bluuebunny/crossref_metadata_2025_split huggingface dataset:
CircSEPT9 promotes breast cancer progression by regulating PTBP3 expression via sponging miR‐625‐5p
Authors: Shi Guangtao , Li Hongbo , Chen Ying , Chen Zhi , Lin Xiaoji 
Published: February 2024

AbstractBackgroundBreast cancer (BC) is a common malignancy which threatens the health of women. Circular RNAs (circRNAs) are critical factors in multiple cancers, including BC. The aim of this experiment was to investigate the molecular mechanisms of circRNA Septin 9 (circSEPT9) in the progression of BC.MethodsCircSEPT9, microRNA‐625‐5p (miR‐625‐5p) and polypyrimidine tract‐binding protein 3 (PTBP3) levels were determined by quantitative real‐time polymerase chain reaction (qRT‐PCR). Western blot was performed to detect the protein levels of PTBP3, E‐cadherin and vimentin. Cell counting kit‐8 assay (CCK8) and thymidine analog 5‐ethynyl‐2′‐deoxyuridine (EDU) was utilized for proliferation examination. Flow cytometry was conducted to measure apoptosis. Transwell assay and wound healing assay to investigate the migration of BC cells. Glucose uptake and lactate production were determined by specific kits. Additionally, dual‐luciferase reporter assay and RNA immunoprecipitation (RIP) assay were utilized to verify the interaction. A murine xenograft model was established to investigate the function of circSEPT9 in BC in vivo.ResultsOverexpression of circSEPT9 was found in BC tissues and cells. Silencing circSEPT9 impeded BC cell proliferation, migration, epithelial–mesenchymal transition (EMT) and glycolytic metabolism but facilitated cell apoptosis in vitro. Meanwhile, circSEPT9 knockdown constrained tumor growth in vivo. MiR‐625‐5p was targeted by circSEPT9. The influence of silencing circSEPT9 on BC cell function was regained by miR‐625‐5p inhibitor. Furthermore, miR‐625‐5p regulated BC cell malignant phenotypes via downregulating PTBP3.ConclusioncircSEPT9 contributed to the malignant progression of BC by up‐regulating PTBP3 via sponging miR‐625‐5p.
NAT10‐mediated mRNA N4‐acetylcytidine modification of MDR1 and BCRP promotes breast cancer progression
Authors: Zhao Cui‐Cui , Sun Xuan , Chen Jing , Geng Bill D. 
Published: February 2024

AbstractBackgroundN‐acetyltransferase 10 (NAT10) serves as a critical enzyme in mediating the N4‐acetylcytidine (ac4C) that ensures RNA stability and effective translation processes. The role of NAT10 in driving the advancement of breast cancer remains uninvestigated.MethodsWe observed an increase in NAT10 expression, both at mRNA level through the analysis of the Cancer Genome Atlas (TCGA) database and at the protein level of tumor tissues from breast cancer patients. We determined that a heightened expression of NAT10 served as a predictor of an unfavorable clinical outcome. By screening the Cancer Cell Line Encyclopedia (CCLE) cell bank, this expression pattern of NAT10 was consistency found across almost all the classic breast cancer cell lines.ResultsFunctionally, interference of NAT10 expression exerts an inhibitory effect on proliferation and invasion of breast cancer cells. By using ac4C RNA immunoprecipitation (ac4c‐RIP) and acRIP‐qPCR assays, we identified a reduction of ac4C enrichment within the ATP binding cassette (ABC) transporters, multidrug resistance protein 1 (MDR1) and breast cancer resistance protein (BCRP), consequent to NAT10 suppression. Expressions of MDR1 and BCRP exhibited a positive correlation with NAT10 expression in tumor tissues, and the inhibition of NAT10 in breast cancer cells resulted in a decrease of MDR1 and BCRP expression. Therefore, the overexpressing of MDR1 and BCRP could partially rescue the adverse consequences of NAT10 depletion. In addition, we found that, remodelin, a NAT10 inhibitor, reinstated the susceptibility of capecitabine‐resistant breast cancer cells to the chemotherapy, both in vitro and in vivo.ConclusionThe results of our study demonstrated the essential role of NAT10‐mediated ac4c‐modification in breast cancer progression and provide a novel strategy for overcoming chemoresistance challenges.
Inpatient admissions and mortality of anorexia nervosa patients according to their preceding psychiatric and somatic diagnoses
Authors: Momen Natalie C. , Petersen Jindong Ding , Yilmaz Zeynep , Semark Birgitte D. , Petersen Liselotte Vogdrup 
Published: February 2024

AbstractObjectiveAnorexia nervosa (AN) is associated with increased risk of mortality, but little is known about the risk of inpatient admissions and mortality outcomes in individuals with diagnoses of both AN and other psychiatric and somatic conditions. We aimed to investigate the inpatient admissions and mortality among people with AN and other diagnosed conditions using Danish national registers.MethodThis retrospective cohort study included individuals diagnosed with AN in Denmark, born 1977–2010. We identified other mental and somatic conditions in this population. We used Cox proportional hazards regression to estimate the risk of inpatient admission and mortality, focusing on (i) the number of other diagnosed conditions, and (ii) specific combinations of conditions diagnosed prior to the AN diagnosis. Categories of inpatient admissions considered were due to: (i) AN, (ii) any psychiatric disorder, and (iii) any somatic disorder. Additionally, competing risks survival analysis was used to calculate the cumulative incidence of inpatient admission and all‐cause mortality over the follow‐up period.ResultsThe study population included 11,489 individuals. The most common conditions individuals had prior to their AN diagnosis were other eating disorders (34.5%) and anxiety disorders (32.7%). During the follow‐up, 3184 (27.7%), 4604 (40.1%), and 6636 (57.8%) individuals were admitted for AN, any psychiatric disorder, and any somatic disorder, respectively; and in total 106 (0.9%) died. The risk of all outcomes was highest among those who had received a higher number of other diagnoses. For most combinations, the risks of admission and mortality were increased.DiscussionOur study presents the prevalence of other conditions in patients with AN in Denmark and elucidates their association with higher rates of inpatient admission and mortality. Our findings highlight the need for comprehensive, multidisciplinary care of patients with AN considering the spectrum of other diagnosed conditions to improve health outcomes.
Barriers and enablers of dementia training in healthcare workers in rural and remote Australia: A scoping review to inform future approaches to training
Authors: Thompson Sandra , Shukralla Heidi , Fyfe Katrina , Newman Ellie , Fitzgerald Kathryn 
Published: February 2024

AbstractIntroductionDementia is now responsible for the greatest burden of disease of any chronic illness in older Australians. Rural and remote communities bear the impacts of this disproportionately. Additional training and education for healthcare staff to support people living with dementia is needed.ObjectiveThe objective of this scoping review was to map and synthesise the evidence related to barriers and enablers of accessing dementia training for Australian healthcare workers located in rural and remote areas.DesignThis scoping review systematically searched multiple databases in January 2023 for peer‐reviewed literature on the topic. Reviewers used Covidence to screen titles and abstracts of located sources, and to screen full‐text articles.FindingsFrom 187 articles screened, seven peer‐reviewed journal articles were included in the final data analysis; all were from Australia or Canada. The most common barrier described was low staffing, precluding release of staff for dementia training. Enablers to participation in dementia training were availability of online training programs, as well as training providers collaborating with end users to ensure the training met their learning needs.DiscussionThis review provides evidence of barriers and enablers specific to rural and remote healthcare workers accessing dementia training. It also explores other approaches to training that have been trialled successfully in different settings.ConclusionAddressing the identified barriers and enablers may assist in developing training approaches appropriate for existing staff, and in meeting training needs for the future workforce.
The safety of sodium glucose transporter 2 inhibitors and trends in clinical and hemodynamic parameters in patients with left ventricular assist devices
Authors: Fardman Alexander , Kodesh Afek , Siegel Allison Joyce , Segev Amitai , Regev Ehud , Maor Elad , Berkovitch Anat , Kuperstein Rafael , Morgan Avi , Nahum Eyal , Peled Yael , Grupper Avishay 
Published: February 2024

AbstractBackgroundThe safety and impact of sodium glucose transporter 2 inhibitors (SGLT2‐I) in patients with left ventricular assist devices (LVAD) are unknown.MethodsA retrospective analysis of all consecutive patients who underwent LVAD Heart Mate 3 (HM3) implantation at a single medical center and received SGLT2‐I therapy following surgery was conducted. LVAD parameters, medical therapy, laboratory tests, echocardiography, and right heart catheterization (RHC) study results were recorded and compared before and after initiation of SGLT2‐I.ResultsSGLT2‐I medications were initiated in 29 (21%) of 138 patients following HM3 implantation (23 (79%) received Empagliflozin and 6 (21%) Dapagliflozin). The mean age at the time of LVAD implantation was 62 ± 6.7 years, 25 (86%) were male, and 23 (79%) had diabetes mellitus. The median time from HM3 implantation to SGLT2‐I initiation was 108 days, IQR (26–477). Following SGLT2‐I therapy, the daily dose of furosemide decreased from 47 to 23.5 mg/day (mean difference = 23.5 mg/d, 95% CI 8.2–38.7, p = 0.004) and significant weight reduction was observed (mean difference 2.5 kg, 95% CI 0.7–4.3, p = 0.008). Moreover, a significant 5.6 mm Hg reduction in systolic pulmonary artery pressure (sPAP) was measured during RHC (95% CI 0.23–11, p = 0.042) in a subgroup of 11 (38%) patients. LVAD parameters were similar before and after SGLT2‐I initiation (p > 0.2 for all). No adverse events were recorded during median follow‐up of 354 days, IQR (206–786).ConclusionSGLT2‐I treatment is safe in LVAD patients and might contribute to reduction in patients sPAP.
Mitochondrial fumarate promotes ischemia/reperfusion‐induced tubular injury
Authors: Li Zuo‐Lin , Huang Ming‐Min , Yu Meng‐Yao , Nie Di‐Fei , Fu Sha‐Li , Di Jing‐Jing , Lan Ting , Liu Bi‐Cheng , Wu Qiu‐Li 
Published: February 2024

AbstractAimMitochondrial dysfunction, a characteristic pathological feature of renal Ischemic/reperfusion injury (I/RI), predisposes tubular epithelial cells to maintain an inflammatory microenvironment, however, the exact mechanisms through which mitochondrial dysfunction modulates the induction of tubular injury remains incompletely understood.MethodsESI‐QTRAP‐MS/MS approach was used to characterize the targeted metabolic profiling of kidney with I/RI. Tubule injury, mitochondrial dysfunction, and fumarate level were evaluated using qPCR, transmission electron microscopy, ELISA, and immunohistochemistry.ResultsWe demonstrated that tubule injury occurred at the phase of reperfusion in murine model of I/RI. Meanwhile, enhanced glycolysis and mitochondrial dysfunction were found to be associated with tubule injury. Further, we found that tubular fumarate, which resulted from fumarate hydratase deficiency and released from dysfunctional mitochondria, promoted tubular injury. Mechanistically, fumarate induced tubular injury by causing disturbance of glutathione (GSH) hemostasis. Suppression of GSH with buthionine sulphoximine administration could deteriorate the fumarate inhibition‐mediated tubule injury recovery. Reactive oxygen species/NF‐κB signaling activation played a vital role in fumarate‐mediated tubule injury.ConclusionOur studies demonstrated that the mitochondrial‐derived fumarate promotes tubular epithelial cell injury in renal I/RI. Blockade of fumarate‐mediated ROS/NF‐κB signaling activation may serve as a novel therapeutic approach to ameliorate hypoxic tubule injury.
Four weeks SGLT2 inhibition improves beta cell function and glucose tolerance without affecting muscle free fatty acid or glucose uptake in subjects with type 2 diabetes
Authors: Voigt Jens Hohwü , Lauritsen Katrine M. , Pedersen Steen Bønløkke , Hansen Troels K. , Møller Niels , Jessen Niels , Laurenti Marcello C. , Dalla Man Chiara , Vella Adrian , Gormsen Lars C. , Søndergaard Esben 
Published: February 2024

AbstractAimsSodium glucose co‐transporter‐2 (SGLT2) inhibition lowers glucose levels independently of insulin, leading to reduced insulin secretion and increased lipolysis, resulting in elevated circulating free fatty acids (FFAs). While SGLT2 inhibition improves tissue insulin sensitivity, the increase in circulating FFAs could reduce insulin sensitivity in skeletal muscle and the liver. We aimed to investigate the effects of SGLT2 inhibition on substrate utilization in skeletal muscle and the liver and to measure beta‐cell function and glucose tolerance.MethodsThirteen metformin‐treated individuals with type 2 diabetes were randomized to once‐daily empagliflozin 25 mg or placebo for 4 weeks in a crossover design. Skeletal muscle glucose and FFA uptake together with hepatic tissue FFA uptake were measured using [18F]FDG positron emission tomography/computed tomography (PET/CT) and [11C]palmitate PET/CT. Insulin secretion and action were estimated using the oral minimal model.ResultsEmpagliflozin did not affect glucose (0.73 ± 0.30 vs. 1.16 ± 0.64, μmol/g/min p = 0.11) or FFA (0.60 ± 0.30 vs. 0.56 ± 0.3, μmol/g/min p = 0.54) uptake in skeletal muscle. FFA uptake in the liver (21.2 ± 10.1 vs. 19 ± 8.8, μmol/100 ml/min p = 0.32) was unaffected.Empagliflozin increased total beta‐cell responsivity (20 ± 8 vs. 14 ± 9, 10−9 min−1, p < 0.01) and glucose effectiveness (2.6 × 10−2 ± 0.3 × 10−2 vs. 2.4 × 10−2 ± 0.3 × 10−2, dL/kg/min, p = 0.02).ConclusionsDespite improved beta‐cell function and glucose tolerance, empagliflozin does not appear to affect skeletal muscle FFA or glucose uptake.
Characteristics of α1‐adrenoceptor antagonists‐induced ejaculatory dysfunction on spontaneous seminal emission in rats
Authors: Yoshizumi Masaru , Ise Shin‐nosuke , Yonezawa Akihiko , Watanabe Chizuko , Sakurada Shinobu , Mizoguchi Hirokazu 
Published: February 2024

AbstractAlthough α1‐adrenoceptor (α1‐AR) antagonists used to treat benign prostatic hyperplasia can cause ejaculation disorders, the aetiology of this adverse event is still controversial. Therefore, we investigated the effects of antagonists with different affinities for α1‐AR subtypes on ejaculatory function and their mechanisms of action in normal rats. In the spontaneous seminal emission (SSE) test, systemically administered prazosin, terazosin, tamsulosin and naftopidil decreased the weight of ejaculated seminal material in a dose‐dependent manner; the potency order was as follows: tamsulosin > terazosin > prazosin > naftopidil. The selective α1D‐AR antagonist BMY7378 had no effect on SSE. Intrathecal tamsulosin and naftopidil did not inhibit SSE. Tamsulosin, the most potent, was ineffective as a single dose and significantly increased seminal vesicle fluid in rats treated for 2 weeks but did not significantly change retrograde ejaculation. These results indicated that the difference in inhibitory potency of the five α1‐AR antagonists against SSE was due to the involvement of α1A‐AR subtypes. Our results further suggested that α1‐AR antagonist‐induced ejaculatory dysfunction at the peripheral level was mainly due to the loss of seminal emission, although some retrograde ejaculation may also be involved.
Investigating the relationship between math literacy and linguistic synchrony in online mathematical discussions through large‐scale data analytics
Authors: Song Yukyeong , Xing Wanli , Li Chenglu , Tian Xiaoyi , Ma Yingbo 
Published: February 2024

AbstractPrevious literature has associated math literacy with linguistic factors such as verbal ability and phonological skills. However, few studies have investigated linguistic synchrony, shown in mathematical discussions. This study modelled math literacy and examined the relationship of math literacy with linguistic synchrony between students and facilitators. We retrieved data from 20,776 online mathematical discussion threads at a secondary school level. First, we assessed students' math literacy based on their discussions and classified them into high‐ and low‐math literacy groups. Then, we conducted Cross‐Recurrence Quantification Analysis (CRQA) to calculate linguistic synchrony within each thread. The result implies that students with high math literacy are more likely to share common words (eg, mathematical terms) with facilitators. At the same time, they would paraphrase the facilitators' words rather than blindly mimic them as the exact sentences or phrases. On the other hand, students with low math literacy tend to use overlapping words with facilitators less frequently and are more likely to repeat the exact same phrases from the facilitators. The findings provide an empirical data analysis and insights into mathematical discussions and linguistic synchrony. In addition, this paper implies the directions to improve online mathematical discussions and foster math literacy.
Practitioner notesWhat is already known about this topic

Mathematical discussions are known to be an effective way to promote math literacy.
Math literacy and linguistic skills have a strong link.
Linguistic synchrony is related to better collaboration and common knowledge building.
What this paper adds

Reveals the relationship between math literacy and linguistic synchrony and deepens the understanding of digital communication in online learning environments.
Provides empirical analysis of natural language data in group discussions using CRQA.
Conceptualizes linguistic synchrony with three sub‐concepts: linguistic concurrence, predictability, and complexity.
Implications for practice and/or policy

Educators and practitioners could utilize the automatic formative assessment of math literacy based on the student's language use in mathematical discussions.
Educational technology researchers and designers could include CRQA indices and recurrence plots in the dashboard design to provide information to support teachers and learners.
Teachers would be able to provide real‐time interventions to promote effective mathematical communication and foster math literacy throughout mathematical discussions.
Lessons from a population‐based bladder cancer registry: exploring why survival is not improving
Authors: Tempo Jake A. , Sii Samuel , Ischia Joseph , Bolton Damien M. , D'Onise Katina , Meng Rosie , Watson David I. , O'Callaghan Michael 
Published: February 2024

ObjectiveTo explore the causes of the decrease in bladder cancer survival that has occurred over the past four decades.MethodsWe extracted data from the South Australian Cancer Registry. Data from the period 1 January 1977 to 31 December 2020 were extracted to explore changes in incidence and survival among a total of 8356 patients diagnosed with ≥pT1 disease. Invasive bladder cancer was defined as ≥pT1 in this study.ResultsInvasive bladder cancer age‐standardized incidence decreased from 7.20 cases per 100 000 people in 1977 to 5.85 cases per 100 000 in 2020. The mean age at diagnosis increased from 68 years to 76 years. The crude incidence for patients aged 80 years and over increased by 3.3% per year (95% confidence interval [CI] 2.1 to 4.6). Overall survival decreased over the study period (hazard ratio [HR] 1.22 [95% CI 1.09 to 1.35]), however, survival increased after adjusting for age at diagnosis (HR 0.80 [95% CI 0.76 to 0.94]). Despite a decrease in non‐bladder cancer‐specific deaths in older people, there was no change in the bladder cancer‐specific death rate in older people (HR 0.94 [95% CI 0.70 to 1.26]). Male sex was associated with higher survival (HR 0.87 [95% CI 0.83 to 0.92]), whereas socioeconomic advantage was not.ConclusionsInvasive bladder cancer survival has decreased over the past 40 years, with the age structure of the population being a significant contributing factor.Patient summaryWe looked at why bladder cancer survival is decreasing using a large cancer registry with information from 1977 to 2020. We found that people are now more likely to be diagnosed at an older age. Older people often live for a shorter time with bladder cancer compared to younger people. Bladder cancer survival has decreased because there are more older people with the disease than previously.
Interlocked: The ethics of care and the ethics of justice in children's discourses on the parent–child relationship in Chile
Authors: del Solar Ana Vergara , Sepúlveda Galeas Mauricio , Leyton Legües Daniela , Cortés‐Morales Susana , González Pilar Anastasía 
Published: February 2024

AbstractThe article begins with a discussion of the contribution of childhood studies to our understanding of children's ethics, taking into account feminist inputs to the debate over the ethics of care and the ethics of justice. Then, based on two qualitative studies carried out in Chile with children between 10 and 13 years of age, the article shows the emphasis the children place on reciprocal care between parents and children. This concern for reciprocity is accompanied by notions of justice and rights in how they evaluate the parent–child relationship. The data reveal the complex ways in which the ethics of care and of justice interlock in the children's discourses. The article concludes by tracing the links between these results and the conditions of productive and reproductive work in contemporary Chile as reflected in the children's discourses, and it shows how children have begun to internalise a focus on children's rights in reflecting on their daily lives.
Multi‐criteria systematic conservation planning for terrestrial vertebrates in a biodiversity hotspot in Mexico
Authors: Monroy‐Gamboa Alina Gabriela , Sánchez‐Cordero Víctor , Sarkar Sahotra 
Published: February 2024

AbstractAnthropogenic loss of biodiversity continues to increase worldwide, and existing conservation area networks (CANs) are inadequate for its adequate representation and persistence. To identify a set of new nominal conservation areas in Oaxaca, a Mesoamerican biodiversity hotspot in Mexico, for terrestrial vertebrate species, we used a multi‐criteria systematic conservation planning approach. Besides minimizing the area incorporated into the nominal CAN, we incorporated 25 socioeconomic variables using multi‐attribute value theory. We constructed a portfolio of nominal CAN solutions for four different scenarios all of which satisfied a 10% representation target for the modeled suitable habitat of each vertebrate species: (1) existing protected area‐based (PA) solution; (2) voluntary conservation area‐based (VCA) solution; (3) PA‐VCA solution; and (4) R‐C solution (rarity‐complementary algorithm). The PA‐VCA and PA solutions were the most expensive in terms of area that had to be included in the nominal CANs (13,352 km2 and 12,587 km2, respectively). In all our multi‐criteria analyses, highest costs were associated with maximizing the number of airports, amount of tourism, and length of available highways in a nominal CAN. We have thus established a portfolio of multi‐criteria solutions to the problem of creating an adequate CAN for the representation of terrestrial vertebrate species.