bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of a chemiluminescence assay for tissue plasminogen activator inhibitor complex and its applicability to gastric cancer
Authors: Ji Yu , Qin Yan , Tan Qi , Qiu Yanru , Han Shuang , Qi Xiaowei 
Published: May 2024

Abstract
Background
Venous thromboembolism (VTE), is a noteworthy complication in individuals with gastric cancer, but the current diagnosis and treatment methods lack accuracy. In this study, we developed a t-PAIC chemiluminescence kit and employed chemiluminescence to detect the tissue plasminogen activator inhibitor complex (t-PAIC), thrombin-antithrombin III complex (TAT), plasmin-α2-plasmin inhibitor complex (PIC) and thrombomodulin (TM), combined with D-dimer and fibrin degradation products (FDP), to investigate their diagnostic potential for venous thrombosis in gastric cancer patients. The study assessed variations in six indicators among gastric cancer patients at different stages.

Results
The t-PAIC reagent showed LOD is 1.2 ng/mL and a linear factor R greater than 0.99. The reagents demonstrated accurate results, with all accuracy deviations being within 5%. The intra-batch and inter-batch CVs for the t-PAIC reagent were both within 8%. The correlation coefficient R between this method and Sysmex was 0.979. Gastric cancer patients exhibited elevated levels of TAT, PIC, TM, D-D, FDP compared to the healthy population, while no significant difference was observed in t-PAIC. In the staging of gastric cancer, patients in III-IV stages exhibit higher levels of the six markers compared to those in I-II stages. The ROC curve indicates an enhancement in sensitivity and specificity of the combined diagnosis of four or six indicators.

Conclusion
Our chemiluminescence assay performs comparably to Sysmex’s method and at a reduced cost. The use of multiple markers, including t-PAIC, TM, TAT, PIC, D-D, and FDP, is superior to the use of single markers for diagnosing VTE in patients with malignant tumors. Gastric cancer patients should be screened for the six markers to facilitate proactive prophylaxis, determine the most appropriate treatment timing, ameliorate their prognosis, decrease the occurrence of venous thrombosis and mortality, and extend their survival.
Implementing a challenge-based learning experience in a bioinstrumentation blended course
Authors: Santos-Díaz Alejandro , Montesinos Luis , Barrera-Esparza María , del Mar Perez-Desentis Maria , Salinas-Navarro David E. 
Published: May 2024

Abstract
Background
Bioinstrumentation is essential to biomedical engineering (BME) undergraduate education and professional practice. Several strategies have been suggested to provide BME students with hands-on experiences throughout the curriculum, promoting their preparedness to pursue careers in industry and academia while increasing their learning and engagement. This paper describes the implementation of challenge-based learning (CBL) in an undergraduate bioinstrumentation blended course over the COVID-19 pandemic.

Methods
The CBL experience was implemented in a third-year bioinstrumentation course from the BME program at Tecnologico de Monterrey. Thirty-nine students enrolled in two sections formed fourteen teams that tackled blended learning activities, including online communication, lab experiments, and in-person CBL activities. Regarding the latter, students were challenged to design, prototype, and test a respiratory or cardiac gating device for radiotherapy. An institutional student opinion survey was used to assess the success of our CBL implementation.

Results
Student responses to the end-of-term survey showed that they strongly agreed that this course challenged them to learn new concepts and develop new skills. Furthermore, they rated the student-lecturer interaction very positively despite the blended format. Overall, students assessed their learning experience positively. However, implementing this CBL experience required a substantial time increase in planning, student tutoring, and constant communication between lecturers and the industry partner.

Conclusion
This work provides an effective instance of CBL for BME education to improve students’ learning experience despite decreased resource efficiency. Our claim is supported by the student’s performance and the positive feedback from our industrial partner.
Measurement and analysis of change in research scholars’ knowledge and attitudes toward statistics after PhD coursework
Authors: Philip Mariyamma 
Published: May 2024

Abstract
Background
Knowledge of statistics is highly important for research scholars, as they are expected to submit a thesis based on original research as part of a PhD program. As statistics play a major role in the analysis and interpretation of scientific data, intensive training at the beginning of a PhD programme is essential. PhD coursework is mandatory in universities and higher education institutes in India. This study aimed to compare the scores of knowledge in statistics and attitudes towards statistics among the research scholars of an institute of medical higher education in South India at different time points of their PhD (i.e., before, soon after and 2–3 years after the coursework) to determine whether intensive training programs such as PhD coursework can change their knowledge or attitudes toward statistics.

Methods
One hundred and thirty research scholars who had completed PhD coursework in the last three years were invited by e-mail to be part of the study. Knowledge and attitudes toward statistics before and soon after the coursework were already assessed as part of the coursework module. Knowledge and attitudes towards statistics 2–3 years after the coursework were assessed using Google forms. Participation was voluntary, and informed consent was also sought.

Results
Knowledge and attitude scores improved significantly subsequent to the coursework (i.e., soon after, percentage of change: 77%, 43% respectively). However, there was significant reduction in knowledge and attitude scores 2–3 years after coursework compared to the scores soon after coursework; knowledge and attitude scores have decreased by 10%, 37% respectively.

Conclusion
The study concluded that the coursework program was beneficial for improving research scholars’ knowledge and attitudes toward statistics. A refresher program 2–3 years after the coursework would greatly benefit the research scholars. Statistics educators must be empathetic to understanding scholars’ anxiety and attitudes toward statistics and its influence on learning outcomes.
Translation and psychometric testing of the Persian Version of nurses’ ethical decision-making in End-of-Life Care Scale
Authors: Pourshahri Erfan , Mohammadi Fateme , Shareinia Habib , Abadi Fozieh , Bijani Mostafa 
Published: May 2024

Abstract
Background
Ethical decision-making in end-of-life care is one of the most challenging aspects of healthcare: providing ethical care to the society is one of the most important responsibilities of healthcare professionals. In order to assess nurses’ ethical decision-making in end-of-life care, researchers need a specialized and comprehensive instrument which is sufficiently valid and reliable. The present study was conducted to translate and test the psychometric properties of the Persian version of Nurses’ Ethical Decision-Making in End-of-Life Care Scale (NEDM-EOLCS).

Methods
This is a cross-sectional, multi-centric study with a methodological design The participants were selected via convenience sampling from five hospitals located in Iran. In total, 1320 nurses (660 for exploratory factor analysis and 660 for confirmatory factor analysis) participated in the study. The original NEDM-EOLCS was translated into Persian and subsequently the psychometric properties of the scale were assessed according to COSMIN criteria.

Results
Exploratory factor analysis (EFA) showed the factor loading of the 55 items to be between 0.62 and 0.88, all of which were significant. Also, exploratory factor analysis showed that 3 factors (perceived professional accountability, moral reasoning/moral agency and moral practice) explained 74.51% of the variance. Confirmatory factor analysis (CFA) results verified the good fit of the data (a chi-square of 21.74, df = 7, P = 0.001) RMSEA = 0.01, CFI = 0.96, NFI = 0.95, and TLI = 0.97). The reliability of the scale was measured in terms of its internal consistency and the Cronbach’s alpha of the whole instrument was found to be 0.98.

Conclusion
The Persian version of NEDM-EOLCS for nurses is sufficiently valid and reliable. Thus, this instrument can be used to measure nurses’ ethical decision-making in end-of-life care and identify the most effective strategies, e.g. educational interventions, to improve ethical decision-making skills in end-of-life care in these healthcare professionals as necessary.
The Healthy Start scheme in England “is a lifeline for families but many are missing out”: a rapid qualitative analysis
Authors: Barrett Millie , Spires Mark , Vogel Christina 
Published: May 2024

Abstract
Background
Healthy Start (HS) is a government scheme in England, Wales and Northern Ireland that offers a financial payment card and free vitamins to families experiencing low income. Pregnant women and families with children < 4 years can use the HS card to buy fruit, vegetables, cow’s milk, infant formula and pulses. HS was fully digitalised in March 2022. While digitalisation has improved the user experience for many families, in the context of the cost-of-living crisis and increasing dietary inequalities, it is important to understand why HS is not reaching more families. This study aimed to (i) assess the perceptions and experiences of HS from stakeholders across the system including those who promote, implement and are eligible for HS, and (ii) identify recommendations to improve the scheme’s effectiveness and uptake.

Methods
The study design was a post-implementation rapid qualitative evaluation using stakeholder interviews. Data were collected between January and June 2023 via semi‐structured interviews (50% online; 50% in person) with 112 stakeholders, including parents (n = 59), non‐government organisations (n = 13), retailers (n = 11) and health and community professionals (n = 29) at national and local levels. Findings were confirmed by a sub-sample of participants.

Results
Six core themes cut across stakeholders’ perceptions and experiences, and stakeholders collectively outlined seven recommendations they felt could be acted upon to maximise uptake and efficiency of HS, with actions at both national and local levels. A novel finding from this study is that raising awareness about HS alone is unlikely to result automatically or universally in higher uptake rate. Recommendations include: continuing to provide this scheme that is universally valued; the need for many families to be provided with a helping hand to successfully complete the application; reframing of the scheme as a child’s right to food and development to ensure inclusivity; improved leadership, coordination and accountability at both national and local levels.

Conclusions
HS provides benefits for child development and family wellbeing. The study’s recommendations should be actioned by national and local governments to enable all families eligible for the scheme to benefit from this nutritional safety net.
Interleukin-21 receptor signaling promotes metabolic dysfunction-associated steatohepatitis-driven hepatocellular carcinoma by inducing immunosuppressive IgA+ B cells
Authors: Xie Ying , Huang Yu , Li Zhi-Yong , Jiang Weihua , Shi Nan-Xi , Lu Yuanzhi , Cao Guangchao , Yin Zhinan , Lin Xue-Jia 
Published: May 2024

Abstract
Background
Dysregulation of immune surveillance is tightly linked to the development of metabolic dysfunction-associated steatohepatitis (MASH)-driven hepatocellular carcinoma (HCC); however, its underlying mechanisms remain unclear. Herein, we aimed to determine the role of interleukin-21 receptor (IL-21R) in MASH-driven HCC.

Methods
The clinical significance of IL-21R was assessed in human HCC specimens using immunohistochemistry staining. Furthermore, the expression of IL-21R in mice was assessed in the STAM model. Thereafter, two different MASH-driven HCC mouse models were applied between IL-21R-deficient mice and wild type controls to explore the role of IL-21R in MASH-driven HCC. To further elucidate the potential mechanisms by which IL-21R affected MASH-driven HCC, whole transcriptome sequencing, flow cytometry and adoptive lymphocyte transfer were performed. Finally, flow cytometry, enzyme-linked immunosorbent assay, immunofluorescent staining, chromatin immunoprecipitation assay and western blotting were conducted to explore the mechanism by which IL-21R induced IgA+ B cells.

Results
HCC patients with high IL-21R expression exhibited poor relapse-free survival, advanced TNM stage and severe steatosis. Additionally, IL-21R was demonstrated to be upregulated in mouse liver tumors. Particularly, ablation of IL-21R impeded MASH-driven hepatocarcinogenesis with dramatically reduction of lipid accumulation. Moreover, cytotoxic CD8+ T lymphocyte activation was enhanced in the absence of IL-21R due to the reduction of immunosuppressive IgA+ B cells. Mechanistically, the IL-21R-STAT1-c-Jun/c-Fos regulatory axis was activated in MASH-driven HCC and thus promoted the transcription of Igha, resulting in the induction of IgA+ B cells.

Conclusions
IL-21R plays a cancer-promoting role by inducing IgA+ B cells in MASH-driven hepatocarcinogenesis. Targeting IL-21R signaling represents a potential therapeutic strategy for cancer therapy.
ESM1 enhances fatty acid synthesis and vascular mimicry in ovarian cancer by utilizing the PKM2-dependent warburg effect within the hypoxic tumor microenvironment
Authors: Zhang Juan , Ouyang Fan , Gao Anbo , Zeng Tian , Li Ming , Li Hui , Zhou Wenchao , Gao Qing , Tang Xing , Zhang Qunfeng , Ran Xiaomin , Tian Gang , Quan Xiyun , Tang Zhenzi , Zou Juan , Zeng Yifei , Long Yunzhu , Li Yukun 
Published: May 2024

Abstract
Background
The hypoxic tumor microenvironment is a key factor that promotes metabolic reprogramming and vascular mimicry (VM) in ovarian cancer (OC) patients. ESM1, a secreted protein, plays an important role in promoting proliferation and angiogenesis in OC. However, the role of ESM1 in metabolic reprogramming and VM in the hypoxic microenvironment in OC patients has not been determined.

Methods
Liquid chromatography coupled with tandem MS was used to analyze CAOV3 and OV90 cells. Interactions between ESM1, PKM2, UBA2, and SUMO1 were detected by GST pull-down, Co-IP, and molecular docking. The effects of the ESM1-PKM2 axis on cell glucose metabolism were analyzed based on an ECAR experiment. The biological effects of the signaling axis on OC cells were detected by tubule formation, transwell assay, RT‒PCR, Western blot, immunofluorescence, and in vivo xenograft tumor experiments.

Results
Our findings demonstrated that hypoxia induces the upregulation of ESM1 expression through the transcription of HIF-1α. ESM1 serves as a crucial mediator of the interaction between PKM2 and UBA2, facilitating the SUMOylation of PKM2 and the subsequent formation of PKM2 dimers. This process promotes the Warburg effect and facilitates the nuclear translocation of PKM2, ultimately leading to the phosphorylation of STAT3. These molecular events contribute to the promotion of ovarian cancer glycolysis and vasculogenic mimicry. Furthermore, our study revealed that Shikonin effectively inhibits the molecular interaction between ESM1 and PKM2, consequently preventing the formation of PKM2 dimers and thereby inhibiting ovarian cancer glycolysis, fatty acid synthesis and vasculogenic mimicry.

Conclusion
Our findings demonstrated that hypoxia increases ESM1 expression through the transcriptional regulation of HIF-1α to induce dimerization via PKM2 SUMOylation, which promotes the OC Warburg effect and VM.
Iron (II)-based metal-organic framework nanozyme for boosting tumor ferroptosis through inhibiting DNA damage repair and system Xc-
Authors: Xue Panpan , Zhuang Huilan , Bai Tingjie , Zeng Xuemei , Deng Jinpeng , Shao Sijie , Yan Shuangqian 
Published: May 2024

AbstractDevelopment of ferroptosis-inducible nanoplatforms with high efficiency and specificity is highly needed and challenging in tumor ferrotherapy. Here, we demonstrate highly effective tumor ferrotherapy using iron (II)-based metal-organic framework (FessMOF) nanoparticles, assembled from disulfide bonds and ferrous ions. The as-prepared FessMOF nanoparticles exhibit peroxidase-like activity and pH/glutathione-dependent degradability, which enables tumor-responsive catalytic therapy and glutathione depletion by the thiol/disulfide exchange to suppress glutathione peroxidase 4, respectively. Upon PEGylation and Actinomycin D (ActD) loading, the resulting FessMOF/ActD-PEG nanoplatform induces marked DNA damage and lipid peroxidation. Concurrently, we found that ActD can inhibit Xc− system and elicit ferritinophagy, which further boosts the ferrotherapeutic efficacy of the FessMOF/ActD-PEG. In vivo experiments demonstrate that our fabricated nanoplatform presents excellent biocompatibility and a high tumor inhibition rate of 91.89%.
Uncovering physical activity trade-offs in transportation policy: A spatial agent-based model of Bogotá, Colombia
Authors: Stankov Ivana , Meisel Jose D. , Sarmiento Olga Lucia , Delclòs-Alió Xavier , Hidalgo Dario , Guzman Luis A. , Rodriguez Daniel A. , Hammond Ross A. , Diez Roux Ana V. 
Published: May 2024

Abstract
Background
Transportation policies can impact health outcomes while simultaneously promoting social equity and environmental sustainability. We developed an agent-based model (ABM) to simulate the impacts of fare subsidies and congestion taxes on commuter decision-making and travel patterns. We report effects on mode share, travel time and transport-related physical activity (PA), including the variability of effects by socioeconomic strata (SES), and the trade-offs that may need to be considered in the implementation of these policies in a context with high levels of necessity-based physical activity.

Methods
The ABM design was informed by local stakeholder engagement. The demographic and spatial characteristics of the in-silico city, and its residents, were informed by local surveys and empirical studies. We used ridership and travel time data from the 2019 Bogotá Household Travel Survey to calibrate and validate the model by SES. We then explored the impacts of fare subsidy and congestion tax policy scenarios.

Results
Our model reproduced commuting patterns observed in Bogotá, including substantial necessity-based walking for transportation. At the city-level, congestion taxes fractionally reduced car use, including among mid-to-high SES groups but not among low SES commuters. Neither travel times nor physical activity levels were impacted at the city level or by SES. Comparatively, fare subsidies promoted city-level public transportation (PT) ridership, particularly under a ‘free-fare’ scenario, largely through reductions in walking trips. ‘Free fare’ policies also led to a large reduction in very long walking times and an overall reduction in the commuting-based attainment of physical activity guidelines. Differential effects were observed by SES, with free fares promoting PT ridership primarily among low-and-middle SES groups. These shifts to PT reduced median walking times among all SES groups, particularly low-SES groups. Moreover, the proportion of low-to-mid SES commuters meeting weekly physical activity recommendations decreased under the 'freefare' policy, with no change observed among high-SES groups.

Conclusions
Transport policies can differentially impact SES-level disparities in necessity-based walking and travel times. Understanding these impacts is critical in shaping transportation policies that balance the dual aims of reducing SES-level disparities in travel time (and time poverty) and the promotion of choice-based physical activity.
Role of gut microbiota in doxorubicin-induced cardiotoxicity: from pathogenesis to related interventions
Authors: Huang Chao , Li Xiaoxia , Li Hanqing , Chen Ruolan , Li Zhaoqing , Li Daisong , Xu Xiaojian , Zhang Guoliang , Qin Luning , Li Bing , Chu Xian-Ming 
Published: May 2024

AbstractDoxorubicin (DOX) is a broad-spectrum and highly efficient anticancer agent, but its clinical implication is limited by lethal cardiotoxicity. Growing evidences have shown that alterations in intestinal microbial composition and function, namely dysbiosis, are closely linked to the progression of DOX-induced cardiotoxicity (DIC) through regulating the gut-microbiota-heart (GMH) axis. The role of gut microbiota and its metabolites in DIC, however, is largely unelucidated. Our review will focus on the potential mechanism between gut microbiota dysbiosis and DIC, so as to provide novel insights into the pathophysiology of DIC. Furthermore, we summarize the underlying interventions of microbial-targeted therapeutics in DIC, encompassing dietary interventions, fecal microbiota transplantation (FMT), probiotics, antibiotics, and natural phytochemicals. Given the emergence of microbial investigation in DIC, finally we aim to point out a novel direction for future research and clinical intervention of DIC, which may be helpful for the DIC patients.
Rare Middle Triassic coleoids from the Alpine-Carpathian system: new records from Slovakia and their significance
Authors: Košťák Martin , Schlögl Ján , Fuchs Dirk , Havrila Milan , Kolar-Jurkovšek Tea , Vörös Attila , Havelcová Martina , Šurka Juraj , Havrila Jakub , Holcová Katarína 
Published: May 2024

AbstractTwo stratigraphically well constrained (by ammonites and conodonts) coleoid remains have been recorded from the Triassic (Anisian) dark-grey organodetritic limestones (Ráztoka Limestone) of Western Carpathians (Hronic Nappe). The limestones deposited at the periphery of a former carbonate platform. It yields a highly diverse cephalopod fauna including nautiloids (2 taxa), ammonoids (7 taxa) and indetermined aulacoceratids. Two unusual coleoid specimens are referred to genus Mojsisovicsteuthis (M. boeckhi) and probably to a new taxon (described as Breviconoteuthis aff. breviconus herein) possessing similar morphological features of genus Breviconoteuthis (Phragmoteuthida) and/or Zugmontites. Based on index ammonites and conodonts, both records are of the uppermost Trinodosus through the lowermost Reitzi zones (Anisian—lower Illyrian). While the genus Mojsisovicsteuthis has been widely dispersed (however its records are rare), the occurrence of Breviconoteuthis and Zugmontites is strictly limited to the Alpine-Carpathian region. Comparing with the holotype and additional specimens stored in the Hungarian Natural History Museum, the overal shell of Mojsisovicsteuthis and its size has been reconstructed. Its relationship to aulacoceratids and phragmoteuthids is briefly discussed. Geochemical record (n-alkanes from the bulk rock) provided a relevant signal of the existence of algal meadows.