bluuebunny/crossref_metadata_2025 huggingface dataset:
Understanding the interplay of colorectal cancer awareness and attitudes among Palestinians: a national cross-sectional study
Authors: Elshami Mohamedraed , Dwikat Mohammad Fuad , Al-Slaibi Ibrahim , Alser Mohammed , Albandak Maram Elena , Ayyad Mohammed , Naji Shoruq Ahmed , Mohamad Balqees Mustafa , Isleem Wejdan Sudki , Shurrab Adela , Yaghi Bashar , Qabaja Yahya Ayyash , Hamdan Fatma Khader , Sweity Raneen Raed , Jneed Remah Tayseer , Assaf Khayria Ali , Hmaid Mohammed Madhat , Awwad Iyas Imad , Alhabil Belal Khalil , Alarda Marah Naser , Alsattari Amani Saleh , Aboyousef Moumen Sameer , Aljbour Omar Abdallah , AlSharif Rinad , Giacaman Christy Teddy , Alnaga Ali Younis , Nemer Ranin Mufid Abu , Almadhoun Nada Mahmoud , Skaik Sondos Mahmoud , Albarqi Shurouq I. , Abu-El-Noor Nasser , Bottcher Bettina
Published: May 2024

Background

In Palestine, colorectal cancer (CRC) is the second most common cause of cancer-related mortality after lung cancer. No studies have examined the relationship between CRC awareness and attitudes. This study aimed to investigate the interplay between CRC awareness and attitudes among the Palestinian population.

Methods

A nationwide cross-sectional survey was carried out between July 2019 and March 2020. Convenience sampling was used to collect data from hospitals, primary healthcare facilities, and public areas in 11 governorates. Modified, translated-into-Arabic versions of the validated Bowel Cancer Awareness Measure and Cancer Awareness Measure-Mythical Causes Scale were utilized to assess the awareness of CRC signs/symptoms, risk factors, and causation myths. The cumulative awareness score for each domain was computed and stratified into tertiles. The top tertile denoted ‘high’ awareness, while the remaining two tertiles denoted ‘low’ awareness.

Results

The final analysis included 4,623 participants; of whom, 3115 (67.4%) reported positive attitudes toward CRC. In total, 1,849 participants (40.0%) had high awareness of CRC signs/symptoms. There was no association between displaying a high awareness of CRC signs/symptoms and having positive attitudes toward CRC. A total of 1,840 participants (38.9%) showed high awareness of CRC risk factors. Participants with high CRC risk factor awareness were more likely to display positive attitudes toward CRC (OR = 1.22, 95% CI: 1.07–1.39). Only 219 participants (4.7%) had high awareness of CRC causation myths. Participants with high awareness of CRC causation myths were more likely to exhibit positive attitudes toward CRC (OR = 2.48, 95% CI: 1.71–3.58).

Conclusion

A high awareness level of CRC risk factors and causation myths was associated with a greater likelihood of demonstrating positive attitudes toward CRC in terms of perceived susceptibility, importance of early detection, and consequences of developing the disease. Future educational interventions should focus on raising public awareness about CRC, with a particular emphasis on risk factors and causation myths, to maximize the potential for shaping favorable attitudes toward the disease.
Increased family psychosocial focus during children’s developmental assessments: a study of parents’ views
Authors: Strøyer de Voss Sarah , Wilson Philip Michael John , Kirk Ertmann Ruth , Overbeck Gritt
Published: May 2024

Background

Family psychosocial challenges during the early years of a child’s life are associated with later mental and physical health problems for the child. An increased psychosocial focus on parents in routine child developmental assessments may therefore be justified.

Methods

Participants in this qualitative study included 11 mothers and one parental couple (mother and father) with children aged 9–23 months. Participants were recruited to Project Family Wellbeing through their general practice in Denmark. Twelve interviews were conducted, transcribed and analysed with a deductive approach. The topic guide drew on the core components of the Health Belief Model, which also served as a framework for the coding that was conducted using thematic analysis.

Results

Results are presented in four themes and 11 subthemes in total. Parents welcome discussion of their psychosocial circumstances during their child’s developmental assessments. Clinicians’ initiatives to address psychosocial challenges and alignment of parents’ and clinicians’ expectations may be required to allow this discussion. A flowing conversation, an open communication style and a trustful relationship facilitate psychosocial discussion. Barriers included short consultation time, concerns about how information was used and when parents found specific psychosocial aspects stigmatising or irrelevant to discuss.

Conclusion

Enquiry about the family’s psychosocial circumstances in routine developmental assessments is acceptable among parents. Alignment of clinical and parental expectations of developmental assessments could facilitate the process. Future research should examine the predictive validity of the various components of developmental assessments.

Trial registration

This is a qualitative study. The study participants are part of the cohort from Project Family Wellbeing (FamilieTrivsel). The project’s trial registry number: NCT04129359. Registered October 16th 2019.
Wine- and stir-frying processing of Cuscutae Semen enhance its ability to alleviate oxidative stress and apoptosis via the Keap 1-Nrf2/HO-1 and PI3K/AKT pathways in H2O2-challenged KGN human granulosa cell line
Authors: Liang Yusha , Shi Yun , Guo Rong , Xu Changli , Fu Mian , Shen Jinyang , Gao Xun , Li Weidong , Qin Kunming
Published: May 2024

Background

Cuscutae Semen (CS) has been prescribed in traditional Chinese medicine (TCM) for millennia as an aging inhibitor, an anti-inflammatory agent, a pain reliever, and an aphrodisiac. Its three main forms include crude Cuscutae Semen (CCS), wine-processed CS (WCS), and stir-frying-processed CS (SFCS). Premature ovarian insufficiency (POI) is a globally occurring medical condition. The present work sought a highly efficacious multi-target therapeutic approach against POI with minimal side effects. Finally, it analyzed the relative differences among CCS, WCS and SFCS in terms of their therapeutic efficacy and modes of action against H2O2-challenged KGN human granulosa cell line.

Methods

In this study, ultrahigh-performance liquid chromatography (UPLC)-Q-ExactiveTM Orbitrap-mass spectrometry (MS), oxidative stress indices, reactive oxygen species (ROS), Mitochondrial membrane potential (MMP), real-time PCR, Western blotting, and molecular docking were used to investigate the protective effect of CCS, WCS and SFCS on KGN cells oxidative stress and apoptosis mechanisms.

Results

The results confirmed that pretreatment with CCS, WCS and SFCS reduced H2O2-induced oxidative damage, accompanied by declining ROS levels and malondialdehyde (MDA) accumulation in the KGN cells. CCS, WCS and SFCS upregulated the expression of antioxidative levels (GSH, GSH/GSSG ratio, SOD, T-AOC),mitochondrial membrane potential (MMP) and the relative mRNA(Nrf2, Keap1, NQO-1, HO-1, SOD-1, CAT). They inhibited apoptosis by upregulating Bcl-2, downregulating Bax, cleaved caspase-9, and cleaved caspase-3, and lowering the Bax/Bcl-2 ratio. They also exerted antioxidant efficacy by partially activating the PI3K/Akt and Keap1-Nrf2/HO-1 signaling pathways.

Conclusions

The results of the present work demonstrated the inhibitory efficacy of CCS, WCS and SFCS against H2O2-induced oxidative stress and apoptosis in KGN cells and showed that the associated mechanisms included Keap1-Nrf2/HO-1 activation, P-PI3K upregulation, and P-Akt-mediated PI3K-Akt pathway induction.
Reflect to interact – fostering medical students’ communication through reflection-focused e-learning
Authors: Janssen Laura , Schick Kristina , Neurohr Tiziana , Pittroff Sylvia Irene Donata , Reiser Sabine , Bauer Johannes , Berberat Pascal O. , Gartmeier Martin
Published: May 2024

Background

Previous research indicates that reflection can foster medical communication competence. However, best practices for embedding reflection in online medical education are missing. This study examined how reflection processes can be promoted and embedded in an e-learning course on physician–patient communication to foster learning.

Methods

We investigated three differently designed e-learning conditions featuring different proportions of reflection triggers and compared their effects on students’ reflections. We had 114 medical students in their first clinical year complete one of the variants: video modelling (VM, n = 39), video reflection (VR, n = 39), or a variant merging both approaches (VMR, n = 36). Each student wrote a total of nine reflections based on the same guiding questions at three time points embedded in the course. The students’ levels of reflection were measured using an adapted version of the REFLECT rubric (scale 0–18).

Results

Students of all course variants achieved good levels of reflection beyond the descriptive level at all three time points, with no significant differences between the variants. The mean reflection scores at the end of the course were M = 14.22 for VM (SD = 2.23), M = 13.56 for VR (SD = 2.48), and M = 13.24 for VMR (SD = 2.21). Students who completed VM showed significantly improved levels of reflection over the course, whereas we found no statistically significant development for those in VR or VMR. The reflection scores correlated significantly positively with each other, as did the text lengths of the written reflections. Reflection scores also correlated significantly positively with text length.

Conclusions

Our study offers a teaching strategy that can foster good levels of reflection, as demonstrated in the three e-learning variants. The developed reflection prompts can be easily embedded in various e-learning environments and enable reflections of good quality, even in settings with limited available teaching time.
The effect of spaced E-Learning on knowledge of basic life support and satisfaction of nursing students: a quasi-experimental study
Authors: Ranjbar Fataneh , Sharif-Nia Hamid , Shiri Maryam , Rahmatpour Pardis
Published: May 2024

Aim

Cardiopulmonary resuscitation (CPR) training is essential for all students, especially nursing students. One of the educational approaches to creating long-term learning in inclusive is spaced learning. Spaced learning consists of three or more training sessions in which information is presented over time and at intervals. The present study was conducted to investigate the effect of basic life support (BLS) training through spaced E-learning on the knowledge and satisfaction of nursing students.

Methods

In this quasi-experimental study with two groups, 106 undergraduate nursing students of Alborz University of Medical Sciences in Iran participated. The control group (n = 47) received BLS training with massed E-learning in one three-hour session, and the intervention group (n = 59) received spaced E-learning in three one-hour sessions. An electronic questionnaire including demographic information and a pre-test of BLS knowledge were sent to both groups. Also, immediately after receiving the training, two weeks later and one month later, they completed a post-test of BLS knowledge. Students were asked to indicate their level of satisfaction with the provided education by completing the SLS-OLE.

Results

The post-test scores immediately after, two weeks later, and one month later of the intervention group were higher than the control group. The results of repeated measurement ANOVA showed that the score changes of knowledge are significant over time (p < 0.001), the number of sessions (p < 0.001), and the interactive effect of them (p < 0.001). There was no statistically significant difference in the level of satisfaction with education in both groups.

Conclusion

Based on the results, BLS training in both groups increased the knowledge of BLS. however, the increase in knowledge and its retention was higher in the intervention group that received the training in spaced learning.
Rethinking causal assumptions about maternal BMI, gestational weight gain, and adverse pregnancy outcomes
Authors: Dodd Jodie M. , Louise Jennie , Deussen Andrea R. , Mitchell Megan , Poston Lucilla
Published: May 2024

Background

The aim of this study was to evaluate commonly assumed causal relationships between body mass index (BMI), gestational weight gain (GWG), and adverse pregnancy outcomes, which have formed the basis of guidelines and interventions aimed at limiting GWG in women with overweight or obesity. We explored relationships between maternal BMI, total GWG (as a continuous variable and as ‘excessive’ GWG), and pregnancy outcomes (including infant birthweight measures and caesarean birth).

Methods

Analysis of individual participant data (IPD) from the i-WIP (International Weight Management in Pregnancy) Collaboration, from randomised trials of diet and/or physical activity interventions during pregnancy reporting GWG and maternal and neonatal outcomes.

Women randomised to the control arm of 20 eligible randomised trials (4370 of 8908 participants) from the i-WIP dataset of 36 randomised trials (total 12,240 women). The main research questions were to characterise the relationship between maternal BMI and (a) total GWG, (b) the risk of ‘excessive’ GWG (using the Institute of Medicine’s guidelines), and (c) adverse pregnancy outcomes as mediated via GWG versus other pathways to determine the extent to which the observed effect of maternal BMI on pregnancy outcomes is mediated via GWG. We utilised generalised linear models and regression-based mediation analyses within an IPD meta-analysis framework.

Results

Mean GWG decreased linearly as maternal BMI increased; however, the risk of ‘excessive’ GWG increased markedly at BMI category thresholds (i.e. between the normal and overweight BMI category threshold and between the overweight and obese BMI category threshold). Increasing maternal BMI was associated with increased risk of all pregnancy outcomes assessed; however, there was no evidence that this effect was mediated via effects on GWG.

Conclusions

There is evidence of a meaningful relationship between maternal BMI and GWG and between maternal BMI and adverse pregnancy outcomes. There is no evidence that the effect of maternal BMI on outcomes is via an effect on GWG. Our analyses also cast doubt on the existence of a relationship between ‘excessive’ GWG and adverse pregnancy outcomes. Our findings challenge the practice of actively managing GWG throughout pregnancy.
Construction of an enzyme-constrained metabolic network model for Myceliophthora thermophila using machine learning-based kcat data
Authors: Wang Yutao , Mao Zhitao , Dong Jiacheng , Zhang Peiji , Gao Qiang , Liu Defei , Tian Chaoguang , Ma Hongwu
Published: May 2024

Background

Genome-scale metabolic models (GEMs) serve as effective tools for understanding cellular phenotypes and predicting engineering targets in the development of industrial strain. Enzyme-constrained genome-scale metabolic models (ecGEMs) have emerged as a valuable advancement, providing more accurate predictions and unveiling new engineering targets compared to models lacking enzyme constraints. In 2022, a stoichiometric GEM, iDL1450, was reconstructed for the industrially significant fungus Myceliophthora thermophila. To enhance the GEM’s performance, an ecGEM was developed for M. thermophila in this study.

Results

Initially, the model iDL1450 underwent refinement and updates, resulting in a new version named iYW1475. These updates included adjustments to biomass components, correction of gene-protein-reaction (GPR) rules, and a consensus on metabolites. Subsequently, the first ecGEM for M. thermophila was constructed using machine learning-based kcat data predicted by TurNuP within the ECMpy framework. During the construction, three versions of ecGEMs were developed based on three distinct kcat collection methods, namely AutoPACMEN, DLKcat and TurNuP. After comparison, the ecGEM constructed using TurNuP-predicted kcat values performed better in several aspects and was selected as the definitive version of ecGEM for M. thermophila (ecMTM). Comparing ecMTM to iYW1475, the solution space was reduced and the growth simulation results more closely resembled realistic cellular phenotypes. Metabolic adjustment simulated by ecMTM revealed a trade-off between biomass yield and enzyme usage efficiency at varying glucose uptake rates. Notably, hierarchical utilization of five carbon sources derived from plant biomass hydrolysis was accurately captured and explained by ecMTM. Furthermore, based on enzyme cost considerations, ecMTM successfully predicted reported targets for metabolic engineering modification and introduced some new potential targets for chemicals produced in M. thermophila.

Conclusions

In this study, the incorporation of enzyme constraint to iYW1475 not only improved prediction accuracy but also broadened the model’s applicability. This research demonstrates the effectiveness of integrating of machine learning-based kcat data in the construction of ecGEMs especially in situations where there is limited measured enzyme kinetic parameters for a specific organism.
Efficacy of Pirikool® 300 CS used for indoor residual spraying on three different substrates in semi-field experimental conditions
Authors: Fodjo Behi Kouadio , Tchicaya Emile , Yao Laurence Aya , Edi Constant , Ouattara Alassane Foungoye , Kouassi Loukou Bernard , Yokoly Firmain N’dri , Benjamin Koudou Guibéhi
Published: May 2024

Background

Vector control using insecticides is a key prevention strategy against malaria. Unfortunately, insecticide resistance in mosquitoes threatens all progress in malaria control. In the perspective of managing this resistance, new insecticide formulations are being tested to improve the effectiveness of vector control tools.

Methods

The efficacy and residual activity of Pirikool® 300 CS was evaluated in comparison with Actellic® 300 CS in experimental huts at the Tiassalé experimental station on three substrates including cement, wood and mud. The mortality, blood-feeding inhibition, exiting behaviour and deterrency of free-flying wild mosquitoes was evaluated. Cone bioassay tests with susceptible and resistant mosquito strains were conducted in the huts to determine residual efficacy.

Results

A total of 20,505 mosquitoes of which 10,979 (53%) wild female Anopheles gambiae were collected for 112 nights. Residual efficacy obtained from monthly cone bioassay was higher than 80% with the susceptible, laboratory-maintained An. gambiae Kisumu strain, from the first to the tenth study period on all three types of treated substrate for both Actellic® 300CS and Pirikool® 300CS. This residual efficacy on the wild Tiassalé strain was over 80% until the 4th month of study on Pirikool® 300CS S treated substrates. Overall 24-h mortalities of wild free-flying An. gambiae sensu lato which entered in the experimental huts over the 8-months trial on Pirikool® 300CS treatment was 50.5%, 75.9% and 52.7%, respectively, on cement wall, wood wall and mud wall. The positive reference product Actellic® 300CS treatment induced mortalities of 42.0%, 51.8% and 41.8% on cement wall, wood wall and mud wall.

Conclusion

Pirikool® 300CS has performed really well against resistant strains of An. gambiae using indoor residual spraying method in experimental huts. It could be an alternative product for indoor residual spraying in response to the vectors' resistance to insecticides.
Cost-effectiveness of village health worker-led integrated community case management (iCCM) versus health facility based management for childhood illnesses in rural southwestern Uganda
Authors: Mulogo Edgar , Ntaro Moses , Wesuta Andrew , Namusisi Jane , Kawungezi Peter , Batwala Vincent , Matte Michael
Published: May 2024

Background

In Uganda, village health workers (VHWs) manage childhood illness under the integrated community case management (iCCM) strategy. Care is provided for malaria, pneumonia, and diarrhoea in a community setting. Currently, there is limited evidence on the cost-effectiveness of iCCM in comparison to health facility-based management for childhood illnesses. This study examined the cost-effectiveness of the management of childhood illness using the VHW-led iCCM against health facility-based services in rural south-western Uganda.

Methods

Data on the costs and effectiveness of VHW-led iCCM versus health facility-based services for the management of childhood illness was collected in one sub-county in rural southwestern Uganda. Costing was performed using the ingredients approach. Effectiveness was measured as the number of under-five children appropriately treated. The Incremental Cost-Effectiveness Ratio (ICER) was calculated from the provider perspective.

Results

Based on the decision model for this study, the cost for 100 children treated was US$628.27 under the VHW led iCCM and US$87.19 for the health facility based services, while the effectiveness was 77 and 71 children treated for VHW led iCCM and health facility-based services, respectively. An ICER of US$6.67 per under five-year child treated appropriately for malaria, pneumonia and diarrhoea was derived for the provider perspective.

Conclusion

The health facility based services are less costly when compared to the VHW led iCCM per child treated appropriately. The VHW led iCCM was however more effective with regard to the number of children treated appropriately for malaria, pneumonia and diarrhoea. Considering the public health expenditure per capita for Uganda as the willingness to pay threshold, VHW led iCCM is a cost-effective strategy. VHW led iCCM should, therefore, be enhanced and sustained as an option to complement the health facility-based services for treatment of childhood illness in rural contexts.
Causal relationship of interleukin-6 and its receptor on sarcopenia traits using mendelian randomization
Authors: Chen Baixing , Li Shaoshuo , Lin Shi , Dong Hang
Published: May 2024

Background

Previous research has extensively examined the role of interleukin 6 (IL-6) in sarcopenia. However, the presence of a causal relationship between IL-6, its receptor (IL-6R), and sarcopenia remains unclear.

Method

In this study, we utilized summary-level data from genome-wide association studies (GWAS) focused on appendicular lean mass (ALM), hand grip strength, and walking pace. Single nucleotide polymorphisms (SNPs) were employed as genetic instruments for IL-6 and IL-6R to estimate the causal effect of sarcopenia traits. We adopted the Mendelian randomization (MR) approach to investigate these associations using the inverse variance weighted (IVW) method as the primary analytical approach. Additionally, we performed sensitivity analyses to validate the reliability of the MR results.

Result

This study revealed a significant negative association between main IL-6R and eQTL IL-6R on the left grip strength were − 0.013 (SE = 0.004, p < 0.001) and -0.029 (SE = 0.007, p < 0.001), respectively. While for the right grip strength, the estimates were − 0.011 (SE = 0.001, p < 0.001) and − 0.021 (SE = 0.008, p = 0.005). However, no evidence of an association for IL-6R with ALM and walking pace. In addition, IL-6 did not affect sarcopenia traits.

Conclusion

Our study findings suggest a negative association between IL-6R and hand grip strength. Additionally, targeting IL-6R may hold potential value as a therapeutic approach for the treatment of hand grip-related issues.
iTRAQ-based proteomic study on monocyte cell model discovered an association of LAMP2 downregulation with HIV-1 latency
Authors: Yin Lin , Wang Qimin , Liu Siyuan , Chen Jun , Zhang Yujiao , Lu Lingqing , Lu Hongzhou , Song Zhigang , Zhang Lijun
Published: May 2024

Background

Patients with immunodeficiency virus-1 (HIV-1) infection are challenging to be cured completely due to the existence of HIV-1 latency reservoirs. However, the knowledge of the mechanisms and biomarkers associated with HIV-1 latency is limited. Therefore, identifying proteins related to HIV-1 latency could provide new insights into the underlying mechanisms of HIV-1 latency, and ultimately contribute to the eradication of HIV reservoirs.

Methods

An Isobaric Tags for Relative and Absolute Quantification (iTRAQ)-labeled subcellular proteomic study was performed on an HIV-1 latently infected cell model (U1, a HIV-1-integrated U937 cell line) and its control (U937). Differentially expressed proteins (DEPs) were analyzed using STRING-DB. Selected DEPs were further evaluated by western blotting and multiple reaction monitoring technology in both cell model and patient-derived cluster of differentiation 4 (CD4)+ T cells. Finally, we investigated the relationship between a specific DEP lysosome-associated membrane glycoprotein 2 (LAMP2) and HIV-1 reactivation by panobinostat or lysosome regulation by a lysosomotropic agent hydroxychloroquine in U1 and U937 cells.

Results

In total, 110 DEPs were identified in U1 cells comparing to U937 control cells. Bioinformatics analysis suggested associations of the altered proteins with the immune response and endosomal/lysosomal pathway. LAMP2, leukocyte surface antigen CD47, CD55, and ITGA6 were downregulated in HIV-1 latent cells. Downregulated LAMP2 was further confirmed in resting CD4+ T cells from patients with latent HIV-1 infection. Furthermore, both HIV-1 reactivation by panobinostat and stimulation with hydroxychloroquine upregulated LAMP2 expression.

Conclusions

Our results indicated the involvement of the endosomal/lysosomal pathway in HIV-1 latency in macrophage cell model. The down-modulation of LAMP2 was associated with HIV latency, and the restoration of LAMP2 expression accompanied the transition of viral latency to active infection. This study provides new insights into the mechanism of HIV-1 latency and potential strategies for eradicating HIV-1 reservoirs by targeting LAMP2 expression.
Knockdown of trem2 promotes proinflammatory microglia and inhibits glioma progression via the JAK2/STAT3 and NF-κB pathways
Authors: Yan Yunji , Bai Shengwei , Han Hongxi , Dai Junqiang , Niu Liang , Wang Hongyu , Dong Qiang , Yin Hang , Yuan Guoqiang , Pan Yawen
Published: May 2024

Background

In the tumor immune microenvironment (TIME), triggering receptor expressed on myeloid cells 2 (trem2) is widely considered to be a crucial molecule on tumor-associated macrophages(TAMs). Multiple studies have shown that trem2 may function as an immune checkpoint in various malignant tumors, mediating tumor immune evasion. However, its specific molecular mechanisms, especially in glioma, remain elusive.

Methods

Lentivirus was transfected to establish cells with stable knockdown of trem2. A Transwell system was used for segregated coculture of glioma cells and microglia. Western blotting, quantitative real-time polymerase chain reaction (qRT‒PCR), and immunofluorescence (IF) were used to measure the expression levels of target proteins. The proliferation, invasion, and migration of cells were detected by colony formation, cell counting kit-8 (CCK8), 5-ethynyl-2’-deoxyuridine (EdU) and transwell assays. The cell cycle, apoptosis rate and reactive oxygen species (ROS) level of cells were assessed using flow cytometry assays. The comet assay and tube formation assay were used to detect DNA damage in glioma cells and angiogenesis activity, respectively. Gl261 cell lines and C57BL/6 mice were used to construct the glioma orthotopic transplantation tumor model.

Results

Trem2 was highly overexpressed in glioma TAMs. Knocking down trem2 in microglia suppressed the growth and angiogenesis activity of glioma cells in vivo and in vitro. Mechanistically, knockdown of trem2 in microglia promoted proinflammatory microglia and inhibited anti-inflammatory microglia by activating jak2/stat1 and inhibiting the NF-κB p50 signaling pathway. The proinflammatory microglia produced high concentrations of nitric oxide (NO) and high levels of the proinflammatory cytokines TNF-α, IL-6, and IL-1β, and caused further DNA damage and promoted the apoptosis rate of tumor cells.

Conclusions

Our findings revealed that trem2 in microglia plays a significant role in the TIME of gliomas. Knockdown of trem2 in microglia might help to improve the efficiency of inhibiting glioma growth and delaying tumor progression and provide new ideas for further treatment of glioma.
Learning from the Active Hospital-Based Cancer Registry in India: An Ethnography Study
Authors: Jena Shubharanjan , Epari Venkatarao , Sahoo Krushna Chandra , Pradhan Smruti Priyambada , Agrawala Sunil , Padhi Sanjukta
Published: May 2024

Purpose

The increasing incidence of cancer in low- and middle-income countries highlights the need for better cancer data management. Hospital-based cancer registries (HBCRs) enhance patient outcomes by managing cancer data, reviewing clinical performance and allocating resources. However, sustainability remains a challenge despite government initiatives. Therefore, this study documented the functionalities, core processes, and team involvement of active HBCRs in India, aiming to identify factors that facilitate their sustainability.

Methods

An ethnographic study was conducted in two Indian hospitals, one specializing in cancer care and the other offering multispecialty services, focusing on their HBCRs. The study involved process observations, interviews, and record reviews, with thematic analysis guided by ethnographic investigations. The staff managing the HBCRs were key participants.

Results

The findings are categorized into three themes: (1) existing management strategies and infrastructure, (2) the implementation process, and (3) the sustainability and scalability of the registry model. This study highlights the key factors necessary for a sustainable HBCR, including human resources, training, and a well-structured management system. The involvement of oncologists and physicians, funding, qualified staff, adequate space, and digitalization are crucial for success. Data management errors can be minimized through training, while interdepartmental coordination and data quality play essential roles.

Conclusion

This study offers critical insights into enhancing cancer surveillance systems, thereby improving cancer care and public health interventions in India and similar contexts worldwide. Policymakers and healthcare practitioners can leverage these findings to strengthen existing systems and address the growing burden of cancer effectively.
Development of an interpretable machine learning model associated with genetic indicators to identify Yin-deficiency constitution
Authors: Li Jing , Zhai Yingying , Cao Yanqi , Xia Yifan , Yu Ruoxi
Published: May 2024

Background

Traditional Chinese Medicine (TCM) defines constitutions which are relevant to corresponding diseases among people. As one of the common constitutions, Yin-deficiency constitution influences a number of Chinese population in the disease onset. Therefore, accurate Yin-deficiency constitution identification is significant for disease prevention and treatment.

Methods

In this study, we collected participants with Yin-deficiency constitution and balanced constitution, separately. The least absolute shrinkage and selection operator (LASSO) and logistic regression were used to analyze genetic predictors. Four machine learning models for Yin-deficiency constitution classification with multiple combined genetic indicators were integrated to analyze and identify the optimal model and features. The Shapley Additive exPlanations (SHAP) interpretation was developed for model explanation.

Results

The results showed that, NFKBIA, BCL2A1 and CCL4 were the most associated genetic indicators with Yin-deficiency constitution. Random forest with three genetic predictors including NFKBIA, BCL2A1 and CCL4 was the optimal model, area under curve (AUC): 0.937 (95% CI 0.844–1.000), sensitivity: 0.870, specificity: 0.900. The SHAP method provided an intuitive explanation of risk leading to individual predictions.

Conclusion

We constructed a Yin-deficiency constitution classification model based on machine learning and explained it with the SHAP method, providing an objective Yin-deficiency constitution identification system in TCM and the guidance for clinicians.
Fusogenic vesicular stomatitis virus combined with natural killer T cell immunotherapy controls metastatic breast cancer
Authors: Nelson Adam , McMullen Nichole , Gebremeskel Simon , De Antueno Roberto , Mackenzie Duncan , Duncan Roy , Johnston Brent
Published: May 2024

Background

Metastatic breast cancer is a leading cause of cancer death in woman. Current treatment options are often associated with adverse side effects and poor outcomes, demonstrating the need for effective new treatments. Immunotherapies can provide durable outcomes in many cancers; however, limited success has been achieved in metastatic triple negative breast cancer. We tested whether combining different immunotherapies can target metastatic triple negative breast cancer in pre-clinical models.

Methods

Using primary and metastatic 4T1 triple negative mammary carcinoma models, we examined the therapeutic effects of oncolytic vesicular stomatitis virus (VSVΔM51) engineered to express reovirus-derived fusion associated small transmembrane proteins p14 (VSV-p14) or p15 (VSV-p15). These viruses were delivered alone or in combination with natural killer T (NKT) cell activation therapy mediated by adoptive transfer of α-galactosylceramide-loaded dendritic cells.

Results

Treatment of primary 4T1 tumors with VSV-p14 or VSV-p15 alone increased immunogenic tumor cell death, attenuated tumor growth, and enhanced immune cell infiltration and activation compared to control oncolytic virus (VSV-GFP) treatments and untreated mice. When combined with NKT cell activation therapy, oncolytic VSV-p14 and VSV-p15 reduced metastatic lung burden to undetectable levels in all mice and generated immune memory as evidenced by enhanced in vitro recall responses (tumor killing and cytokine production) and impaired tumor growth upon rechallenge.

Conclusion

Combining NKT cell immunotherapy with enhanced oncolytic virotherapy increased anti-tumor immune targeting of lung metastasis and presents a promising treatment strategy for metastatic breast cancer.
Association of area- and volumetric-mammographic density and breast cancer risk in women of Asian descent: a case control study
Authors: Mariapun Shivaani , Ho Weang-Kee , Eriksson Mikael , Mohd Taib Nur Aishah , Yip Cheng-Har , Rahmat Kartini , Hall Per , Teo Soo-Hwang
Published: May 2024

Background

Mammographic density (MD) has been shown to be a strong and independent risk factor for breast cancer in women of European and Asian descent. However, the majority of Asian studies to date have used BI-RADS as the scoring method and none have evaluated area and volumetric densities in the same cohort of women. This study aims to compare the association of MD measured by two automated methods with the risk of breast cancer in Asian women, and to investigate if the association is different for premenopausal and postmenopausal women.

Methods

In this case–control study of 531 cases and 2297 controls, we evaluated the association of area-based MD measures and volumetric-based MD measures with breast cancer risk in Asian women using conditional logistic regression analysis, adjusting for relevant confounders. The corresponding association by menopausal status were assessed using unconditional logistic regression.

Results

We found that both area and volume-based MD measures were associated with breast cancer risk. Strongest associations were observed for percent densities (OR (95% CI) was 2.06 (1.42–2.99) for percent dense area and 2.21 (1.44–3.39) for percent dense volume, comparing women in highest density quartile with those in the lowest quartile). The corresponding associations were significant in postmenopausal but not premenopausal women (premenopausal versus postmenopausal were 1.59 (0.95–2.67) and 1.89 (1.22–2.96) for percent dense area and 1.24 (0.70–2.22) and 1.96 (1.19–3.27) for percent dense volume). However, the odds ratios were not statistically different by menopausal status [p difference = 0.782 for percent dense area and 0.486 for percent dense volume].

Conclusions

This study confirms the associations of mammographic density measured by both area and volumetric methods and breast cancer risk in Asian women. Stronger associations were observed for percent dense area and percent dense volume, and strongest effects were seen in postmenopausal individuals.
High-definition transcranial direct current stimulation (HD-tDCS) in major depressive disorder with anxious distress—a study protocol for a double-blinded randomized sham-controlled trial
Authors: Zhang Danwei , Zhao Bei , Sun Xue , Ding Kaimo , Sun Jingjing , Tao Sheng
Published: May 2024

Background

Comorbid anxiety disorders and anxious distress are highly prevalent among individuals with major depressive disorder (MDD). The presence of the DSM-5 anxious distress specifier (ADS) has been associated with worse treatment outcomes and chronic disease course. Few studies have evaluated the therapeutic effects of High-definition transcranial direct current stimulation (HD-tDCS) on depressive and anxiety symptoms among MDD patients with ADS. The current randomized controlled trial aims to assess the efficacy of HD-tDCS as an augmentation therapy with antidepressants compared to sham-control in subjects of MDD with ADS.

Methods

MDD patients with ADS will be recruited and randomly assigned to the active HD-tDCS or sham HD-tDCS group. In both groups, patients will receive the active or sham intervention in addition to their pre-existing antidepressant therapy, for 2 weeks with 5 sessions per week, each lasting 30 min. The primary outcome measures will be the change of depressive symptoms, clinical response, and the remission rate as measured with the 17-item Hamilton Depression Rating Scale (HDRS-17) before and after the intervention and at the 2nd and 6th week after the completed intervention. Secondary outcome measures include anxiety symptoms, cognitive symptoms, disability assessment, and adverse effects.

Discussion

The HD-tDCS applied in this trial may have treatment effects on MDD with ADS and have minimal side effects.

Trial registration

The trial protocol is registered with www.chictr.org.cn under protocol registration number ChiCTR2300071726. Registered 23 May 2023.
Sex- and species-specific contribution of CD99 to T cell costimulation during multiple sclerosis
Authors: Winschel Ingo , Willing Anne , Engler Jan Broder , Walkenhorst Mark , Meurs Nina , Binkle-Ladisch Lars , Woo Marcel S. , Pfeffer Lena Kristina , Sonner Jana K. , Borgmeyer Uwe , Hagen Sven Hendrik , Grünhagel Benjamin , Claussen Janna M. , Altfeld Marcus , Friese Manuel A.
Published: May 2024

Background

Differences in immune responses between women and men are leading to a strong sex bias in the incidence of autoimmune diseases that predominantly affect women, such as multiple sclerosis (MS). MS manifests in more than twice as many women, making sex one of the most important risk factor. However, it is incompletely understood which genes contribute to sex differences in autoimmune incidence. To address that, we conducted a gene expression analysis in female and male human spleen and identified the transmembrane protein CD99 as one of the most significantly differentially expressed genes with marked increase in men. CD99 has been reported to participate in immune cell transmigration and T cell regulation, but sex-specific implications have not been comprehensively investigated.

Methods

In this study, we conducted a gene expression analysis in female and male human spleen using the Genotype-Tissue Expression (GTEx) project dataset to identify differentially expressed genes between women and men. After successful validation on protein level of human immune cell subsets, we assessed hormonal regulation of CD99 as well as its implication on T cell regulation in primary human T cells and Jurkat T cells. In addition, we performed in vivo assays in wildtype mice and in Cd99-deficient mice to further analyze functional consequences of differential CD99 expression.

Results

Here, we found higher CD99 gene expression in male human spleens compared to females and confirmed this expression difference on protein level on the surface of T cells and pDCs. Androgens are likely dispensable as the cause shown by in vitro assays and ex vivo analysis of trans men samples. In cerebrospinal fluid, CD99 was higher on T cells compared to blood. Of note, male MS patients had lower CD99 levels on CD4+ T cells in the CSF, unlike controls. By contrast, both sexes had similar CD99 expression in mice and Cd99-deficient mice showed equal susceptibility to experimental autoimmune encephalomyelitis compared to wildtypes. Functionally, CD99 increased upon human T cell activation and inhibited T cell proliferation after blockade. Accordingly, CD99-deficient Jurkat T cells showed decreased cell proliferation and cluster formation, rescued by CD99 reintroduction.

Conclusions

Our results demonstrate that CD99 is sex-specifically regulated in healthy individuals and MS patients and that it is involved in T cell costimulation in humans but not in mice. CD99 could potentially contribute to MS incidence and susceptibility in a sex-specific manner.
Cooperative Localization under Ionospheric Scintillation Events
Authors: Silva Paulo R. P. , Bruno Marcelo G. S. , Moraes Alison O.
Published: May 2024

Ionospheric scintillation causes major impairments to Global Navigation Satellite System (GNSS) in low-latitude regions. In severe scenarios, this event can lead to complete loss of lock, thus making GNSS measurements unusable for navigation. In this paper, we derive a cooperative localization algorithm where a set of partially connected aircraft exchange messages with neighboring nodes on the network to improve their own position estimates. We consider the scintillation events as abrupt changes in the measurement variance, which are modeled by a discrete-valued Markov process at the nodes which have access to GNSS measurements. Simulation results show that Markovian modeling and cooperation via factor graph message passing reduce the average 3D root mean square localization error and yield an average vertical position error that meets civil aviation standards for approach and landing.
Upper bounds for the spectral radius of matrices having the Perron–Frobenius property
Authors: Li Kaimin , Li Chaoqian
Published: May 2024

A new upper bound for the spectral radius of matrices having the Perron–Frobenius property is given by considering the position of positive entries. Some examples involving the largest zero of polynomials and the spectral radius of the iterative matrix for the Perron–Frobenius splitting are given to show the superiority of the theoretical result.
A proximal gradient method with double inertial steps for minimization problems involving demicontractive mappings
Authors: Mouktonglang Thanasak , Chaiwino Wipawinee , Suparatulatorn Raweerote
Published: May 2024

In this article, we present a novel proximal gradient method based on double inertial steps for solving fixed points of demicontractive mapping and minimization problems. We also establish a weak convergence theorem by applying this method. Additionally, we provide a numerical example related to a signal recovery problem.
MTG_CD: Multi-scale learnable transformation graph for fault classification and diagnosis in microservices
Authors: Chen Juan , Zhang Rui , Chen Peng , Ren Jianhua , Wu Zongling , Wang Yang , Li Xi , Xiong Ling
Published: May 2024

The rapid advancement of microservice architecture in the cloud has led to the necessity of effectively detecting, classifying, and diagnosing run failures in microservice applications. Due to the high dynamics of cloud environments and the complex dependencies between microservices, it is challenging to achieve robust real-time system fault identification. This paper proposes an interpretable fault diagnosis framework tailored for microservice architecture, namely Multi-scale Learnable Transformation Graph for Fault Classification and Diagnosis(MTG_CD). Firstly, we employ multi-scale neural transformation and graph structure adjacency matrix learning to enhance data diversity while extracting temporal-structural features from system monitoring metrics Secondly, a graph convolutional network (GCN) is utilized to fuse the extracted temporal-structural features in a multi-feature modeling approach, which helps to improve the accuracy of anomaly detection. To identify the root cause of system faults, we finally conduct a coarse-grained level diagnosis and exploration after obtaining the results of classifying the fault data. We evaluate the performance of MTG_CD on the microservice benchmark SockShop, demonstrating its superiority over several baseline methods in detecting CPU usage overhead, memory leak, and network delay faults. The average macro F1 score improves by 14.05%.
Evaluation of antioxidant and anti-inflammatory activity and identification of bioactive compound from the marine diatom, Odontella aurita extract
Authors: Cuong Do Manh , Yang Sun Hee , Kim Ji Soo , Moon Jeong Yong , Choi Jongkeun , Go Gyung Min , Cho Somi Kim
Published: May 2024

Increased production of reactive oxygen species (ROS) leads to oxidative stress, with its damaging effect extending to the mitochondria and plasma membrane. Further, prolonged inflammation can result in chronic disease development. The marine microdiatom Odontella aurita is recognized for its potential in food and pharmaceutical development. Moreover, it contains antioxidant and anti-inflammatory properties. However, studies regarding the efficacy of their varying extract forms and their underlying mechanisms remain scarce. Therefore, this study aims to explore the antioxidant and anti-inflammatory effects of Odontella aurita extracts obtained using various extraction methods (hot water, 70% ethanol, and chloroform:methanol (CM)). Among the three Odontella aurita extracts, the CM extract demonstrated superior efficacy in protecting RAW 264.7 cells from H2O2-induced cytotoxicity. It significantly lowered the levels of ROS and enhanced the expression of superoxide dismutase and glutathione peroxidase. Furthermore, the CM extract outperformed other extracts in inhibiting LPS-induced nitric oxide production, reducing mRNA levels in nitric oxide synthase, cyclooxygenase, and the proinflammatory cytokines interleukin IL-1β, IL-6, TNFα. Additionally, CM extract effectively suppressed the activation of NF-κB/IκBα and JAK2-STAT3 in LPS-induced RAW 264.7 cells. HPLC–UV analysis revealed a remarkable 33-fold higher fucoxanthin content in CM compared to the ethanol extract. GC–MS analysis identified elevated levels of cholest-5-en-3-ol, phytol, eicosapentaenoic acid methyl ester, methyl palmitate, palmitoleic acid methyl ester, and neophytadiene in the CM extract. These findings suggest that Odontella aurita CM extract is a promising antioxidant candidate for preventing or treating inflammatory diseases, consequently emphasizing its potential for further development.

Graphical Abstract