bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular analysis for ovarian cancer detection in patient-friendly samples
Authors: Wever Birgit M.M. , Schaafsma Mirte , Bleeker Maaike C.G. , van den Burgt Yara , van den Helder Rianne , Lok Christianne A.R. , Dijk Frederike , van der Pol Ymke , Mouliere Florent , Moldovan Norbert , van Trommel Nienke E. , Steenbergen Renske D.M. 
Published: September 2023

ABSTRACTBackgroundHigh ovarian cancer mortality rates motivate the development of effective and patient-friendly diagnostics. Here, we explored the potential of molecular testing in patient-friendly samples for ovarian cancer detection.Patients and methodsHome-collected urine, cervicovaginal self-samples, and clinician-taken cervical scrapes were prospectively collected from 54 patients diagnosed with a highly suspicious ovarian mass (benign n=25, malignant n=29). All samples were tested for nine methylation markers, using quantitative methylation-specific PCRs that were verified on ovarian tissue samples, and compared to unpaired patient-friendly samples of 110 healthy controls. Copy number analysis was performed on a subset of urine samples of ovarian cancer patients by shallow whole-genome sequencing.ResultsThree methylation markers were significantly elevated in full void urine of ovarian cancer patients as compared to healthy controls (C2CD4D,p=0.008;CDO1,p=0.022;MAL,p=0.008), of which two were also discriminatory in cervical scrapes (C2CD4D,p=0.001;CDO1,p=0.004). When comparing benign and malignant ovarian masses,GHSRshowed significantly elevated methylation levels in the urine sediment of ovarian cancer patients (p=0.024). Other methylation markers demonstrated comparably high methylation levels in benign and malignant ovarian masses. Cervicovaginal self-samples showed no elevated methylation levels in patients with ovarian masses as compared to healthy controls. Copy number changes were identified in 4 out of 23 urine samples of ovarian cancer patients.ConclusionOur study revealed increased methylation levels of ovarian cancer-associated genes and copy number aberrations in the urine of ovarian cancer patients. Our findings support continued research into urine biomarkers for ovarian cancer detection and highlight the importance of including benign ovarian masses in future studies to develop a clinically useful test.HIGHLIGHTSOvarian cancer is often diagnosed at an advanced stage with a poor prognosisWe studied the potential of molecular testing in different types of patient-friendly material for ovarian cancer detectionElevated methylation of ovarian cancer-associated genes can be measured in cervical scrapes and urineCopy number aberrations are detectable in urine of ovarian cancer patientsDNA-based testing in cervical scrapes and urine could aid ovarian cancer diagnosis upon further developmentGRAPHICAL ABSTRACTCreated withBioRender.com.
Generative Artificial Intelligence for Clinical Communication: Implications for Non-Pharmacological Interventions in Health Care
Authors: Hanai Akiko , Ishikawa Tetsuo , Kawauchi Shoichiro , Iida Yuta , Kawakami Eiryo 
Published: September 2023

AbstractObjectivesThe objective of this study was to evaluate the potential of Generative Artificial Intelligence (AI) in facilitating clinical communication, particularly in addressing sexual health concerns, which are often challenging for patients to discuss.MethodsWe employed the Generative Pre-trained Transformer-3.5 (GPT) as the generative AI platform and utilized DocsBot for citation retrieval (June 2023). A structured prompt was devised to generate 100 questions from the AI, based on epidemiological survey data regarding sexual difficulties among cancer survivors. These questions were submitted to Bot1 (standard GPT) and Bot2 (sourced from two clinical guidelines). The responses from both bots were compared to assess consistency and adherence to clinical guidelines.ResultsOur analysis revealed no censorship of sexual expressions or medical terms. The most common themes among the generated questions were cancer treatment, sexual health, and advice. The similarity rate between responses from Bot1 and Bot2 averaged 92.5% (range 77.0% to 98.4%), with notably lower similarity for items not covered in the guidelines. Despite the lack of reflection on guideline recommendations, counseling and other non-pharmacological interventions were significantly more prevalent in both bots’ responses compared to drug interventions, with odds ratios of 4.8 (p=0.04) in Bot1 and 14.9 (p<0.001) in Bot2.DiscussionGenerative AI can serve for providing health information on sensitive topics such as sexual health, despite the potential for policy-restricted content. There was a significant skew towards non-pharmacological interventions in responses, possibly due to the prohibitive nature of medical topics. This shift warrants attention as it could potentially trigger patients’ expectations for non-pharmacological interventions.
Multi-ancestry Polygenic Mechanisms of Type 2 Diabetes Elucidate Disease Processes and Clinical Heterogeneity
Authors: Smith Kirk , Deutsch Aaron J. , McGrail Carolyn , Kim Hyunkyung , Hsu Sarah , Mandla Ravi , Schroeder Philip H. , Westerman Kenneth E. , Szczerbinski Lukasz , Majarian Timothy D. , Kaur Varinderpal , Williamson Alice , Claussnitzer Melina , Florez Jose C. , Manning Alisa K. , Mercader Josep M. , Gaulton Kyle J. , Udler Miriam S. 
Published: September 2023

AbstractWe identified genetic subtypes of type 2 diabetes (T2D) by analyzing genetic data from diverse groups, including non-European populations. We implemented soft clustering with 650 T2D-associated genetic variants, capturing known and novel T2D subtypes with distinct cardiometabolic trait associations. The twelve genetic clusters were distinctively enriched for single-cell regulatory regions. Polygenic scores derived from the clusters differed in distribution between ancestry groups, including a significantly higher proportion of lipodystrophy-related polygenic risk in East Asian ancestry. T2D risk was equivalent at a BMI of 30 kg/m2in the European subpopulation and 24.2 (22.9- 25.5) kg/m2in the East Asian subpopulation; after adjusting for cluster-specific genetic risk, the equivalent BMI threshold increased to 28.5 (27.1-30.0) kg/m2in the East Asian group, explaining about 75% of the difference in BMI thresholds. Thus, these multi-ancestry T2D genetic subtypes encompass a broader range of biological mechanisms and help explain ancestry-associated differences in T2D risk profiles.
Predictors of vaccination card retention in Tamale Metropolis, Ghana
Authors: Konlan Matthew Y. , Mahama Fuseini , Abubakari Braimah B. , Konka Paul , Appiah Benedict O. , Yeboah Maxwell O. , Kwarteng Peter G. , Apea Porbilla O. , Adjei Michael R. , Adokiya Martin N. , Boadum Oheneba , Abiwu Hilarius A. K. 
Published: September 2023

AbstractBackgroundThe home-based vaccination card (HBR) is an important health record for determining vaccination status of children during surveys, particularly in low- and middle-income countries (LMICs). However, there are limited evidence on the factors that influence its retention in Ghana. We assessed the predictors of vaccination card retention in Tamale Metropolis, GhanaMethodsWe conducted a cross-sectional study from 21stDecember 2022 to 10thJanuary 2023 among children aged 0-59 months in the Tamale Metropolis. Multi-stage sampling was used to select caregivers of children aged 0-59 months for enrolment in the study. Data were collected using validated questionnaire through face-to-face interviews of caregivers. A vaccination card was retained if it was presented for physical inspection by research assistants. The factors that influence vaccination card retention were determined in a multivariate logistic regression analysis at p<0.05.ResultsA total of 1,566 eligible children were enrolled in this study. Vaccination card retention was 89.5%. Negative predictors of card retention included: being resident in the Nyohini (AOR=0.26; 95% CI=0.15-0.47) and Tamale Central (AOR= 0.52; 95% CI=0.30-0.92) sub-Metro areas, and children belonging to age group 24-59 months (AOR=0.40; 95% CI=0.23-0.67). On the other hand, paying for the vaccination card (AOR=5.20; 95% CI=2.98-9.04) was a positive predictor of vaccination card retention.ConclusionIn this study, vaccination card retention among children aged 0-59 months was higher than national estimates. Vaccination card retention was mainly influenced by place of residence, age of child and mode of acquisition of the card such as out-of-pocket payment. There is need to design and deliver tailored messages including the importance of vaccination card retention to caregivers of children based on geographic context. Additionally, the vaccination cards should be supplied to health facilities and made readily accessible to caregivers to prevent out-of-pocket payment.
Verbenone and L-arginine fromDaucus carotaSeeds Attenuate Oxidative Stress in Streptozotocin-Nicotinamide (STZ-NAD)-Induced Diabetic Mice: Evidence fromIn vitroandIn vivoStudies
Authors: Tijjani Habibu , Ibrahim Umar , Tijani Sadiq , Alka Sadiya , Olatunde Ahmed , Kura Aminu Umar , Gagman Haladu Ali , Saliu Oluremi A. , Idowu Oluwafemi A. , Ebhodaghe Frank Eromosele 
Published: September 2023

AbstractFree radicals are produced in diabetes mellitus (DM), due to protein glycosylation and glucose autooxidation. However, compounds from plants were proven to be effective in the management of DM and related conditions. This study evaluated the antioxidant effect of verbenone, L-arginine, and their ratio combinations in diabetic mice. DM was induced in mice by intraperitoneal (IP) injection of streptozotocin and nicotinamide adenine dinucleotide (NAD) and the diabetic mice were treated with verbenone, L-arginine, and their ratios for 28 days. In thein vitrostudy, L-arginine expressed higher 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity, while verbenone and L-arginine expressed higher nitric oxide (NO) and hydrogen peroxide (H2O2) scavenging activities, especially at higher concentrations when compared with vitamin C. At the end of the treatment period, the levels of blood glucose, total protein, and malondialdehyde were significantly increased while the levels of reduced glutathione, nitrite, and activities of glutathione peroxidase, glutathione transferase, catalase, superoxide dismutase were significantly decreased in the diabetic untreated mice. However, these diabetes-induced alterations were reversed to normal levels after the administration of verbenone, L-arginine, and their ratio combinations at 100 and 200 mg/kg body weight. Furthermore,in silicostudies revealed the antioxidant potential of both verbenone and L-arginine by their interaction with antioxidant proteins, expressing their potential antioxidant properties. The results of the study indicated that verbenone, L-arginine, and their ratio combination possess antioxidant property and attenuate oxidative stress in diabetic mice.HighlightsVerbenone and L-arginine are natural compounds found inDaucus carotaseeds and other plants.Verbenone and L-arginine possessin vitroandin vivoantioxidant activities.Verbenone, L-arginine and their ratio combination (1:1) enhance the activities of antioxidant enzymes in streptozotocin-nicotinamide (NAD-STZ) induced diabetic mice.Furthermore, the two compounds interacted with antioxidant proteins, expressing their potential antioxidant property in anin silicomodel.
Marmosets mutually compensate for differences in rhythms when coordinating vigilance
Authors: Phaniraj Nikhil , Brügger Rahel K. , Burkart Judith M. 
Published: September 2023

AbstractSynchronisation is widespread in animals, and studies have often emphasised how this seemingly complex phenomenon can emerge from very simple rules. However, the amount of flexibility and control that animals might have over synchronisation properties, such as the strength of coupling, remains underexplored. Here, we studied how pairs of marmoset monkeys coordinated vigilance while feeding. By modelling them as coupled oscillators, we noted that (1) individual marmosets do not show perfect periodicity in vigilance behaviours, (2) even then, pairs of marmosets developed a tendency to take turns being vigilant, a case of anti-phase synchrony, (3) marmosets could couple flexibly; the coupling strength varied with every new joint feeding bout, and (4) marmosets could control the coupling strength; dyads showed increased coupling if they began in a more desynchronised state. Such flexibility and control over synchronisation require more than simple interaction rules. Minimally, animals must estimate the current degree of asynchrony and adjust their behaviour accordingly. Moreover, the fact that each marmoset is inherently non-periodic adds to the cognitive demand. Overall, our study taps into the cognitive aspects of synchronisation and provides a mathematical framework to investigate the phenomenon more widely, where individuals may not display perfectly rhythmic behaviours.
Advancement in Cellular Topographic and Nanoparticle Capture Imaging by High Resolution Microscopy Incorporating a Freeze-Drying and Gaseous Nitrogen-based Approach
Authors: Uryu Kunihiro , Soplop Nadine , Sheahan Timothy P. , Catanese Maria-Teresa , Huynh Chuong , Pena John , Boudreau Nancy , Matei Irina , Kenific Candia , Hashimoto Ayako , Hoshino Ayuko , Rice Charles M. , Lyden David 
Published: September 2023

AbstractScanning electron microscopy (SEM) offers an unparalleled view of the membrane topography of mammalian cells by using a conventional osmium (OsO4) and ethanol-based tissue preparation. However, conventional SEM methods limit optimal resolution due to ethanol and lipid interactions and interfere with visualization of fluorescent reporter proteins. Therefore, SEM correlative light and electron microscopy (CLEM) has been hindered by the adverse effects of ethanol and OsO4on retention of fluorescence signals. To overcome this technological gap in achieving high-resolution SEM and retain fluorescent reporter signals, we developed a freeze-drying method with gaseous nitrogen (FDGN). We demonstrate that FDGN preserves cyto-architecture to allow visualization of detailed membrane topography while retaining fluorescent signals and that FDGN processing can be used in conjunction with a variety of high-resolution imaging systems to enable collection and validation of unique, high-quality data from these approaches. In particular, we show that FDGN coupled with high resolution microscopy provided detailed insight into viral or tumor-derived extracellular vesicle (TEV)-host cell interactions and may aid in designing new approaches to intervene during viral infection or to harness TEVs as therapeutic agents.
SARS-CoV-2 NSP14 governs mutational instability and assists in making new SARS-CoV-2 variants
Authors: Hassan Sk. Sarif , Bhattacharya Tanishta , Nawn Debaleena , Jha Ishana , Basu Pallab , Redwan Elrashdy M. , Lundstrom Kenneth , Barh Debmalya , Andrade Bruno Silva , Tambuwala Murtaza M. , Aljabali Alaa A. , Hromić-Jahjefendić Altijana , Baetas-da-Cruz Wagner , Uversky Vladimir N. 
Published: September 2023

AbstractSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the rapidly evolving RNA virus behind the COVID-19 pandemic, has spawned numerous variants since its 2019 emergence. The multifunctional NSP14 enzyme, possessing exonuclease and mRNA capping capabilities, serves as a key player. Notably, single and co-occurring mutations within NSP14 significantly influence replication fidelity and drive variant diversification. This study comprehensively examines 120 co-mutations, 68 unique mutations, and 160 conserved residues across NSP14 homologs, shedding light on their implications for phylogenetic patterns, pathogenicity, and residue interactions. Quantitative physicochemical analysis categorizes 3953 NSP14 variants into three clusters, revealing genetic diversity. This research underscores the dynamic nature of SARS-CoV-2 evolution, primarily governed by NSP14 mutations. Understanding these genetic dynamics provides valuable insights for therapeutic and vaccine development.
Targeting EIF4A triggers an interferon response to synergize with chemotherapy and suppress triple-negative breast cancer
Authors: Zhao Na , Kabotyanski Elena B. , Saltzman Alexander B. , Malovannaya Anna , Yuan Xueying , Reineke Lucas C. , Lieu Nadia , Gao Yang , Pedroza Diego A , Calderon Sebastian J , Smith Alex J , Hamor Clark , Safari Kazem , Savage Sara , Zhang Bing , Zhou Jianling , Solis Luisa M. , Hilsenbeck Susan G. , Fan Cheng , Perou Charles M. , Rosen Jeffrey M. 
Published: September 2023

AbstractProtein synthesis is frequently dysregulated in cancer and selective inhibition of mRNA translation represents an attractive cancer therapy. Here, we show that therapeutically targeting the RNA helicase eIF4A by Zotatifin, the first-in-class eIF4A inhibitor, exerts pleiotropic effects on both tumor cells and the tumor immune microenvironment in a diverse cohort of syngeneic triple-negative breast cancer (TNBC) mouse models. Zotatifin not only suppresses tumor cell proliferation but also directly repolarizes macrophages towards an M1-like phenotype and inhibits neutrophil infiltration, which sensitizes tumors to immune checkpoint blockade.Mechanistic studies revealed that Zotatifin reprograms the tumor translational landscape, inhibits the translation ofSox4 andFgfr1, and induces an interferon response uniformly across models. The induction of an interferon response is partially due to the inhibition ofSox4translation by Zotatifin. A similar induction of interferon-stimulated genes was observed in breast cancer patient biopsies following Zotatifin treatment. Surprisingly, Zotatifin significantly synergizes with carboplatin to trigger DNA damage and an even heightened interferon response resulting in T cell-dependent tumor suppression. These studies identified a vulnerability of eIF4A in TNBC, potential pharmacodynamic biomarkers for Zotatifin, and provide a rationale for new combination regimens comprising Zotatifin and chemotherapy or immunotherapy as treatments for TNBC.One Sentence SummaryTargeting EIF4A sensitizes TNBC to immune therapy and chemotherapy by suppressing Sox4, inducing an interferon response, and reprograming the tumor immune microenvironment.
Simulation-based Benchmarking of Ancient Haplotype Inference for Detecting Population Structure
Authors: Tretmanis Jazeps Medina , Jay Flora , Ávila-Arcos María C. , Huerta-Sanchez Emilia 
Published: September 2023

AbstractPaleogenomic data has informed us about the movements, growth, and relationships of ancient populations. It has also given us context for medically relevant adaptations that appear in present-day humans due to introgression from other hominids, and it continues to help us characterize the evolutionary history of humans. However, ancient DNA (aDNA) presents several practical challenges as various factors such as deamination, high fragmentation, environmental contamination of aDNA, and low amounts of recoverable endogenous DNA, make aDNA recovery and analysis more difficult than modern DNA. Most studies with aDNA leverage only SNP data, and only a few studies have made inferences on human demographic history based on haplotype data, possibly because haplotype estimation (or phasing) has not yet been systematically evaluated in the context of aDNA. Here, we evaluate how the unique challenges of aDNA can impact phasing quality. We also develop a software tool that simulates aDNA taking into account the features of aDNA as well as the evolutionary history of the population. We measured phasing error as a function of aDNA quality and demographic history, and found that low phasing error is achievable even for very ancient individuals (∼ 400 generations in the past) as long as contamination and read depth are adequate. Our results show that population splits or bottleneck events occurring between the reference and phased populations affect phasing quality, with bottlenecks resulting in the highest average error rates. Finally, we found that using estimated haplotypes, even if not completely accurate, is superior to using the simulated genotype data when reconstructing changes in population structure after population splits between present-day and ancient populations.AvailabilityAll software used for simulation and analysis is available at github.com/Jazpy/Paleogenomic-Datasim
Pigmentation level of human iPSC-derived retinal pigment epithelium cell does not indicate a specific gene expression profile
Authors: Nakai-Futatsugi Yoko , Jin Jianshi , Ogawa Taisaku , Sakai Noriko , Maeda Akiko , Hironaka Ken-ichi , Fukuda Masakazu , Danno Hiroki , Tanaka Yuji , Hori Seiji , Shiroguchi Katsuyuki , Takahashi Masayo 
Published: September 2023

AbstractRetinal pigment epithelium (RPE) cells show heterogeneous level of pigmentation when culturedin vitro. To know whether their color in appearance is correlated with the function of the RPE, we analyzed the color intensities of human-induced pluripotent stem cell-derived RPE cells (iPSC-RPE) together with the gene expression profile at the single cell level. For this purpose, we utilized our recent invention, Automated Live imaging and cell Picking System (ALPS), which enabled photographing each cell before RNA-sequencing analysis to profile the gene expression of each cell. While our iPSC-RPE were categorized in 4 clusters by gene expression, the color intensity of iPSC-RPE did not project any specific gene expression profiles. We reasoned this by less correlation between the actual color and the gene expressions that directly define the level of pigmentation, from which we hypothesized the color of RPE cells may be a temporal condition not strongly indicating the functional characteristics of the RPE.
Emotional showdown on social media: analyzing user reactions to the 2016 US presidential campaign
Authors: Bagić Babac Marina 
Published: September 2023

Purpose
Social media platforms are highly visible platforms, so politicians try to maximize their benefits from their use, especially during election campaigns. On the other side, people express their views and sentiments toward politicians and political issues on social media, thus enabling them to observe their online political behavior. Therefore, this study aims to investigate user reactions on social media during the 2016 US presidential campaign to decide which candidate invoked stronger emotions on social media.

Design/methodology/approach
For testing the proposed hypotheses regarding emotional reactions to social media content during the 2016 presidential campaign, regression analysis was used to analyze a data set that consists of Trump’s 996 posts and Clinton’s 1,253 posts on Facebook. The proposed regression models are based on viral (likes, shares, comments) and emotional Facebook reactions (Angry, Haha, Sad, Surprise, Wow) as well as Russell’s valence, arousal, dominance (VAD) circumplex model for valence, arousal and dominance.

Findings
The results of regression analysis indicate how Facebook users felt about both presidential candidates. For Clinton’s page, both positive and negative content are equally liked, while Trump’s followers prefer funny and positive emotions. For both candidates, positive and negative content influences the number of comments. Trump’s followers mostly share positive content and the content that makes them angry, while Clinton’s followers share any content that does not make them angry. Based on VAD analysis, less dominant content, with high arousal and more positive emotions, is more liked on Trump’s page, where valence is a significant predictor for commenting and sharing. More positive content is more liked on Clinton’s page, where both positive and negative emotions with low arousal are correlated to commenting and sharing of posts.

Originality/value
Building on an empirical data set from Facebook, this study shows how differently the presidential candidates communicated on social media during the 2016 election campaign. According to the findings, Trump used a hard campaign strategy, while Clinton used a soft strategy.