bluuebunny/crossref_metadata_2025_split huggingface dataset:
Specialty palliative care use among cancer patients: A population-based study
Authors: Cassel J. Brian , McClish Donna , Buxton David , Yanni Leanne , Roberts Seth , Skoro Nevena , May Peter , Del Fabbro Egidio , Noreika Danielle 
Published: November 2024

AbstractBackgroundRigorous population-based assessments of the use of specialty palliative care (SPC) in the US are rare.Settings/subjectsThis study examined SPC use among cancer patients in a mid-sized metropolitan area in Southeast US.MeasurementsIn this cancer decedent cohort study, data were acquired and linked from the state-wide cancer registry; state-wide hospital discharge dataset; and local SPC providers.Results12,030 individuals with cancer were included in this study; only 2,958 (24.6%) used SPC. Of the 9,072 persons who did not use SPC, 3,877 (42.7%) went only to hospitals that did not offer SPC; and 3,517 (38.8%) went to hospitals that offered SPC but did not use it. About half of SPC recipients (1493; 50.5%) first received SPC in the final 30 days of life, including 768 (26.0%) in the final week of life. Characteristics associated with using SPC use included being in an socio-economic status quintile other than the lowest; being younger; being Black; having a solid (versus hematological) cancer; having a shorter survival with cancer; dying in the latter two years of the study; being from an area of low or complete rurality; having a hospital admission in the final 60 days prior to initiation of PC or death; having more days in hospital; and living within 15 miles of a hospital offering SPC.ConclusionsIn this population-based study, only one-quarter of cancer patients used SPC, and for half who did so, it came in the final 30 days of life.Key MessageThis novel population-based study found that about 25% of cancer patients who died 2012-2015 had used of specialty palliative care (SPC). Half of them first received SPC in the final month of life. Characteristics associated with SPC included being Black, younger, and residing within 15 miles of a hospital offering SPC.
Honey bees are resilient to the long-term presence of alcohol in their diet
Authors: Ostap-Chec Monika , Bajorek Daniel , Antoł Weronika , Stec Daniel , Miler Krzysztof 
Published: November 2024

AbstractPrevious studies on various organisms have suggested that low doses of ethanol can have stimulatory effects, while higher doses may lead to toxicity, a response known as hormesis. Low ethanol concentrations occur naturally in the environment, particularly in fermenting fruits and flower nectar, where pollinators such as honey bees may encounter it. This study aimed to investigate the potential hormetic effects of low-level ethanol consumption on honey bees. Bees were divided into three groups: one provided with only sucrose solution, one both with sucrose and 0.5% ethanol in sucrose, and one with only 1% ethanol in sucrose. The bees were exposed to these diets for 14 days, and their performance was assessed through survivorship, flight endurance, body mass, lipid content, and trehalose and ethanol levels in the haemolymph. The results showed no significant differences in most parameters between the groups. However, bees constantly exposed to 1% ethanol had slightly higher trehalose levels compared to the control group, suggesting a possible adaptive response to ethanol exposure. Ethanol levels in the haemolymph differed significantly between groups, with bees exposed to ethanol showing its detectable levels in their system. While no clear hormetic effects were observed in terms of improved performance, the elevated trehalose levels in bees constantly exposed to 1% ethanol may indicate adaptations protecting from ethanol-induced damage. The study provides insights into how honey bees tolerate low-level ethanol exposure and highlights the need for further research on the ecological implications of ethanol consumption in pollinators.
Detecting Special Genes in Marine Symbionts: A Phylogeny-Deviation Approach Identifies Recombination-Enhancing Variants
Authors: Zhou Xiaolin , Li Weijie , Xie Siya , Xia Kang , Xiao Mei , Yang Xiaojing , Li Zhiyuan 
Published: November 2024

AbstractDifferent microbes possess special traits that enable adaptation to their specific niches, often through specialized genes. Identifying such species-special genes provides insights into microbial physiology and offers new tools for bioengineering. However, beyond the search for orphan genes, there are few methods for detecting genes that are homologous to those in other species yet contain unusual functional regions. In investigating the extreme recombination frequency of the marine symbiont bacteriumCa. E. kahalalidifaciens, we developed a computational approach to identify vairants that substantially deviate from phylogenetic expectations. This unbiased strategy successfully identified multiple Holliday junctions-related genes inCa. E. kahalalidifaciensas candidates responsible for its exceptional recombination capacity. Heterologous expression of these gene variants inEscherichia colisignificantly enhanced recombination efficiency. These high-efficient variants offer insights into improving tools for genetic manipulations, and our gene-identification approach can be applied broadly for microbial genome mining.
Exploring the latent space of transcriptomic data with topic modeling
Authors: Valle Filippo , Caselle Michele , Osella Matteo 
Published: November 2024

AbstractThe availability of high-dimensional transcriptomic datasets is increasing at a tremendous pace, together with the need for suitable computational tools. Clustering and dimensionality reduction methods are popular go-to methods to identify basic structures in these datasets. At the same time, different topic modeling techniques have been developed to organize the deluge of available data of natural language using their latent topical structure.This paper leverages the statistical analogies between text and transcriptomic datasets to compare different topic modeling methods when applied to gene expression data. Specifically, we test their accuracy in the specific task of discovering and reconstructing the tissue structure of the human transcriptome and distinguishing healthy from cancerous tissues. We examine the properties of the latent space recovered by different methods, highlight their differences, and the pros and cons of the methods across different tasks. Finally, we show that the latent topic space can be a useful embedding space, where a basic neural network classifier can annotate transcriptomic profiles with high accuracy.
A threshold level of JNK activates damage-responsive enhancers via JAK/STAT to promote tissue regeneration
Authors: Quinn John W. , Lee Mariah C. , Van Hazel Chloe , Wilson Melissa A. , Harris Robin E. 
Published: November 2024

AbstractTissue regeneration requires the directed activity of numerous genes, which are often reused from development. Although the identities of many key factors have been established, how their expression is activated and subsequently coordinated over regenerative time remains unclear. One highly conserved signal central to diverse examples of regeneration is the stress activated MAP kinase JNK. InDrosophila, damage-induced JNK signaling promotes expression of multiple genes that direct proliferation, growth and changes in cellular identity. However, how these JNK targets are selectively upregulated in the context of injury, and subsequently expressed in specific patterns responsible for repair is unknown. Our work previously characterized Damage-Responsive, Maturity-Silenced (DRMS) enhancers; regulatory elements that are activated directly by JNK to promote regenerative gene expression. Here we have investigated how the damage-responsive (DR) module of these enhancers are engaged, finding that cell death is entirely dispensable for their activation. We identify JAK/STAT signaling as an additional direct input into DR enhancers downstream of JNK, which acts to broaden DR enhancer activity into the wound periphery where JNK levels are insufficient to promote regenerative gene expression alone. Finally, we demonstrate that a distinct threshold level of JNK activity exists that must be achieved to activate regenerative signaling via DR enhancers, which, alongside input from JAK/STAT, results in their temporally and spatially appropriate expression necessary for regeneration.Author SummaryWound healing and regeneration require the activation of multiple genes whose expression must be carefully coordinated to direct the necessary changes in cell division, identity and organ development that promote the restoration of tissue integrity and patterning. TheDrosophilaimaginal disc is a well-established model of regeneration that we have used to better understand spatiotemporal control of reparative gene expression. The response to damage in imaginal discs is primarily mediated thorough the conserved JNK signaling pathway, but how JNK leads to the diversity of gene expression that occurs around a wound is not well understood. Our work previously characterized discrete genomic regions called Damage-Responsive (DR) enhancers that respond to JNK to activate genes of the regeneration program. Here we show that the behavior of these enhancers depends on a threshold level of JNK and that they integrate both JNK and its immediate downstream target JAK/STAT to establish the proper regionality of gene expression, promoting the necessary spread of regenerative signaling around a wound. These findings improve our understanding of how wound patterning is established by discrete regulatory elements that are activated by damage.
Environmental DNA reveals temporal and spatial variability of invertebrate communities in arid-lands ephemeral water bodies
Authors: Hedges Brock A , Beasley-Hall Perry G , Dorey James B , Weinstein Philip , Austin Andrew D , Guzik Michelle T 
Published: November 2024

AbstractContextThroughout semi-arid and arid Australia surface freshwater is rare, and where it does occur, it is often ephemeral. This is the case for freshwater granite rock-holes that occur throughout much of southern Australia. Rock-holes support freshwater invertebrate communities, however, the ongoing threat of climate change means that this ecosystem is likely to experience hydrological disruptions. Rock-holes are also likely to be heavily impacted by invasive vertebrates. However, the ecology of this ecosystem is poorly understood despite its relative ecological significance and the extent of its associated threats.Aims and methodsTo provide a baseline ecological understanding of this ecosystem we documented species richness and variability at a series of rock-holes in the Gawler bioregion in South Australia using an environmental DNA approach.Key resultsMetabarcoding recorded invertebrates from 22 orders and 45 families. Community composition varied among rock-holes and throughout the year, with a peak in species richness in winter.Conclusions and implicationsThese findings demonstrate the importance of these ecosystems to a range of endemic taxa. We propose establishment of monitoring programs, development of custom barcode reference libraries for the rock-hole ecosystem and future research into the likely impacts of climate change on the communities associated with them.
Environmental DNA and wildlife camera traps uncover complimentary vertebrate visitation patterns at freshwater granite rock-holes
Authors: Hedges Brock Adam , Beasley-Hall Perry G , Berry Tina E , Dawkins Kathryn L , Austin Andrew D , Weinstein Philip , Guzik Michelle T 
Published: November 2024

AbstractFreshwater ecosystems are in decline globally. In Australia, threatening processes include invasive species, increasing drought frequency, climate change and changes to land use, all of which have been associated with declining vertebrate diversity, particularly in Australia’s arid interior. Efficient monitoring tools are required to effectively monitor and conserve freshwater ecosystems and their associated vertebrate communities. Environmental DNA (eDNA) metabarcoding is one tool that shows promise for monitoring these systems, but knowledge of how eDNA data compares to more established ecological assessment techniques is limited. To address this knowledge gap, we sampled vertebrate eDNA from seven freshwater water bodies of proposed conservation importance in the Australian arid-lands, at three timepoints to measure visitation and compare our findings to camera trapping data at the same locations. Using eDNA we detected 19 species of vertebrates, including native species (such as macropods, wombats and emus) and invasive species (such as feral goats, cats and foxes). In contrast, camera traps detected 32 species, and was much more successful at detecting bird visitation than eDNA. These communities varied both spatially between rock-holes, and temporally, with summer collection periods being distinct from winter-spring. Our results demonstrate the success of eDNA metabarcoding as a tool for monitoring vertebrate visitation to arid-lands freshwater ecosystems that is complementary to more traditional survey methods such as wildlife camera trapping. Finally, we provide conservation recommendations for these vertebrate communities and discuss the efficacy of eDNA for monitoring freshwater resources in arid-lands environments.
Topologically distinct and equivalent multiple efferent arterioles in the human glomeruli
Authors: Li Joshua Jing Xi , Teoh Jeremy Yuen Chun , Lai Hei Ming 
Published: November 2024

AbstractWe revisit the assumption that the human glomerulus consists of a capillary network with one afferent arteriole and only one efferent arteriole. Using three-dimensional tissue imaging, we unambiguously demonstrate the existence of multiple efferent arterioles via total reconstruction of a full human glomerular capillary network. Through graph network analysis, we found these multiple efferent arterioles can be topologically distinct or equivalent with reference to the global glomerular capillary network, and were strategically positioned with respect to the afferent arteriole. We also found the extraglomerular connections between two efferent arterioles may have significant contributions to the redistribution of intraglomerular blood flow. These new findings can provide new paradigms in the regulation and dysfunction of glomerular ultrafiltration, the crosstalk between intra- and extraglomerular factors, and the cross-coupling between nephrons.
ABRpresto: An algorithm for automatic thresholding of the Auditory Brainstem Response using resampled cross-correlation across subaverages
Authors: Shaheen Luke A. , Buran Brad N. , Suthakar Kirupa , Koehler Seth D. , Chung Yoojin 
Published: November 2024

AbstractThe auditory brainstem response (ABR) is an essential diagnostic indicator of overall cochlear health, used extensively in both basic research and clinical studies. A key quantification of the ABR is threshold, the lowest sound level that elicits a response. Because the morphology of ABR waveforms shift with stimulus level and the overall signal-to-noise ratio is low, threshold estimation is not straightforward. Although several algorithmic approaches have been proposed, the current standard practice remains the visual evaluation of ABR waveforms as a function of stimulus level.We developed an algorithm based on the cross-correlation of two independent averages of responses to the same stimulus. For each stimulus level, the individual responses to each tone-pip are randomly split into two groups. The median waveform for each group is calculated, and then the normalized cross-correlation between these median waveforms is obtained. This process is repeated 500 times to obtain a resampled cross-correlation distribution. For each frequency, the mean values of these distributions are computed for each level and fit with a sigmoid or a power law function to estimate the threshold.Algorithmic thresholds demonstrated robust and accurate performance, achieving 92% accuracy within ±10 dB of human-rated thresholds on a large pool of mouse data. This performance was better than that of several published algorithms on the same dataset. This algorithm has now fully replaced the manual estimation of ABR thresholds for our preclinical studies, thereby saving significant time and enhancing objectivity in the process.
XPO1 inhibition modulates the Wnt/β-catenin signaling pathway to reduce colorectal cancer tumorigenesis
Authors: Evans Andrew E. , Afroz Sahida , Magstadt Alexa , Dixon Dan A. 
Published: November 2024

ABSTRACTColorectal Cancer (CRC) is the second leading cause of cancer-related death in the U.S. and high-risk individuals face a notably higher likelihood of developing CRC based on their genetic background. Hence, there is a compelling need for innovative chemopreventive treatments aimed at minimizing CRC tumorigenesis. Exportin 1 (XPO1; also referred to as CRM1) plays a pivotal role in transporting proteins from the nucleus to the cytoplasm. Various cancers overexpress XPO1, including CRC, and Selective Inhibitors of Nuclear Export (SINE) compounds, such as Eltanexor (KPT-8602), have been developed to target XPO1. Eltanexor demonstrates fewer adverse effects than its precursors and is currently under evaluation in Phase I/II clinical trials. This research evaluates Eltanexor as a chemopreventive agent for CRC. Our findings indicate Eltanexor treatment inhibits expression of the common chemoprevention target in CRC, cyclooxygenase-2 (COX-2). This occurs by Eltanexor-dependent reduction of Wnt/β-catenin signaling. Furthermore, XPO1 inhibition leads to forkhead transcription factor O subfamily member 3a (FoxO3a) nuclear retention, which can modulate β-catenin/TCF transcriptional activity.In vivooral treatment of Eltanexor to Apcmin/+mice (a mouse model for Familial Adenomatosis Polyposis) was well-tolerated andreduced tumor burden by approximately 3-fold, along with decreased tumor size. Drug sensitivity assays using organoids from Apcmin/+micetumors show increased sensitivity to Eltanexor compared to wild-type organoids. Collectively, these findings highlight XPO1 as a potent target for CRC chemoprevention.SIGNIFICANCEIn this study, we show the XPO1 inhibitor, Eltanexor, reduces COX-2 by modulating the Wnt/β-catenin signaling pathway and acts as an effective chemopreventive agent in the Familial Adenomatous Polyposis (FAP) mouse model, Apcmin/+mice.
The integrated stress response promotes macrophage inflammation and migration in autoimmune diabetes
Authors: Wang Jiayi E. , Muralidharan Charanya , Nargis Titli , Enriquez Jacob R. , Anderson Ryan M. , Mirmira Raghavendra G. , Tersey Sarah A. 
Published: November 2024

ABSTRACTType 1 Diabetes (T1D) is an autoimmune disease characterized by the destruction of insulin producing pancreatic β-cells. Macrophages infiltrate islets early in T1D pathogenesis, preceding the influx of T- and B-lymphocytes. The integrated stress response (ISR), a cellular pathway activated during stress, coordinates adaptive changes in gene expression to maintain cell function and survival. To study the ISR in macrophages, bone-marrow derived macrophages were treated with a pharmacological inhibitor of the ISR (ISRIB) and polarized to a proinflammatory M1-like state. We found a reduction in the number of proinflammatory macrophages as well as a reduction in iNOS mRNA and protein levels with ISRIB treatment. RNA-sequencing revealed a reduction in pathways related to stress responses, including ER stress, reactive oxygen species (ROS) regulation, and autophagy as well as migration pathway genes. ISRIB treatment led to decreased macrophage migration after stimulation in vitro and decreased macrophages to the site of injury after tailfin cut in zebrafish in vivo. Pre-diabetic female non-obese diabetic (NOD) mice administered ISRIB demonstrated an overall reduction in the macrophage numbers in the pancreatic islets. Additionally, the insulitic area of pancreata from ISRIB treated NOD mice had increased PD-L1 levels. Our study provides new insights into ISR signaling in macrophages and demonstrates that the ISR might serve as a potential target for intervention in macrophages during early T1D pathogenesis.
Expression Profile of Human Bitter Taste Receptors in Human Aortic and Coronary Artery Endothelial Cells
Authors: Kochany Paweł , Opiełka Mikołaj , Słonimska Paulina , Gulczynski Jacek , Kostrzewa Tomasz , Łoś Andrzej , Znaniecki Łukasz , Mickiewicz Agnieszka , Iżycka-Świeszewska Ewa , Sachadyn Paweł , Woźniak Michał , Gruchała Marcin , Górska-Ponikowska Magdalena 
Published: November 2024

AbstractHuman bitter taste receptors (TAS2Rs) are G protein-coupled receptors primarily associated with bitter taste perception, in the oral cavity. Many dietary compounds and drugs function as TAS2Rs agonists, activating their intracellular signaling pathways. Emerging evidence indicates TAS2Rs expression in extraoral tissues, including the cardiovascular system, where their functional role remains underexplored.. This study investigates TAS2Rs expression in primary human aortic and coronary artery endothelial cells. Using digital PCR (dPCR), we confirmed the mRNA expression of all 25 TAS2R subtypes in both cell lines. The expression levels were substantially higher in human coronary artery endothelial cells compared to human aortic endothelial cells. We confirmed the protein expression of TAS2R10 and TAS2R38 proteins using Western blot. These findings mark the first identification of TAS2Rs in these endothelial cells, suggesting a potential role in vascular physiology. These findings suggest a potential role for TAS2Rs in vascular physiology, prompting further research into their impact on endothelial function in cardiovascular health and pathology.
Study the Effect of Green Method Synthesis Cu- nanoparticles with Ionization Radiation on Lactate Dehydrogenase (LDH)
Authors: Sih Baydaa T. 
Published: November 2024

AbstractCopper nanoparticles (Cu-NPs) hold considerable importance in the fields of medicine and pharmacy owing to their pronounced affinity for glucose. These nanoparticles are synthesized utilizing environmentally friendly vitamin C extracted from Iraqi lemons, possessing dimensions of less than 20 nanometers and exhibiting both star and spherical morphologies, which are conducive to efficient cellular penetration.Optical assessments, including ultraviolet absorption, X-ray diffraction, Fourier-transform infrared spectroscopy (FTIR), and scanning electron microscopy (SEM), have validated that the sizes of Cu-NPs are indeed optimal for applications in biomedicine.Lactate dehydrogenase (LDH) is an enzymatic protein that plays a pivotal role in cellular respiration. A study conducted on cancer patients undergoing radiotherapy, administered at a total dose of 30 Gy divided into 12 sessions of 2.5 Gy per session, revealed a significant elevation in LDH enzyme levels in both in vivo and in vitro samples, with notable increases up to 7.5 Gy, followed by behavioral alterations observed at dosages of 10 and 15 Gy. The initial doses of irradiation were found to enhance the effectiveness of LDH, thereby facilitating the proliferation of cancer cells.In an effort to mitigate this effect, Cu-NPs were employed, resulting in a reduction of HDL activity by -36% in the control samples. Nevertheless, exposure to X-ray irradiation modified the characteristics of Cu-NPs, leading to an increase in HDL enzyme values, which may be attributed to alterations in nanostructure or surface interactions.