bluuebunny/crossref_metadata_2025_split huggingface dataset:
High‐dose intranasal insulin in an adaptive dose‐escalation study in healthy human participants
Authors: Schmitzberger Florian , Fowler Jennifer , Hsu Cindy H. , Pai Manjunath P. , Neumar Robert W. , Meurer William J. , Silbergleit Robert 
Published: November 2024

AbstractIntranasal insulin is a putative neuroprotective therapy after cardiac arrest, but safety in humans at doses extrapolated from animal models is unknown. This phase I, open‐label adaptive dose‐escalation study explores the maximum tolerated dose of intranasal insulin in healthy human participants. Placebo or insulin at doses from 0 to 1000 units was given to healthy participants intranasally on repeated weekly visits. Serum glucose, insulin, and C‐peptide levels were measured serially at 0, 15, 30, 60, 120, 180, and 240 min after administration. Twenty‐four participants (12 female, median age 53, IQR 35–61) were enrolled. There was minimal change in average serum glucose after administration of intranasal insulin. Average serum insulin increased slightly in a dose‐dependent manner, reaching maximum concentrations at 15 min. C‐peptide decreased over time from administration in all groups. One participant had severe hypoglycemia (24 mg/dL at 45 min) and a different participant had mild hypoglycemia (51 mg/dL at 30 min), both after receiving 600 U intranasal insulin. Hypoglycemic episodes were associated with increases in serum insulin. Both participants continued in the study without hypoglycemia after additional doses. High‐dose intranasal insulin up to 1000 U was generally well tolerated, with minimal measurable systemic absorption and without significant aggregate changes in mean glucose. Idiosyncratic episodic systemic absorption and hypoglycemia require further study and additional caution in potential clinical application. Further study of its target engagement and efficacy as a neuroprotective therapy after cardiac arrest at these doses is warranted.
Use cases of registry‐based randomized controlled trials—A review of the registries' contributions and constraints
Authors: Kubesch Nadine , Gaitonde Sneha , Petriti Uarda , Bakker Elisabeth , Basu Swati , Birks Laura Ellen , Aubrun Elodie , de Vries Sieta T. , Schneider Rahel 
Published: November 2024

AbstractRegistry‐based randomized controlled trials (RRCTs) can combine the advantages of registries with those of randomization. This review aimed to expand the current knowledge on RRCT utilization and implementation by providing a comprehensive overview of RRCT use cases. A targeted literature search was conducted through July 2023 to identify articles on RRCTs. Information regarding the RRCT characteristics, their utilization, and the registries' contributions and the constraints faced was extracted. Descriptive statistics were used. We identified 102 RRCTs in 110 publications. RRCTs were mostly performed for the assessment of medical devices or surgical/clinical procedures (n = 45), followed by drugs (n = 30). More than half of the RRCTs were conducted in the Nordic countries (n = 58) and the most used registry types were health service registries/administrative health data (n = 63), followed by disease registries (n = 46). Approximately half of the RRCTs (n = 53) utilized additional data sources aside from registry data. The contribution of a registry to the RRCT was mostly for data collection and study follow‐up (n = 90–92), followed by patient recruitment (n = 56–61), and randomization (n = 28–38), with varying levels of transparency in reporting. We collated author‐reported constraints related to the used registries into four overarching themes, that is, data availability and completeness, data quality, representativeness, and registry infrastructure and accessibility. This review shows that RRCTs are already used in different domains and geographic regions. Guidelines on structured and transparent reporting of RRCT methods and the optimal use are, however, needed to inform decision‐making by health authorities and to reach their full potential.
Sustainable Portfolio Construction via Machine Learning: ESG, SDG and Sentiment
Authors: Feng Xin , von Mettenheim Hans‐Jörg , Sermpinis Georgios , Stasinakis Charalampos 
Published: November 2024

ABSTRACTThis study proposes portfolio construction strategies based on novel sentiment, ESG and SDG scores. We utilize natural language processing to establish a novel daily score system that mitigates concerns of different rating standards. The portfolios constructed are optimized via machine learning algorithms on a monthly basis using daily historical returns. Utilizing the equal‐weighted portfolios as benchmarks, we empirically show that our optimized portfolios exhibit better trading performance in both the SPX500 and STOXX600 indices. The findings demonstrate that nonlinear models such as random forests, neural networks, and genetic algorithms can perform better than other machine learning models in portfolio management.
Prioritizing Conservation Areas for the Hyacinth Macaw (Anodorhynchus hyacinthinus) in Brazil From Low‐Coverage Genomic Data
Authors: Vilaça Sibelle Torres , Dalapicolla Jeronymo , Soares Renata , Guedes Neiva Maria Robaldo , Miyaki Cristina Y. , Aleixo Alexandre 
Published: November 2024

ABSTRACTEstimates of current genetic diversity and population connectivity are especially important for endangered species that are subject to illegal harvesting and trafficking. Genetic monitoring can also ensure that management units are sustaining viable populations, while estimating genetic structure and population dynamics can influence genetic rescue efforts and reintroduction from captive breeding and confiscated animals. The Hyacinth Macaw (Anodorhynchus hyacinthinus) is a charismatic endangered species with a fragmented (allopatric) distribution. Using low coverage genomes, we aimed to investigate the dynamics across the remaining three large disjunct populations of Hyacinth Macaws in Brazil to inform conservation strategies. We obtained low coverage DNA data for 54 individuals from seven sampling sites. Our results showed that Hyacinth Macaws have four genetically structured clusters with relatively high levels of diversity. The Pantanal biome had two genetically distinct populations, with no obvious physical barriers that might explain this differentiation. We detected signs of gene flow between populations, with some geographical regions being more connected than others. Estimates of effective population size in the past million years of the species' evolutionary history showed a decline trend with the lowest Ne in all populations reached within the last few thousand years. Our findings suggest that populations from the Pantanal biome are key to connecting sites across its distribution, and maintaining the integrity of this habitat is important for protecting the species. Given the genetic structure found, we also highlight the need of conserving all wild populations to ensure the protection of the species' evolutionary potential.
Biosensing and Biosensors—Terminologies, Technologies, Theories and Ethics
Authors: Misera Jan , Melchert Johannes , Bork‐Hüffer Tabea 
Published: November 2024

ABSTRACTWhich biosensing technologies are geographers using in their research, and what exactly do they measure? What are the theoretical origins of geographic interests in biosensing? This article provides an overview of the variety of biosensors applied in biosensing research, tracks the theoretical debates and roots of geographic engagement with biosensing, and discusses the potentials, limitations and ethical implications of applying biosensors. We critically reflect on the varied terminologies that have been used to describe a rapidly evolving array of biosensing technologies and methodologies and suggest a common understanding for key terms such as “biosensing” (technologies or methodologies), “biosensors,” “wearable biosensors” and “biosignals.” We offer an overview of the broader theoretical debates that have inspired geographers turn to biosensing, including behavioral geography, more‐than‐representational theory, critical neurogeography, the mobilities and biosociality paradigms, and visual geographies. These have called for methodologies that can capture affects neglected in representational research, follow people, things and technologies as they are mobile in space and time, investigate the links between brain, cognition and biopolitics or attend to visualities in everyday life. Although geographers have so far engaged with a limited number of the ever‐growing variety of available (bio‐)sensors, the development and application of biosensing methodologies is vibrant, highly diverse and very promising for diverse geographical research questions and fields. Going forward, we particularly encourage experimentation with eye‐trackers, which come closest to measuring instantaneous responses to environmental stimuli and offer interesting opportunities for the analysis of social and material environments through the visual data they create. Finally, we conclude with a call for a stronger emphasis on data ethics, procedural ethics and ethics of care in biosensing, which have so far received too little attention in these often interdisciplinary and complex biosensing research endeavors.
Virological and Clinical Outcomes of Influenza Outpatients Treated With Baloxavir, Oseltamivir, or Laninamivir in the 2023–2024 Season
Authors: Goto Takeyuki , Kawai Naoki , Bando Takuma , Takasaki Yoshio , Shindo Shizuo , Sato Tomonori , Tani Naoki , Chong Yong , Ikematsu Hideyuki 
Published: November 2024

ABSTRACTBackgroundClinical data on patients infected with influenza B Victoria (BV) after the approval of baloxavir is lacking.MethodsThis observational study of the Japanese 2023–2024 influenza season analyzed data from 25 outpatients with A(H1N1)pdm09, 36 with A(H3N2), and 65 with BV. Viral samples were collected before and after administering an antiviral (70 patients received baloxavir and 56 received a neuraminidase inhibitor), on days 1, 5, and 10. Isolated viruses after culturing were amplified using RT‐PCR and sequenced to detect mutations of concern, including acidic protein (PA)‐amino acid (AA) E23X/I38X for influenza A and M34X/I38X for BV. Fever and symptoms were tracked via self‐reporting diaries.ResultsNo PA‐AA‐substituted virus was detected from 126 pre‐treatment samples. In the baloxavir cohort, one (7.1%, 1/14) PA I38F‐substituted A(H1N1)pdm09 and two (11.1%, 2/18) PA I38T‐substituted A(H3N2) viruses were isolated on day 5 but not on day 10. No (0%, 0/37) PA‐AA‐substituted BV was detected on day 5 or after. The virus isolation rate on day 5 was higher among patients with BV than with influenza A in both baloxavir (35.1% vs. 14.3% for A(H1N1)pdm09 and 16.7% for A(H3N2)) and oseltamivir‐treated patients (44.4% vs. 0% for A(H1N1)pdm09 and 33.3% for A(H3N2)). Patients with PA‐AA‐substituted influenza A after baloxavir administration did not have longer fever duration than those without virus isolation or with wild‐type virus on day 5, for both A(H1N1)pdm09 and A(H3N2).ConclusionsBaloxavir‐resistant variants were not detected in influenza BV before treatment, as with A. The emergence of PA‐AA‐substituted influenza A after baloxavir administration was temporal and did not cause prolonged symptoms. No baloxavir‐resistant BV variants were observed after baloxavir administration.
Mixed Methods Studies Using Secondary Analysis in Nursing and Midwifery: A Methodological Review
Authors: Fàbregues Sergi , Younas Ahtisham , Inayat Shahzad , Escalante‐Barrios Elsa Lucia , Durante Angela 
Published: November 2024

ABSTRACTAimTo identify mixed methods studies in nursing and midwifery using secondary analysis and to examine their methodological characteristics.DesignMethodological review.MethodsA systematic search was conducted to identify empirical mixed methods studies in nursing and midwifery that used secondary analysis. A data extraction sheet was developed based on previous methodological reviews of secondary analysis and mixed methods.Data SourcesSCOPUS, Web of Science and CINAHL were searched from inception to March 10, 2023. Supplementary searches were conducted in two methodological journals and six nursing journals.ResultsA total of 26 mixed methods studies published between 2000 and 2022 were included in the review. Of these, only 13 studies explicitly mentioned the type of mixed methods design used. Twenty studies showed evidence of integration of the quantitative and qualitative components. Most of these studies integrated the components at the interpretation stage, whereas fewer integrated the components during data collection. None of the studies mentioned the rationale for using secondary analysis in the context of a mixed methods study.ConclusionThe included studies demonstrated fairly good reporting of mixed methods features, although they generally lacked a rationale for the use of secondary data.Implications for the profession and/or patient careAdequate reporting of mixed methods studies using secondary analysis is essential in order to allow readers to assess whether secondary analysis was appropriately incorporated into a mixed methods study and whether the potential of secondary analysis was fully exploited.ImpactThis review provides a set of recommendations to transparently report information regarding the research process and results obtained in mixed methods studies using secondary analysis.Reporting MethodItems relevant to methodological reviews included in the PRISMA Extension for Scoping Reviews (PRISMA‐ScR) were considered for reporting the review.
Multidimensional Plasma Lipids Affect Preeclampsia/Eclampsia: A Mendelian Randomization Study
Authors: Shi Shaole , Wu Fangyuan , Zhao Shanshan , Wang Zilian , Fan Yongqiang 
Published: November 2024

ABSTRACTCirculating lipids play a crucial role during pregnancy and may impact various pregnancy‐related diseases. This study employed a two‐sample Mendelian randomization (MR) framework to investigate the causal relationship between alterations in multidimensional plasma lipid levels and the risk of preeclampsia or eclampsia, offering deeper insight into this association. The inverse variance weighted (IVW) method was utilized as the main analysis. Summary statistics from plasma lipidomics of 7174 Finnish individuals and summary data on preeclampsia/eclampsia from the FinnGen consortium involving 219 817 European participants were employed. Sensitivity analyses were conducted to evaluate heterogeneity and pleiotropy. The study identified 17 lipid species from a total of 179 lipid species associated with susceptibility to preeclampsia/eclampsia. Notably, ten species, including six triacylglycerols (TAGs) (50:1, 48:1, 56:4, 49:2, 48:2, 54:3), a diacylglycerol (DAG) (16:1_18:1), and three sphingomyelins (SMs) (d36:1, d34:1, d38:1), were found to increase the risk of preeclampsia/eclampsia. Conversely, seven species, including five phosphatidylcholines (PCs) (16:1_20:4, O‐18:1_20:4, 18:1_20:4, 16:0_20:4, 17:0_20:4) and two phosphatidylethanolamines (PEAs) (18:0_20:4, 16:0_20:4), all containing arachidonic acid (ARA) in the sn‐2 position, were associated with a reduced risk of preeclampsia/eclampsia (all p < 0.05). The results of the stratified analysis were consistent with these findings. Furthermore, reverse MR analysis indicated that preeclampsia/eclampsia does not causally affect plasma levels of these lipids. Our findings established a causal relationship between specific plasma lipid species and modulation of preeclampsia/eclampsia risk, providing improved resolution for risk assessment and potential therapeutic targets in the disease.
Nodularin‐R Synergistically Enhances Abiraterone Against Castrate‐ Resistant Prostate Cancer via PPP1CA Inhibition
Authors: Huang Yiqiao , Cen Yi , Wu Hualing , Zeng Guohao , Su Zhengming , Zhang Zhiming , Feng Shourui , Jiang Xianhan , Wei Anyang 
Published: November 2024

ABSTRACTClinically, most prostate cancer (PCa) patients inevitably progress to castration‐resistant prostate cancer (CRPC) with poor prognosis after androgen deprivation therapy (ADT), including abiraterone, the drug of choice for ADT. Therefore, it is necessary to explore the resistance mechanism of abiraterone in depth. Genome‐wide CRISPR/Cas9 knockout technology was used to screen CRPC cell line 22Rv1 for abiraterone‐resistant genes. Combined with bioinformatics, a key gene with high expression and poor prognosis in CRPC patients was screened. Then, the effects of target gene on abiraterone‐resistant 22Rv1 cell function were explored by silencing and overexpression. Further, a natural product with potential targeting effect was identified and validated by molecular docking and protein expression. Molecular dynamics simulations revealed potential mechanism for the natural product affecting target protein expression. Finally, the combined anti‐CRPC effects of the natural product and abiraterone were validated by cellular and in vivo experiments. Five common resistance genes (KCNJ3, COL2A1, PPP1CA, MDH2 and EXOSC5) were identified successfully, among which high PPP1CA expression had the worst prognosis for disease‐free survival. Moreover, PPP1CA was highly expressed in abiraterone‐resistant 22Rv1 cells. Silencing PPP1CA increased cell sensitivity to abiraterone while promoting apoptosis and inhibiting clone formation. Overexpressing PPP1CA exerted the opposite effects. Molecular docking revealed the binding mode of the natural product nodularin‐R to PPP1CA with a dose‐dependent manner for inhibition. Mechanistically, nodularin‐R attenuates the interaction between PPP1CA and USP11 (deubiquitinating enzyme), potentially promoting PPP1CA degradation. Additionally, combination of 2.72 μM nodularin‐R and 54.5 μM abiraterone synergistically inhibited the resistant 22Rv1 cell function. In vivo experiments also revealed that combination therapy significantly inhibited tumour growth and reduced inducible expression of PPP1CA. PPP1CA is a key driver for abiraterone resistance, and nodularin‐R enhances the anti‐CRPC effects of abiraterone by inhibiting PPP1CA.
Survival and Complications of Partial Coverage Restorations on Posterior Teeth—A Systematic Review and Meta‐Analysis
Authors: Prott L. S. , Pieralli S. , Klein P. , Spitznagel F. A. , Ibrahim F. , Metzendorf M.‐I. , Carrasco‐Labra A. , Blatz M. B. , Gierthmuehlen P. C. 
Published: November 2024

ABSTRACTObjectiveTo determine the clinical performance of partial coverage restorations (PCR) (onlays, occlusal veneers, and partial crowns) composed of different ceramic and ceramic‐based materials to treat extended posterior defects.Materials and MethodsMEDLINE, Scopus, CENTRAL, ClinicalTrials.gov, and the International Clinical Trials Registry Platform were searched (inception‐February 2024) for randomized controlled trials (RCT) comparing posterior PCRs composed of different ceramic and ceramic‐based materials with a minimum follow‐up of 1 year.ResultsSix RCTs were included. Resin matrix ceramic (RMC) and lithium disilicate (LDS) restorations had a 3‐year survival rate of 89.3% (95% CI 76.4–95.3) and 93.7% (95% CI 83.7–97.7), respectively, and leucite‐reinforced glass ceramic (LRGC) restorations a range between 96.1% (95% CI 90.1–98.9) compared with RMC and 98.3% (95% CI 90.8–100) compared with LDS. After 1–3 years of follow‐up, LDS slightly outperformed RMC on restoration failure and loss of retention (1.56 more failures and 1.78 more loss of retentions for RMC per 100 restoration‐years [low certainty evidence]). No statistically significant differences between ceramic and ceramic‐based materials were detected in short‐term follow‐up (1–3 years of follow‐up). The long‐term performance of posterior PCRs is uncertain.ConclusionThe survival of LDS restorations may slightly outperform RMC restorations after 3 years of follow‐up across outcomes, except for bulk fracture. RCTs providing medium to long‐term data are needed.Clinical SignificanceCeramic and ceramic‐based PCRs are a reliable treatment option to restore extended posterior defects.
Surface Roughness on Cementoenamel Junction After Rubber‐Dam Clamp Application
Authors: Erden Kayalidere Ezgi , Sahin Merve , Korkut Bora , Mudok Tangul , Caliskan Yanikoglu Funda 
Published: November 2024

ABSTRACTObjectiveTo investigate the surface roughness on cementoenamel junction after application of various rubber‐dam retraction clamps for different durations.Materials and MethodsFifty‐four extracted human molar teeth were used. Various retraction clamps were placed on the cementoenamel junction. There are three main examination groups in the study. Group 1 (n = 6) included a polymer clamp (SoftClamp, Kerr Hawe, Switzerland), Group 2 (n = 6) included a metal clamp with a flat edge (Black Line RDCM7X, Hu‐Friedy Group, USA), and Group 3 (n = 6) included a metal clamp with a serrated edge (Fiesta Color Coded, Coltene, USA). All clamps were applied for 30 min, 1, and 2 h. Surface roughness measurements were performed using a profilometer before and after the clamp application and surface morphology was assessed through the SEM images. One‐way ANOVA was used to compare three or more groups. Percentage changes were evaluated using the Kruskal–Wallis test, followed by Dunn's test for post hoc analyses. The deemed significance was set at p < 0.05.ResultsBetween the initial and the final roughness measurements, after 30 min of clamp application, only Group 3 showed significant increases in roughness (p = 0.001). After 1 and 2 h of clamp application, there were significant increases in roughness for all groups. No significant differences in percentage changes for all groups in 30 min and 2 h of application (p = 0.220 and p = 0.091, respectively). However, Group 1 presented significantly lower surface roughness in percentage after the 1 h of application (p = 0.040). No significant differences in the percentage changes in roughness were observed within the groups for 30 min, 1, and 2 h applications (p = 0.220, p = 0.884, and p = 0.755 for Groups 1, 2, and 3, respectively). In SEM analysis, deep point microstructure defects were seen as the clamp application time increased.ConclusionsRubber‐dam clamp application may cause damage to the cementoenamel junction area. However, the level of damage is clamp‐type‐dependent. Slight scratch‐type damages were observed on teeth with plastic clamps, while metal clamps generally caused cracks. The increase in the duration of the same rubber‐dam clamp application was not considered an effective factor regarding the damage.Clinical SignificanceDuring rubber‐dam isolation, clamp type and duration of the application may cause damage to the tooth surface or progress an existing defect. Examining the teeth before selecting the clamp might be beneficial for minimizing dental tissue damage.