bluuebunny/crossref_metadata_2025_split huggingface dataset:
Review article: Primer for clinical researchers on innovative trial designs for emergency medicine
Authors: Lee Katherine J , Middleton Melissa , Mahar Robert K 
Published: November 2024

AbstractRandomised trials have long been recognised as the gold standard research tool for evidence‐based medicine. The past decade has seen the emergence of several innovative trial designs that are revolutionising how trials are conducted. These innovative designs enable more efficient, pragmatic trials that can address complex research questions which were previously not possible. In this paper, we provide an overview of the key innovative designs that are likely to be useful in the emergency medicine context, namely cluster crossover and stepped wedge designs, sequential multiple assignment randomised trial (SMART) designs, and platform trials. We describe the main features of each design, outline their pros and cons, and describe when they may or may not be useful. We also provide examples of these innovative designs in contexts that are relevant to emergency medicine.
Pollen morphology and its taxonomic significance in the genus Euphorbia L. (Euphorbiaceae), from northern Pakistan: Insights for honeybees‐plant interactions
Authors: Shah Hussain , Ahmad Mushtaq , Zafar Muhammad , Farah Mohammad Abul , Ahmad Shabir , Ullah Ateef , Khan Amjad , Abdullah Muhammad , Anwar Tauseef , Iqbal Rashid , Aghayeva Saltanat , Ercisli Sezai , Ashraf Muhammad , Elshikh Mohamed S. 
Published: November 2024

AbstractEuphorbia L. includes 2055 species with native range of this genus being cosmopolitan. In the present study, we assessed pollen morphology of 18 species of this genus occurring mostly in northern Pakistan. Pollen morphology of Euphorbia species is poorly investigated for its taxonomic significance. Here, we examined quantitative characters, including polar diameter, equatorial diameter, P/E ratio. Exine thickness, colpi length, and width were also examined. Among the qualitative characters, pollen shape, type, exine sculpturing, and aperture features were determined. The main aim of this study is to determine and investigate the foraging behavior of the honeybees that interact with Euphorbia species. The current finding will be helpful in melissopalynological analysis for developing beekeeping practices and can be used in the authentication of honey. Pollen quantitative traits applied through a multivariate analysis and diverse sampling also improve botanical and geographical characterization of a particular region. In addition, it is concluded that some palynomorphs of Euphorbia species may contain secondary compounds and can promote signs of toxicity in honeybees. However, the beekeepers wrongly correlate the fact that milky latex from Euphorbia taxa has burning and skin irritation effects on other animals, particularly humans, with honeybee deaths, which might be due to other factors. Our observations indicate with the sense that actual forage plants may not poison their pollinators and honeybees might occasionally be dead due to unidentified factors. We have suggested that beekeepers should attempt to identify the root causes for occasional bee deaths in the area.
Development of SNP Panels from Low‐Coverage Whole Genome Sequencing (lcWGS) to Support Indigenous Fisheries for Three Salmonid Species in Northern Canada
Authors: Beemelmanns Anne , Bouchard Raphaël , Michaelides Sozos , Normandeau Eric , Jeon Hyung‐Bae , Chamlian Badrouyk , Babin Charles , Hénault Philippe , Perrot Océane , Harris Les N. , Zhu Xinhua , Fraser Dylan , Bernatchez † Louis , Moore Jean‐Sébastien 
Published: November 2024

ABSTRACTSingle nucleotide polymorphism (SNP) panels are powerful tools for assessing the genetic population structure and dispersal of fishes and can enhance management practices for commercial, recreational and subsistence mixed‐stock fisheries. Arctic Char (Salvelinus alpinus), Brook Trout (Salvelinus fontinalis) and Lake Whitefish (Coregonus clupeaformis) are among the most harvested and consumed fish species in Northern Indigenous communities in Canada, contributing significantly to food security, culture, tradition and economy. However, genetic resources supporting Indigenous fisheries have not been widely accessible to northern communities (e.g. Inuit, Cree, Dene). Here, we developed Genotyping‐in‐Thousands by sequencing (GT‐seq) panels for population assignment and mixed‐stock analyses of three salmonids, to support fisheries stewardship or co‐management in Northern Canada. Using low‐coverage Whole Genome Sequencing data from 418 individuals across source populations in Cambridge Bay (Nunavut), Great Slave Lake (Northwest Territories), James Bay (Québec) and Mistassini Lake (Québec), we developed a bioinformatic SNP filtering workflow to select informative SNP markers from genotype likelihoods. These markers were then used to design GT‐seq panels, thus enabling high‐throughput genotyping for these species. The three GT‐seq panels yielded an average of 413 autosomal loci and were validated using 525 individuals with an average assignment accuracy of 83%. Thus, these GT‐seq panels are powerful tools for assessing population structure and quantifying the relative contributions of populations/stocks in mixed‐stock fisheries across multiple regions. Interweaving genomic data derived from these tools with Traditional Ecological Knowledge will ensure the sustainable harvest of three culturally important salmonids in Indigenous communities, contributing to food security programmes and the economy in Northern Canada.
Defining Objective BASDAI Cut‐Offs for Disease Activity States and Improvement Scores in Axial Spondyloarthritis: A Multicentric Collaboration
Authors: Goswami Rudra Prosad , Chatterjee Moumita , Das Shyamashis 
Published: November 2024

ABSTRACTObjectiveTo estimate objective cut‐off values for Bath ankylosing Spondylitis Disease Activity Index (BASDAI) corresponding to Ankylosing Spondylitis Disease Activity Score with CRP (ASDAS) cut‐off values (1.3, 2.1, and 3.5), and for interval changes (ΔBASDAI) corresponding to ΔASDAS (1.1 and 2).MethodsIn this multicentric study, adult patients with active axial spondyloarthritis (axSpA) treated with either tofacitinib 5 mg twice daily or adalimumab 40 mg subcutaneously fortnightly were recruited. Available paired data on BASDAI and ASDAS and paired interval change of these parameters (taken at least 3‐months apart) were analyzed. Cut‐off values for BASDAI were determined from a multinomial logistic regression and that for ΔBASDAI were determined with ordinal logistic regression with predicted probabilities. Diagnostics were assessed with correct classification rate (CRR), polychoric correlations (PCC), Goodman and Kruskal Gamma (GKG), and Matthew's correlation coefficient (MCC).ResultsTotal 962 observations of paired data and 670 interval change data were available from 266 patient (mean age 35 years, mean disease duration 7 years, mean BASDAI 2.7, and mean ASDAS 2.1). Following ASDAS classes were observed: inactive disease 131 (13.6%), moderate disease activity 322 (33.5%), high disease activity 420 (43.65%), and very high disease activity 89 (9.25%). The three cut‐offs generated for BASDAI were 0.8, 2.5, and 6 for BASDAI and those for ΔBASDAI were 2 and 4. The CRR for BASDAI cut‐offs was 65.59 and that for ΔBASDAI was 54.9. For the BASDAI cut‐offs, both PCC and GKG showed high values (> 0.85) and the MCC was 0.471.ConclusionIn patients with axSpA, without any clinical or serological confounders, BASDAI values 0.8, 2.5, and 6 corresponded to ASDAS‐CRP values 1.3, 2.1, and 3.5, respectively, and ΔBASDAI values of 2 and 4 correspond to ΔASDAS cut‐offs of 1.1 and 2.
The role of FOXK2–FBXO32 in breast cancer tumorigenesis: Insights into ribosome‐associated pathways
Authors: Liao Fuben , Zhu Jinjin , He Junju , Liu Zheming , Yao Yi , Song Qibin 
Published: November 2024

AbstractObjectiveTo search for a new biomarker that can predict the efficacy and prognosis of tumor immunotherapy.MethodFOXK2 genes were analyzed using single‐cell sequencing in pan‐cancer bulk RNA‐seq from the TCGA database. We used algorithms to predict their immune infiltration. Functional enrichment and ChIP‐seq identified potential downstream gene, FBXO32. FBXO32's role in cancer immune response was explored through analysis.ResultsSignificant up‐regulation of FOXK2 was observed in prostate adenocarcinoma (PRAD), uterine corpus endometrial carcinoma (UCEC), bladder urothelial carcinoma (BLCA), colorectal cancer (CRC), pancreatic ductal adenocarcinoma (PDAC), and stomach adenocarcinoma (STAD), while no such increase was found in lung cancer (lung adenocarcinoma [LUAD], lung squamous cell carcinoma [LUSC]) or thyroid carcinoma (THCA) tumor and adjacent tissues. FOXK2 expression correlated with patient prognosis, with lower expression associated with better immune response and survival and higher expression of its downstream gene FBXO32 linked to worse overall survival (OS) and immune infiltration. FOXK2 has the potential to be used as a prognostic indicator and target for treatment in individuals with cancer.ConclusionOur research provides insights into the significance of FOXK2 in cancer and indicates its potential as both a prognostic indicator and target for treatment. The ribosome‐associated pathways involving FOXK2 and FBXO32 could be pivotal in the advancement of tumors, offering possible avenues for targeted and individualized immunotherapy approaches. Additional research is required to completely understand the mechanisms that are responsible for the participation of FOXK2 and its subsequent gene FBXO32 in cancer, as well as to explore the possible advantages of focusing on FOXK2 for cancer treatment.
USP8‐mediated PTK7 promotes PIK3CB‐related pathway to accelerate the malignant progression of non‐small cell lung cancer
Authors: Kong Wencui , Feng Xuegang , Yu Zongyang , Qi Xingfeng , Zhao Zhongquan 
Published: November 2024

AbstractBackgroundProtein tyrosine kinase 7 (PTK7) has been found to be highly expressed in non‐small cell lung cancer (NSCLC), but its specific molecular mechanism needs to be further explored.MethodsPTK7 mRNA expression in NSCLC tumor tissues was examined by quantitative real‐time PCR. The protein levels of PTK7, ubiquitin‐specific peptidase 8 (USP8), PIK3CB, and PI3K/AKT were determined by western blot. Human monocytes (THP‐1) were induced into macrophages and then co‐cultured with the conditioned medium of NSCLC cells. Macrophage M2 polarization was assessed by detecting CD206+ cells using flow cytometry. The interaction between PTK7 and USP8 or PIK3CB was assessed by Co‐IP assay. Animal study was performed to evaluate the effects of PTK7 knockdown and PIK3CB on NSCLC tumorigenesis in vivo.ResultsPTK7 expression was higher in NSCLC tumor tissues and cells. After silencing of PTK7, NSCLC cell proliferation, invasion, and macrophage M2 polarization were inhibited, while cell apoptosis was promoted. USP8 enhanced PTK7 protein expression by deubiquitination, and the repressing effects of USP8 knockdown on NSCLC cell growth, invasion, and macrophage M2 polarization were reversed by PTK7 overexpression. PTK7 interacted with PIK3CB, and PIK3CB overexpression could abolish the regulation of PTK7 silencing on NSCLC cell progression. USP8 positively regulated PIK3CB expression by PTK7, thus activating PI3K/AKT pathway. Downregulation of PTK7 reduced NSCLC tumorigenesis by decreasing PIK3CB expression.ConclusionUSP8‐deubiquitinated PTK7 facilitated NSCLC malignant behavior via activating the PIK3CB/PI3K/AKT pathway, providing new idea for NSCLC treatment.
An online assessment of pricing for ready‐to‐drink alcohol products: Implications for risk and policy solutions
Authors: Rossheim Matthew E. , Tillett Kayla K. , Vasilev Viktor , LoParco Cassidy R. , Agwuncha Theresa , Sekhon Vishaldeep K. , Mendoza Edna P. , Townsend Olivia , Julian Maria T. , Treffers Ryan D. , Livingston Melvin D. , Siegel Michael B. , Jernigan David H. 
Published: November 2024

AbstractBackgroundAlcohol pricing policies can reduce population‐level alcohol consumption. To inform these policies, it is essential to understand the price per standard alcoholic drink of the least expensive brands. This study focused on prices of ready‐to‐drink products because of their accessibility, popularity among young people, and market expansion in recent years.MethodsIn 2023, we systematically identified 39 retail stores selling alcohol online in Fort Worth, Texas. For each product, we recorded information regarding brand name, alcohol‐by‐volume (abv), liquid volume, and price (n = 10,818). Ready‐to‐drink products encompassed beer, malt liquor, cider, premixed cocktails, and flavored alcoholic beverages (FAB) including hard beverages (seltzer, soda, tea, lemonade), excluding wine and distilled spirits. We limited analyses to brands sold by at least three stores and deduplicated products within stores. Our analytic sample size was 3924.ResultsThe least expensive brands included the following: Four Loko, MXD Drinks Co., Steel Reserve (High Gravity Lager and Alloy Series), Hurricane High Gravity, Natural Ice, Natty Daddy, Clubtails, Sauza Agave Cocktails, Truly Extra, and Icehouse. The average abv among all products was 5.9%. Among the 20 least expensive brands, the average abv was 9.0%, and 70% were available in single‐serve containers.ConclusionsThe least expensive brands of ready‐to‐drink alcohol products were often high abv, single‐serve containers of FAB, malt liquor, or beer. Retail price assessments can strengthen the case for policy solutions, such as targeted taxes and re‐classification of products, to reduce the risks posed by low‐priced alcohol. The current study identifies some brands these retail assessments should include.
Hospital obstetric volume and maternal outcomes: Does hospital size matter?
Authors: Holowko Natalie , Ladfors Linnea V. , Örtqvist Anne K. , Ahlberg Mia , Stephansson Olof 
Published: November 2024

AbstractIntroductionIn recent decades, centralization of health care has resulted in a number of obstetric unit closures. While studies support better infant outcomes in larger facilities, few have investigated maternal outcomes. We investigated obstetric unit closures over time and whether obstetric volume is associated with onset of labor, postpartum hemorrhage (PPH) and obstetric anal sphincter injury (OASIS).Material and MethodsAll births registered in Sweden between 1992 and 2019 (Medical Birth Register, N = 2 931 140), linked with data on sociodemographic characteristics and maternal/infant diagnoses, were used to describe obstetric unit closures. After excluding congenital malformations, obstetric volume was categorized (low: 0–1999, medium: 2000–3999, high: ≥4000 births per year). Restricting to 2004 onwards (after most closures), the association between volume and onset of labor (spontaneous as reference) was estimated. Restricting to spontaneous, full‐term (≥37 weeks gestation) cephalic births, we then investigated the association between volume and PPH and, after excluding planned cesarean sections, OASIS. Odds ratios from multilevel (logistic) models clustered by hospital were estimated.ResultsThe 20 dissolved obstetric units (1992–2019) had relatively stable volume until their closure. Compared to the average, women birthing in the highest volume hospitals were older (31.3 years vs. 30.4) and a higher proportion had >12 years of education (57 vs. 51%). Compared to high‐volume hospitals, there was no significant difference in labor starting by elective cesarean section or induction, rather than spontaneously, among low (OR 0.88, 95% CI: 0.73–1.06) and medium (OR 0.84, 95% CI 0.71–1.01) volume hospitals. There were lower odds of PPH among low (OR 0.72, 95% CI 0.63–0.85) and medium (OR 0.83, 95% CI 0.72–0.97) volume hospitals. No significant association was found between obstetric volume and OASIS (low: OR 0.98, 95% CI 0.82–1.18; medium: OR 0.90, 95% CI 0.77–1.05).ConclusionsThere was not a strong relationship between obstetric volume and maternal outcomes. Reduced odds of PPH for women birthing in smaller units may be due to triaging high‐risk pregnancies to larger hospitals. While there was no significant association between obstetric volume and onset of labor or OASIS, other important factors related to closures, such as workload and overcrowding, should be investigated.
Prediction of uterine rupture in singleton pregnancies with one prior cesarean birth undergoing TOLAC: A cross‐sectional study
Authors: Arkerson Brittany J. , Muraca Giulia M. , Thakur Nisha , Javinani Ali , Khalil Asma , D'Souza Rohan , Mustafa Hiba J. 
Published: November 2024

AbstractIntroductionBeing able to counsel patients with one prior cesarean birth on the risk of uterine rupture with a trial of labor after cesarean, (TOLAC) is an important aspect of prenatal care. Despite uterine rupture being a catastrophic event, there is currently no successful, validated prediction model to predict its occurrence.Material and MethodsThis was a cross‐sectional study using US national birth data between 2014 and 2021. The primary objective was to identify risk factors for uterine rupture during TOLAC and to generate a prediction model for uterine rupture among singleton gestations with one prior cesarean as their only prior birth. The secondary objective was to describe the maternal and neonatal morbidity associated with uterine rupture. The association of all candidate variables with uterine rupture was tested with uni‐ and multi‐variable logistic regression analyses. We included term and preterm singleton pregnancies with one prior birth that was cesarean birth (CB) with cephalic presentation undergoing TOLAC. We excluded pregnancies with major structural anomalies and chromosomal abnormalities. The Receiver Operating Characteristics (ROC) Curve was generated. p value <0.001 was considered statistically significant.ResultsOf the 270 329 singleton pregnancies with one prior CB undergoing TOLAC during the study period, there were 957 cases of uterine rupture (3.54 cases per 1000). Factors associated with uterine rupture in multivariable models were an interpregnancy interval < 18 months vs the reference interval of 24–35 months (aOR 1.55; 95% CI, 1.19–2.02), induction of labor (aOR 2.31; 95% CI, 2.01–2.65), and augmentation of labor (aOR 1.94; 95% CI, 1.70–2.21). Factors associated with reduced rates of uterine rupture were maternal age < 20 years (aOR 0.33, 95% CI 0.15–0.74) and 20–24 years (aOR 0.79, 95% CI 0.64–0.97) vs the reference of 25–29 years and gestational age at delivery 32–36 weeks vs the reference of 37–41 weeks (aOR 0.55, 95% CI 0.38–0.79). Incorporating these factors into a predictive model for uterine rupture yielded an area under the receiver‐operating curve of 0.66. Additionally, all analyzed maternal and neonatal morbidities were increased in the setting of uterine rupture compared to non‐rupture.ConclusionsUterine rupture prediction models utilizing TOLAC characteristics have modest performance.
Effects of supplementation with mature coconut water on oxidative stress, semen quality, reproductive hormone levels, and sexual behavior in Boer bucks
Authors: Mohd‐Zainurian Nur Faizah Nadia , Esah Haizal Danial , Mohamad‐Fauzi Nuradilla , Hashim Noor Hashida , Mazlishah Mohd Shahmi Hakimi , Shamsuddin Shamsul Azlin Ahmad , Mohd‐Yusuf Yusmin , Aziz Nor Azlina Abd 
Published: November 2024

AbstractMature coconut water (MCW) has been demonstrated to contain bioactive compounds with antioxidant properties. In vivo research showed that MCW supplementation increased semen quality in rats, suggesting that it may boost reproductive performance. This study investigated the impact of MCW on the reproduction of Boer bucks. Two groups of 12 sexually mature bucks were given either plain water (control) or MCW at 5 mL/kg of body weight daily for 60 days. Sexual behaviors were studied using the focal observation technique, whereas semen was collected for quality assessment. Oxidative stress markers, namely, malondialdehyde (MDA) and glutathione (GSH), along with reproductive hormones, specifically luteinizing hormone (LH), follicle‐stimulating hormone (FSH), and testosterone, were quantified in blood serum samples via enzyme‐linked immunosorbent assay (ELISA). The oxidative stress analysis showed elevated GSH and reduced MDA levels, accompanied by enhanced sperm quality, including superior motility, concentration, viability, and fewer morphological abnormalities (p < 0.05), in the group receiving MCW. Moreover, there was a rise in LH, FSH, and testosterone levels with improved sexual behaviors (p < 0.05), including a reduced latency to the first mount, increased mount attempts, higher libido, and prolonged kicking and sniffing durations. In conclusion, MCW may improve reproductive health and fertility in Boer bucks.
Design and validation of an electroencephalogram‐supported approach to tracking real‐time cognitive load variations for adaptive video‐based learning
Authors: Pei Leisi , Jong Morris Siu‐Yung , Shang Junjie , Ouyang Guang 
Published: November 2024

Cognitive load is a critical internal state associated with learners' learning process and significantly influences learning outcomes. With the worldwide popularity of video‐based learning (VBL), tracking real‐time cognitive load variations becomes more and more important for the timely provision of adaptive learning support during the learning process. This study proposed and validated an electroencephalogram (EEG)‐supported approach to tracking real‐time cognitive load variations during continuous VBL. We recruited 108 healthy adult participants to watch a specially designed video lecture with a sequence of interconnected slides of equal length. EEG signals were continuously recorded throughout the session. The video lecture was designed with varying levels of content difficulty (ie, rated from 1 to 5) across slides and was narrated at three different speeds (ie, slow, normal and fast) to induce cognitive load variations. For each slide, the cognitive load was quantified using both subjective ratings (ie, self‐reported difficulty) and an EEG‐derived measure (ie, alpha power). Through linear mixed model analysis, we demonstrated the feasibility of using alpha power to track real‐time cognitive load variations during the continuous VBL process after controlling the effect of mental fatigue. This study provides a foundation for developing learning enhancement technologies that enable the timely provision of adaptive learning support in VBL.
Practitioner notesWhat is already known about this topic

Video‐based learning has become a prevailing learning method for the current generation.
Tracking the internal learning state of learners is essential for the timely provision of adaptive learning support during the video‐based learning process.
Cognitive load is a critical aspect of internal learning state.
While EEG has been proven to be valuable in assessing average cognitive load of a task, few studies have investigated the feasibility of utilizing EEG to track real‐time cognitive load variations in a task.
What this paper adds

An EEG‐supported approach was proposed to track real‐time cognitive load variations in video‐based learning.
A high consistency was found between subjective ratings and EEG‐derived measure of cognitive load.
The presence of mental fatigue exerted a significant impact on EEG‐derived measure of cognitive load.
Implications for practice and/or policy

Generative AI can be leveraged to facilitate mass production of lectures required in the approach.
Real‐time tracking of cognitive load variations in video‐based learning enables the timely provision of adaptive learning supports.
Additional research is warranted to mitigate the effect of mental fatigue on real‐time tracking of cognitive load variations.