlings under controlled conditions to monitor host colonization by these microorganisms. Intriguingly, in spite of a relatively homogeneous composition of bacteria in individual seeds, the microbes colonizing early-stage seedlings, particularly during their initial leaf development, vary extensively, even among seedlings of seeds from the same spike. Applying a neutral assembly model, we show that the transmission of microbiomes from seeds to seedlings is primarily governed by selective processes, whereas post-transmission microbial assembly in seedlings is governed by stochastic events.ConclusionsOverall, this study introduces a novel experimental approach for investigating microbiome inheritance in plants. By leveraging high replication of seeds from the same wheat plant and field, we provide new insights into the stochastic nature of seed-associated microbiome composition and transmission in wheat.