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Background: Despite advancements in antimicrobial therapies, bacteremia remains a life-threatening condition. Appropriate antimicrobials must be promptly administered to ensure patient survival. However, diagnosing bacteremia based on blood cultures is time-consuming and not something emergency department (ED) personnel are routinely trained to do., Methods: This retrospective cohort study developed several machine learning (ML) models to predict bacteremia in adults initially presenting with fever or hypothermia, comprising logistic regression, random forest, extreme gradient boosting, support vector machine, k-nearest neighbor, multilayer perceptron, and ensemble models. Random oversampling and synthetic minority oversampling techniques were adopted to balance the dataset. The variables included demographic characteristics, comorbidities, immunocompromised status, clinical characteristics, subjective symptoms reported during ED triage, and laboratory data. The study outcome was an episode of bacteremia., Results: Of the 5063 patients with initial fever or hypothermia from whom blood cultures were obtained, 128 (2.5 %) were diagnosed with bacteremia. We combined 36 selected variables and 10 symptoms subjectively reported by patients into features for analysis in our models. The ensemble model outperformed other models, with an area under the receiver operating characteristic curve (AUROC) of 0.930 and an F1-score of 0.735. The AUROC of all models was higher than 0.80., Conclusion: The ML models developed effectively predicted bacteremia among febrile or hypothermic patients in the ED, with all models demonstrating high AUROC values and rapid processing times. The findings suggest that ED clinicians can effectively utilize ML techniques to develop predictive models for addressing clinical challenges., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Background: Adequate death preparation positively influences families' experience before death and during bereavement. However, how to prepare families in non-Western cultures has received scant attention., Aim: To explore family caregivers' experiences in preparing for a relative's death in specialist palliative care in Taiwan., Design: A qualitative study employing reflexive thematic analysis of data collected from semi-structured interviews was conducted., Setting/participants: Twenty-two family caregivers from seven hospitals participated., Results: The overarching theme was 'getting everything right to have no regrets between the dead and the living'. We developed two themes to explain preparations for the time surrounding and after the death, including the deceased' afterlife: (1) 'having a good ending but not the end of the relationship', which addresses preparations for the death itself, the funeral, the afterlife and maintaining connections and (2) 'using religious beliefs and cultural norms to guide preparation', which explores perceptions of a good death, including refrain from strong emotions before and after the death., Conclusion: Funeral arrangements, enhancing the deceased's afterlife and maintaining connections to the deceased are crucial for families' experiences which can be impacted by actions they take as they prepare for the death. A culturally appropriate death is beneficial for the dying relative which includes preparing to not show strong emotions during and after the death. These insights inform the importance of the cultural context in death preparation in Taiwan and provide perspectives for palliative care beyond Western culture, potentially benefiting Chinese populations, predominantly East Asian and Buddhist societies., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose: The Palliative Care Outcomes Collaboration (PCOC) aims to enhance patient outcomes systematically. However, identifying crucial items and accurately determining PCOC phases remain challenging. This study aims to identify essential PCOC data items and construct a prediction model to accurately classify PCOC phases in terminal patients., Methods: A retrospective cohort study assessed PCOC data items across four PCOC phases: stable, unstable, deteriorating, and terminal. From July 2020 to March 2023, terminal patients were enrolled. A multinomial mixed-effect regression model was used for the analysis of multivariate PCOC repeated measurement data., Results: The dataset comprised 1933 terminally ill patients from 4 different hospice service settings. A total of 13,219 phases of care were analyzed. There were significant differences in the symptom assessment scale, palliative care problem severity score, Australia-modified Karnofsky performance status, and resource utilization groups-activities of daily living among the four PCOC phases of care. Clinical needs, including pain and other symptoms, declined from unstable to terminal phases, while psychological/spiritual and functional status for bed mobility, eating, and transfers increased. A robust prediction model achieved areas under the curves (AUCs) of 0.94, 0.94, 0.920, and 0.96 for stable, unstable, deteriorating, and terminal phases, respectively., Conclusions: Critical PCOC items distinguishing between PCOC phases were identified, enabling the development of an accurate prediction model. This model enhances hospice care quality by facilitating timely interventions and adjustments based on patients' PCOC phases., (© 2024. The Author(s).)

Issue: Proper application of clinical reasoning is a prerequisite toward safe practice. Formal instruction on clinical reasoning remains lacking in medical curricula, especially in preparation for the transition from pre-clinical to clinical years. Evidence: Although medical educators have published abundantly on clinical reasoning and acknowledge this to be an essential part of medical education, there remains a global curricular deficiency in developing this skillset. Here we introduce the reader to clinical reasoning frameworks with an emphasis upon practical application. Our focus is upon medical students transitioning from pre-clinical to clinical years of medical school who tend to be overwhelmed with facts but have limited sense of diagnostic approaches due to lack of instruction. Implications: In understanding systematic approaches to clinical reasoning of relevance to medical diagnosis, students will be able to process knowledge in a clinically relevant and discriminatory manner to facilitate problem solving. Upon internship and residency, they will be better prepared for self-learning and reflection as they understand how to hone their capability for diagnosis and management. Medical educators need to acknowledge that clinical reasoning is a practical academic discipline requiring greater curricular emphasis.

Substantial under-notification of TB among non-citizens has been noted previously. Foreign workers with TB who were deported previously could stay for anti-TB treatment since 2014. We assessed whether TB notification improved.We used the National Health Insurance (NHI) reimbursement database to identify potential TB cases that required notification. We matched potential TB cases with the national TB registry to determine whether they had been notified. Cases notified within 7 days of the initiation of anti-TB treatment were classified as having timely notification.Of 53,208 potential TB cases identified in 2016-2020, 96.6% had been notified. The notification proportion increased from 95.5% in 2016 to 97.1% in 2020 among citizens and from 89.0% in 2016 to 96.9% in 2020 among non-citizens. Factors significantly associated with non-notification among non-citizens were previously notified TB (aOR 35.5, 95% CI 17.7-70.9), without health insurance (aOR 15.4, 95% CI 9.3-25.2) and having only one visit to health care facilities in 6 months (aOR 2.3, 95% CI 1.4-3.8). The proportion of TB cases notified within 7 days was 87% overall, 86.2% among citizens, and 96.5% among non-citizens.TB notification has improved, especially among non-citizens, following a policy change that allows foreign workers to stay for anti-TB treatment..

By using omics, we can now examine all components of biological systems simultaneously. Deep learning-based drug prediction methods have shown promise by integrating cancer-related multi-omics data. However, the complex interaction between genes poses challenges in accurately projecting multi-omics data. In this research, we present a predictive model for drug response that incorporates diverse types of omics data, comprising genetic mutation, copy number variation, methylation, and gene expression data. This study proposes latent alignment for information mismatch in integration, which is achieved through an attention module capturing interactions among diverse types of omics data. The latent alignment and attention modules significantly improve predictions, outperforming the baseline model, with MSE = 1.1333, F1-score = 0.5342, and AUROC = 0.5776. High accuracy was achieved in predicting drug responses for piplartine and tenovin-6, while the accuracy was comparatively lower for mitomycin-C and obatoclax. The latent alignment module exclusively outperforms the baseline model, enhancing the MSE by 0.2375, the F1-score by 4.84%, and the AUROC by 6.1%. Similarly, the attention module only improves these metrics by 0.1899, 2.88%, and 2.84%, respectively. In the interpretability case study, panobinostat exhibited the most effective predicted response, with a value of -4.895. We provide reliable insights for drug selection in personalized medicine by identifying crucial genetic factors influencing drug response.

Phosphatase and tensin homolog (PTEN) is vital for B cell development, acting as a key negative regulator in the PI3K signaling pathway. We used CD23-cre to generate PTEN-conditional knockout mice (CD23-cKO) to examine the impact of PTEN mutation on peripheral B cells. Unlike mb1-cre-mediated PTEN deletion in early B cells, CD23-cKO mutants exhibited systemic inflammation with increased IL-6 production in mature B cells upon CpG stimulation. Inflammatory B cells in CD23-cKO mice showed elevated phosphatidylinositol 3-phosphate [PI(3)P] levels and increased TLR9 endosomal localization. Pharmacological inhibition of PI(3)P synthesis markedly reduced TLR9-mediated IL-6. Single-cell RNA-sequencing (RNA-seq) revealed altered endocytosis, BANK1, and NF-κB1 expression in PTEN-deficient B cells. Ectopic B cell receptor (BCR) expression on non-inflammatory mb1-cKO B cells restored BANK1 and NF-κB1 expression, enhancing TLR9-mediated IL-6 production. Our study highlights PTEN as a crucial inflammatory checkpoint, regulating TLR9/IL-6 axis by fine-tuning PI(3)P homeostasis. Additionally, BCR downregulation prevents the differentiation of inflammatory B cells in PTEN deficiency., Competing Interests: The authors declare no competing interests., (© 2024 The Author(s).)

Introduction: The World Health Organisation has implemented multiple HIV prevention policies and strived to achieve the 90-90-90 goal by 2020, achieving the 95-95-95 goal by 2030, which refers to 95% of patients living with HIV knowing their HIV status, 95% of patients living with HIV receiving continual care and medication, and 95% of patients living with HIV exhibiting viral suppression. However, how to measure the status of viral suppression varies, and it is hard to indicate the quality of HIV care. The study aimed to examine the long-term viral load suppression in these cases and explore potential factors affecting the control of long-term viral load., Methods: This study analyzed viral load testing data from HIV patients who are still alive during the period from notification up to 2019-2020. Three indicators were calculated, including durable viral suppression, Viremia copy-years, and Viral load > 1,500 copies/ml, to assess the differences between them., Results: Among the 27,706 cases included in the study, the proportion of persistent viral load suppression was 87%, with 4% having viral loads exceeding 1,500 copies/ml. The average duration from notification to viral load suppression was 154 days, and the geometric mean of annual viral replication was 90 copies*years/ml. Regarding the last available viral load measurement, 96% of cases had an undetectable viral load. However, we observed that 9.3% of cases, while having an undetectable viral load for their last measurement, did not show consistent long-term viral load suppression. An analysis of factors associated with non-persistent viral load suppression revealed higher risk in younger age groups, individuals with an educational level of high school or below, injection drug users, cases from the eastern region, those seeking care at regional hospitals, cases with drug resistance data, individuals with lower healthcare continuity, and those with an initial CD4 count below 350 during the study period., Conclusions: The recommendation is to combine it with the indicator of sustained viral load suppression for a more accurate assessment of the risk of HIV transmission within the infected community., (© 2024. The Author(s).)

The conception of vascularized organ-on-a-chip models provides researchers with the ability to supply controlled biological and physical cues that simulate the in vivo dynamic microphysiological environment of native blood vessels. The intention of this niche research area is to improve our understanding of the role of the vasculature in health or disease progression in vitro by allowing researchers to monitor angiogenic responses and cell-cell or cell-matrix interactions in real time. This review offers a comprehensive overview of the essential elements, including cells, biomaterials, microenvironmental factors, microfluidic chip design, and standard validation procedures that currently govern angiogenesis-on-a-chip assemblies. In addition, we emphasize the importance of incorporating a microvasculature component into organ-on-chip devices in critical biomedical research areas, such as tissue engineering, drug discovery, and disease modeling. Ultimately, advances in this area of research could provide innovative solutions and a personalized approach to ongoing medical challenges.

Introduction: The government-funded pre-exposure prophylaxis (PrEP) programme was targeted to those aged under 30 years or serodiscordant couples and implemented in September 2018-October 2020 in Taiwan. The study aimed to examine the effectiveness of the programme and the relationship between sexually transmitted disease (STD) and HIV seroconversion., Methods: This study was a retrospective cohort analysis with questionnaires designed for participants who joined the aforementioned programme in the PrEP-designated hospitals. The questionnaires included sociodemographic factors, sexual risk behaviours, number and types of sexual partners, and usage of narcotics filled in at the beginning of the programme and every 3 months. The McNemar test was used for the paired questionnaire analysis. The HIV seroconversion status among STD-notified patients nationwide was confirmed by using the data linkage method, followed up until October 2021 with stratification of PrEP programme participation or not., Results: The programme recruited 2155 people. 11 participants (0.5%) had seroconversion within the programme, while 26 (1.2%) had seroconversion after withdrawing from the programme. Overall, 1892 subjects with repeated questionnaires were included in the analysis for behaviour changes with median follow-up of 289 days. After joining the programme, 94.7% of them claimed that they had sexual behaviours: the rate of those who had condomless sex rose to 5.5% (p<0.001) and the rate of those who used narcotics decreased to 2% (p<0.001), compared with their response in the pre-questionnaire. Notably, the frequency of non-use of narcotics in recent 3 months increased from 16.9% to 38.4% in the pre-questionnaire and post-questionnaire responses, among the 177 who had claimed narcotics usage in recent 12 months (p=0.003). More HIV seroconversion was found among patients with STD who did not join the programme than those who joined the programme (8.7% vs 4.9%, p=0.031)., Conclusions: The government-funded programme showed HIV case reduction and positive changes in health behaviours except for condomless sex which had increased prevalence. The reduction of HIV cases was also observed among people with STD. More resources should be allocated to the PrEP programme., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Background: Adverse effects of rigorously lowering low-density lipoprotein cholesterol on cognition have been reported; therefore, we aimed to study the contribution of serum cholesterol in cognitive decline in older people with or without dementia., Methods: Cognitive function was assessed by the Cognitive Abilities Screening Instrument (CASI). We investigated associations between serum cholesterol with cognitive decline using multiple regressions controlling for the effects of demographics, vascular risk factors, and treatments., Results: Most associations between cholesterol and CASI scores could be explained by non-linear and inverted U-shaped relationships (R 2  = 0.003-0.006, p < 0.016, Šidákcorrection). The relationships were most evident between changes in cholesterol and CASI scores in older people at the preclinical or prodromal stages of dementia (R 2  = 0.02-0.064, p values < 0.016). There were no differences in level of changes in CASI scores between individuals in 1st decile and 10th decile groups of changes in cholesterol (p = 0.266-0.972). However, individuals in the 1st decile of triglyceride changes and with stable and normal cognitive functions showed significant improvement in CASI scores compared to those in the 10th decile (t(202) = 2.275, p values < 0.05)., Conclusion: These findings could implicate that rigorously lowering cholesterol may not be suitable for the prevention of cognitive decline among older people, especially among individuals in preclinical or prodromal stages of dementia., (© 2024. The Author(s).)

Background: Cingulin (CGN) is a pivotal cytoskeletal adaptor protein located at tight junctions. This study investigates the link between CGN mutation and increased cancer susceptibility through genetic and mechanistic analyses and proposes a potential targeted therapeutic approach., Methods: In a high-cancer-density family without known pathogenic variants, we performed tumor-targeted and germline whole-genome sequencing to identify novel cancer-associated variants. Subsequently, these variants were validated in a 222 cancer patient cohort, and CGN c.3560C > T was identified as a potential cancer-risk allele. Both wild-type (WT) (c.3560C > C) and variant (c.3560C > T) were transfected into cancer cell lines and incorporated into orthotopic xenograft mice model for evaluating their effects on cancer progression. Western blot, immunofluorescence analysis, migration and invasion assays, two-dimensional gel electrophoresis with mass spectrometry, immunoprecipitation assays, and siRNA applications were used to explore the biological consequence of CGN c.3560C > T., Results: In cancer cell lines and orthotopic animal models, CGN c.3560C > T enhanced tumor progression with reduced sensitivity to oxaliplatin compared to the CGN WT. The variant induced downregulation of epithelial marker, upregulation of mesenchymal marker and transcription factor, which converged to initiate epithelial-mesenchymal transition (EMT). Proteomic analysis was conducted to investigate the elements driving EMT in CGN c.3560C > T. This exploration unveiled overexpression of IQGAP1 induced by the variant, contrasting the levels observed in CGN WT. Immunoprecipitation assay confirmed a direct interaction between CGN and IQGAP1. IQGAP1 functions as a regulator of multiple GTPases, particularly the Rho family. This overexpressed IQGAP1 was consistently associated with the activation of Rac1, as evidenced by the analysis of the cancer cell line and clinical sample harboring CGN c.3560C > T. Notably, activated Rac1 was suppressed following the downregulation of IQGAP1 by siRNA. Treatment with NSC23766, a selective inhibitor for Rac1-GEF interaction, resulted in the inactivation of Rac1. This intervention mitigated the EMT program in cancer cells carrying CGN c.3560C > T. Consistently, xenograft tumors with WT CGN showed no sensitivity to NSC23766 treatment, but NSC23766 demonstrated the capacity to attenuate tumor growth harboring c.3560C > T., Conclusions: CGN c.3560C > T leads to IQGAP1 overexpression, subsequently triggering Rac1-dependent EMT. Targeting activated Rac1 is a strategy to impede the advancement of cancers carrying this specific variant., (© 2024. The Author(s).)

This study examined children's adherence to the Singapore Integrated 24-Hour Activity Guidelines for Early Childhood in infants, toddlers and preschoolers aged 0-6 years. A total of 901 caregivers, comprising 219 infants, 379 toddlers, and 303 preschoolers, provided information regarding their children's physical activity (PA), screen viewing time (SVT), and sleep durations on both weekdays and weekends. Meeting the 24-hour integrated activity guidelines was defined as follows: for infants ≥ 30 minutes per day of tummy time or floor-based play; zero SVT; total sleep of 14-17 hours per day for ages 0-3 months, 12-16 hours per day for ages 4-11 months; for toddlers ≥ 180 minutes of total PA per day; zero SVT under 2 years; <1 hour for ages 2 to less than 3 years; and a total sleep of 11-14 hours per day; for preschoolers ≥ 180 minutes of total PA per day; SVT <1 hour per day; total sleep of 10-13 hours per day for those aged 3-5 years, and 10-11 hours per day for 6-year-olds. Chi-squared tests were used to examine the differences in guideline adherence between weekdays and weekends. Compared to weekdays, during weekends there was a higher proportion of toddlers and preschoolers adhering to the PA guidelines (68.9% vs 50.1%; 78.9% vs 55.4%, respectively, p<0.05), and a lower proportion of toddlers adhering to SVT (38.8% vs 21.8%; p = 0.001). There was a declining adherence to all three activity guidelines as age groups progressed from infants (44.7%) to toddlers (15.8%) and then to preschoolers (9.4%). Concurrently, there was a decrease in adherence to SVT recommendations across the age groups, with adherence rates being highest among infants (83.1%), followed by toddlers (15.8%), and preschoolers (9.4%). Decreasing compliance with all three guidelines, coupled with a corresponding decline in adherence to SVT guidelines as children transition from toddlerhood to preschool age, is a cause for concern. This underscores the need for proactive efforts to educate caregivers about reducing or eliminating SVT among infants and young children., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Quah et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Previous studies revealed that hormone replacement therapy (HRT) probably has a protective effect for preventing dementia in post-menopausal women. However, the results were still controversial. The association between cholesterol levels and incident dementia in older women is not fully understood either. We conducted a retrospective analysis on a cohort of non-demented women aged older than 50 years, which was registered in the History-based Artificial Intelligence Clinical Dementia Diagnostic System database from September 2015 to August 2021. We followed this cohort longitudinally to examine the rates of conversion to dementia. Using a Cox regression model, we investigated the impact of the quartile of total cholesterol (TC) levels on incident dementia, adjusting for age, sex, education, neuropsychiatric symptoms, neuropsychological assessments, HRT, as well as various vascular risk factors and medications. We examined a cohort of 787 participants, comprising 539 (68.5%) individuals who did not develop dementia (non-converters). Among these non-converters, 68 individuals (12.6%) were treated with HRT. By contrast, there were 248 (31.5%) who did develop dementia (converters). Among the converters, 28 individuals (11.3%) were treated with HRT. The average follow-up durations were 2.9 ± 1.5 and 3.3 ± 1.6 years for non-converters and converters, respectively. Compared to the lowest quartile of TC levels (<153), the hazard ratios (HR) for converting to dementia were 0.61, 0.58, and 0.58 for the second (153-176), third (177-201), and highest (>201) quartiles, respectively (all p < 0.05). However, the low-density lipoprotein cholesterol (LDL-C) level and HRT did not alter the rate of conversion to dementia. In conclusion, the lowest quartile of TC increased incident dementia in post-menopausal women without dementia; however, HRT did not contribute to conversion to dementia. Some studies suggest that post-menopausal women who have reduced estrogen levels might have an increased risk of Alzheimer's disease if they also have high cholesterol. Nonetheless, the evidence is inconclusive, as not all studies support this finding. The "Lower LDL-C is better" strategy for preventing cardiac vascular disease should be re-examined for the possible serial adverse effects of new onset dementia due to very low cholesterol levels.

Background: Many methodologies for selecting histopathological images, such as sample image patches or segment histology from regions of interest (ROIs) or whole-slide images (WSIs), have been utilized to develop survival models. With gigapixel WSIs exhibiting diverse histological appearances, obtaining clinically prognostic and explainable features remains challenging. Therefore, we propose a novel deep learning-based algorithm combining tissue areas with histopathological features to predict cancer survival., Methods: The Cancer Genome Atlas Colon Adenocarcinoma (TCGA-COAD) dataset was used in this investigation. A deep convolutional survival model (DeepConvSurv) extracted histopathological information from the image patches of nine different tissue types, including tumors, lymphocytes, stroma, and mucus. The tissue map of the WSIs was segmented using image processing techniques that involved localizing and quantifying the tissue region. Six survival models with the concordance index (C-index) were used as the evaluation metrics., Results: We extracted 128 histopathological features from four histological types and five tissue area features from WSIs to predict colorectal cancer survival. Our method performed better in six distinct survival models than the Whole Slide Histopathological Images Survival Analysis framework (WSISA), which adaptively sampled patches using K-means from WSIs. The best performance using histopathological features was 0.679 using LASSO-Cox. Compared to histopathological features alone, tissue area features increased the C-index by 2.5%. Based on histopathological features and tissue area features, our approach achieved performance of 0.704 with RIDGE-Cox., Conclusions: A deep learning-based algorithm combining histopathological features with tissue area proved clinically relevant and effective for predicting cancer survival., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Stem-end rot disease has been causing damage to the production of pomelos in Vietnam. The cur-rent study aimed to (i) isolate fungal pathogens causing pomelo stem-end rot disease (PSERD) and (ii) discover Trichoderma spp. that had an antagonistic ability against pathogens under in vitro conditions. Fungi causing PSERD were isolated from pomelo fruits with symptoms of stem-end rot disease and collected from pomelo farms in Ben Tre province, Vietnam. Moreover, 50 fungal strains of Trichoderma spp. also originated from soils of these pomelo farms in Ben Tre province and were dual-tested with the fungal pathogen on the PDA medium. The results demonstrated that 11 pathogenic fungi causing PSERD were isolated from the fruit and showed mycelial growth of roughly 5.33-8.77 cm diameter at 72 h after inoculation. The two fungi that exhibited the fast-est growth, namely, S-P06 and S-P07, were selected. ITS sequencing of the S-P06 and S-P07 fungi resulted in Lasiodiplodia theobromae. All the 50 Trichoderma spp. strains were allowed to antago-nize against the S-P06 and S-P07 strains under in vitro conditions. The greatest antagonistic effi-ciency was found in Trichoderma spp. T-SP19 at 85.4-86.2% and T-SP32 at 84.7-85.4%. The two antagonists were identified as Trichoderma asperellum T-SP19 and T-SP32. The selected strains of Trichoderma asperellum were potent as a biological control for fruit plants.

Background: 3 months of weekly rifapentine plus isoniazid (3HP) and 4 months of daily rifampicin (4R) are recommended for tuberculosis preventive treatment. As these regimens have not been compared directly, we used individual patient data and network meta-analysis methods to compare completion, safety, and efficacy between 3HP and 4R., Methods: We conducted a network meta-analysis of individual patient data by searching PubMed for randomised controlled trials (RCTs) published between Jan 1, 2000, and Mar 1, 2019. Eligible studies compared 3HP or 4R to 6 months or 9 months of isoniazid and reported treatment completion, adverse events, or incidence of tuberculosis disease. Deidentified individual patient data from eligible studies were provided by study investigators and outcomes were harmonised. Methods for network meta-analysis were used to generate indirect adjusted risk ratios (aRRs) and risk differences (aRDs) with their 95% CIs., Findings: We included 17 572 participants from 14 countries in six trials. In the network meta-analysis, treatment completion was higher for people on 3HP than for those on 4R (aRR 1·06 [95% CI 1·02-1·10]; aRD 0·05 [95% CI 0·02-0·07]). For treatment-related adverse events leading to drug discontinuation, risks were higher for 3HP than for 4R for adverse events of any severity (aRR 2·86 [2·12-4·21]; aRD 0·03 [0·02-0·05]) and for grade 3-4 adverse events (aRR 3·46 [2·09-6·17]; aRD 0·02 [0·01-0·03]). Similar increased risks with 3HP were observed with other definitions of adverse events and were consistent across age groups. No difference in the incidence of tuberculosis disease between 3HP and 4R was found., Interpretation: In the absence of RCTs, our individual patient data network meta-analysis indicates that 3HP provided an increase in treatment completion over 4R, but was associated with a higher risk of adverse events. Although findings should be confirmed, the trade-off between completion and safety must be considered when selecting a regimen for tuberculosis preventive treatment., Funding: None., Translations: For the French and Spanish translations of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Competing Interests: Declaration of competing interest None.

Automatic liver tumor detection from computed tomography (CT) makes clinical examinations more accurate. However, deep learning-based detection algorithms are characterized by high sensitivity and low precision, which hinders diagnosis given that false-positive tumors must first be identified and excluded. These false positives arise because detection models incorrectly identify partial volume artifacts as lesions, which in turn stems from the inability to learn the perihepatic structure from a global perspective. To overcome this limitation, we propose a novel slice-fusion method in which mining the global structural relationship between the tissues in the target CT slices and fusing the features of adjacent slices according to the importance of the tissues. Furthermore, we design a new network based on our slice-fusion method and Mask R-CNN detection model, called Pinpoint-Net. We evaluated proposed model on the Liver Tumor Segmentation Challenge (LiTS) dataset and our liver metastases dataset. Experiments demonstrated that our slice-fusion method not only enhance tumor detection ability via reducing the number of false-positive tumors smaller than 10mm, but also improve segmentation performance. Without bells and whistles, a single Pinpoint-Net showed outstanding performance in liver tumor detection and segmentation on LiTS test dataset compared with other state-of-the-art models.

Purpose: Malnutrition is highly prevalent in head and neck cancer (HNC) patients, with weight loss being one of the major nutritional indicators. The objective of this study was to investigate the impact of weight loss on treatment interruptions and unplanned hospital admissions in HNC patients undergoing radiotherapy (RT) with or without chemotherapy., Methods: In this retrospective cohort study, consecutive HNC patients who started RT between January 2011 and December 2019 were included. Data from a total of 1086 subjects with 747 (68.8%) nasopharyngeal carcinomas (NPCs) and 31.2% (N=339) non-NPC patients were analysed. Body weight (BW) was measured before, during, and after RT treatment. Factors associated with ≥10% weight loss, treatment interruption, and unplanned admissions were analysed using multivariate logistic regression., Results: The prevalence of ≥10% weight loss was 26.8% (N=288), with 32.7% (N=243) in NPC and 13.5% (N=45) in non-NPC patients. The prevalence of RT delay in patients with ≥10% vs. <10% weight loss was 6.2% vs. 7.0% (p=0.668) in NPC patients and 42.2% vs. 50.5% (p=0.300) in non-NPC patients. The prevalence of unplanned admissions in patients with ≥10% vs. <10% weight loss was 51.9% vs. 25.3% (p<0.001) in NPC patients and 68.9% vs. 27.0% (p<0.001) in non-NPC patients., Conclusion: In our study, ≥10% weight loss was found to be associated with a higher rate of unplanned admissions but not with RT delay or chemotherapy interruption., Clinical Implications: With the knowledge of the impact of weight loss on hospital admissions and the characteristics of patients with weight loss, nutritional intervention can be effectively focused on the stratification of patients for intensive nutritional support to reduce weight loss., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

This study aimed to examine the prevalence of adherence to 24 h activity guidelines in children and adolescents from Asia-Pacific cities. In 1139 children aged 5-18 years, moderate-to-vigorous physical activity (MVPA), screen viewing time (SVT), sleep duration, child weight, height, sex, and age were parent-reported. Descriptive statistics were used to assess the number of guidelines met, and prevalence of adherence to activity guidelines by city and child sex. Prevalence of meeting all three 24 h activity guidelines was low across all countries (1.8-10.3%) ( p < 0.05). Children from Thiruvananthapuram, India had the highest [10.3% (95% CI: 6.0-17.0)], while those from Tokyo, Japan had the lowest prevalence [1.8% (95% CI: 0.5-7.0)] of meeting all three guidelines. The highest prevalence of meeting individual MVPA, SVT and sleep guidelines was found in India [67.5% (95% CI: 58.8-75.1)], Kelaniya, Sri Lanka [63.2% (95% CI: 58.7-67.4)] and Kowloon, Hong Kong [59.4% (95% CI: 51.1-65.3)], respectively. Overall, a higher prevalence of boys met all three guidelines, compared to girls [5.9% (95% CI: 4.1-8.1) vs. 4.7% (3.1-6.6), p = 0.32]. The prevalence of adhering to all three activity guidelines was low in all five participating cities, with a higher proportion of boys meeting all guidelines.

Sprouty2 (SPRY2) is known to inhibit the RAS/MAPK/ERK pathway, and is a potential study target for cancer. The effect of SPRY2 in colorectal cancer (CRC) and whether it is influenced by KRAS mutation are not known. We manipulated SPRY2 gene expression and used an activating KRAS-mutant plasmid to determine its effect on CRC cell function in vitro and/or in vivo. We performed SPRY2 immunohistochemical staining in 143 CRC specimens and analyzed the staining results with various clinicopathological characteristics in relation to KRAS mutation status. SPRY2 knockdown in Caco-2 cells carrying the wild-type (WT) KRAS gene upregulated phosphorylated ERK (p-ERK) levels and increased cell proliferation in vitro, but inhibited cell invasion. However, SPRY2 knockdown in SW480 cells (activating KRAS mutant) or Caco-2 cells transfected with KRAS-mutant plasmid did not significantly alter p-ERK levels, cell proliferation, or invasion. The xenografts of SPRY2-knockdown Caco-2 cells were larger with less deep muscle invasion than those of control cells. The clinical cohort study revealed a positive association of SPRY2 protein expression with pT status, lymphovascular invasion, and perineural invasion in KRAS-WT CRCs. However, the associations were not observed in KRAS-mutant CRCs. Interestingly, high SPRY2 expression was related to shorter cancer-specific survival in both KRAS-WT and KRAS-mutant CRC patients. Our study demonstrated the dual role of SPRY2 as an inhibitor of RAS/ERK-driven proliferation and as a promoter of cancer invasion in KRAS-WT CRC. SPRY2 may promote the invasion and progression of KRAS-WT CRC, and might also enhance KRAS-mutant CRC progression through pathways other than invasion., (© 2023 Wiley Periodicals LLC.)

Introduction: Early childhood is a critical period for growth and development. Adopting healthy lifestyle behaviours during this period forms the foundation for future well-being and offers the best protection against non-communicable diseases. Singapore studies have shown that many young children are not achieving the recommendations on physical activity, sedentary behaviour and sleep. A workgroup was set up to develop recommendations for caregivers of infants, toddlers and preschoolers (aged <7 years) on how to integrate beneficial activities within a daily 24-hour period for optimal development and metabolic health., Method: The Grading of Recommendations Assessment, Development and Evaluation (GRADE)- ADOLOPMENT approach was employed for adoption, adaption or de novo development of recommendations. International and national guidelines were used as references, and an update of the literature reviews up to September 2021 was conducted through an electronic search of PubMed, Embase and Cochrane Central Register of Controlled Trials (CENTRAL) databases., Results: Four consensus statements were developed for each age group: infants, toddlers and preschoolers. The statements focus on achieving good metabolic health through regular physical activity, limiting sedentary behaviour, achieving adequate sleep and positive eating habits. The 13th consensus statement recognises that integration of these activities within a 24-hour period can help obtain the best results., Conclusion: This set of recommendations guides and encourages caregivers of Singapore infants, toddlers and preschoolers to adopt beneficial lifestyle activities within each 24-hour period., Competing Interests: There was no conflict of interest for all authors

This study aims to analyze tire wear particulate matter (TWP) from tread rubber with different formulations and to compare the concentration of TWP with different wear devices. The TWP generated during the abrasion of truck and bus radial (TBR) tires were examined, and the effect of using different types of rubber and carbon black (CB) were investigated. When natural rubber (NR) was solely used as the tire tread rubber material, there was a higher concentration of 5-10 µm TWP. However, when the tread formulation consisted of NR mixed with butadiene rubber, the TWP concentration decreased. Changing the type of CB also reduced the amount of TWP in the 2.5 µm size range. The TWP concentration in the specimens increased with increasing speed and vertical load. The TWP generated during the abrasion tests using wear testers and tire simulators exhibited similar trends. These findings suggest that modifying tire tread formulations can effectively control the distribution and amount of TWP generation.

Polypropylene (PP) is used as a housing material in automotive headlamps but can cause fogging as a result of absorbed moisture and temperature differences between the exterior and interior of the housing. In this study, PP was combined with a graphene/montmorillonite hybrid (MMT-G) to yield a nanocomposite with reduced moisture absorption. Crucially, the modified nanofiller had low hydrophilicity and good compatibility with the PP matrix. Notably, the water contact angle of the MMT-G improved by 676%. Furthermore, the maximum moisture absorption of the PP/MMT-G nanocomposites was reduced by up to 11.22% compared to that of commercial PP composites, and the weight of the headlamp housing was decreased by 3.6%. Therefore, the designed nanocomposites are expected to help mitigate headlamp fogging while slightly reducing the housing weight.

Background: The metabolome is the best representation of cancer phenotypes. Gene expression can be considered a confounding covariate affecting metabolite levels. Data integration across metabolomics and genomics to establish the biological relevance of cancer metabolism is challenging. This study aimed to eliminate the confounding effect of metabolic gene expression to reflect actual metabolite levels in microsatellite instability (MSI) cancers., Methods: In this study, we propose a new strategy using covariate-adjusted tensor classification in high dimensions (CATCH) models to integrate metabolite and metabolic gene expression data to classify MSI and microsatellite stability (MSS) cancers. We used datasets from the Cancer Cell Line Encyclopedia (CCLE) phase II project and treated metabolomic data as tensor predictors and data on gene expression of metabolic enzymes as confounding covariates., Results: The CATCH model performed well, with high accuracy (0.82), sensitivity (0.66), specificity (0.88), precision (0.65), and F1 score (0.65). Seven metabolite features adjusted for metabolic gene expression, namely, 3-phosphoglycerate, 6-phosphogluconate, cholesterol ester, lysophosphatidylethanolamine (LPE), phosphatidylcholine, reduced glutathione, and sarcosine, were found in MSI cancers. Only one metabolite, Hippurate, was present in MSS cancers. The gene expression of phosphofructokinase 1 (PFKP), which is involved in the glycolytic pathway, was related to 3-phosphoglycerate. ALDH4A1 and GPT2 were associated with sarcosine. LPE was associated with the expression of CHPT1, which is involved in lipid metabolism. The glycolysis, nucleotide, glutamate, and lipid metabolic pathways were enriched in MSI cancers., Conclusions: We propose an effective CATCH model for predicting MSI cancer status. By controlling the confounding effect of metabolic gene expression, we identified cancer metabolic biomarkers and therapeutic targets. In addition, we provided the possible biology and genetics of MSI cancer metabolism., (© 2023. The Author(s).)

Background: The association between human epidermal growth factor receptor-2 (HER2) amplification and brain metastasis (BM) in patients having colorectal cancer (CRC) has been suggested but not yet established. This study investigated the expression patterns of HER2, its association with BM, and its prognostic value in patients having CRC., Methods: We retrospectively identified 99 patients having metastatic CRC (mCRC) and BM (the BM cohort) and compared them with a cohort of 249 patients having mCRC and without BM (the stage IV cohort) by propensity score matching. Immunohistochemical studies of HER2 on all available paraffin-embedded tumour samples, either from the primary tumour, the metastasis (brain and/or extracranial sites) or both, were performed and analysed. HER2 fluorescent in situ hybridisation was applied when necessary. The expression of HER2 was compared and correlated with survival., Results: HER2 amplifications were detected in 16 (18.4%) of 87 and 9 (3.6%) of 249 patients who had specimens available in the BM and stage IV cohorts, respectively (P < .001). After propensity score matching, HER2 amplification was significantly associated with BM (odds ratio: 5.38, P = .003). HER2 heterogeneity was frequently observed not only at the single tumour level but also in paired tumour samples. A marginally significant longer survival since BM was found in patients having HER2-amplified mCRC than in those without (P = .07)., Conclusions: HER2 amplification was significantly associated with BM in patients having mCRC and might have prognostic value for survival since BM. Given the heterogeneity of HER2 expression, the testing of HER2 status on available tissues from both primary and metastatic tumours should be encouraged., Competing Interests: Conflict of interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Limited efficacy has been observed when using opioids to treat neuropathic pain. Lidocaine patches reduce neuropathic pain in postherpetic neuralgia, but their benefits for cancer-related neuropathic pain remain unclear. This study aimed to investigate a treatment for cancer-related neuropathic pain., Methods: We conducted a prospective, open-label, single-arm study to assess the efficacy and safety of lidocaine transdermal patches in patients experiencing localized, superficial, neuropathic cancer pain. Terminal cancer patients already receiving opioid treatment participated in the 3-day study. The primary endpoint was pain intensity evaluated by the numerical rating scale (NRS). The secondary endpoints were the pain relief score and the quality of analgesic treatment., Results: The results showed a significant difference in the median NRS over 3 days (Kruskal-Wallis test, p < 0.0001). The median NRS pain intensity from Day 1 to Day 3 was 4.0 with 95% C.I. (3.3, 5.0), 3.0 (2.5, 3.5), and 2.6 (2.0, 3.0), respectively. The difference between the median NRS pain intensities of any 2 days was significant (Wilcoxon signed-rank test, p < 0.0001). The generalized estimating equation (GEE) estimation model showed significant differences between the NRS pain intensities on any 2 days. There was no significant difference in the pain relief score or the quality of analgesic treatment., Conclusions: In this study, the 5% lidocaine transdermal patch reduced the NRS pain intensity in neuropathic cancer patients already receiving opioid treatment. Treatment of localized and superficial neuropathic pain caused by cancer was well tolerated and effective., (© 2023. The Author(s).)

The most popular tools for predicting pathogenicity of single amino acid variants (SAVs) were developed based on sequence-based techniques. SAVs may change protein structure and function. In the context of van der Waals force and disulfide bridge calculations, no method directly predicts the impact of mutations on the energies of the protein structure. Here, we combined machine learning methods and energy scores of protein structures calculated by Rosetta Energy Function 2015 to predict SAV pathogenicity. The accuracy level of our model (0.76) is higher than that of six prediction tools. Further analyses revealed that the differential reference energies, attractive energies, and solvation of polar atoms between wildtype and mutant side-chains played essential roles in distinguishing benign from pathogenic variants. These features indicated the physicochemical properties of amino acids, which were observed in 3D structures instead of sequences. We added 16 features to Rhapsody (the prediction tool we used for our data set) and consequently improved its performance. The results indicated that these energy scores were more appropriate and more detailed representations of the pathogenicity of SAVs.

Background: Circulating phospholipid species have been shown to predict Alzheimer's disease (AD) prognosis but the link between phospholipid disturbances and subcortical small vessel cerebrovascular disease (CeVD) common in AD patients is not known., Objective: Mass-spectrometry lipidomics was applied to quantify serum diacyl, alkenyl (ether), alkyl, and lyso phospholipid species in individuals with extensive CeVD (n = 29), AD with minimal CeVD (n = 16), and AD with extensive CeVD (n = 14), and compared them to age-matched controls (n = 27). Memory was assessed using the California Verbal Learning Test. 3.0T MRI was used to assess hippocampal volume, atrophy, and white matter hyperintensity (WMH) volumes as manifestations of CeVD., Results: AD was associated with significantly higher concentrations of choline plasmalogen 18:0&#95;18:1 and alkyl-phosphocholine 18:1. CeVD was associated with significantly lower lysophospholipids containing 16:0. Phospholipids containing arachidonic acid (AA) were associated with poorer memory in controls, whereas docosahexaenoic acid (DHA)-containing phospholipids were associated with better memory in individuals with AD+CeVD. In controls, DHA-containing phospholipids were associated with more atrophy, and phospholipids containing linoleic acid and AA were associated with less atrophy. Lysophospholipids containing 16:0, 18:0, and 18:1 were correlated with less atrophy in controls, and of these, alkyl-phosphocholine 18:1 was correlated with smaller WMH volumes. Conversely, 16:0&#95;18:1 choline plasmalogen was correlated with greater WMH volumes in controls., Conclusion: This study demonstrates discernable differences in circulating phospholipids in individuals with AD and CeVD, as well as new associations between phospholipid species with memory and brain structure that were specific to contexts of commonly comorbid vascular and neurodegenerative pathologies.

Owing to stringent international environmental and fuel efficiency requirements for lightweight automotive systems, polymer composites have attracted widespread attention. Polypropylene (PP) is a widely employed commercial polymer because of its lightweight and low cost. In this study, PP nanocomposites were fabricated to reduce the moisture absorption of PP composites in automotive headlamp housings. Alkylated chemically modified graphene (CMG-R) was synthesized to reduce the surface hydrophilicity of graphene and increase compatibility with the PP matrix. Fourier transform-infrared spectroscopy and scanning electron microscopy were performed to analyze the nanofillers. X-ray diffraction was performed to determine the interlayer spacing of the nanofiller resulting from surface treatment. Differential scanning calorimetry was used to analyze the crystallinity of the nanocomposites. The results indicated that the improved hydrophobicity of the nanofiller due to alkylation reduced the maximum moisture absorption of the PP nanocomposites by 15% compared to PP composites. The findings of this study are useful for reducing fogging in automotive headlamps.

The C-C chemokine motif ligand 5 (CCL5) and its receptors have recently been thought to be substantially involved in the development of obesity-associated adipose tissue inflammation and insulin resistance. However, the respective contributions of tissue-derived and myeloid-derived CCL5 to the etiology of obesity-induced adipose tissue inflammation and insulin resistance, and the involvement of monocytic myeloid-derived suppressor cells (MDSCs), remain unclear. This study used CCL5-knockout mice combined with bone marrow transplantation (BMT) and mice with local injections of shCCL5/shCCR5 or CCL5/CCR5 lentivirus into bilateral epididymal white adipose tissue (eWAT). CCL5 gene deletion significantly ameliorated HFD-induced inflammatory reactions in eWAT and protected against the development of obesity and insulin resistance. In addition, tissue (non-hematopoietic) deletion of CCL5 using the BMT method not only ameliorated adipose tissue inflammation by suppressing pro-inflammatory M-MDSC (CD11b + Ly6G - Ly6C hi ) accumulation and skewing local M1 macrophage polarization, but also recruited reparative M-MDSCs (CD11b + Ly6G - Ly6C low ) and M2 macrophages to the eWAT of HFD-induced obese mice, as shown by flow cytometry. Furthermore, modulation of tissue-derived CCL5/CCR5 expression by local injection of shCCL5/shCCR5 or CCL5/CCR5 lentivirus substantially impacted the distribution of pro-inflammatory and reparative M-MDSCs as well as macrophage polarization in bilateral eWAT. These findings suggest that an obesity-induced increase in adipose tissue CCL5-mediated signaling is crucial in the recruitment of tissue M-MDSCs and their trans-differentiation to tissue pro-inflammatory macrophages, resulting in adipose tissue inflammation and insulin resistance.

Digital Interprofessional Learning Client Documentation (D-IPL Client Docs) is an initiative designed to develop student interprofessional communication skills through electronic record writing and a virtual simulation (VS) or live virtual simulation (LVS) case conference. The aims of the study were to (a) identify whether D-IPL Client Docs supports student learning in the affective domain and (b) compare the learning outcomes for students participating in the VS versus the LVS case conference. Data were drawn from 83 Bachelor of Social Work students who had participated with other health professional students in the D-IPL Client Docs activities. The reflective journals submitted by this cohort of social work students were analyzed qualitatively and quantitatively using the Griffith University Affective Learning Scale. Qualitative analyses revealed that the activities enabled students in both groups to learn about themselves, their roles, and the roles of others, and the benefits of interprofessional collaboration in optimizing client outcomes. Quantitatively, the VS mode appeared to be more effective in supporting students to develop higher order affective learning; however, the effect size was small. Future studies should involve a larger sample size and include students from various professions to ascertain the transferability of findings.

In Taiwan, 14,308 locally acquired COVID-19 cases among customers and employees in Sexy Tea shops were the first cases from May 9-August 28, 2021 (weeks 19-34). Nine weeks after the community spread of COVID-19 began, the proportion of people living with HIV (PLHIV) among the COVID-19 patients peaked at 35.7%, affecting 192 HIV patients, while the prevalence of HIV infection was 0.15%. In addition to a nationwide Level 3 epidemic alert, the Taiwan Centers for Disease Control (Taiwan CDC) launched four strategies to contain this outbreak among PLHIV in this prevaccine era, including improving the quality of contact tracing, delivering health information via peer navigators, expanding SARS-CoV-2 screening and encouraging vaccination, and addressing hesitancy. The outbreak of COVID-19 related to Alpha strain among PLHIV in 2021 ceased four weeks after peaking and lasted eight weeks., Competing Interests: Declaration of competing interest The authors have no conflicts of interest relevant to this article., (Copyright © 2022. Published by Elsevier B.V.)

Background: Colorectal cancer (CRC), the most common cancer type, causes high morbidity and mortality. Patients who develop drug resistance to oxaliplatin-based regimens have short overall survival. Thus, identifying molecules involved in the development of oxaliplatin resistance is critical for designing therapeutic strategies., Methods: A proteomic screen was performed to reveal altered protein kinase phosphorylation in oxaliplatin-resistant (OR) CRC tumour spheroids. The function of CHK2 was characterised using several biochemical techniques and evident using in vitro cell and in vivo tumour models., Results: We revealed that the level of phospho-CHK2(Thr68) was elevated in OR CRC cells and in ~30% of tumour samples from patients with OR CRC. We demonstrated that oxaliplatin activated several phosphatidylinositol 3-kinase-related kinases (PIKKs) and CHK2 downstream effectors and enhanced CHK2/PARP1 interaction to facilitate DNA repair. A phosphorylation mimicking CHK2 mutant, CHK2T68D, but not a kinase-dead CHK2 mutant, CHK2D347A, promoted DNA repair, the CHK2/PARP1 interaction, and cell growth in the presence of oxaliplatin. Finally, we showed that a CHK2 inhibitor, BML-277, reduced protein poly(ADP-ribosyl)ation (PARylation), FANCD2 monoubiquitination, homologous recombination and OR CRC cell growth in vitro and in vivo., Conclusion: Our findings suggest that CHK2 activity is critical for modulating oxaliplatin response and that CHK2 is a potential therapeutic target for OR CRC., (© 2022. The Author(s).)

Programmed death-ligand 1 (PD-L1) is an immune checkpoint molecule that can regulate immune responses in the tumor microenvironment (TME); however, the clinical applications of PD-L1 in early-stage colorectal cancer (CRC) remain unclear. In this study, we aimed to investigate the relationship between PD-L1 expression and survival outcome and explore its relevant immune responses in CRC. PD-L1 expression was evaluated by immunohistochemical staining to determine the tumor proportion score and combined positive score (CPS) in a Taiwanese CRC cohort. The oncomine immune response research assay was conducted for immune gene expression analyses. CRC datasets from the TCGA database were reappraised for PD-L1-associated gene enrichment analyses using GSEA. The high expression of PD-L1 (CPS ≥ 5) was associated with longer recurrence-free survival ( p = 0.031) and was an independent prognostic factor as revealed by multivariate analysis. High PD-L1 expression was related to six immune-related gene signatures, and CXCL9 is the most significant overexpressed gene in differential analyses. High CXCL9 expression correlated with increased infiltration levels of immune cells in the TME, including CD8+ T lymphocytes and M1 macrophages. These findings suggest that high PD-L1 expression is a prognostic factor of early-stage CRC, and CXCL9 may play a key role in regulating PD-L1 expression.

Synthetic lethality (SL) is an emerging therapeutic paradigm in cancer. We introduced a different approach to prioritize SL gene pairs through literature mining and RAS -mutant high-throughput screening (HTS) data. We matched essential genes from text-mining and mutant genes from the COSMIC and CCLE HTS datasets to build a prediction model of SL gene pairs. CCLE gene expression data were used to enrich the essential-mutant SL gene pairs using Spearman's correlation coefficient and literature mining. In total, 223 essential trigger terms were extracted and ranked. The threshold of the essential gene score ( S g ) was set to 10. We identified 586 genes essential for the SL prediction model of colon cancer. Seven essential RAS -mutant SL gene pairs were identified in our model, including CD82 - KRAS / NRAS, PEBP1 - NRAS, MT - CO2 - HRAS, IFI27 - NRAS / KRAS, and SUMO1 - HRAS gene pairs. Using RAS -mutant HTS data validation, we identified two potential SL gene pairs, including the CD82 (essential gene)- KRAS (mutant gene) pair and CD82 - NRAS pair in the DLD-1 colon cancer cell line (Spearman's correlation p- values = 0.004786 and 0.00249, respectively). Based on further annotations by PubChem, we observed that digitonin targeted the complex comprising CD82 , especially in KRAS -mutated HCT116 cancer cells. Moreover, we experimentally demonstrated that CD82 exhibited selective vulnerability in KRAS -mutant colorectal cancer. We used literature mining and HTS data to identify candidates for SL targets for RAS- mutant colon cancer., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Author(s).)