bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adverse Events Reporting in Digital Interventions Evaluations for Psychosis: A Systematic Literature Search and Individual Level Content Analysis of Adverse Event Reports
Authors: Allan Stephanie , Ward Thomas , Eisner Emily , Bell Imogen H , Cella Matteo , Chaudhry Imran B , Torous John , Kiran Tayyeba , Kabir Thomas , Priyam Aansha , Richardson Cara , Reininghaus Ulrich , Schick Anita , Schwannauer Matthias , Syrett Suzy , Zhang Xiaolong , Bucci Sandra 
Published: April 2024

Abstract

Background
Digital health interventions (DHIs) have significant potential to upscale treatment access to people experiencing psychosis but raise questions around patient safety. Adverse event (AE) monitoring is used to identify, record, and manage safety issues in clinical trials, but little is known about the specific content and context contained within extant AE reports. This study aimed to assess current AE reporting in DHIs.

Study Design
A systematic literature search was conducted by the iCharts network (representing academic, clinical, and experts by experience) to identify trials of DHIs in psychosis. Authors were invited to share AE reports recorded in their trials. A content analysis was conducted on the shared reports.

Study Results
We identified 593 AE reports from 18 DHI evaluations, yielding 19 codes. Only 29 AEs (4.9% of total) were preidentified by those who shared AEs as being related to the intervention or trial procedures. While overall results support the safety of DHIs, DHIs were linked to mood problems and psychosis exacerbation in a few cases. Additionally, 27% of studies did not report information on relatedness for all or at least some AEs; 9.6% of AE reports were coded as unclear because it could not be determined what had happened to participants.

Conclusions
The results support the safety of DHIs, but AEs must be routinely monitored and evaluated according to best practice. Individual-level analyses of AEs have merit to understand safety in this emerging field. Recommendations for best practice reporting in future studies are provided.
First evaluation of the impact of a targeted subunit vaccine against bovine viral diarrhea virus in feedlot cattle
Authors: Bellido Demian , Gumina Emanuel R , Rodríguez Senes Gonzalo J , Chiariotti Franco M , Audrito Maximiliano , Sueldo Pedro M , Sueldo Gustavo M , Wigdorovitz Andrés 
Published: April 2024

Abstract
Bovine respiratory disease (BRD) is a serious health and economic problem in the beef industry, which is often associated with transportation and caused by different pathogens. In this study, we evaluated the effect of a novel subunit targeted vaccine against bovine viral diarrhea virus (BVDV) in feedlot cattle, a major viral agent of BRD. The core of this novel vaccine is the fusion of the BVDV structural glycoprotein, E2, to a single-chain antibody, APCH, together termed, APCH-E2. The APCH antibody targets the E2 antigen to the major histocompatibility type II molecule (MHC-II) present in antigen-presenting cells. To evaluate the vaccine, 2,992 animals were randomly allocated into two groups, control group (N = 1,491) and treatment group (N = 1,501). Animals of both groups received the routine sanitary plan: two doses of clostridial, respiratory, and rabies vaccines. Animals within the treatment group also received two doses of a targeted subunit vaccine against BVDV. Serum samples were taken on the day of the first inoculation (T0) and 90 d later (T90). Viral circulation was monitored using an anti-P80 ELISA (virus-specific) and immune response was evaluated by anti-E2 ELISA (detects virus and vaccine immune responses). Only animals treated for respiratory disease were considered positive cases of BRD. Results demonstrate that the control group had significantly more animals treated for BRD cases compared to the treatment group (5.9% vs. 3.7%, P = 0.02). The control group had a greater number of animals positive for anti-P80 antibodies and significantly fewer animals positive for anti-E2 antibodies compared to the treatment group (69% vs. 61% and 71% vs. 99%, respectively, P = 0.003), consistent with natural viral circulation within this group. The treatment group, conversely, had fewer animals positive for anti-P80 antibodies and a greater number of animals positive for anti-E2 antibodies, consistent with a robust vaccine-induced antibody response and a reduction of the BVDV circulation within this group. The data indicate the new subunit targeted vaccine induced greater anti-E2 antibodies and reduced the amount of BVD virus circulation within the treatment group leading to a fewer number of animals needing to be treated for BRD.
Dimethyl itaconate inhibits antigen‐specific Th17 cell responses and autoimmune inflammation via modulating NRF2/STAT3 signaling
Authors: Wang Ying , Yang Chao , Hou Yubiao , Wang Jiali , Zhang Kailang , Wang Lihua , Sun Deming , Li Xiaorong , Wei Ruihua , Nian Hong 
Published: April 2024

AbstractPathogenic Th17 cells play a crucial role in autoimmune diseases like uveitis and its animal model, experimental autoimmune uveitis (EAU). Dimethyl itaconate (DMI) possesses potent anti‐inflammatory effects. However, there is still a lack of knowledge about the role of DMI in regulating pathogenic Th17 cells and EAU. Here, we reported that intraperitoneal administration of DMI significantly inhibited the severity of EAU via selectively suppressing Th17 cell responses. In vitro antigen stimulation studies revealed that DMI dramatically decreased the frequencies and function of antigen‐specific Th17, but not Th1, cells. Moreover, DMI hampered the differentiation of naive CD4+ T cells toward pathogenic Th17 cells. DMI‐treated DCs produced less IL‐1β, IL‐6, and IL‐23, and displayed an impaired ability to stimulate antigen‐specific Th17 activation. Mechanistically, DMI activated the NRF2/HO‐1 pathway and suppressed STAT3 signaling, which subsequently restrains p‐STAT3 nuclear translocation, leading to decreased pathogenic Th17 cell responses. Thus, we have identified an important role for DMI in regulating pathogenic Th17 cells, supporting DMI as a promising therapy in Th17 cell‐driven autoimmune diseases including uveitis.
Oxidized phospholipid POVPC contributes to vascular calcification by triggering ferroptosis of vascular smooth muscle cells
Authors: Lu Lihe , Ye Yuanzhi , Chen Yajun , Feng Liyun , Huang Jiali , Liang Qingchun , Lan Zirong , Dong Qianqian , Liu Xiaoyu , Li Yining , Zhang Xiuli , Ou Jing‐Song , Chen An , Yan Jianyun 
Published: April 2024

AbstractVascular calcification is an actively regulated biological process resembling bone formation, and osteogenic differentiation of vascular smooth muscle cells (VSMCs) plays a crucial role in this process. 1‐Palmitoyl‐2‐(5′‐oxo‐valeroyl)‐sn‐glycero‐3‐phosphocholine (POVPC), an oxidized phospholipid, is found in atherosclerotic plaques and has been shown to induce oxidative stress. However, the effects of POVPC on osteogenic differentiation and calcification of VSMCs have yet to be studied. In the present study, we investigated the role of POVPC in vascular calcification using in vitro and ex vivo models. POVPC increased mineralization of VSMCs and arterial rings, as shown by alizarin red staining. In addition, POVPC treatment increased expression of osteogenic markers Runx2 and BMP2, indicating that POVPC promotes osteogenic transition of VSMCs. Moreover, POVPC increased oxidative stress and impaired mitochondria function of VSMCs, as shown by increased ROS levels, impairment of mitochondrial membrane potential, and decreased ATP levels. Notably, ferroptosis triggered by POVPC was confirmed by increased levels of intracellular ROS, lipid ROS, and MDA, which were decreased by ferrostatin‐1, a ferroptosis inhibitor. Furthermore, ferrostatin‐1 attenuated POVPC‐induced calcification of VSMCs. Taken together, our study for the first time demonstrates that POVPC promotes vascular calcification via activation of VSMC ferroptosis. Reducing the levels of POVPC or inhibiting ferroptosis might provide a novel strategy to treat vascular calcification.
Neurotensin modulates ovarian vascular permeability via adherens junctions
Authors: Pearson Andrew C. , Shrestha Ketan , Curry Thomas E. , Duffy Diane M. 
Published: April 2024

AbstractNeurotensin (NTS) is a 13‐amino acid peptide which is highly expressed in the mammalian ovary in response to the luteinizing hormone surge. Antibody neutralization of NTS in the ovulatory follicle of the cynomolgus macaque impairs ovulation and induces follicular vascular dysregulation, with excessive pooling of red blood cells in the follicle antrum. We hypothesize that NTS is an essential intrafollicular regulator of vascular permeability. In the present study, follicle injection of the NTS receptor antagonist SR142948 also resulted in vascular dysregulation. To measure vascular permeability changes in vitro, primary macaque ovarian microvascular endothelial cells (mOMECs) were enriched from follicle aspirates and studied in vitro. When treated with NTS, permeability of mOMECs decreased. RNA sequencing (RNA‐Seq) of mOMECs revealed high mRNA expression of the permeability‐regulating adherens junction proteins N‐cadherin (CDH2) and K‐cadherin (CDH6). Immunofluorescent detection of CDH2 and CDH6 confirmed expression and localized these cadherins to the cell–cell boundaries, consistent with function as components of adherens junctions. mOMECs did not express detectable levels of the typical vascular endothelial cadherin, VE‐cadherin (CDH5) as determined by RNA‐Seq, qPCR, western blot, and immunofluorescence. Knockdown of CDH2 or CDH6 via siRNA abrogated the NTS effect on mOMEC permeability. Collectively, these data suggest that NTS plays an ovulation‐critical role in vascular permeability maintenance, and that CDH2 and CDH6 are involved in the permeability modulating effect of NTS on the ovarian microvasculature. NTS can be added to a growing number of angiogenic regulators which are critical for successful ovulation.
Two founder variants account for over 90% of pathogenic BRCA alleles in Orkney and Shetland
Authors: Kerr Shona M. , Klaric Lucija , Muckian Marisa D. , Cowan Emma , Snadden Lesley , Tzoneva Gannie , Shuldiner Alan R. , Miedzybrodzka Zosia , Wilson James F. 
Published: April 2024

AbstractFor breast and ovarian cancer risk assessment in the isolated populations of the Northern Isles of Orkney and Shetland (in Scotland, UK) and their diasporas, quantifying genetically driftedBRCA1andBRCA2pathogenic variants is important. Two actionable variants in these genes have reached much higher frequencies than in cosmopolitan UK populations. Here, we report aBRCA2splice acceptor variant, c.517-2A>G, found in breast and ovarian cancer families from Shetland. We investigated the frequency and origin of this variant in a population-based research cohort of people of Shetland ancestry, VIKING I. The variant segregates with female breast and ovarian cancer in diagnosed cases and is classified as pathogenic. Exome sequence data from 2,108 participants with three or more Shetlandic grandparents in VIKING I was used to estimate the population prevalence of c.517-2A>G in Shetlanders. Nine VIKING I research volunteers carry this variant, on a shared haplotype (carrier frequency 0.4%). This frequency is ∼130-fold higher than in UK Biobank, where the small group of carriers has a different haplotype. Records of birth, marriage and death indicate genealogical linkage of VIKING I carriers to a founder from the Isle of Whalsay, Shetland, similar to our observations for theBRCA1founder variant from Westray, Orkney. In total, 93.5% of pathogenic BRCA variant carriers in Northern Isles exomes are accounted for by these two drifted variants. We thus provide the scientific evidence of an opportunity for screening people of Orcadian and Shetlandic origins for each drifted pathogenic variant, particularly women with Westray or Whalsay ancestry.
Spatially heterogeneous selection and inter-varietal differentiation maintain population structure and local adaptation in a widespread conifer
Authors: Peláez Pablo , Lorenzana Gustavo P. , Baesen Kailey , Montes Jose Ruben , De La Torre Amanda R. 
Published: April 2024

AbstractDouglas-fir (Pseudotsuga menziesii) plays a critical role in the ecology and economy of Western North America. This conifer species comprises two distinct varieties: the coastal variety (var.menziesii) along the Pacific coast, and the interior variety (var.glauca) spanning the Rocky Mountains into Mexico, with instances of inter-varietal hybridization in Washington and British Columbia. Recent investigations have focused on assessing environmental pressures shaping Douglas-fir’s genomic variation for a better understanding of its evolutionary and adaptive responses. Here, we characterize range-wide population structure, estimate inter-varietal hybridization levels, identify candidate loci for climate adaptation, and forecast shifts in species and variety distribution under future climates.Using a custom SNP-array, we genotyped 540 trees revealing four distinct clusters with asymmetric admixture patterns in the hybridization zone. Higher genetic diversity observed in coastal and hybrid populations contrasts with lower diversity in inland populations of the southern Rockies and Mexico, exhibiting a significant isolation by distance pattern, with less marked but still significant isolation by environment. For both varieties, we identified candidate loci associated with local adaptation, with hundreds of genes linked to processes such as stimulus response, reactions to chemical compounds, and metabolic functions. Ecological niche modeling showed contrasting potential distribution shifts among varieties in the coming decades.Overall, our findings provide crucial insights into the population structure and adaptive potential of Douglas-fir, with the coastal variety being the most likely to preserve its evolutionary path throughout the present century, which carry implications for the conservation and management of this species across their range.
Weighting of sensory cues reflect changing patterns of visual investment during ecological divergence inHeliconiusbutterflies
Authors: Borrero José , Perez Elisa Mogollon , Wright Daniel Shane , Lozano Daniela , Rueda-Muñoz Geraldine , Pardo-Diaz Carolina , Salazar Camilo , Montgomery Stephen H. , Merrill Richard M. 
Published: April 2024

AbstractIntegrating information across sensory modalities enables animals to orchestrate a wide range of complex behaviours. The relative importance placed on one sensory modality over another reflects the reliability of cues in a particular environment and corresponding differences in neural investment. As populations diverge across environmental gradients, the reliability of sensory cues may shift, favouring divergence in neural investment and the weight given to different sensory modalities. During their divergence across closed-forest and forest-edge habitats, closely related butterfliesHeliconius cydnoandH. melpomeneevolved distinct brain morphologies, with the former investing more in vision. Quantitative genetic analyses suggest selection drove these changes, but their behavioural effects remain uncertain. We hypothesised that divergent neural investment may alter sensory weighting. We trained individuals in an associative learning experiment using multimodal colour and odour cues. When positively rewarded stimuli were presented in conflict pairing positively trained colour with negatively trained odour, andvice-versa,H. cydnofavoured visual cues more strongly thanH. melpomene. Hence, differences in sensory weighting may evolve early during divergence and are predicted by patterns of neural investment. These findings, alongside other examples, imply that differences in sensory weighting stem from divergent investment as adaptations to local sensory environments.
MODERATE ALCOHOL CONSUMPTION INDUCES LASTING IMPACTS ON PREFRONTAL CORTICAL SIGNALING IN MICE
Authors: Smith Grace C. , Griffith Keith R. , Sicher Avery R. , Brockway Dakota F. , Proctor Elizabeth A. , Crowley Nicole A. 
Published: April 2024

ABSTRACTBoth alcohol use disorder (AUD) and Alzheimer’s Disease and Related Dementias (ADRD) appear to include disruption in the balance of excitation and inhibition in the cortex, but their potential interactions are unclear. We examined the effect of moderate voluntary binge alcohol consumption on the aged, pre-disease neuronal environment by measuring intrinsic excitability and spontaneous neurotransmission on prefrontal cortical pyramidal (excitatory, glutamatergic) and non-pyramidal (inhibitory, GABAergic) neurons following a prolonged period of abstinence from alcohol in mice. Results highlight that binge alcohol consumption has lasting impacts on the electrophysiological properties of prefrontal cortical neurons. A profound increase in excitatory events onto layer 2/3 non-pyramidal neurons following alcohol consumption was seen, along with altered intrinsic excitability of pyramidal neurons, which could have a range of effects on Alzheimer’s Disease progression in humans. These results indicate that moderate voluntary alcohol influences the pre-disease environment in aging and highlight the need for further mechanistic investigation into this risk factor.HIGHLIGHTSModerate voluntary alcohol consumption leads to disruption of prefrontal cortical signaling at protracted ages in both male and female miceExcitatory glutamatergic events onto prelimbic cortex GABAergic neurons, but not pyramidal neurons, are increased 6 months following alcohol exposureBoth pyramidal neurons and GABAergic neurons show altered intrinsic excitability 6 months following alcohol exposure
Afrothismia ugandensissp. nov. (Afrothismiaceae), Critically Endangered and endemic to Budongo Central Forest Reserve, Uganda
Authors: Cheek Martin , Gereau Roy E. , Kalema James 
Published: April 2024

AbstractThe fully mycotrophicAfrothismia ugandensis(Afrothismiaceae), formerly described asA. winklerivar.budongensisCowley, is renamed, redescribed and illustrated from the Budongo Forest in Western Uganda. This change in status is supported by eight newly elucidated qualitative morphological diagnostic characters despite the overall similarity withA. winkleri, a species restricted to Cameroon and Gabon.Afrothismia ugandensisis remarkable in the genus for occurring in semi-deciduous (not evergreen) forest and for having ellipsoid or ovoid (vs. globose) root bulbils. It has only been recorded twice, first in August 1940, and most recently in June 1998, despite targeted searches in recent years. In both 1940 and 1998, only single individuals appear to have been detected. A single site for the species is known with certainty. It is here assessed as Critically Endangered (CR B2ab (iii); D1) using the IUCN 2012 categories and criteria.Afrothismia ugandensisis threatened by forest degradation and clearance due to illegal selective small-holder logging for firewood and charcoal, timber and limited agriculture.
Assessing Drivers of Gender Balance and Racial Makeup of Editorial Board Members in Biomedical Engineering
Authors: Ahmad Fariha , Jackson Hannah , Kuhn Matthew , Danko Katherine , Grande-Allen Jane 
Published: April 2024

AbstractScientific journal editors serve as gatekeepers with the decision-making power of assigning reviewers to manuscripts. Serving as an editor is also an important stage in a young academic’s career progression, and an indicator of high regard/acceptance within one’s academic field. For both of these reasons, it is important to have representation with members of underrepresented groups serving in these roles. In this paper, we explore the gender and racial distribution among editorial boards for peer-reviewed scientific journals that are relevant to the field of biomedical engineering (BME). Further, we examine changes in these distributions from 2016 to 2021, amidst societal shifts catalyzed by movements such as #metoo and Black Lives Matter (BLM). Despite BME’s reputation for a relatively high percentage of female degree-earners, this study reveals stark disparities in gender and racial representation among editorial leadership positions. Through meticulous data collection and analysis of 75 BME journals— including 44 for which data from both 2016 and 2021 were analyzed—it was found that while the proportion of female editors increased over time, this proportion consistently fell short of the expected standard, which was based on current BME degree awardee values. Moreover, the percentage of Black editors remained stagnant. Correlation analyses between gender, race, and changes in journal impact factor (ΔJIF) revealed nuanced trends, in some cases showing that increasing ΔJIFs were associated with decreasing proportions of female editors. The study underscores the urgent need for changes in social and policy standards to address gender and racial inequities in BME [editorial] leadership, both of which will be necessary to foster greater diversity and inclusivity throughout the field.
Rating Pome Fruit Quality Traits Using Deep Learning and Image Processing
Authors: Nguyen Nhan H. , Michaud Joseph , Mogollon Rene , Zhang Huiting , Hargarten Heidi , Leisso Rachel , Torres Carolina A. , Honaas Loren , Ficklin Stephen 
Published: April 2024

AbstractQuality assessment of pome fruits (i.e.apples and pears) is used not only crucial for determining the optimal harvest time, but also the progression of fruit-quality attributes during storage. Therefore, it is typical to repeatedly evaluate fruits during the course of a postharvest experiment. This evaluation often includes careful visual assessments of fruit for apparent defects and physiological symptoms. A general best practice for quality assessment is to rate fruit using the same individual rater or group of individuals raters to reduce bias. However, such consistency across labs, facilities, and experiments is often not feasible or attainable. Moreover, while these visual assessments are critical empirical data, they are often coarse-grained and lack consistent objective criteria. Granny, is a tool designed for rating fruit using machine-learning and image-processing to address rater bias and improve resolution. Additionally, Granny supports backwards compatibility by providing ratings compatible with long-established standards and references, promoting research program continuity. Current Granny ratings include starch content assessment, rating levels of peel defects, and peel color analyses. Integrative analyses enhanced by Granny’s improved resolution and reduced bias, such as linking fruit outcomes to global scale-omics data, environmental changes, and other quantitative fruit quality metrics like soluble solids content and flesh firmness, will further enrich our understanding of fruit quality dynamics. Lastly, Granny is open-source and freely available.