bluuebunny/crossref_metadata_2025 huggingface dataset:
Genetically predicted gut microbiota mediate the association between plasma lipidomics and primary sclerosing cholangitis
Authors: Zhou Jie , Zhu Dagang , Xu Yixin , Chen Chao , Wang Kun
Published: May 2024

Background

Primary sclerosing cholangitis (PSC) is a complex disease with pathogenic mechanisms that remain to be elucidated. Previous observational studies with small sample sizes have reported associations between PSC, dyslipidemia, and gut microbiota dysbiosis. However, the causality of these associations is uncertain, and there has been no systematic analysis to date.

Methods

The datasets comprise data on PSC, 179 lipid species, and 412 gut microbiota species. PSC data (n = 14,890) were sourced from the International PSC Study Group, while the dataset pertaining to plasma lipidomics originated from a study involving 7174 Finnish individuals. Data on gut microbiota species were derived from the Dutch Microbiome Project study, which conducted a genome-wide association study involving 7738 participants. Furthermore, we employed a two-step Mendelian randomization (MR) analysis to quantify the proportion of the effect of gut microbiota-mediated lipidomics on PSC.

Results

Following a rigorous screening process, our MR analysis revealed a causal relationship between higher levels of gene-predicted Phosphatidylcholine (O-16:1_18:1) (PC O-16:1_18:1) and an increased risk of developing PSC (inverse variance-weighted method, odds ratio (OR) 1.30, 95% confidence interval (CI) 1.03–1.63). There is insufficient evidence to suggest that gene-predicted PSC impacts the levels of PC O-16:1_18:1 (OR 1.01, 95% CI 0.98–1.05). When incorporating gut microbiota data into the analysis, we found that Eubacterium rectale-mediated genetic prediction explains 17.59% of the variance in PC O-16:1_18:1 levels.

Conclusion

Our study revealed a causal association between PC O-16:1_18:1 levels and PSC, with a minor portion of the effect mediated by Eubacterium rectale. This study aims to further explore the pathogenesis of PSC and identify promising therapeutic targets. For patients with PSC who lack effective treatment options, the results are encouraging.
Specific plasma microRNA profiles could be potential non-invasive biomarkers for biochemical pregnancy loss following embryo transfer
Authors: Shen Lang , Zeng Hong , Fu Yu , Ma Wenmin , Guo Xiaoling , Luo Guoqun , Hua Rui , Wang Xiaocong , Shi Xiao , Wu Biao , Luo Chen , Quan Song
Published: May 2024

Background

Plasma microRNAs act as biomarkers for predicting and diagnosing diseases. Reliable non-invasive biomarkers for biochemical pregnancy loss have not been established. We aim to analyze the dynamic microRNA profiles during the peri-implantation period and investigate if plasma microRNAs could be non-invasive biomarkers predicting BPL.

Methods

In this study, we collected plasma samples from patients undergoing embryo transfer (ET) on ET day (ET0), 11 days after ET (ET11), and 14 days after ET (ET14). Patients were divided into the NP (negative pregnancy), BPL (biochemical pregnancy loss), and CP (clinical pregnancy) groups according to serum hCG levels at day11~14 and ultrasound at day28~35 following ET. MicroRNA profiles at different time-points were detected by miRNA-sequencing. We analyzed plasma microRNA signatures for BPL at the peri-implantation stage, we characterized the dynamic microRNA changes during the implantation period, constructed a microRNA co-expression network, and established predictive models for BPL. Finally, the sequencing results were confirmed by Taqman RT-qPCR.

Results

BPL patients have distinct plasma microRNA profiles compared to CP patients at multiple time-points during the peri-implantation period. Machine learning models revealed that plasma microRNAs could predict BPL. RT-qPCR confirmed that miR-181a-2-3p, miR-9-5p, miR-150-3p, miR-150-5p, and miR-98-5p, miR-363-3p were significantly differentially expressed between patients with different reproductive outcomes.

Conclusion

Our study highlights the non-invasive value of plasma microRNAs in predicting BPL.
Navigating geographical disparities: access to obstetric hospitals in maternity care deserts and across the United States
Authors: Fontenot Jazmin , Brigance Christina , Lucas Ripley , Stoneburner Ashley
Published: May 2024

Background

Access to maternity care in the U.S. remains inequitable, impacting over two million women in maternity care “deserts." Living in these areas, exacerbated by hospital closures and workforce shortages, heightens the risks of pregnancy-related complications, particularly in rural regions. This study investigates travel distances and time to obstetric hospitals, emphasizing disparities faced by those in maternity care deserts and rural areas, while also exploring variances across races and ethnicities.

Methods

The research adopted a retrospective secondary data analysis, utilizing the American Hospital Association and Centers for Medicaid and Medicare Provider of Services Files to classify obstetric hospitals. The study population included census tract estimates of birthing individuals sourced from the U.S. Census Bureau's 2017-2021 American Community Survey. Using ArcGIS Pro Network Analyst, drive time and distance calculations to the nearest obstetric hospital were conducted. Furthermore, Hot Spot Analysis was employed to identify areas displaying significant spatial clusters of high and low travel distances.

Results

The mean travel distance and time to the nearest obstetric facility was 8.3 miles and 14.1 minutes. The mean travel distance for maternity care deserts and rural counties was 28.1 and 17.3 miles, respectively. While birthing people living in rural maternity care deserts had the highest average travel distance overall (33.4 miles), those living in urban maternity care deserts also experienced inequities in travel distance (25.0 miles). States with hotspots indicating significantly higher travel distances included: Montana, North Dakota, South Dakota, and Nebraska. Census tracts where the predominant race is American Indian/Alaska Native (AIAN) had the highest travel distance and time compared to those of all other predominant races/ethnicities.

Conclusions

Our study revealed significant disparities in obstetric hospital access, especially affecting birthing individuals in maternity care deserts, rural counties, and communities predominantly composed of AIAN individuals, resulting in extended travel distances and times. To rectify these inequities, sustained investment in the obstetric workforce and implementation of innovative programs are imperative, specifically targeting improved access in maternity care deserts as a priority area within healthcare policy and practice.
Factors influencing presentation delay among cancer patients: a cross-sectional study in Malaysia
Authors: Gyeltshen Tshewang , Teh Hoon Shien , Loo Ching Ee , Hing Nicholas Yee Liang , Lim Wei Yin , Subramaniam Shridevi , Wong Wen Jun , Wong Zoie Shui-Yee , Hwong Wen Yea
Published: May 2024

Background

Cancer represents a significant global public health challenge, with escalating incidence rates straining healthcare systems. Malaysia, like many nations, has witnessed a rise in cancer cases, particularly among the younger population. This study aligns with Malaysia’s National Strategic Plan for Cancer Control Programme 2021–2025, emphasizing primary prevention and early detection to address cancer’s impact. Therefore, we aim to describe the timeliness of cancer care for symptom presentation, socio-demographic, patient, as well as organizational-related factors among patients in Malaysia diagnosed with breast, colorectal, nasopharyngeal, and cervical cancer.

Methods

This cross-sectional study enrolled adult cancer patients diagnosed with breast, cervical, colorectal, or nasopharyngeal cancer from 2015 to 2020 in seven public hospitals/oncology centres across Malaysia. Data were collected through patient-administered surveys and medical records. Presentation delay, defined as the duration between symptom onset and the patient's first visit to a healthcare professional exceeding 30 days, was the primary outcome. Statistical analysis included descriptive statistics and chi-square tests.

Results

The study included 476 cancer patients, with breast cancer (41.6%), colorectal cancer (26.9%), nasopharyngeal cancer (22.1%), and cervical cancer (9.5%). Over half (54.2%) experienced presentation delays with a median interval of 60 days. Higher proportions of presentation delay were observed among nasopharyngeal cancer patients, employed patients with lower socioeconomic statuses, and those without family history of cancer. Most patients self-discovered their first cancer symptoms (80%), while only one-third took immediate action for medical check-ups. Emotional and organizational factors, such as long waiting times during doctor's visits (47%), were potential barriers to seeking cancer care.

Conclusion

This study highlights the significant problem of presentation delay among cancer patients in Malaysia. The delay is influenced by various factors encompassing sociodemographic characteristics, health-seeking behaviours, and healthcare system-related issues. A comprehensive approach addressing both individual barriers and institutional obstacles is imperative to mitigate this presentation delay and improve cancer outcomes.
Long-term exposure to PM2.5 and mortality in a national cohort in South Korea: effect modification by community deprivation, medical infrastructure, and greenness
Authors: Byun Garam , Kim Sera , Choi Yongsoo , Kim Ayoung , Team AiMS-CREATE , Lee Jong-Tae , Bell Michelle L.
Published: May 2024

Background

Long-term exposure to PM2.5 has been linked to increased mortality risk. However, limited studies have examined the potential modifying effect of community-level characteristics on this association, particularly in Asian contexts. This study aimed to estimate the effects of long-term exposure to PM2.5 on mortality in South Korea and to examine whether community-level deprivation, medical infrastructure, and greenness modify these associations.

Methods

We conducted a nationwide cohort study using the National Health Insurance Service-National Sample Cohort. A total of 394,701 participants aged 30 years or older in 2006 were followed until 2019. Based on modelled PM2.5 concentrations, 1 to 3-year and 5-year moving averages of PM2.5 concentrations were assigned to each participant at the district level. Time-varying Cox proportional-hazards models were used to estimate the association between PM2.5 and non-accidental, circulatory, and respiratory mortality. We further conducted stratified analysis by community-level deprivation index, medical index, and normalized difference vegetation index to represent greenness.

Results

PM2.5 exposure, based on 5-year moving averages, was positively associated with non-accidental (Hazard ratio, HR: 1.10, 95% Confidence Interval, CI: 1.01, 1.20, per 10 µg/m3 increase) and circulatory mortality (HR: 1.22, 95% CI: 1.01, 1.47). The 1-year moving average of PM2.5 was associated with respiratory mortality (HR: 1.33, 95% CI: 1.05, 1.67). We observed higher associations between PM2.5 and mortality in communities with higher deprivation and limited medical infrastructure. Communities with higher greenness showed lower risk for circulatory mortality but higher risk for respiratory mortality in association with PM2.5.

Conclusions

Our study found mortality effects of long-term PM2.5 exposure and underlined the role of community-level factors in modifying these association. These findings highlight the importance of considering socio-environmental contexts in the design of air quality policies to reduce health disparities and enhance overall public health outcomes.
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

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

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

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

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

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

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

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

Development 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

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

Doxorubicin (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

Two 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.
Predicting healthcare expenditure based on Adjusted Morbidity Groups to implement a needs-based capitation financing system
Authors: Martínez-Pérez Jorge-Eduardo , Quesada-Torres Juan-Antonio , Martínez-Gabaldón Eduardo
Published: May 2024

Background

Due to population aging, healthcare expenditure is projected to increase substantially in developed countries like Spain. However, prior research indicates that health status, not merely age, is a key driver of healthcare costs. This study analyzed data from over 1.25 million residents of Spain's Murcia region to develop a capitation-based healthcare financing model incorporating health status via Adjusted Morbidity Groups (AMGs). The goal was to simulate an equitable area-based healthcare budget allocation reflecting population needs.

Methods

Using 2017 data on residents' age, sex, AMG designation, and individual healthcare costs, generalized linear models were built to predict healthcare expenditure based on health status indicators. Multiple link functions and distribution families were tested, with model selection guided by information criteria, residual analysis, and goodness-of-fit statistics. The selected model was used to estimate adjusted populations and simulate capitated budgets for the 9 healthcare districts in Murcia.

Results

The gamma distribution with logarithmic link function provided the best model fit. Comparisons of predicted and actual average costs revealed underfunded and overfunded areas within Murcia. If implemented, the capitation model would decrease funding for most districts (up to 15.5%) while increasing it for two high-need areas, emphasizing allocation based on health status and standardized utilization rather than historical spending alone.

Conclusions

AMG-based capitated budgeting could improve equity in healthcare financing across regions in Spain. By explicitly incorporating multimorbidity burden into allocation formulas, resources can be reallocated towards areas with poorer overall population health. Further policy analysis and adjustment is needed before full-scale implementation of such need-based global budgets.
Geodetic plate coupling and seismic potential on the main Himalayan thrust in Nepal
Authors: Tabei Takao , Ohzono Mako , Silwal Bishow R. , Bhandari Rajendra P. , Adhikari Lok B. , Chand Janak B. , Kandel Thakur P.
Published: May 2024

We model interseismic plate coupling distribution on the Main Himalayan Thrust (MHT) in Nepal through the inversion of secular GNSS velocity data. To complement previously published data, we compile velocity data from ten additional continuous stations to improve spatial resolution in central and mid-western Nepal. A regional non-planar structural model is adopted to reproduce the MHT fault plane. In general, the coupling pattern seems nearly binary, indicating that transition from full coupling to decoupling is occurring sharply in very narrow zones. In eastern Nepal (> 84.5ºE), plate coupling is very strong from the surface to intermediate depths, including the source region of the 2015 Mw 7.8 Gorkha earthquake. Geodetically estimated slip deficit rates are consistent with the rupture history of great earthquakes in the east revealed by geomorphological observations. In the west (< 83.0ºE), a weakly coupled zone extends laterally at intermediate depths, whereas the coupling in the shallower part remains very strong. Although the slip deficit rate in the west is significantly smaller than that in the east, seismic moment accumulated, since the last complete rupture in 1505 may be capable of generating a future great event. In central Nepal, estimated slip deficit rates are comparable with those in the east, and no great event has been documented over the past several centuries. Thus, the seismic risk may be most urgent in central Nepal. The development of local seismicity and crustal deformation should be carefully monitored.

Graphical Abstract
Healthy eating among people on opioid agonist therapy: a qualitative study of patients’ experiences and perspectives
Authors: Furulund Einar , Druckrey-Fiskaaen Karl Trygve , Carlsen Siv-Elin Leirvåg , Madebo Tesfaye , Fadnes Lars T. , Lid Torgeir Gilje
Published: May 2024

People with substance use disorders often have unhealthy diets, high in sweets and processed foods but low in nutritious items like fruits and vegetables, increasing noncommunicable disease risks. This study investigates healthy eating perceptions and barriers among individuals with opioid use disorder undergoing opioid agonist therapy. Interviews with 14 participants at opioid agonist therapy clinics in Western Norway, using a semi-structured guide and systematic text condensation for analysis, reveal that most participants view their diet as inadequate and express a desire to improve for better health. Barriers to healthy eating included oral health problems, smoking habits, and limited social relations, while economic factors were less of a concern for the participants. Participants did find healthy eating easier when they were in social settings. This study underscores the importance of understanding and addressing these barriers and facilitators to foster healthier eating patterns in this population, potentially enhancing overall health and well-being.
Accuracy of the recording of pneumonia events in English electronic healthcare record data in patients with chronic obstructive pulmonary disease
Authors: Adamson Alexander J. , Kallis Constantinos , Douglas Ian , Quint Jennifer K.
Published: May 2024

Background

In primary care, identifying pneumonia events in people with chronic obstructive pulmonary disease (COPD) may be challenging due to similarities in symptoms with COPD exacerbations and lack of diagnostic testing. This study explored the accuracy of pneumonia diagnosis coded in primary care by comparing diagnosis in primary care with diagnosis in hospital.

Methods

A study population of people with COPD in England was created using the Clinical Practice Research Datalink Aurum database linked with Hospital Episode Statistics inpatient data. Pneumonia codes only, and pneumonia code with associated clinical and/or treatment codes (chest x-ray, symptoms, antibiotics, sputum and blood culture) were used to determine pneumonia events in primary care. Events that were followed by hospitalisation within 7 days were used to estimate the positive predictive value (PPV) of pneumonia coding in primary care, using primary diagnosis of pneumonia in secondary care as the gold standard. The PPV of primary care recording of hospitalised pneumonia was also calculated.

Results

Two hundred seventy-four thousand one hundred fifty-six COPD patients were eligible for inclusion, of whom 7,560 had an eligible pneumonia event in primary care diagnosed between 2015–2019 which was not ‘hospital-acquired’ and was diagnosed and entered on the same day. Of the 2,094 events which were followed by hospitalisation within 7 days, 1,208 had a primary diagnosis of pneumonia in hospital, representing a PPV of pneumonia coding in primary care of 57.7% (95% CI 55.6%-59.8%). Another 284 (13.6%) were diagnosed as a COPD exacerbation and 114 (5.4%) were diagnosed as another respiratory disease. Use of additional pneumonia clinical and treatment codes had a modest effect on the PPV but substantially lowered the number of events. Of the 33,603 eligible pneumonia events identified in secondary care, only 11,445 were recorded in primary care within 42 days, representing a sensitivity of 34.1% (95% CI 33.6%-34.6%).

Conclusions

Use of primary care pneumonia codes and associated clinical and treatment codes to determine pneumonia is not recommended due to significant levels of misdiagnosis and many hospitalised events failing to be recorded in primary care.
Spirituality and behavioural addictions: narrative review
Authors: Kanabar Mitika , Kathiresan Preethy , Elkholy Hussien , Zonoozi Arash Khojasteh , Orsolini Laura , Long Jiang , Farokhnia Mehdi , Bhad Roshan , Butner Jenna L. , Fonseca Francina , Phan Vicky , Achab Sophia , Potenza Marc N.
Published: May 2024

The relationship between spirituality and behavioural addictions is complex. Although some studies have suggested spirituality to be a protective factor helping in recovery from addictive behaviours, others have found spirituality to be a potential risk factor. To better understand the relationship between spirituality and various behavioural addictions, this review summarises the literature on the association between spirituality and the following behavioural addictions: gaming disorder, gambling disorder, problematic internet use, problematic smartphone use, compulsive sexual behaviour disorder and compulsive buying/shopping disorder. Implications for clinical practice and future research are discussed.
POLÍTICAS PÚBLICAS DE PREVENÇÃO E COMBATE ÀS DESIGUALDADES INJUSTAS
Authors: Zambam Neuro José , Séllos-Knoerr Viviane Coêlho de , Portela Irene Maria
Published: May 2024

Objetivos: Apresentar um roteiro de temas e comentários para a leitura dessa obra, destacando a compreensão de políticas públicas de Sen, a alguns temas estratégicos para a sua compreensão simplificada e mais abrangente e, por vezes, bem delimitada, priorizando temas que contribuam para a prevenção e superação das desigualdades injustas e, dada sua interdependência, aprimorem a democracia e os processos de participação e decisão. Avaliar as políticas públicas em contextos complexos, desiguais e necessitados de soluções que humanizem as relações humanas, sociais e ambientais democraticamente construídas.
Metodologia: A metodologia usada no trabalho foi feita pelo método dedutivo com base em revisão bibliográfica.
Resultados: A legitimidade das políticas públicas está relacionada a diversas referências que atestam desde a sua necessidade, as condições de implementação até o seu resultado final. “Glória incerta: a Índia e suas contradições” é uma importante análise de referência para esta abordagem, que visa à apresentação da obra com seus temas estratégicos (simbólicos) que contribuem para a solução das desigualdades injustas.
Contribuições: A compreensão atualizada de políticas públicas orienta para a superação de graves problemas sociais em vista da equidade social. A missão do Estado e o papel dos demais atores sociais é de cooperação, em que a transparência e o debate público são essenciais para uma efetiva participação de todos nas decisões.
Cutting-edge computational systems and emerging technologies applied to e-government and virtual environments
Authors: Υφαντής Βασίλειος
Published: May 2024

Αυτή η διατριβή εμβαθύνει στη συσχέτιση καινοτόμων τεχνολογιών και παροχής δημόσιων υπηρεσιών, εξετάζοντας τόσο τις επιχειρηματικές όσο και τις τεχνικές διαστάσεις εντός της κυβέρνησης. Ο κύριος στόχος της μελέτης είναι να συγκρίνει τις συμβατικές προσεγγίσεις για την παροχή δημόσιων υπηρεσιών, που περιλαμβάνουν φυσικές επισκέψεις σε κυβερνητικά γραφεία και τη χρήση τεχνολογιών αιχμής, ιδιαίτερα του Metaverse. Μέσω μιας σχολαστικής αξιολόγησης βασικών παραγόντων όπως η απόδοση χρόνου, η κατανάλωση ενέργειας, οι περιβαλλοντικές επιπτώσεις (καυσαέρια) και η σχέση κόστους-αποτελεσματικότητας, στόχος αυτής της έρευνας είναι να προσφέρει μια ολοκληρωμένη κατανόηση των θεμάτων που σχετίζονται με κάθε μέθοδο παροχής δημόσιων υπηρεσιών. Αυτή η ενδελεχής ανάλυση επιχειρεί να προσφέρει πληροφορίες για τα πιθανά πλεονεκτήματα και δυσκολίες που παρουσιάζει η ενσωμάτωση τεχνολογιών αιχμής στην παροχή δημόσιων υπηρεσιών. Τα αποτελέσματα αυτής της διατριβής προσφέρουν στους υπεύθυνους χάραξης πολιτικής σημαντικές νέες πληροφορίες επισημαίνοντας τα οφέλη και τα μειονεκτήματα της εφαρμογής αναδυόμενων τεχνολογιών στον δημόσιο τομέα. Καθώς οι κυβερνήσεις σε όλο τον κόσμο αντιμετωπίζουν το έργο του εκσυγχρονισμού της παροχής υπηρεσιών, αυτή η έρευνα εξοπλίζει τους υπεύθυνους λήψης αποφάσεων με προοπτικές που βασίζονται σε δεδομένα για την ενημέρωση των στρατηγικών επιλογών. Ουσιαστικά, η μελέτη χρησιμεύει ως κρίσιμος πόρος για τη διαμόρφωση πολιτικών που όχι μόνο ενισχύουν την αποτελεσματικότητα της παροχής δημόσιων υπηρεσιών αλλά και ευθυγραμμίζονται με ευρύτερους κοινωνικούς στόχους, συμπεριλαμβανομένης της βιωσιμότητας και της σχέσης κόστους-αποτελεσματικότητας.
Κριτική Ανάλυση των Οπτικοακουστικών Μέσων: Μεθοδολογίες και Καλές Πρακτικές
Authors: Παπαδημητρίου Σοφία , Σοφός Αλιβίζος
Published: May 2024

Η εκπαίδευση στα Μέσα έχει ζωτική σημασία όχι μόνο για την καλλιέργεια κριτικής στάσης και δεξιοτήτων δημιουργικής παραγωγής, αλλά για τη δημοκρατική διαδικασία γενικότερα, με τη δημιουργία ενημερωμένων και ενεργών πολιτών. Τα Οπτικοακουστικά (Ο/Α) Μέσα έχουν κυρίαρχο ρόλο στην καθημερινότητα των μαθητών και σήμερα οι ψηφιακές τεχνολογίες προσφέρουν δυνατότητες ανοικτής πρόσβασης, κριτικής προσέγγισης και παραγωγής Ο/Α Μέσων. Η μάθηση στηριζόμενη στα ψηφιακά Ο/Α Μέσα προϋποθέτει ότι οι εκπαιδευτικοί μπορούν να ενθαρρύνουν, συμβουλεύσουν, καθοδηγήσουν και υποστηρίξουν τους μαθητές τους και να συμμετάσχουν σε πιο ανοικτές μορφές εκπαίδευσης και μάθησης. Είναι σημαντικό, οι εκπαιδευτικοί να γνωρίζουν μεθόδους αξιοποίησης των Ο/Α αλλάζοντας τις διδακτικές πρακτικές τους και στοχεύοντας στην ενεργητική μάθηση. Στο άρθρο παρουσιάζονται μεθοδολογίες και καλές πρακτικές κριτικής ανάλυσης, αποκωδικοποίησης μηνυμάτων της γλώσσας των Ο/Α Μέσων, οι οποίες στη συνέχεια εφαρμόστηκαν από εκπαιδευτικούς που συμμετείχαν σε εξ αποστάσεως πρόγραμμα επιμόρφωσης του Πανεπιστη μίου Αιγαίου. Στη συνέχεια καταγράφονται τα σχόλια των εκπαιδευτικών από τον αναστοχασμό των εφαρμογών και τα συμπεράσματα από την κριτική προσέγγιση μαθητικών ταινιών, διαφημίσεων και Ο/Α μηνυμάτων καθώς και της στερητικής εμπειρίας από «Μια μέρα μακριά από τα Μέσα».