bluuebunny/crossref_metadata_2025_split huggingface dataset:
A global study of the geographic range size of epiphytes
Authors: Svahnström Vida J. , Lughadha Eimear Nic , Forest Félix , Leão Tarciso C.C. 
Published: November 2023

AbstractEpiphytes have long been considered to have larger geographic range sizes than terrestrial plants, yet evidence for this claim comes from studies at restricted geographic and taxonomic scales and is contrary to that of some recent studies. We examined if epiphytes have larger or smaller range sizes than terrestrial plants and tested if epiphytism is a likely driver of differences in range size globally across angiosperms. We integrated global datasets on angiosperm taxonomy, distribution, and lifeform to calculate three range size metrics. We tested if there were significant differences in mean range size between epiphytes and terrestrial plants across angiosperms and within epiphyte-rich families using ordinary and phylogenetic regression models. On average, epiphytes have larger range sizes than closely related terrestrial species, supporting the hypothesis that epiphytism favours dispersal into larger areas. However, species in families where epiphytism is prevalent tend to have small range sizes regardless of their lifeform. A high proportion of epiphytes and their close relatives are rare or have vulnerably small range sizes, yet epiphytism per se does not cause rarity. Evolutionary histories and shared traits of epiphyte-rich lineages likely underlie the observed rarity and small ranges.
PROTACable is an Integrative Computational Pipeline of 3-D Modeling and Deep Learning to Automate the De Novo Design of PROTACs
Authors: Mslati Hazem , Gentile Francesco , Pandey Mohit , Ban Fuqiang , Cherkasov Artem 
Published: November 2023

AbstractProteolysis-targeting chimeras (PROTACs) that engages two biological targets at once is a promising technology in degrading clinically relevant protein targets. Since factors that influence the biological activities of PROTACs are more complex than those of a small molecule drug, we explored a combination of computational chemistry and deep learning strategies to forecast PROTAC activity and enable automated design. A new method named PROTACable was developed for de novo design of PROTACs, which includes a robust 3-D modeling workflow to model PROTAC ternary complexes using a library of E3 ligase and linker and an SE(3)-equivariant graph transformer network to predict the activity of newly designed PROTACs. PROTACable is available athttps://github.com/giaguaro/PROTACable/.
Cellular zinc status alters chromatin accessibility and binding of transcription factor p53 to genomic sites
Authors: Damon Leah J. , Ocampo Daniel , Sanford Lynn , Jones Taylor , Allen Mary A. , Dowell Robin D. , Palmer Amy E. 
Published: November 2023

AbstractZinc (Zn2+) is an essential metal required by approximately 2500 proteins. Nearly half of these proteins act on DNA, including > 850 human transcription factors, polymerases, DNA damage response factors, and proteins involved in chromatin architecture. How these proteins acquire their essential Zn2+cofactor and whether they are sensitive to changes in the labile Zn2+pool in cells remain open questions. Here, we examine how changes in the labile Zn2+pool affect chromatin accessibility and transcription factor binding to DNA. We observed both increases and decreases in accessibility in different chromatin regions via ATAC-seq upon treating MCF10A cells with elevated Zn2+or the Zn2+-specific chelator tris(2-pyridylmethyl)amine (TPA). Transcription factor enrichment analysis was used to correlate changes in chromatin accessibility with transcription factor motifs, revealing 477 transcription factor motifs that were differentially enriched upon Zn2+perturbation. 186 of these transcription factor motifs were enriched in Zn2+and depleted in TPA, and the majority correspond to Zn2+finger transcription factors. We selected TP53 as a candidate to examine how changes in motif enrichment correlate with changes in transcription factor occupancy by ChIP-qPCR. Using publicly available ChIP-seq and nascent transcription datasets, we narrowed the 50,000+ ATAC-seq peaks to 2164 TP53 targets and subsequently selected 6 high-probability TP53 binding sites for testing. ChIP-qPCR revealed that for 5 of the 6 targets, TP53 binding correlates with the local accessibility determined by ATAC-seq. These results demonstrate that changes in labile zinc directly alter chromatin accessibility and transcription factor binding to DNA.
Gain of function inlinc-133compensates fordaf-18/PTENloss and rescues survival
Authors: Huang Wei , Dai Fangzhou , Zhang Lu , Yin Xue , Qu Zhi , Zheng Shanqing 
Published: November 2023

AbstractDAF-18, homology of PTEN, possess tumor suppressor activity. Loss ofdaf-18causes cell growth in L1 diapauseC. elegansis well studied; however, the reason why survival is dramatically shortened is not well elaborated. We found thatlinc-133gain of function can fully restore the shortened survival caused bydaf-18loss. When lipid phosphatase activity of DAF-18 is defective, thelinc-133gain of function interacts with 14-3-3 proteins to obstruct DAF-16 translocation from the nucleus to the cytoplasm. However, the dysfunction of protein phosphatase activity of DAF-18 caused high levels of aggregated proteins. Thelinc-133gain of function can induce HSP chaperones to select and process the aggregated proteins for degradation through ubiquitination. Our work demonstrates that protein homeostasis controlled by the protein phosphatase activity of DAF-18 is the main factor affecting survival and identifies a new function of thelinc-133gene, which can compensate for the loss ofdaf-18.
Epigenetic age acceleration is related to cognition and cognitive decline in the Elderly: Results of the Austrian Stroke Prevention Study
Authors: Gampawar Piyush , Kumar Veeranki Sai Pavan , Petrovic Katja-Elisabeth , Schmidt Reinhold , Schmidt Helena 
Published: November 2023

AbstractEpigenetic clocks, an estimate of biological age based on DNA methylation (DNAmAge) are gaining prominence as potential markers of brain ageing. However, consensus is lacking as the repertoire of DNAmAges expands, particularly concerning their ability to predict age-related cognitive changes. In our cohort of 785 elderly, we examined 11 DNAmAges, evaluating their associations with brain ageing in cross-sectional and longitudinal settings. Our results highlighted DNAmAges as strong predictors of cognitive change compared to baseline cognition, albeit varying performance across cognitive domains. DunedinPACE excelled in predicting baseline cognition, while Zhang’s clocks and principal component-based PhenoAge (PCPheno) performed best in predicting cognitive decline. DNAmAges elucidated substantial cognitive variability, matching or surpassing the predictive power of vascular risk factors and ApoE4 genotypes. Notably, in ApoE4 carriers, Zhang’s clock and PCPheno exhibited significantly larger effects, explaining over five times the variability in memory decline compared to non-carriers.
ALifelikeguided journey through the pathophysiology of pulmonary hypertension - from measured metabolites to the mechanism of action of drugs
Authors: Weinstein Nathan , Carlsen Jørn , Schulz Sebastian , Stapleton Timothy , Henriksen Hanne Hee , Travnik Evelyn , Johansson Pär Ingemar 
Published: November 2023

AbstractPulmonary hypertension (PH) is a pathological condition that affects approximately 1% of the population. The prognosis for many patients is poor, even after treatment. Our knowledge about the pathophysiological mechanisms that cause or are involved in the progression of PH is incomplete. Additionally, the mechanism of action of many drugs used to treat pulmonary hypertension, including sotatercept, requires elucidation. Using our graph-powered knowledge mining softwareLifelikein combination with a very small patient metabolite data set, we demonstrate how we derive detailed mechanistic hypotheses on the mechanisms of PH pathophysiology and clinical drugs. In PH patients, the concentration of hypoxanthine, 12(S)-HETE, glutamic acid, and sphingosine 1 phosphate is significantly higher, while the concentration of L-arginine and L-histidine is lower than in healthy controls. Using the graph-based data analysis, gene ontology, and semantic association capabilities ofLifelike, led us to connect the differentially expressed metabolites with G-protein signaling and SRC. Then, we associated SRC with IL6 signaling. Subsequently, we found associations that connect SRC, and IL6 to Activin and BMP signaling. Lastly, we analyzed the mechanisms of action of several existing and novel pharmacological treatments for PH.Lifelikeelucidated the interplay between G-protein, interleukin 6, activin, and BMP signaling. Those pathways regulate hallmark pathophysiological processes of PH, including vasoconstriction, endothelial barrier function, cell proliferation, and apoptosis. The results highlight the importance of SRC, ERK1, AKT, and MLC activity in PH. The molecular pathways affected by existing and novel treatments for PH also converge on these molecules. Importantly, sotatercept affects SRC, ERK1, AKT, and MLC simultaneously. The present study shows the power of mining knowledge graphs usingLifelike’s diverse set of data analytics functionalities for developing knowledge-driven hypotheses on PH pathophysiological and drug mechanisms and their interactions. We believe thatLifelikeand our presented approach will be valuable for future mechanistic studies of PH, other diseases, and drugs.
The role of systemic therapies in current and emerging opportunities for de-intensification in melanoma: a scoping review protocol
Authors: Soon Jennifer A , Franchini Fanny , Ijzerman Maarten , McArthur Grant A 
Published: November 2023

AbstractObjectiveThe purpose of this scoping review is to identify the role of systemic therapies in current and emerging opportunities to de-intensify systemic treatment of cutaneous melanoma. It will also seek to comment on the proportion of studies that include patient-reported outcomes and quality of life measures.IntroductionWith healthcare costs rising, focus is shifting towards maximising health outcomes per dollar. One approach to optimising value is through de-intensification, which is the rationalisation of routine treatment without compromising patient outcomes. Since 2013, successful clinical trials of high-cost immune checkpoint, BRAF and MEK inhibition have led to these drugs becoming ubiquitous in melanoma management. Pipeline therapies such as relatlimab and Tumour Infiltrating Lymphocyte (TIL) therapy are expected to have a similar or even greater cost. We hypothesize that neoadjuvant and response-directed strategies will be identified as well as the emerging potential of prognostic and predictive tools.Inclusion criteriaThis review aims to include studies of adult patients with cutaneous melanoma that report on de-escalation or de-intensification of internationally accepted standard-of-care systemic therapies or the use of systemic therapies to de-intensify subsequent surgery or radiotherapy. Systemic treatment across any stage of disease will be considered. A full-text English-language version must be available for a study to be eligible.MethodsA systematic search strategy has been developed for MEDLINE, EMBASE and PubMed from 1 January 2013 to 30 June 2023. Additional texts will be sourced from grey literature, Google Scholar and reference scanning. Two authors will screen abstracts and full texts facilitated by the Covidence software. Disagreements will be resolved by consensus or a third reviewer. The first author (JS) will perform data extraction whilst a second author (FF) will review a random selection of papers to ensure consistent interpretation. De-intensification strategies will be categorised by concept, potential impact on resource utilisation and patient outcomes, and strength of evidence. Data will be synthesised qualitatively and quantitatively. Results will be reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR).The results of this scoping review will directly inform a melanoma consumer and clinician survey exploring their perspectives on de-intensification strategies.
Association Between Major Depressive Disorder and the Development of Cerebral Small Vessel Disease: A Mendelian Randomization Study
Authors: Lu Ting , Luo Lijun , Yang Jie , Li Yueying , Chen Daiyi , Sun Haiyang , Liao Huijuan , Zhao Wen , Ren Zhixuan , Xu Yan , Yu Shiyao , Cheng Xiao , Sun Jingbo 
Published: November 2023

AbstractBackgroundAlthough observational studies indicate a complex, bidirectional association between major depressive disorder (MDD) and cerebral small vessel disease (CSVD), the results are frequently inconsistent. This study investigated the potential correlation of MDD with both CSVD clinical outcomes and imaging markers, utilizing a bidirectional Mendelian randomization (MR) study design.MethodsInstrumental variables for both MDD and CSVD were extracted from the latest or most extensive genome-wide association study (GWAS) data available for each phenotype. Clinical outcomes and imaging markers of CSVD were defined using several parameters. The inverse variance weighting (IVW) method with additional sensitivity and heterogeneity analyses was used. Furthermore, a separate GWAS for depression was used to validate our significant findings.ResultsIn the forward MR analyses, the genetically predicted risk of MDD was positively associated with two CSVD phenotypes showing microscopic white matter (WM) damage: mean diffusivity (IVW OR = 2.191, 95 % CI 1.226 to 3.917, p = 0.008) and WM-enlarged perivascular space (OR = 1.053 95 % CI 1.006 to 1.101, p = 0.026). The use of an independent database for depression yielded no significant risk of depression associated with these two CSVD traits. Furthermore, reverse MR analyses showed no evidence of reverse causality between MDD and an altered CSVD risk.ConclusionsThis study utilizing MR imaging findings supports a substantial causal association between MDD and CSVD-related indicators of impaired WM microstructure. It is necessary to exercise caution when extending these results to individuals with depression.
PREDICTING LEVEL OF COMPLIANCE WITH INFECTION PREVENTION AND CONTROL PRACTICES AMONG HEALTHCARE WORKERS IN SOUTHERN NIGERIA USING ORDINAL LOGISTIC REGRESSION MODEL
Authors: Onyeloili Maureen C 
Published: November 2023

ABSTRACTIntroductionAdherence to infection prevention and control guidelines is critical to improving the quality of hospital care based on their efficacy in reducing the occurrence of infections that compromise patients’ outcomes. However, the impact of predictors on IPC compliance among healthcare workers has not been adequately reported.ObjectivesThis study aims to demonstrate the utility of the Ordinal Logistic regression model in identifying the impact of personal and organizational characteristics on health workers’ level of compliance with infection prevention and control at the University of Port Harcourt Teaching Hospital.MethodsA cross-sectional study design using a self-administered questionnaire was adopted. A sample of 235 respondents was chosen using a proportionate stratified random sampling method. We analyzed data using descriptive statistics and the ordinal Logistic regression model.ResultThe study result shows that IPC compliance among Health workers in UPTH is high, 77%. Predictors of compliance were found to be age group 35-45years (AOR= 7.679, CI= 1.214 -48.577), training (AOR=0.401, CI: 0.189, 0.849), knowledge, (AOR= 0.45, CI: 0.207, 0.978), management support (AOR=0.45, CI 0.16, 0.968) as they were found to be statistically significant with the level of compliance with infection prevention and control.ConclusionThere is relatively high Compliance with Infection Prevention and Control; this can be further improved through improved management commitment and increased surveillance of health workers.KEY MESSAGEWhat is already known on this topic: Several studies conducted have reported various factors affecting compliance with infection prevention and control among healthcare workers.What this study adds:The impact of the predictors on IPC compliance among healthcare workers has not been adequately reported. Hence, there is a methodology gap in the literature. The findings of this study gave insight and quantified the contribution of each predictor to Infection Prevention and Control compliance level, thus, deploying epidemiological and statistical methodology in Infection Prevention and Control studies.How this study might affect research, practice or policy:The study provides information that serves as a proactive guide on resource allocation and areas of improvement in the Infection Prevention and Control Compliance program for program evaluators, facility managers, health agencies, stakeholders, and other policymakers. It provides researchers with guidance on adopting epidemiological methodology in conducting evidence-based studies.
Nurses’ Satisfaction with and Demand for the National Cancer Patient Home-Care Pilot Program
Authors: Kim Jung Ha , Lee Jang Won , Kim Jung Yoon , Hong Yong Eun , Jang Sol Bi , Lee Woo Jeong , Oh Kyung Hee , Kim Young Ae 
Published: November 2023

AbstractIn December 2021, the “National Cancer Patient Home-Care Pilot Program” was launched in South Korea. However, there were medical institutions with low participation and where services were not provided. Therefore, this study aimed to investigate the progress of, satisfaction with, and needs of nurses’ regarding a pilot program for home care of cancer patients with a stoma. Data were collected through a survey administered to nurses from November 13, 2022, to January 19, 2023; a total of 207 nurses responded. After excluding non-answers, 196 nurses were included in the final study population. The questionnaire sought information on the characteristics of the respondent, status of management of stoma patients, status of the home-care pilot program, satisfaction with the program, and needs of the nurses. The data were analyzed using descriptive statistics. A total of 196 nurses participated in the survey, of whom 42 nurses (21.4%) participated in the home-care pilot program. Thirty-five nurses (85.4 %) were satisfied with the home-care pilot program. Thirty nurses (71.4%) reported that implementation of home care had to be expanded and standards of care improved. To vitalize and expand the pilot program for home care for cancer patients with a stoma, better medical services must be provided by improving the medical fee standard. This will enable more patients and medical institutions to participate in the pilot program.
Benchmarking Machine Learning Methods for Synthetic Lethality Prediction in Cancer
Authors: Feng Yimiao , Long Yahui , Wang He , Ouyang Yang , Li Quan , Wu Min , Zheng Jie 
Published: November 2023

ABSTRACTSynthetic lethality (SL) is a type of genetic interaction that occurs when defects in two genes cause cell death, while a defect in a single gene does not. Targeting an SL partner of a gene mutated in cancer can selectively kill tumor cells. Traditional wet-lab experiments for SL screening are resource-intensive. Hence, many computational methods have been developed for virtual screening of SL gene pairs. This study benchmarks recent machine learning methods for SL prediction, including three matrix factorization and eight deep learning models. We scrutinize model performance using various data splitting scenarios, negative sample ratios, and negative sampling methods on both classification and ranking tasks to assess the models’ generalizability and robustness. Our benchmark analyzed performance differences among the models and emphasized the importance of data and real-world scenarios. Finally, we suggest future directions to improve machine learning methods for SL discovery in terms of predictive power and interpretability.
Partial resistance to thyroid hormone-induced tachycardia and cardiac hypertrophy in mice lacking thyroid hormone receptor β
Authors: Dore Riccardo , Sentis Sarah Christine , Johann Kornelia , Lopez-Alcantara Nuria , Resch Julia , Moeller Lars Christian , Fuehrer Dagmar , Obermayer Benedikt , Opitz Robert , Mittag Jens 
Published: November 2023

AbstractBackgroundThyroid hormones regulate cardiac functions mainly via direct actions in the heart and binding to the thyroid hormone receptor (TR) isoforms α1 and β. While the role of the most abundantly expressed isoform, TRα1, is widely studied and well characterized, the role of TRβ in regulating heart functions is still poorly understood, primarily due to the accompanying elevation of circulating thyroid hormone in mice lacking TRβ (TRβ-KO). However, their hyperthyroidism is ameliorated at thermoneutrality, which allows studying the role of TRβ without this confounding factor.MethodsHere we non-invasively monitored heart rate in TRβ-KO mice over several days using radiotelemetry at different housing temperatures (22°C and 30°C), and upon T3 administration in comparison to wildtype animals.ResultsTRβ-KO mice displayed normal average heart rate at both 22°C and 30°C with only minor changes in heart rate frequency distribution, which was confirmed by independent electrocardiogram recordings in freely-moving conscious mice. Parasympathetic nerve activity was, however, impaired in TRβ-KO mice at 22°C, and only partly rescued at 30°C. As expected, oral treatment with pharmacological doses of T3 at 30°C led to tachycardia in wildtypes, accompanied by broader heart rate frequency distribution and increased heart weight, while TRβ-KO mice showed blunted tachycardia, as well as resistance to changes in heart rate frequency distribution and heart weight. At the molecular level, these observations were paralleled by a blunted cardiac mRNA induction of several important genes, including the pacemaker channelsHcn2andHcn4, as well asKcna7.ConclusionsThe phenotyping of TRβ-KO mice conducted at thermoneutrality allows novel insights on the role of TRβ in cardiac functions in absence of the usual confounding hyperthyroidism. Even though TRβ is expressed at lower levels than TRα1 in the heart, our findings demonstrate an important role for this isoform in the cardiac response to thyroid hormones.
Building a super-resolution fluorescence cryomicroscope
Authors: Last Mart G. F. , Voortman Lenard M. , Sharp Thomas. H. 
Published: November 2023

AbstractCorrelating super-resolution fluorescence microscopy with cryo-electron tomography is a recent advancement in the field of cryo-electron microscopy that enables targeted, high-resolution imaging of specific biomolecules of interest. Critical to this approach is that the cryo-correlated light and electron microscopy (cryoCLEM) workflow requires samples to be cryogenically fixed prior to imaging, and thus a fluorescence microscope is required that can maintain the cryogenically preserved state of the sample while also being capable of super-resolution imaging. In this report, we outline the blueprint of a microscope that was designed for single molecule localization microscopy of cryosamples, and we describe the rationale behind its design. All specifications, including a detailed 3d model of the entire assembly, are freely available viaccb.lumc.nl/downloads-231.