bluuebunny/crossref_metadata_2025 huggingface dataset:
Glyceryl triacetate promotes blood–brain barrier recovery after ischemic stroke through lipogenesis-mediated IL-33 in mice
Authors: Wei Haidong , Zhen Luming , Wang Shiquan , Yang Liufei , Zhang Shuyue , Zhang Yuanyuan , Jia Pengyu , Wang Tianyue , Wang Kui , Zhang Yan , Ma Lei , Lv Jianrui , Zhang Pengbo
Published: November 2023

Background

Lipid metabolism has a crucial role in neural repair in neurodegenerative diseases. We recently revealed that lipogenesis-mediated interleukin-33 (IL-33) upregulation lead to blood–brain barrier (BBB) repair after ischemic stroke. However, manipulating the key enzyme fatty acid synthase (FASN) to enhance lipogenesis was very challenging. Glyceryl triacetate (GTA) was used as a donor of acetate and precursor of acetyl coenzyme A, the key substrate for de novo lipogenesis catalyzed by FASN. Therefore, we hypothesized that GTA would promote lipogenesis the peri-infarct after ischemic stroke and contribute to the BBB repair through IL-33.

Methods

Middle cerebral artery occlusion (MCAO) was performed on C57BL mice and GTA was gavage administrated (4 g/kg) on day 2 and 4 after MCAO. Lipogenesis was evaluated by assessment of the protein level of FASN, lipid droplets, and fatty acid products through liquid chromatography-mass spectrometry in the peri-infarct area on day 3 after MCAO, respectively. BBB permeability was determined by extravasation of Evans blue, IgG and dextran, and levels of tight junction proteins in the peri-infarct area on day 7 after MCAO, respectively. Infarct size and neurological defects were assessed on day 7 after MCAO. Brain atrophy on day 30 and long-term sensorimotor abilities after MCAO were analyzed as well. The inhibitor of FASN, C75 and the virus-delivered FASN shRNA were used to evaluate the role of FASN-driven lipogenesis in GTA-improved BBB repair. Finally, the therapeutic potential of recombinant IL-33 on BBB repair and neurological recovery was evaluated.

Results

We found that treatment with GTA increased the lipogenesis as evidenced by lipid droplets level and lauric acid content, but not the FASN protein level. Treatment with GTA increased the IL-33 level in the peri-infarct area and decreased the BBB permeability after MCAO. However, infarct size and neurological defect score were unchanged on day 7 after MCAO, while the long-term recovery of sensorimotor function and brain atrophy were improved by GTA. Inhibition of lipogenesis using C75 or FASN shRNA reversed the beneficial effect of GTA. Finally, exogenous IL-33 improved BBB repair and long-term functional recovery after stroke.

Conclusion

Collectively, we concluded that treatment with GTA improved the BBB repair and functional recovery after ischemic stroke, probably by the enhancement of lipogenesis and IL-33 expression.

Graphical Abstract
RhoA suppresses pseudorabies virus replication in vitro
Authors: Li Xin-Man , Wang Shi-Ping , Wang Jin-Yuan , Tang Ting , Wan Bo , Zeng Lei , Wang Jiang , Chu Bei-Bei , Yang Guo-Yu , Pan Jia-Jia
Published: November 2023

The porcine pseudorabies virus (PRV) is one of the most devastating pathogens and brings great economic losses to the swine industry worldwide. Viruses are intracellular parasites that have evolved numerous strategies to subvert and utilize different host processes for their life cycle. Among the different systems of the host cell, the cytoskeleton is one of the most important which not only facilitate viral invasion and spread into neighboring cells, but also help viruses to evade the host immune system. RhoA is a key regulator of cytoskeleton system that may participate in virus infection. In this study, we characterized the function of RhoA in the PRV replication by chemical drugs treatment, gene knockdown and gene over-expression strategy. Inhibition of RhoA by specific inhibitor and gene knockdown promoted PRV proliferation. On the contrary, overexpression of RhoA or activation of RhoA by chemical drug inhibited PRV infection. Besides, our data demonstrated that PRV infection induced the disruption of actin stress fiber, which was consistent with previous report. In turn, the actin specific inhibitor cytochalasin D markedly disrupted the normal fibrous structure of intracellular actin cytoskeleton and decreased the PRV replication, suggesting that actin cytoskeleton polymerization contributed to PRV replication in vitro. In summary, our data displayed that RhoA was a host restriction factor that inhibited PRV replication, which may deepen our understanding the pathogenesis of PRV and provide further insight into the prevention of PRV infection and the development of anti-viral drugs.
Bridge symptoms between parenting styles and proximal psychological risk factors associated with adolescent suicidal thoughts: a network analysis
Authors: Ou Wenwen , Yang Yumeng , Chen Yafei , Li Yunjing , Yang Siqi , Lu Yimei , Li Liang , Huang Mei , Ma Mohan , Lv Guanyi , Zhao Xiaotian , Qing Yaqi , Ju Yumeng , Zhang Yan
Published: November 2023

Background

Parenting styles and the associated proximal psychological factors are suggested to increase suicidal risks in adolescents. However, how the two factors interact and confer risks on the emergence of adolescent suicidal thoughts remains unclear. Herein, we used a network approach to investigate their interrelationship and explore whether the network properties predict adolescent suicidal thoughts.

Methods

Self-report questionnaires were completed by 1171 students aged 12–16. Network analyses were performed by Gaussian graphical models estimating the adolescent psychosocial network structure of parenting styles and psychological variables including depression, anxiety, affective lability, rumination, and resilience. Furthermore, we re-examined the network by adding a variable measuring active suicidal thoughts. Moreover, we conducted linear regressions to examine the predictive utility of bridge symptoms for adolescent suicidal thoughts.

Results

Resilience, Afraid, Rumination, Concentration, and affective lability (Anger) had the highest bridge strengths in the adolescent psychosocial network. Among the identified bridge symptoms, Resilience was negatively correlated with active suicidal thoughts (regularized edge weights = -0.181, bootstrapped 95% CIs: [-0.043, -0.155]), whereas affective lability (from Anxiety to Depression, Anger), Rumination, and Afraid were positively correlated with active suicidal thoughts, with edge weights (bootstrapped 95% CIs) ranging from 0.057 (0.001, 0.112) to 0.081(0.026, 0.136). Regression analysis showed that bridge strength was significantly correlated with active suicidal thoughts (R2 = 0.432, P = 0.001).

Conclusion

Negative parenting styles may drive and maintain suicidal thoughts by modifying the key proximal psychological variables. Our findings highlight the important role of bridge symptoms, which may serve as vital targets for triggering adolescent suicide.
Safe surgical corridor for iliosacral screw placement in unstable pelvic fractures: a computed-tomography-guided validation study of the “triangulation method”
Authors: ZHENG Yu-Bo , ZHAO Xin , ZHENG Qiang , SANG Xi-Guang
Published: November 2023

Background

The percutaneous iliosacral screw technique represents a global standard fixation method for unstable fractures of the posterior pelvic ring. However, the inaccurate positioning of iliosacral screws is associated with a significant risk of severe intra-operative complications. Therefore, this study aimed to investigate the relationship between the skin entry point of the transverse iliosacral screw of the first sacral vertebral body and the anterior superior iliac spine and the greater trochanter of the femur using computed-tomography-guided validation.

Methods

Overall, 91 consecutive patients admitted to a tertiary referral center in China for posterior pelvic ring fixation via the “triangulation method” using computed-tomography-guided validation between January 1, 2020, and December 31, 2020, were included in this retrospective observational cohort study. Modeling and simulated iliosacral screw placement were performed using the Mimics software. The distance between the three points of interest was measured, and their relationship in a rectangular coordinate system was determined. Patients were categorized according to gender, body mass index, and femoral rotation angle to investigate the factors affecting the positional relationship between the three points.

Results

An equilateral triangular relationship was observed between the positioning points of the transverse iliosacral screw, anterior iliac spine, and greater trochanter. Additionally, 95% of the entry points were within a circle radius centered 12 mm at the apex of an equilateral triangle comprising the anterior superior iliac spine and the greater trochanter as the base. The entry point in the femoral external rotation was more dorsal than that in the internal femoral rotation. Furthermore, the entry point in females was more rostral than that in males, and the entry point in overweight patients was more dorsal than that in normal-weight patients.

Conclusions

The skin entry point of the percutaneous iliosacral screw can be located by drawing an equilateral triangle from the anterior superior iliac spine and the greater trochanter as the base to the dorsum end of the patient’s head. In summary, this retrospective cohort study validated the safety and efficacy of the “triangulation methods” for percutaneous fixation of unstable posterior pelvic ring injuries.
In-hospital extracorporeal cardiopulmonary resuscitation for patients with out-of-hospital cardiac arrest: an analysis by time-dependent propensity score matching using a nationwide database in Japan
Authors: Okada Yohei , Komukai Sho , Irisawa Taro , Yamada Tomoki , Yoshiya Kazuhisa , Park Changhwi , Nishimura Tetsuro , Ishibe Takuya , Kobata Hitoshi , Kiguchi Takeyuki , Kishimoto Masafumi , Kim Sung-Ho , Ito Yusuke , Sogabe Taku , Morooka Takaya , Sakamoto Haruko , Suzuki Keitaro , Onoe Atsunori , Matsuyama Tasuku , Nishioka Norihiro , Matsui Satoshi , Yoshimura Satoshi , Kimata Shunsuke , Kawai Shunsuke , Makino Yuto , Kiyohara Kosuke , Zha Ling , Ong Marcus Eng Hock , Iwami Taku , Kitamura Tetsuhisa
Published: November 2023

Background

Extracorporeal cardiopulmonary resuscitation (ECPR) has been proposed as a rescue therapy for patients with refractory cardiac arrest. This study aimed to evaluate the association between ECPR and clinical outcomes among patients with out-of-hospital cardiac arrest (OHCA) using risk-set matching with a time-dependent propensity score.

Methods

This was a secondary analysis of the JAAM-OHCA registry data, a nationwide multicenter prospective study of patients with OHCA, from June 2014 and December 2019, that included adults (≥ 18 years) with OHCA. Initial cardiac rhythm was classified as shockable and non-shockable. Patients who received ECPR were sequentially matched with the control, within the same time (minutes) based on time-dependent propensity scores calculated from potential confounders. The odds ratios with 95% confidence intervals (CI) for 30-day survival and 30-day favorable neurological outcomes were estimated for ECPR cases using a conditional logistic model.

Results

Of 57,754 patients in the JAAM-OHCA registry, we selected 1826 patients with an initial shockable rhythm (treated with ECPR,n = 913 and control,n = 913) and a cohort of 740 patients with an initial non-shockable rhythm (treated with ECPR,n = 370 and control,n = 370). In these matched cohorts, the odds ratio for 30-day survival in the ECPR group was 1.76 [95%CI 1.38–2.25] for shockable rhythm and 5.37 [95%CI 2.53–11.43] for non-shockable rhythm, compared to controls. For favorable neurological outcomes, the odds ratio in the ECPR group was 1.11 [95%CI 0.82–1.49] for shockable rhythm and 4.25 [95%CI 1.43–12.63] for non-shockable rhythm, compared to controls.

Conclusion

ECPR was associated with increased 30-day survival in patients with OHCA with initial shockable and even non-shockable rhythms. Further research is warranted to investigate the reproducibility of the results and who is the best candidate for ECPR.

Graphical Abstract
Return to work after hospitalization for sepsis: a nationwide, registry-based cohort study
Authors: Skei Nina Vibeche , Moe Karoline , Nilsen Tom Ivar Lund , Aasdahl Lene , Prescott Hallie C. , Damås Jan Kristian , Gustad Lise Tuset
Published: November 2023

Background

Sepsis survivors commonly experience functional impairment, which may limit return to work. We investigated return to work (RTW) of patients hospitalized with sepsis and the associations with patient and clinical characteristics.

Methods

Working-age patients (18–60 years) admitted to a Norwegian hospital with sepsis between 2010 and 2021 were identified using the Norwegian Patient Registry and linked to sick-leave data from the Norwegian National Social Security System Registry. The main outcome was proportion of RTW in patients hospitalized with sepsis at 6 months, 1 year, and 2 years after discharge. Secondary outcomes were time trends in age-standardized proportions of RTW and probability of sustainable RTW (31 days of consecutive work). The time trends were calculated for each admission year, reported as percentage change with 95% confidence interval (CI). Time-to-event analysis, including crude and adjusted hazard risk (HRs), was used to explore the association between sustainable RTW, characteristics and subgroups of sepsis patients (intensive care unit (ICU) vs. non-ICU and COVID-19 vs. non-COVID-19).

Results

Among 35.839 hospitalizations for sepsis among patients aged 18–60 years, 12.260 (34.2%) were working prior to hospitalization and included in this study. The mean age was 43.7 years. At 6 months, 1 year, and 2 years post-discharge, overall estimates showed that 58.6%, 67.5%, and 63.4%, respectively, were working. The time trends in age-standardized RTW for ICU and non-ICU sepsis patients remained stable over the study period, except the 2-year age-standardized RTW for non-ICU patients that declined by 1.51% (95% CI − 2.22 to − 0.79) per year, from 70.01% (95% CI 67.21 to 74.80) in 2010 to 57.04% (95% CI 53.81–60.28) in 2019. Characteristics associated with sustainable RTW were younger age, fewer comorbidities, and fewer acute organ dysfunctions. The probability of sustainable RTW was lower in ICU patients compared to non-ICU patients (HR 0.56; 95% CI 0.52–0.61) and higher in patients with COVID-19-related sepsis than in sepsis patients (HR 1.31; 95% CI 1.15–1.49).

Conclusion

Absence of improvement in RTW proportions over time and the low probability of sustainable RTW in sepsis patients need attention, and further research to enhance outcomes for sepsis patients is required.
The BET degrader ZBC260 suppresses stemness and tumorigenesis and promotes differentiation in triple-negative breast cancer by disrupting inflammatory signaling
Authors: Sharma Deeksha , Hager Cody G. , Shang Li , Tran Lam , Zhu Yongyou , Ma Aihui , Magnuson Brian , Lesko Matthew W. , Wicha Max S. , Burness Monika L.
Published: November 2023

Background

Breast cancer stem cells (BCSCs) are resistant to standard therapies, facilitate tumor dissemination, and contribute to relapse and progression. Super-enhancers are regulators of stemness, and BET proteins, which are critical for super-enhancer function, are a potential therapeutic target. Here, we investigated the effects of BET proteins on the regulation of breast cancer stemness using the pan-BET degrader ZBC260.

Methods

We evaluated the effect of ZBC260 on CSCs in TNBC cell lines. We assessed the effect of ZBC260 on cellular viability and tumor growth and measured its effects on cancer stemness. We used RNA sequencing and stemness index to determine the global transcriptomic changes in CSCs and bulk cells and further validated our findings by qPCR, western blot, and ELISA.

Results

ZBC260 potently inhibited TNBC growth both in vitro and in vivo. ZBC260 reduced stemness as measured by cell surface marker expression, ALDH activity, tumorsphere number, and stemness index while increasing differentiated cells. GSEA analysis indicated preferential downregulation of stemness-associated and inflammatory genes by ZBC260 in ALDH+CSCs.

Conclusions

The BET degrader ZBC260 is an efficient degrader of BET proteins that suppresses tumor progression and decreases CSCs through the downregulation of inflammatory genes and pathways. Our findings support the further development of BET degraders alone and in combination with other therapeutics as CSC targeting agents.
Video augmentation of the WHO cone assay to quantify mosquito behavioural responses to insecticide-treated nets
Authors: Jones Jeff , Matope Agnes , Barreaux Priscille , Gleave Katherine , Steen Keith , Ranson Hilary , McCall Philip J. , Foster Geraldine M.
Published: November 2023

Background

Insecticide-treated nets (ITNs) using pyrethroids have been the main vector control tools deployed in malaria endemic countries and are responsible for the dramatic reduction in African malaria cases in the early 2000s. The World Health Organization (WHO) cone test was designed to assess the rapid toxicity effects of pyrethroid exposure on mosquito vectors but has yielded no insights beyond 60-min knockdown and 24-h mortality. As dual-active-ingredient (AI) ITNs become more widespread, bioassays that can provide realistic assessment of single- and dual-treated ITNs (i.e. nets with more than one active ingredient) are urgently needed.

Methods

We present an augmentation of the cone test that enables accurate quantification of vector behavioural responses (specifically movement, spatial and temporal occupancy) to ITNs using video recording and bespoke software that uses background segmentation methods to detect spatial changes in the movement of mosquitoes within the cone. Four strains of Anopheles gambiae sensu lato (s.l.) were exposed to four ITNs (PermaNet 2.0, PermaNet 3.0, Olyset Net, Interceptor G2) and untreated nets in these modified cone tests. Life history data (post-exposure blood-feeding, blood meal weight, longevity) for individual mosquitoes were recorded.

Results

All mosquitoes responded to the presence of ITNs, spending from 1.48 to 3.67 times more time in the upper region of the cone, depending on the ITN type. Of all ITNs, PermaNet 2.0 provoked the smallest change in behavioural response. Activity in the cone influenced observed post-exposure longevity, and in resistant strains exposed to Interceptor G2, the higher the activity, the greater the risk of dying, as long as the proportion of activity at the net surface was less than 50%. All ITNs inhibited blood-feeding, and smaller blood meals were taken when mosquitoes fed.

Conclusions

The additional mosquito behaviour data obtained by using this modification to the WHO cone test provides unique insight into the innate responses of different mosquito strains on untreated nets and the entomological mode of action of ITNs, important evidence when evaluating ITN characteristics.

Graphical Abstract
The role of admixture in the rare variant contribution to inflammatory bowel disease
Authors: Astore Courtney , Sharma Shivam , Nagpal Sini ,   NIDDK IBD Genetics Consortium, Cutler David J. , Rioux John D. , Cho Judy H. , McGovern Dermot P. B. , Brant Steven R. , Kugathasan Subra , Jordan I. King , Gibson Greg
Published: November 2023

Background

Identification of rare variants involved in complex, polygenic diseases like Crohn’s disease (CD) has accelerated with the introduction of whole exome/genome sequencing association studies. Rare variants can be used in both diagnostic and therapeutic assessments; however, since they are likely to be restricted to specific ancestry groups, their contributions to risk assessment need to be evaluated outside the discovery population. Prior studies implied that the three known rare variants in NOD2 are absent in West African and Asian populations and only contribute in African Americans via admixture.

Methods

Whole genome sequencing (WGS) data from 3418 African American individuals, 1774 inflammatory bowel disease (IBD) cases, and 1644 controls were used to assess odds ratios and allele frequencies (AF), as well as haplotype-specific ancestral origins of European-derived CD variants discovered in a large exome-wide association study. Local and global ancestry was performed to assess the contribution of admixture to IBD contrasting European and African American cohorts.

Results

Twenty-five rare variants associated with CD in European discovery cohorts are typically five-fold lower frequency in African Americans. Correspondingly, where comparisons could be made, the rare variants were found to have a predicted four-fold reduced burden for IBD in African Americans, when compared to European individuals. Almost all of the rare CD European variants were found on European haplotypes in the African American cohort, implying that they contribute to disease risk in African Americans primarily due to recent admixture. In addition, proportion of European ancestry correlates the number of rare CD European variants each African American individual carry, as well as their polygenic risk of disease. Similar findings were observed for 23 mutations affecting 10 other common complex diseases for which the rare variants were discovered in European cohorts.

Conclusions

European-derived Crohn’s disease rare variants are even more rare in African Americans and contribute to disease risk mainly due to admixture, which needs to be accounted for when performing cross-ancestry genetic assessments.
The key cellular senescence related molecule RRM2 regulates prostate cancer progression and resistance to docetaxel treatment
Authors: Cheng Bisheng , Li Lingfeng , Wu Yongxin , Luo Tianlong , Tang Chen , Wang Qiong , Zhou Qianghua , Wu Jilin , Lai Yiming , Zhu Dingjun , Du Tao , Huang Hai
Published: November 2023

Background

Prostate cancer is a leading cause of cancer-related deaths among men worldwide. Docetaxel chemotherapy has proven effective in improving overall survival in patients with castration-resistant prostate cancer (CRPC), but drug resistance remains a considerable clinical challenge.

Methods

We explored the role of Ribonucleotide reductase subunit M2 (RRM2), a gene associated with senescence, in the sensitivity of prostate cancer to docetaxel. We evaluated the RRM2 expression, docetaxel resistance, and ANXA1 expression in prostate cancer cell lines and tumour xenografts models. In addition, We assessed the impact of RRM2 knockdown, ANXA1 over-expression, and PI3K/AKT pathway inhibition on the sensitivity of prostate cancer cells to docetaxel. Furthermore, we assessed the sensitivity of prostate cancer cells to the combination treatment of COH29 and docetaxel.

Results

Our results demonstrated a positive association between RRM2 expression and docetaxel resistance in prostate cancer cell lines and tumor xenograft models. Knockdown of RRM2 increased the sensitivity of prostate cancer cells to docetaxel, suggesting its role in mediating resistance. Furthermore, we observed that RRM2 stabilizes the expression of ANXA1, which in turn activates the PI3K/AKT pathway and contributes to docetaxel resistance. Importantly, we found that the combination treatment of COH29 and docetaxel resulted in a synergistic effect, further augmenting the sensitivity of prostate cancer cells to docetaxel.

Conclusion

Our findings suggest that RRM2 regulates docetaxel resistance in prostate cancer by stabilizing ANXA1-mediated activation of the PI3K/AKT pathway. Targeting RRM2 or ANXA1 may offer a promising therapeutic strategy to overcome docetaxel resistance in prostate cancer.

Graphical Abstract
Potential ‘anti-cancer’ effects of esketamine on proliferation, apoptosis, migration and invasion in esophageal squamous carcinoma cells
Authors: Li Chao , Shi Jingpu , Wei Sisi , Jia Huiqun
Published: November 2023

Background

Esketamine, an N-methyl-D-aspartate receptor antagonist, is commonly used for anesthesia and analgesia clinically. It was reported to negatively regulate cell proliferation, metastasis and apoptosis in cancer cells, including lung cancer and pancreatic cancer. However, its impact on esophageal squamous cell carcinoma (ESCC) malignance and underlying mechanism remain elusive. This study was aimed to investigate the antitumor effects of esketamine on ESCC in vitro.

Methods

ESCC cell lines (KYSE-30 and KYSE-150) were cultured and treated with different concentrations (0.1, 0.2, 0.4, 0.8, 1, 2 mM) of esketamine. Their proliferation, apoptosis, migration and invasion were assessed with various assays. Furthermore, mass spectrometry-based proteomic analysis and GO/KEGG enrichment analysis were applied to characterize the differentially expressed proteins (DEPs) with or without esketamine treatment. Some key proteins identified from proteomic analysis were further validated with Western blotting and bioinformatics analysis.

Results

Esketamine significantly inhibited the proliferation, migration, invasion and promoted apoptosis of the both types of cell lines in a dose- and time-dependent manner. A total of 321 common DEPs, including 97 upregulated and 224 downregulated proteins, were found with HPLC–MS analyses. GO/KEGG enrichment analysis suggested that esketamine affected cell population proliferation, GTPase activity and Apelin signaling pathway. The ERCC6L, AHR and KIF2C protein expression was significantly downregulated in these ESCC cells treated with esketamine compared to the controls and their changes were associated with the suppressive effects of esketamine on ESCC through bioinformatics analysis.

Conclusions

Our work demonstrated that esketamine has potential anti-ESCC properties in vitro but subjected to further in vivo and clinical study.
Damage and Deterioration Mechanism of Coal Gangue Mixed Pumice Aggregate Concrete Under Freeze–Thaw Cycles
Authors: Li Wen , Wang Hailong , Zhang Wenyan
Published: November 2023

The world is facing the problem of depletion of natural sand and gravel resources, and a large amount of coal gangue solid waste is produced in Inner Mongolia, China, which has low utilization rate and causes ecological pollution. In order to improve the gangue in the mining infrastructure construction of a wide range of application prospects, the use of coal gangue as the coarse aggregate of pumice concrete is of great significance. Inner Mongolia is a cold region, and gangue mixed aggregate concrete (MFC) will certainly face the damage caused by freeze–thaw cycles. Therefore, design gangue by different volume replacement rate (0%, 20%, 40%, 60%, 80%,
100%) to replace pumice coarse aggregate. The results show that with the increase of gangue substitution rate, the mass loss rate, relative dynamic elastic modulus, and peak stress of MFC decrease, but the trend of peak strain increases. It is mainly attributed to the less Al2O3 and SiO2 content of gangue, which makes the MFC hydration products decrease with the increase of substitution rate and more original microcracks and pores in the specimens. In addition, the damage model of MFC was established by using Weibull statistical distribution theory and the principle of LEMAITRE equivalent effect variation assumption, and the damage evolution characteristics were explored by combining the experimental results. It can provide the theoretical basis for the application of MFC in cold regions.
Digital social innovation based on Big Data Analytics for health and well-being of society
Authors: Batko Kornelia
Published: November 2023

Background

Any nation's health policy aims to properly care for its citizens and the society's quality of life. Since in the healthcare system, the population's health is the essential component of national wealth, health is treated as a public good and a social value. Therefore, in recent times, in addition to traditional instruments for promoting healthy lifestyles, health policy has increasingly turned to information instruments and digital technologies.

Aims

The paper aims to recognize the role of Big Data Analytics (BDA) in developing Digital Social Innovation (DSI) in the healthcare field. The proposal of the author's Individual Health Plan Platform (IHPP) solution is presented as an example of Digital Social Innovation.

Material and methods

The research is based on a critical analysis of the literature, followed by a Focus Group study aimed at determining the potential of Big Data Analytics, including especially analysis based on data from wearables, to help manage one's health and improve the society's well-being. The focus research also included verification of the research model presented in the article and evaluation of the proposed solution, the Individual Health Plan Platform, including the possibilities of its implementation as a solution to complement healthcare provided by medical facilities in Poland.

Results

The results of the focus group interviews show that analysing data from wearables and the proposed IHPP could be helpful in managing one's own health and helping to level important problems in healthcare.

Conclusion

One of the goals of this paper was to determine the role of BDAs in the development of social innovations in healthcare. From the analysis of the literature, results of the focus group study and discussion, it was concluded that Big Data Analytics has the potential to develop social innovation in healthcare.
The AI generation gap: Are Gen Z students more interested in adopting generative AI such as ChatGPT in teaching and learning than their Gen X and millennial generation teachers?
Authors: Chan Cecilia Ka Yuk , Lee Katherine K. W.
Published: November 2023

This study aimed to explore the experiences, perceptions, knowledge, concerns, and intentions of Generation Z (Gen Z) students with Generation X (Gen X) and Generation Y (Gen Y) teachers regarding the use of generative AI (GenAI) in higher education. A sample of students and teachers were recruited to investigate the above using a survey consisting of both open and closed questions. The findings showed that Gen Z participants were generally optimistic about the potential benefits of GenAI, including enhanced productivity, efficiency, and personalized learning, and expressed intentions to use GenAI for various educational purposes. Gen X and Gen Y teachers acknowledged the potential benefits of GenAI but expressed heightened concerns about overreliance, ethical and pedagogical implications, emphasizing the need for proper guidelines and policies to ensure responsible use of the technology. The study highlighted the importance of combining technology with traditional teaching methods to provide a more effective learning experience. Implications of the findings include the need to develop evidence-based guidelines and policies for GenAI integration, foster critical thinking and digital literacy skills among students, and promote responsible use of GenAI technologies in higher education.
A newly revised estimation of bulk densities and examination of the shape of individual Ryugu grains
Authors: Miyazaki Akiko , Yada Toru , Yogata Kasumi , Hatakeda Kentaro , Nakato Aiko , Nishimura Masahiro , Nagashima Kana , Kumagai Kazuya , Hitomi Yuya , Soejima Hiromichi , Tahara Rui , Kanemaru Rei , Nakano Arisa , Yoshitake Miwa , Iwamae Ayako , Furuya Shizuho , Tsuchiyama Akira , Tachibana Shogo , Michikami Tatsuhiro , Okada Tatsuaki , Abe Masanao , Usui Tomohiro
Published: November 2023

The bulk density of grains from a celestial body is a fundamental property related to its composition and structure, contributing to the understanding of its evolutionary history. In this study, we provide the bulk density of 637 grains returned from the C-type near-Earth asteroid 162173 Ryugu. This is the largest number of grains to date for the curation activity, corresponding to 38 wt.% of the total returned samples (approximately 5.4 g). Although several densities of the Ryugu grains were reported, the volume estimation of some samples showed uncertainties. Therefore, we applied a new volume estimation model calibrated by X-ray micro-computed tomography (XCT) to the Ryugu grains to more accurately estimate their bulk density. The obtained average bulk density of 637 Ryugu grains was 1.79 ± 0.31 g/cm3 (1σ variation) for weights of 0.5‒100 mg (sub-mm ‒to 10 mm) irrespective of their 3D shapes characterized by three axial length ratios, considered to be a representative of the returned samples. The bulk density distributions of the grains in Chambers A and C were statistically distinguishable, with mean values of 1.81 ± 0.30 and 1.76 ± 0.33 g/cm3 (1σ variations), respectively. Despite the small difference, bulk density may have differed by sampling site. The obtained average bulk density value of A + C samples was almost the same as that of 16 Ryugu grains estimated based on CT scanned data, and was consistent with the densities of CI chondrites (1.57–1.91 g/cm3). The axial ratios of the grains in Chambers A and C were similar and those of the 724 returned samples and the flying particles ejected during the sampling operations were also similar, suggesting that relatively small Ryugu materials (mm‒cm in size) are similar in shape. The minor difference between the Rygu grains and flying particles could be attributed to events such as scraping during sampling operations and transportation.

Graphical Abstract
A rare case of localized peliosis hepatis during adjuvant chemotherapy including oxaliplatin mimicking a liver metastasis of colon cancer
Authors: Dejima Akira , Seyama Yasuji , Nakano Daisuke , Takao Misato , Natsume Soichiro , Takao Mikiya , Nakamori Sakiko , Kanai Tatsuya , Horiguchi Shinichiro , Kawai Kazushige
Published: November 2023

Background

Oxaliplatin-based regimens are commonly used as adjuvant chemotherapy following surgery for colorectal cancer. Adverse events associated with oxaliplatin include blue liver, which is caused by sinusoidal dilation and diffuse peliosis hepatis. We report herein a case of localized peliosis hepatis closely resembling a metastatic liver tumor.

Case presentation

The patient, a 50-year-old male, underwent a robotically assisted colectomy for rectosigmoid colon cancer, which was discovered when hematochezia occurred. The patient received a diagnosis of pStage IIIb and was treated with four courses of CAPOX as adjuvant chemotherapy starting at postoperative month 1. At postoperative month 4, contrast-enhanced computed tomography (CT) of the abdomen revealed a 20-mm, low-density area with heterogeneous internal structure in S6/7 of the liver. Abdominal ultrasound and gadolinium ethoxybenzyl-diethylenetriaminepentaacetic acid-enhanced magnetic resonance imaging (EOB-MRI) findings led to a diagnosis of metastatic liver tumor, for which a laparoscopic partial hepatectomy was performed. The resected lesion was a dark reddish-brown nodule with indistinct margins that appeared to be continuous with the surrounding area. Histopathological analysis revealed severe, localized dilatation of the sinusoids and congestion consistent with the gross nodule. Based on these findings, localized peliosis hepatis associated with oxaliplatin-induced sinusoidal damage was diagnosed.

Conclusions

Localized peliosis hepatis associated with oxaliplatin use can be difficult to distinguish from a metastatic liver tumor on imaging studies.
Evaluating the effect of vitamin D supplementation on serum levels of 25-hydroxy vitamin D, 1,25-dihydroxy vitamin D, parathyroid hormone and renin–angiotensin–aldosterone system: a systematic review and meta-analysis of clinical trials
Authors: Khodadadiyan Alireza , Rahmanian Mahdi , Shekouh Dorsa , Golmohammadi Melika , Ghaedi Arshin , Bazrgar Aida , Sayadi Mehrab , Bazrafshan Mehdi , Heydari Aigin , Bazrafshan Drissi Hamed
Published: November 2023

Background

Vitamin D, one of the most essential micronutrients, is crucial in various health outcomes. However, previous studies showed conflicting results and uncertainty about vitamin D supplementation's optimal dosage and duration. In this study, we aimed to evaluate the vitamin D supplements efficiency on serum levels of 25-hydroxy vitamin D (25(OH)D), 1,25-dihdroxy vitamin D (1,25(OH)2D), parathyroid hormone (PTH) and renin–angiotensin–aldosterone system (RAAS) in adults.

Methods

A systematic analysis of eligible and relevant randomized-controlled trials (RCT) published before April 2023 assessing the effect of vitamin D supplementations applied. The studies were identified by searching several databases, including Pubmed, Scopus, Web of Science, ProQuest, and Cochrane Register of controlled trials.

Results

Five eligible RCTs with 346 participants in the intervention and 352 participants in the control group were assessed in our project. According to the results, there was a substantial change in 25(OH)D (SMD: 2.2, I2: 92.3, 95% Confidence Interval (CI): 1.38–3.02, P-value: 0.048) and 1,25(OH)2D (SMD:1.23, I2: 86.3, 95% CI: 0.01- 2.44, P-value < 0.010) affected by vitamin D intervention. Regarding Parathyroid hormone (PTH), however, vitamin D intervention showed a remarkable decrease (SMD: -0.75, I2: 82.4, 95% CI: (-1.3)—(-0.18), P-value < 0.010). Moreover, sensitivity analysis showed significant publication bias in terms of 25(OH)D.

Conclusion

Vitamin D supplements significantly increase the serum levels of 25(OH)D and 1,25(OH)2D and decrease PTH levels. While some studies reported decreasing effect of vitamin D supplements on RAAS activity, some reported no changes.
Correlations between subfoveal choroidal thickness, macular thickness, and visual outcome in neovascular age-related macular degeneration using swept source OCT: insights from intravitreal aflibercept treatment
Authors: Beraldo Daniel P. , Rezende Marcussi P. , Alexander João G. , Polido Júlia , Belfort Rubens , Cabral Thiago
Published: November 2023

Background

Age-related macular degeneration (AMD) is a leading cause of visual impairment among individuals aged 50 and above, often resulting in irreversible vision loss (1). Currently, antiangiogenic therapy is the primary treatment approach for neovascular AMD (2). The choroid has gained significant attention in recent years due to its involvement in various ocular pathologies (7). The objective of this study was to evaluate visual acuity and correlate pre-treatment variables, such as foveal thickness and choroidal thickness, with post-treatment outcomes.

Materials and Methods

This study was designed as a prospective interventional study to investigate the changes in choroidal and macular thickness in patients with neovascular AMD who received intravitreal aflibercept injections. The study utilized medical records and employed Swept Source Optical Coherence Tomography (OCT-SS) for evaluation. The data was collected from patients treated in Presidente Prudente, Brazil, during a three-month load dose period.

Results

The best-corrected mean visual acuity significantly improved from 1.0 logarithm of the minimum resolution angle (logMAR) units to 0.55 logMAR after treatment with aflibercept (p < 0.001). Patients undergoing treatment exhibited a significant decrease in average macular thickness from 323 μm to 232 μm (p = 0.001), as well as a reduction in choroidal thickness from 206 μm to 172 μm (p = 0.031), while maintaining intraocular pressure within the normal range (p = 0.719) without significant variation. Statistically significant associations were found between the difference in pre- and post-treatment choroidal thickness and the pretreatment values of macular thickness (p = 0.005) and choroidal thickness (p = 0.013). There was also a statistically significant correlation between the difference in pre- and post-treatment macular thickness and the pretreatment macular thickness value (p < 0.001).

Conclusion

In this study, aflibercept exhibited remarkable effectiveness in reducing macular and choroidal thickness, as evaluated using OCT-SS, and significantly improved visual acuity in patients with neovascular AMD. The assessment of both choroidal and macular changes, as well as their correlations, can provide valuable insights for clinicians, enabling them to make well-informed therapeutic decisions and effectively monitor treatment outcomes. Notably, this study contributes to the existing body of literature as the first to establish a correlation between pretreatment foveal thickness, variation in choroidal thickness, and post-treatment choroidal thickness.
Cardiovascular disease incidence rates: a study using routinely collected health data
Authors: Ramroth Johanna , Shakir Rebecca , Darby Sarah C. , Cutter David J. , Kuan Valerie
Published: November 2023

Background

There is substantial evidence that systemic anticancer therapies and radiotherapy can increase the long-term risk of cardiovascular disease (CVD). Optimal management decisions for cancer patients therefore need to take into account the likely risks from a proposed treatment option, as well as its likely benefits. For CVD, the magnitude of the risk depends on the incidence of the disease in the general population to which the patient belongs, including variation with age and sex, as well as on the treatment option under consideration. The aim of this paper is to provide estimates of CVD incidence rates in the general population of England for use in cardio-oncology and in other relevant clinical, research and health policy contexts.

Methods

We studied a population-based representative cohort, consisting of 2,633,472 individuals, derived by electronic linkage of records from primary care with those of admitted-patient care in England during April 1, 2010, to April 1, 2015. From 38 individual CVDs available via the linked dataset we identified five relevant categories of CVD whose risk may be increased by cancer treatments: four of heart disease and one of stroke.

Results

We calculated incidence rates by age-group and sex for all relevant CVD categories combined, for the four relevant categories of heart disease combined, and for the five relevant CVD categories separately. We present separate incidence rates for all 38 individual CVDs available via the linked dataset. We also illustrate how our data can be used to estimate absolute CVD risks in a range of people with Hodgkin lymphoma treated with chemotherapy and radiotherapy.

Conclusions

Our results provide population-based CVD incidence rates for a variety of uses, including the estimation of absolute risks of CVD from cancer treatments, thus helping patients and clinicians to make appropriate individualized cancer treatment decisions.

Graphical Abstract

Graphical Abstract: Cardiovascular incidence rates for use in cardio-oncology and elsewhere: A presentation of age- and sex-specific cardiovascular disease (CVD) incidence rates for use in calculation of absolute cardiovascular risks of cancer treatments, and in other clinical, research and health policy contexts. Abbreviations
– CVD: cardiovascular disease; y: years
The landscape of drug resistance in Plasmodium falciparum malaria in the Democratic Republic of Congo: a mapping systematic review
Authors: Kayiba Nadine Kalenda , Tshibangu-Kabamba Evariste , Rosas-Aguirre Angel , Kaku Natsuko , Nakagama Yu , Kaneko Akira , Makaba Dieudonné Mvumbi , Malekita Doudou Yobi , Devleesschauwer Brecht , Likwela Joris Losimba , Zakayi Pius Kabututu , DeMol Patrick , Lelo Georges Mvumbi , Hayette Marie-Pierre , Dikassa Paul Lusamba , Kido Yasutoshi , Speybroeck Niko
Published: November 2023

Context

The Democratic Republic of Congo (DRC), one of the most malaria-affected countries worldwide, is a potential hub for global drug-resistant malaria. This study aimed at summarizing and mapping surveys of malaria parasites carrying molecular markers of drug-resistance across the country.

Methods

A systematic mapping review was carried out before July 2023 by searching for relevant articles through seven databases (PubMed, Embase, Scopus, African Journal Online, African Index Medicus, Bioline and Web of Science).

Results

We identified 1541 primary studies of which 29 fulfilled inclusion criteria and provided information related to 6385 Plasmodium falciparum clinical isolates (collected from 2000 to 2020). We noted the PfCRT K76T mutation encoding for chloroquine-resistance in median 32.1% [interquartile interval, IQR: 45.2] of analyzed malaria parasites. The proportion of parasites carrying this mutation decreased overtime, but wide geographic variations persisted. A single isolate had encoded the PfK13 R561H substitution that is invoked in artemisinin-resistance emergence in the Great Lakes region of Africa. Parasites carrying various mutations linked to resistance to the sulfadoxine–pyrimethamine combination were widespread and reflected a moderate resistance profile (PfDHPS A437G: 99.5% [IQR: 3.9]; PfDHPS K540E: 38.9% [IQR: 47.7]) with median 13.1% [IQR: 10.3] of them being quintuple IRN–GE mutants (i.e., parasites carrying the PfDHFR N51I–C59R–S108N and PfDHPS A437G–K540E mutations). These quintuple mutants tended to prevail in eastern regions of the country. Among circulating parasites, we did not record any parasites harboring mutations related to mefloquine-resistance, but we could suspect those with decreased susceptibility to quinine, amodiaquine, and lumefantrine based on corresponding molecular surrogates.

Conclusions

Drug resistance poses a serious threat to existing malaria therapies and chemoprevention options in the DRC. This review provides a baseline for monitoring public health efforts as well as evidence for decision-making in support of national malaria policies and for implementing regionally tailored control measures across the country.
Prevalence and risk factors associated with drug-resistant epilepsy in adult epileptic patients
Authors: Marouf Hazem , Mohamed Lobna A. , El Ftatary Amr , Gaber Dina Elsayed
Published: November 2023

Background

Despite the plethora of pharmacotherapy and acquisition of new AEDs, there is a hard core of patients who persistently fail to respond to optimal treatment and continue to suffer from refractory seizures. We aimed to study the prevalence and risk factors for development of drug-resistant epilepsy (DRE). All adult patients with epilepsy (PWE) who attended the epilepsy outpatient clinic and were maintained on at least two anti-epileptic drugs (AEDs) were profiled for drug response in accordance with the International League against Epilepsy (ILAE) 2010 consensus definition for DRE. Data collected included demographics, detailed history of seizures, medications history, past medical and psychiatric history, electroencephalogram, and brain imaging findings.

Results

The prevalence rate of DRE was 21.3% in the study population. Significant variables on univariate analysis were the following: male gender (OR: 5.409, CI 1.661–17.617, p < 0.005), presence of GTC (OR: 4.187, CI 1.304–13.445, p < 0.016), no change in frequency after AEDs use (OR: 4.465, CI 1.211–16.468, p < 0.025), bad response to first AEDs (OR: 9.000, CI 2.437–33.244, p < 0.001), presence of developmental delay (OR: 10.612, CI 1.347–83.589, p < 0.025), presence of abnormal neurological examination (OR: 4.227, CI 1.145–15.601, p < 0.030), generalized epilepsy (OR: 3.886, CI 1.141–13.233, p < 0.030), presence of structural etiology (OR: 3.467, CI 1.152–10.431, p < 0.027), abnormal EEG findings (OR: 3.467, CI 1.152–10.431, p < 0.027), presence of focal activity in EEG (OR: 5.344, CI 1.155–24.713, p < 0.032), and abnormal imaging findings (OR: 3.524, CI 1.083–11.473, p < 0.036). In the logistic regression analysis, two variables were statistically significant: bad response to the first AED and no change in seizure frequencies with treatment. Our study showed that older age at seizure onset was a protective factor for DRE.

Conclusions

The current study suggests that significant risk factors for DRE are younger age at epilepsy onset, poor response to first AED and lack of change in seizure frequencies after adjusting treatment.