Category: 3. Business

  • Stitching Human Rights into Fashion: The Unseen Cost in Global Supply Chains

    Stitching Human Rights into Fashion: The Unseen Cost in Global Supply Chains

    Fashion, a multi-trillion-dollar business, wraps us in style and individuality, from the colorful Parisian catwalks to the clothes we wear in everyday life. Beauty and affordability come at a high price, though; under the fabric that conceals glamor stands a bitter reality, which can be summarized as many pieces of clothes are assembled by exploited hands, which are not under surveillance of buyers in the developed world. Due to the highly sophisticated, transnational supply chain network between fashionably obsessed, clothing-loving countries, modern-day human rights violations have become a thriving business, and the real, hidden price of our addiction to fast fashion has finally found its outlet.

    Human rights groups and labor activists have been highlighting vicissitudes of the gross exploitation of garment factories, especially in Southeast Asia, South Asia, and Latin America, over the past decades. The growth in the race to the bottom observed with the constant striving of big global companies to keep their production increasingly less expensive has placed the costs of cost reduction on the workers, many of whom are women and isolated groups.

    The list of abuses is disturbingly long and consistent:

    •         Poverty Wages: Garment workers get low salaries that they cannot withstand feeding or housing the family, despite living in backbreaking conditions. Such wages are usually far below the minimum living wages.

    •         Exhausting schedules and optional overtime: Twelve to fourteen hours a day, six or seven days a week, are the typical schedules, especially during the peak season. Denial of overtime working may make an employee dismissed.

    •         Unsafe Working Conditions: Factories have poor ventilation, fire escapes, and basic protective gear. A dramatic illustration that negligence has fatal consequences is the collapse of the Rana Plaza building in Bangladesh in 2013 that took away the lives of more than 1,100 garment workers.

    •         Child and Forced Labor: There is still an incidence of child labor along different points in the supply system, as witnessed in some companies picking cotton to manufacture garments. Vulnerable people are also trapped through forced labor, which is usually based on debt bondage or holding of identity papers.

    •         Restriction of Union Rights: Trying to organize and claim improved conditions, the workers often get intimidated, harassed, and even hard fired by the factory owners, often with implicit acceptance on behalf of the representatives of the brands.

    •         Gender-Based Violence and Harassment: Women comprising such a great percentage of the garment working population are more prone to sexual harassment, verbal abuse, and unfairness done to them by their supervisors.

    Global supply chains are quite complex systems, and this makes accountability extremely difficult. An individual garment can include raw materials produced in one nation, then it is spun and woven in another country, it is dyed and finished in another location, and then it is finally assembled in a fourth country. Every link introduces subcontractors, which gives brands a convenient excuse of being unaware of or declining direct responsibility for the activities on the lower levels of their supply chain.

    As Dr. Anya Sharma, a researcher of labor ethics, says, the fashion industry has crushed the tricks of staying opaque. The exploitation always occurs there, at several steps below, where things are not seen so clearly, and yet there is desperate competition for contracts to exploit people inhumanly.

    Consumers are also involved unwillingly. What people call the attractiveness of fast fashion, meaning stylish apparel at shockingly low prices, is what drives an overproduction-overconsumption paradigm. When a t-shirt is cheaper than a cup of coffee, it is a clear indication that someone somewhere is being seriously exploited.

    Nonetheless, this can be changed. Consumer awareness is rising and making brands more ethically responsible when it comes to sourcing and more transparent. At least, such movements as Fashion Revolution make consumers ask brands the question of “Who made my clothes?” and require better accountability. Some ethical fashion labels are showing that it is possible to pay good salaries and provide decent working conditions and still make a profit.

    The governments also play the pivotal role of implementing strict labor legislation, and corporations should be accountable. To develop the process of universal human rights into international norms, international collaboration is required.

    In the end, the future of fashion has a common responsibility to human dignity. As students, consumers, and people of future professions, we can insist on doing better. As we all learn to educate ourselves, to purchase ethical brands, to lobby for better regulations, and, perhaps most importantly, to buy less and buy better so that we can start to weave the fabric that puts the human right back into what we wear, no one will be taken advantage of to clothe our backs.

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  • Identifying diagnostic biomarkers for Electroacupuncture Treatment of

    Identifying diagnostic biomarkers for Electroacupuncture Treatment of

    Introduction

    Rheumatoid arthritis (RA) is the most prevalent chronic inflammatory arthritis, which can cause progressive destruction of joint cartilage.1 RA can manifest at any age, with its peak incidence typically observed in individuals aged 30–60. As a challenging chronic condition, RA significantly impairs patients’ quality of life and imposes substantial societal and economic burdens. With a prevalence of approximately 0.3% to 1%, RA is often associated with various chronic diseases, further exacerbating healthcare demands and caregiving responsibilities.2

    Currently, radical treatment for RA is limited. The therapeutic management of RA predominantly involves non-steroidal anti-inflammatory drugs (NSAIDs), conventional biological disease-modifying antirheumatic drugs (DMARDs), glucocorticoids, and other pharmacological interventions. These approaches aim to mitigate inflammation, retard disease progression, and optimize patients’ quality of life.3 However, the side effects of these drugs are controversial. Acupuncture has been practiced in Asia for over two millennia as a complementary and alternative therapeutic modality.4 Clinical studies have shown that electroacupuncture (EA) significantly relieved pain and joint swelling in RA patients and improved their quality of life without significant adverse effects.5–7 Preclinical studies have also shown that EA can significantly improve the levels of pro-inflammatory factors in the peripheral blood of RA patients to improve the internal environment for the development and progression of RA.8,9 Identifying the targeted genes underlying the therapeutic effects of EA in alleviating RA can provide critical insights for further mechanistic investigations10 and facilitate the development of standardized treatment protocols.11 However, the exact target genes of EA for RA, especially in peripheral blood, remained unidentified.

    With the development of gene microarray and bioinformatics technologies, more and more studies were focused on exploring the mechanisms of RA occurrence and key genes at the transcriptomic level.12,13 In the context of precision medicine and personalized health care, Traditional Chinese Medicine (TCM) has received increasing attention for providing personalized medical services based on TCM theories. Several studies have utilized bioinformatics analysis to identify hub targets involved in the pathogenesis of RA and validated the regulatory effects of Chinese herbal medicine on these hub targets through animal experiments. Furthermore, network pharmacology approaches were employed to elucidate the bioactive components responsible for the therapeutic efficacy.14,15 These findings provided valuable references for identifying key targets underlying EA-mediated RA alleviation. Current studies primarily aimed to elucidate how EA alleviates RA by modulating phenotype-specific genes,16,17 yet there remained a paucity of research employing bioinformatics technologies to systematically identify EA-targeted genes for RA treatment. Given the limited availability of gene targets for EA in RA, this study aimed to fill this gap by identifying the diagnostic markers for EA treatment in RA using bioinformatics tools and machine learning algorithms.

    This research retrieved mRNA expression datasets related to RA from the GEO database. The differentially expressed genes (DEGs) of RA in peripheral blood compared to normal samples and the DEGs altered by EA were obtained by differential analysis, respectively, and 26 DEGs associated with EA for RA were obtained by taking the intersection. Two diagnostic-related genes were identified by three machine learning methods, and the diagnostic efficacy of the two genes was evaluated by constructing diagnostic models. Furthermore, we determined the regulatory effects of EA on two diagnostic-related genes using qPCR.

    Materials and Methods

    Dataset Collection

    The RA relative microarray datasets were downloaded from the Gene Expression Omnibus (GEO) database (https://www.ncbi.nlm.nih.gov/geo/ and Table 1). Transcriptome data for GSE15573 and GSE59526 were obtained from peripheral blood. GSE15573 contained 15 normal samples and 18 RA samples, and GSE59526 contained 8 RA samples and 7 samples treated with EA. Transcriptome data for GSE17755, GSE205962, and GSE93272 were obtained from peripheral blood. GSE17755 contained 53 normal samples with 112 RA samples and GSE205962 contained 4 normal samples with 16 RA samples. To compare differences in the regulation of RA peripheral blood target genes by EA and drugs, blood samples associated with disease-modifying antirheumatic drugs (DMARDs) were downloaded from a dataset (GSE93272) containing 43 normal samples, 115 RA samples, 40 samples treated with infliximab (IFX), 37 samples treated with methotrexate (MTX), and 40 samples treated with tocilizumab (TCZ). The GSE15573 dataset was normalized using the “normalize quantiles” function in BeadStudio Software. The GSE59526 and GSE93272 datasets were normalized using the MAS 5.0 algorithm in GeneSpring Software. The GSE17755 dataset was normalized by global ratio median normalization. The GSE205962 dataset was analyzed using the RMA method with Affymetrix default analysis settings, applying global scaling as the normalization method. According to item 1 and 2 of Article 32 of the Measures for Ethical Review of Life Science and Medical Research Involving Human Subjects (dated February 18, 2023, China), this part of the bioinformatics analysis in this study was exempt from ethical approval.

    Table 1 The Details of Gene Expression Datasets

    Identification of Differentially Expressed Genes (DEGs) Related to EA in RA

    The filtering threshold was as follows: P-value < 0.05 and |log2-fold change| ≥ 0.1. DEGs related to RA were identified by comparing normal people with RA patients. DEGs related to EA treatment were identified by comparing RA patients with those who received EA treatment. By taking the intersection of DEGs related to RA and DEGs related to EA treatment, we obtained DEGs related to EA in RA.

    Identification of Diagnostic Biomarkers for RA Patients

    Diagnostic biomarkers were identified using three distinct machine learning algorithms. Specifically, the least absolute shrinkage and selection operator (LASSO) algorithm was implemented using the “glmnet” package to identify potential biomarkers, with parameters set at alpha = 1, nlambda = 100, and λmin determined as the optimal λ. LASSO effectively reduces subset size and serves as a biased estimator for handling complex collinearity. It is also efficient in selecting a limited set of predictive features. The advantages of the random forest algorithm include minimal tuning of hyperparameters and handling non-linear relationships. It also has the capability to predict continuous variables with a high degree of accuracy, sensitivity, and specificity,18 as demonstrated in this study using the “randomForest” package with nTree = 500 as the specified parameters. The top ten genes exhibiting mean decrease Gini (MDG) were identified as potential biomarkers. The support vector machine recursive feature elimination (SVM-RFE) technique is utilized to prevent overfitting and is a commonly used discriminant method for regression, classification, and pattern recognition analyses. It can improve the discriminative ability of biomarkers in classification and regression tasks, while effectively removing irrelevant features. This method was implemented using the “e1071” package, and the performance was evaluated based on the average misjudgment rates obtained from 10‐fold cross‐validations. The strategic integration of these three machine learning algorithms enhanced the confidence in selected biomarkers through complementary feature selection paradigms.

    Establishment and Evaluation of Nomogram

    The Nomogram model was developed using the “rms” package to generate calibration curves and clinical decision curves, facilitating the evaluation of clinical utility and discriminative performance of the model in the context of RA. Additionally, the “pROC” package was utilized to compute the area under the receiver operating characteristic (ROC) curve along with 95% confidence intervals (CI).

    Animals

    Eighteen specific pathogen free (SPF) male Sprague-Dawley (SD) rats aged 8 weeks weighing 160–200 g were procured from Shanghai B&K Laboratory Animals Co., Ltd. and accommodated in the Experimental Animal Center of Shanghai University of Traditional Chinese Medicine. The rats were provided with free access to food and water within a 12-hour light-dark cycle. All animal handling protocols adhered to the guidelines set forth by the National Research Council’s Guide for the Care and Use of Laboratory Animals and were sanctioned by the Experimental Animal Ethics Committee of Shanghai University of Traditional Chinese Medicine (PZSHUTCM2401080014).

    Model Establishment

    Eighteen rats were divided into three groups using random assignment (n = 6 per group): (1) Control group, (2) CFA group and (3) CFA + EA group. In the CFA and CFA + EA groups, the CFA model was prepared according to previous research. Rats were anesthetized with 2–3% isoflurane (RWD Life Science Company, Shenzhen, Guangdong, China) and 100 μL CFA suspension was injected into the right hindpaw of the rats, while saline was administered to the control group.19 Successful model induction was evidenced by the development of ipsilateral paw edema and mechanical allodynia in rats post-modeling.

    Evaluation of Pain-Response Behavior

    The paw withdrawal threshold (PWT) was assessed using an electronic von Frey anesthesiometer (IITC 2391, USA) following the methodology described by Vivancos.20 This test was conducted to observe the progression of mechanical allodynia in CFA-induced rats and to evaluate the analgesic efficacy of EA. Rats underwent testing on day 0 before the model was created, as well as on days 1, 3, and 7 following EA. Before each evaluation, the rats were acclimated in Plexiglas enclosures for a period of 30 minutes. The pressure was applied to the midplantar area of the hindpaw using a polypropylene tip connected to an electronic von Frey device. The threshold for response was automatically measured when the hindpaw reacted to the pressure. The mean value of three consecutive measurements of the PWT was calculated for each paw after recording it thrice with a 5-minute interval between each measurement.

    EA Treatment

    Stainless steel needles (0.25 × 40 mm, Huatuo) were inserted into the Kunlun (BL60) and Zusanli (ST36) acupoints on the right side to a depth of about 5 mm. A 2 Hz, 1 mA electrical signal was administered on the needles daily for 30 minutes using a stimulation device (Model G6805-2A; Shanghai Huayi Co., Shanghai, China). The treatment with EA started on the first day after the surgery and continued for 7 days. Following the final PWT assessment, the rats were anesthetized with isoflurane (5%) and blood samples were collected from the abdominal aorta into ethylenediaminetetraacetic acid (EDTA) tubes. Subsequently, the rats were euthanized via cervical dislocation, and their peripheral blood was gathered for further biological investigations.

    Real-Time Fluorescence Quantitative PCR

    The results of our bioinformatics analysis were confirmed by qPCR validation of peripheral blood samples from all rats. The primers utilized have been documented in Table 2. Total RNA was isolated with a total RNA extraction solution following the manufacturer’s protocol (Servicebio, Wuhan, China). Three individual reactions were conducted for every sample, with the average and standard deviation computed for each data point. The 2−ΔΔCT method was employed to quantify mRNA expression levels of diagnostic biomarkers, with GAPDH serving as the internal reference.

    Table 2 Specific Primer Sequences Used in qPCR

    Statistical Analysis

    The experimental data was statistically analyzed based on the GraphPad Prism software and presented as the mean ± standard deviation (SD). Statistical analysis of the control, CFA, and CFA + EA groups was performed using One-way ANOVA followed by Bonferroni post hoc tests applied for qPCR analysis, while behavioral analysis was conducted using two-way ANOVA with Bonferroni post hoc testing. A P-value of less than 0.05 was considered statistically significant for all analyses.

    Results

    Screening of DEGs Related to EA in RA

    The differential expression analysis revealed 2428 DEGs related to RA, with 1671 downregulated and 757 upregulated genes (Figure 1A and B). Similarly, a total of 486 DEGs related to EA treatment were identified, with 228 downregulated and 258 upregulated genes (Figure 1C and D). By taking the intersection of two groups of DEGs, a total of 26 DEGs related to EA in RA were identified (Figure 1E).

    Figure 1 Identification of DEGs related to EA in RA. The volcano plot (A) and heatmap (B) for DEGs related to RA. The volcano plot (C) and heatmap (D) for DEGs related to EA treatment. (E) Venn diagram of the intersection of DEGs related to RA and DEGs related to EA treatment.

    Determination of the Diagnostic Biomarkers

    As shown in Figure 2A and B, the LASSO regression algorithm identified ten potential candidate biomarkers. Then, the random forest algorithm determined the top ten candidate genes ranked by MeanDecreaseGini (Figure 2C and D). As for SVM-RFE, when the number of features was 9, the accuracy was maximized (Figure 2E), and the error was minimized (Figure 2F). After combining the results of three algorithms, two diagnostic biomarkers were identified: VEGFB and ARHGAP17 (Figure 2G).

    Figure 2 Identification of diagnostic biomarkers. The lambda values (A) and minimum (B) of diagnostic biomarkers were identified by LASSO. (C) Potential diagnostic biomarkers selection via Random Forest. (D) MeanDecreaseGini showed the rank of genes in accordance with their relative importance. (E) Accuracy and (F) error of 10-fold cross-validation in SVM-RFE algorithms, respectively. (G) The intersection of diagnostic biomarkers screened by three machine algorithms.

    Diagnostic Efficacy of Diagnostic Biomarkers

    Based on the expression of two genes, a diagnostic nomogram was constructed for RA to assess its diagnostic specificity and sensitivity (Figure 3A). ROC curves were generated to evaluate the diagnostic utility of individual genes and the nomogram. Figure 3B illustrated that VEGFB (0.819) and ARHGAP17 (0.978) had AUC values exceeding 0.75. In addition, the nomogram model (AUC = 0.981) based on two genes showed better diagnostic performance than two genes alone (Figure 3C). Based on the calibration curve analysis in Figure 3D, the nomogram model demonstrated comparable accuracy to the true positivity rate. The clinical decision curves revealed that the Nomogram model developed with two genes had a high predictive ability for RA, as the model curve outperformed the two threshold curves for benefits (Figure 3E).

    Figure 3 Construction of the nomogram model and efficacy assessment. (A) The nomogram of diagnostic biomarkers for risk prediction of RA. (B) The ROC curves of each diagnostic biomarker. (C) The ROC curve of the nomogram model. (D) The calibration curve of nomogram model prediction in RA. (E) DCA results to evaluate the clinical value of the nomogram model.

    Identification and Verification of Diagnostic Biomarkers

    The diagnostic effectiveness of two genes for RA was validated on peripheral blood samples from three external datasets with RA. The AUC values of VEGFB and ARHGAP17 were 0.692 and 0.815 in GSE17755 (Figure 4A), respectively, and the diagnostic model showed promising efficacy in RA (AUC = 0.817) (Figure 4D). Besides, the AUC values of VEGFB and ARHGAP17 genes were 0.721 and 0.767 in GSE93272 (Figure 4B), respectively, and the diagnostic model showed good efficacy in RA (AUC = 0.794) (Figure 4E). The AUC values of VEGFB and ARHGAP17 genes were 0.922 and 0.945 in GSE205962 (Figure 4C), respectively, and the diagnostic model showed good efficacy in RA (AUC = 1.000) (Figure 4F).

    Figure 4 The ROC curves of each diagnostic biomarker and the nomogram model in GSE17755 (A and D), GSE93272 (B and E) and GSE205962 (C and F).

    In addition, the diagnostic biomarkers showed differential expression in the training and validation cohorts. The expression levels of ARHGAP17 and VEGFB in the peripheral blood of patients with RA were significantly decreased in GSE15573 (Figure 5A and B), GSE17755 (Figure 5C and D), GSE93272 (Figure 5E and F), and GSE205962 (Figure 5G and H) compared to healthy individuals. Besides, EA can increase the levels of VEGFB and ARHGAP17 in the peripheral blood of RA patients (Figure 6A and B), with comparable effectiveness to DMARDs such as IFX (Figure 6C and D), MTX (Figure 6E and F), and TCZ (Figure 6G and H).

    Figure 5 Expression levels of ARHGAP17 and VEGFB in the GSE15573 (A and B), GSE17755 (C and D), GSE93272 (E and F), and GSE205962 (G and H). *p < 0.05, **p < 0.01, ***p < 0.001, compared to the Control group.

    Figure 6 Comparison of ARHGAP17 and VEGFB expression levels following treatment with EA (A and B), IFX (C and D), MTX (E and F), and TCZ (G and H). *p < 0.05, **p < 0.01, ***p < 0.001, compared to the RA group.

    EA Demonstrated Analgesic Effects in CFA-Induced Mechanical Allodynia

    Measurement of PWT in the ipsilateral hindpaws of rats showed hyperalgesia induced by CFA and antihyperalgesic effects of EA. As shown in Figure 7, the baseline values of PWT prior to injection of CFA did not exhibit significant differences across groups. Following the administration of CFA, the PWT of the CFA group and the CFA+EA group exhibited a significant decrease in comparison to the control group and the hyperalgesia endured for a minimum duration of one week. After receiving EA therapy, the rats in the CFA+EA group demonstrated a significant improvement in PWT starting from the first day as compared to the CFA group, indicating that EA significantly alleviated mechanical allodynia in CFA rats.

    Figure 7 The effects of EA on mechanical allodynia induced by CFA. ***p < 0.001 compared to the control group; ##p < 0.01, compared to the CFA group.

    The qPCR analysis showed a significant reduction in ARHGAP17 and VEGFB mRNA expression levels in the peripheral blood of the CFA group compared to the control group. Conversely, EA can significantly increase the expression of ARHGAP17 and VEGFB in the peripheral blood of CFA rats (Figure 8A and B).

    Figure 8 The effect of EA on regulating the diagnostic biomarkers. The mRNA expression of ARHGAP17 (A) and VEGFB (B) were analyzed by qPCR. ***p < 0.001 compared to the control group; ###p < 0.001 compared to the CFA group.

    Discussion

    This study identified 26 genes associated with the therapeutic effects of EA on RA. Machine learning algorithms were employed to identify two genes, ARHGAP17 and VEGFB, as potential diagnostic biomarkers, and their diagnostic efficacy was subsequently validated through the construction of a Nomogram model. Meanwhile, we demonstrated through various validation datasets that both diagnostic markers were significantly decreased in RA patients and exhibited excellent diagnostic performance. Furthermore, we found that these two biomarkers could effectively reflect the therapeutic effects of DMARDs and EA on RA, serving as prognostic indicators for evaluating treatment efficacy in RA. To further validate these findings, we established a CFA model, which revealed that the transcription levels of ARHGAP17 and VEGFB were significantly reduced in the peripheral blood of CFA-treated rats. Notably, EA therapy reversed this reduction, suggesting its potential therapeutic benefits for RA.

    Rho guanosine triphosphatases (GTPases) function as molecular switches and have been implicated in the dysregulation associated with the pathogenesis of RA.21 The enzymatic activity of Rho GTPases is stringently regulated by Rho GTPase-activating proteins (GAPs), which play a crucial role in modulating signaling accuracy and preventing aberrant activation. ARHGAP17 (Rho GTPase Activating Protein 17), also known as RICH1, belongs to the GTPase-activating proteins (GAP) family, widely expressed in human tissues, and functions as a negative regulator of GTPases. Current research on ARHGAP17 has primarily focused on its role in cancer,22 while the potential involvement of ARHGAP17 in the effects of EA remained unexplored. Notably, the Rho GTPase (RAC1) is involved in the progression of various pain conditions,23–25 and EA has been shown to alleviate pain by suppressing RAC1 expression.26 To date, no studies have established the diagnostic or therapeutic value of ARHGAP17 in RA. Interestingly, existing evidence indicated that ARHGAP17 may suppress RAC1 expression and reduce cellular apoptosis.22 Our study demonstrated that EA can reverse the decreased expression of ARHGAP17 in the peripheral blood of CFA rats, suggesting that EA may exert its anti-inflammatory and analgesic effects by promoting ARHGAP17 expression, thereby inhibiting the activation of the Rho GTPase and mitigating the progression of RA.

    Vascular endothelial growth factors (VEGFs) are the crucial molecule that promotes angiogenesis, which is a characteristic pathological feature of RA.27 Notably, a previous study has demonstrated that serum VEGF levels in RA patients correlated positively with disease severity,28 suggesting that VEGF may serve as a valuable molecular biomarker for evaluating the severity of RA. However, emerging evidence suggested that VEGF not only promoted inflammation and angiogenesis but also facilitated subchondral bone regeneration in arthritic joints.29 A preliminary study found that promoting VEGF expression within the joint can enhance lymphatic drainage, thereby reducing the severity of RA.30 As one of the subtypes of VEGF, VEGFB can be regulated by vagus nerve electrical stimulation, suppressing inflammatory responses through activation of the PI3K/AKT-FoxO3A-VEGF-A/B signaling cascade.31 This study revealed that EA can upregulate VEGFB expression in the peripheral blood of RA patients and CFA rats. This finding appeared contradictory to previous research demonstrating that EA suppressed VEGF mRNA expression in synovial tissue of adjuvant arthritis rats.32 We hypothesized that the inconsistent results may be due to differences in the regulation of VEGF subtypes by EA.

    This study was not the first to apply bioinformatics analysis to identify potential biomarkers involved in EA treatment for RA. However, compared with previous research,32 it incorporated a broader range of machine learning algorithms and validated the findings across multiple validation datasets. The present study has the following limitations: Firstly, the datasets employed in this study contained a relatively limited number of EA treatment cases. Additionally, we did not evaluate biomarker diagnostic efficacy across diverse demographic subgroups or perform batch-effect correction on the dataset. Secondly, due to experimental limitations, this study did not expand on the diagnostic efficacy of biomarkers in clinical RA patients or the regulatory effects of EA on these biomarkers. Current animal models exhibited limited capacity to fully recapitulate the complex pathogenesis of RA, thereby constraining accurate assessment of diagnostic biomarker performance and EA therapeutic efficacy across disease subtypes. Therefore, further clinical experiments are needed to extend the application of biomarkers.

    Conclusion

    The present study identified two potential diagnostic biomarkers for RA using bioinformatics and machine learning approaches, and revealed that EA modulated the expression of these genes in peripheral blood. These findings not only provided new potential biomarkers for RA diagnosis but also offered novel therapeutic targets for EA-based treatment in RA management. However, further clinical trials are necessary to validate the diagnostic efficacy of biomarkers for different populations and the regulatory effects of EA on these biomarkers.

    Abbreviations

    CFA, Complete Freund’s Adjuvant; DEGs, Differentially expressed genes; DMARDs, disease-modifying antirheumatic drugs; EA, Electroacupuncture; GEO, Gene Expression Omnibus; IFX, Infliximab; LASSO, Least absolute shrinkage and selection operator; MDG, Mean decrease Gini; MTX, Methotrexate; NSAIDs, Non-steroidal anti-inflammatory drugs; PWT, Paw withdrawal threshold; RA, Rheumatoid arthritis; ROC, Receiver operating characteristic; SVM-RFE, Support vector machine recursive feature elimination; TCM, Traditional Chinese Medicine; TCZ, Tocilizumab.

    Data Sharing Statement

    The datasets analyzed for this study can be found in the GEO (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc = GSE15573, GSE59526, GSE17755, GSE205962, and GSE93272).

    Funding

    This research was fund by Shanghai Chinese Medicine Three-Year Action Plan Project (ZY(2021-2023)-0202, ZY(2021-2023)-0502).

    Disclosure

    The authors report no conflicts of interest in this work.

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    21. Zeng R, Zhuo Z, Luo Y, Sha W, Chen H. Rho GTPase signaling in rheumatic diseases. iScience. 2022;25(1):103620. doi:10.1016/j.isci.2021.103620

    22. Wang L, Yang X, Wan L, Wang S, Pan J, Liu Y. ARHGAP17 inhibits pathological cyclic strain-induced apoptosis in human periodontal ligament fibroblasts via Rac1/Cdc42. Clin Exp Pharmacol Physiol. 2020;47(9):1591–1599. doi:10.1111/1440-1681.13336

    23. Wan Y, Zhou J, Zhang P, Lin X, Li H. Inhibition of spinal Rac1 attenuates chronic inflammatory pain by regulating the activation of astrocytes. Cell Signalling. 2024;114:110972. doi:10.1016/j.cellsig.2023.110972

    24. Chen Z, Zhang S, Nie B, et al. Distinct roles of srGAP3-Rac1 in the initiation and maintenance phases of neuropathic pain induced by paclitaxel. J Physiol. 2020;598(12):2415–2430. doi:10.1113/jp279525

    25. Xu L, Yang L, Wu Y, et al. Rac1/PAK1 signaling contributes to bone cancer pain by regulation dendritic spine remodeling in rats. Mol Pain. 2023;19:17448069231161031. doi:10.1177/17448069231161031

    26. Wu Q, Cai C, Ying X, et al. Electroacupuncture inhibits dendritic spine remodeling through the srGAP3-Rac1 signaling pathway in rats with SNL. Bio Res. 2023;56(1):26. doi:10.1186/s40659-023-00439-0

    27. MacDonald IJ, Liu SC, Su CM, Wang YH, Tsai CH, Tang CH. Implications of angiogenesis involvement in arthritis. Int J Mol Sci. 2018;19(7):2012. doi:10.3390/ijms19072012

    28. Kim JW, Kong JS, Lee S, et al. Angiogenic cytokines can reflect the synovitis severity and treatment response to biologics in rheumatoid arthritis. Exp Mol Med. 2020;52(5):843–853. doi:10.1038/s12276-020-0443-8

    29. Rong M, Liu D, Xu X, et al. A superparamagnetic composite hydrogel scaffold as in vivo dynamic monitorable theranostic platform for osteoarthritis regeneration. Adv Mater. 2024;36(35):e2405641. doi:10.1002/adma.202405641

    30. Luo B, Wu Y, Liu SL, et al. Vagus nerve stimulation optimized cardiomyocyte phenotype, sarcomere organization and energy metabolism in infarcted heart through FoxO3A-VEGF signaling. Cell Death Dis. 2020;11(11):971. doi:10.1038/s41419-020-03142-0

    31. Zhu J, Su C, Chen Y, Hao X, Jiang J. Electroacupuncture on ST36 and GB39 acupoints inhibits synovial angiogenesis via downregulating HIF-1α/VEGF expression in a rat model of adjuvant arthritis. Evid Based Complement Alternat Med. 2019;2019:5741931. doi:10.1155/2019/5741931

    32. Shen C, Gu B, Tang M, et al. Biomarkers identification of early rheumatoid arthritis via bioinformatics approach and experimental verification. Ann Clin Lab Sci. 2024;54(5):661–670.

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  • FTX Stops Repayments in China, Russia, Afghanistan

    FTX is asking the court to approve a plan that might prevent users in 49 countries

    Written by:

    Olumide Adesina


    •
    Saturday, July 5, 2025
    •
    1 min read

    •
    Last updated: Saturday, July 5, 2025



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    FTX

    Quick overview

    • FTX is seeking court approval to prevent users in 49 countries, including China and Russia, from receiving creditor repayments due to local cryptocurrency laws.
    • Chinese users account for 82% of the affected claim value and may face significant financial impact from this proposal.
    • The FTX Trust plans to notify creditors if legal advice suggests that disbursing funds would violate local laws, allowing them to formally object within 45 days.
    • Affected users have expressed strong concerns about the ethical implications of dismissing their claims based on jurisdictional restrictions.

    FTX is asking the court to approve a plan that might prevent users in 49 countries where cryptocurrency is illegal from receiving billions in creditor repayments.

    Three People Has Been Identified And Charged For The $400 Million FTX Hack Attack

    Chinese users are reportedly responsible for 82% of the impacted claim value and may be disproportionately affected. In a court filing dated July 2, FTX proposed designating 49 nations as “Potentially Restricted Jurisdictions,” including China, Russia, Afghanistan, and Ukraine.

    The FTX Trust will first seek legal opinions for each jurisdiction, and payouts will proceed if deemed legally permissible, even though claims from these regions will automatically be marked as “disputed.”

    However, the Trust will formally notify affected creditors if legal advice indicates that disbursing funds would be in violation of local laws. Following this, impacted users will have forty-five days to submit a formal objection, which can include a challenge in a U.S. court.

    Those affected by the proposal have reacted strongly. Some argue that it raises serious ethical concerns, despite the FTX Recovery Trust framing it as a legal compliance issue. One user on X commented, “FTX accepted users from China when things were fine.” Now, it seems unfair to completely dismiss their claims due to “restricted jurisdiction.”

    He referred to creditors in the affected nations as “victims” who still need payment. “While mainland China does not support cryptocurrency trading, residents… are allowed to hold cryptocurrencies… The claims process uses USD for settlement… they are allowed to hold USD overseas,” stated another Chinese claimant who goes by the username “Will.”

    Others felt despair; one user asked, “Is there anything that could be done? Or did they steal all of the money?” Sunil, an advocate for FTX creditors, questioned why wire transfer settlements are not supported.

    Olumide Adesina

    Financial Market Writer

    Olumide Adesina is a French-born Nigerian financial writer. He tracks the financial markets with over 15 years of working experience in investment trading.

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  • Trump says will ‘take a look’ at deporting Musk





    Trump says will ‘take a look’ at deporting Musk – Daily Times





























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  • Canadian dollar inches up against Pak rupee – 5 July 2025

    Canadian dollar inches up against Pak rupee – 5 July 2025

    LAHORE – The buying rate of Canadian dollar moved up slightly as it stood at Rs208.6 in open market of Pakistan on Saturday, according to an online currency exchange portal.

    The private exchange companies are selling the Canadian Dollar for Rs213.6, reflecting its dominance over the local currency.

    The local currency rates reflect ongoing trend in the forex market influenced by regional demand, remittance inflows, and overall economic sentiments.

    How much is $1000 CAD in PKR?

    As of July 5, they buying rate of the Canadian dollar stands at Rs208.6. It means an individual can convert $1000 CAD for Rs208,600 in open market.

    Remittances play a crucial role in supporting the economies of developing countries. They provide a stable source of income for millions of families, helping them meet basic needs such as food, healthcare, and education.

    These funds also boost national foreign exchange reserves and contribute to poverty reduction. Unlike loans or aid, remittances flow directly to households, encouraging local spending and investment.

    In May 2025, overseas Pakistanis living in Canada sent $69.55 million in wake of the remittances.

    According to the SBP, the workers’ remittances from overseas to Pakistan, recording a significant growth of 28.8 percent during eleven months of fiscal year 2024-25, reached nearly US$ 35 billion in the period from July to May while monthly inflows in May increased to $ 3.69 billion.

    During May 2025, the workers’ remittances recorded an inflow of US$ 3.686 billion, depicting 16 percent growth over April 25 and 13.7 percent yearly increase against May 2024, the statistics showed.

    Currency exchange is a key component of the global economy and holds special importance for countries such as Pakistan.

    It refers to the process of converting one nation’s currency into another, which supports international trade, tourism, and investment.

    In Pakistan, exchange rates influence the value of the rupee compared to major currencies like the US dollar and UAE dirham. A stronger exchange rate makes imports cheaper and helps control inflation, while a weaker rate can boost exports.

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  • Knowledge, Attitudes, and Practices Among Patients Undergoing Gastroin

    Knowledge, Attitudes, and Practices Among Patients Undergoing Gastroin

    Introduction

    Globally, diseases of the digestive system, including functional gastrointestinal disorders, gastritis, and peptic ulcers, are common and contribute significantly to both morbidity and mortality.1 Chronic gastritis affects over half of the world’s population, underscoring its widespread impact.2 Epidemiological studies suggest that the morbidity rate for peptic ulcers and associated disorders could be as high as 10%; however, recent years have shown a declining trend in incidence, particularly due to improved H. pylori eradication strategies and proton pump inhibitor use.3,4 The burden of gastrointestinal diseases remains high due to the prevalence of both benign conditions, such as acute and chronic gastroenteritis, and malignant diseases like colorectal and gastric cancers, which, while distinct, also represent major global public health concerns. These cancers rank as the third and fourth most common cancers globally, each causing approximately 800,000 deaths annually.5,6 These conditions lead to considerable pain and disability, while also placing a heavy financial strain on both families and society.

    Gastrointestinal endoscopy represents the gold standard for diagnosing and monitoring digestive diseases. While primarily performed under conscious sedation, this procedure can provoke significant anxiety and psychological distress in patients, potentially affecting both procedure outcomes and patient compliance with future screening recommendations.7 Despite its clinical benefits, gastrointestinal endoscopy can provoke anxiety, fear, and even stress reactions among patients, as reported in numerous studies.8,9 Endoscopy is primarily utilized in outpatient settings and is well-known for its effectiveness in diagnosing and treating gastrointestinal disorders.10 Given the increasing global incidence of digestive system diseases, the role of endoscopy is more critical than ever.11,12

    The KAP framework provides a structured approach to understanding how patients’ knowledge influences their attitudes and subsequent health behaviors. In the context of gastrointestinal endoscopy, this understanding is particularly crucial as patient preparation and cooperation directly impact procedure quality and diagnostic yield. It is based on the idea that knowledge has a beneficial effect on attitudes, which in turn influence behaviors.13,14 Inadequate knowledge and negative attitudes may lead to poor bowel preparation, increased anxiety, refusal to undergo the procedure, or reduced compliance with follow-up recommendations-factors that can significantly compromise diagnostic accuracy and therapeutic outcomes.9,15 With the increasing prevalence of gastrointestinal disorders, ranging from benign conditions such as gastritis to life-threatening cancers, there is a critical need to understand patient experiences and behaviors to enhance clinical outcomes. Gastrointestinal endoscopy, an essential diagnostic and therapeutic tool, often triggers anxiety and fear among patients, potentially affecting their willingness to undergo necessary procedures. This study is pivotal as it focuses on a patient group whose insights are crucial for the efficacy of endoscopic procedures and overall treatment success. By examining patients’ understanding, reactions, and adjustments post-endoscopy, healthcare providers can develop targeted communication strategies and support mechanisms that enhance patient comfort, increase engagement, and promote adherence. This approach ultimately leading to optimized healthcare resource utilization and improved health outcomes.

    Despite extensive research on the technology and effectiveness of endoscopy,16–18 studies delving into patient feedback post-examination remain limited. A recent narrative review by Minciullo et al (2022) summarized available tools for assessing patient satisfaction in digestive endoscopy, emphasizing its importance as a quality indicator.19 While that review primarily focused on satisfaction measurement, our study explores patients’ KAP, offering a broader behavioral and cognitive perspective that complements satisfaction-based evaluations. This study aimed to quantify patients’ knowledge levels regarding gastrointestinal endoscopy procedures; assess attitudes and psychological barriers towards endoscopic examination; evaluate adherence to pre- and post-procedure care instructions; and examine the connections between knowledge, attitudes, and practices to identify targeted intervention opportunities. These specific objectives will help address the current gap in understanding patient perspectives and guide the development of evidence-based educational programs. Therefore, herein, we sought to explore the KAP of patients toward gastrointestinal endoscopy in the Endoscopy Unit.

    Materials and Methods

    Study Design and Participants

    The required sample size was estimated using the formula for cross-sectional studies:20 n = Z² × P × (1 – P) / d², where n is the sample size, Z is the standard normal deviate at 95% confidence level (Z = 1.96), P is the expected proportion (assumed to be 50% for maximum variability), and d is the margin of error (set at 4%). Based on this formula, a minimum sample size of 384 was required. Considering potential non-response or invalid submissions, we distributed a larger number of questionnaires. Ultimately, 612 valid responses were obtained, meeting the minimum statistical power requirement.

    This cross-sectional study used a survey to collect data at the author’s Hospital from December 2023 to February 2024. Consecutive adult patients who were referred for diagnostic gastrointestinal endoscopy were enrolled using convenience sampling. To minimize heterogeneity, patients with a confirmed inflammatory bowel disease diagnosis or those undergoing therapeutic procedures were excluded. The research received approval from the Medical Ethics Committee of the author’s Hospital, and all the study participants provided informed consent.

    Inclusion criteria were the following: 1) those who underwent gastrointestinal endoscopy (gastroscopy or colonoscopy); 2) those who voluntarily participated; 3) those who were conscious and able to cooperate.

    Exclusion criteria were the following: 1) those with critical condition; 2) those who underwent gastrointestinal endoscopy for gastrointestinal bleeding; 3) those unable to complete the questionnaire for other reasons.

    Questionnaire

    The questionnaire was developed through a systematic review of relevant literature and current clinical practice guidelines. Content validity was established through an expert panel review by two gastroenterologists and two endoscopy nurses.21,22 Following the questionnaire’s design, a pilot study was carried out involving 76 participants, generating a Cronbach’s α coefficient = 0.912, indicative of good internal consistency. The final questionnaire included 4 dimensions: knowledge, attitude, practice, and demographic characteristics, comprising basic patient demographics, reasons for seeking medical care, daily routines, and dietary habits. The knowledge section consisted of 9 questions, with responses scored assigned 2 points for “complete understanding”, 1 point for “partial understanding”, and 0 for “lack of understanding”, generating a total score of 0 to 18. The attitude section consisted of 7 questions, rated on a five-point Likert scale from “strongly agree” to “strongly disagree”, with scores ranging from 5 points to 1 point and a total score range of 7 to 35. The practice section included 8 items, also rated on a five-point Likert scale from “always” to “never”, with values ranging from 5 points to 1 point and a total score of 8 to 40. According to Bloom’s cutoff, participants who scored > 80% of the total were classified as possessing satisfactory knowledge, constructive attitudes, and active practices, while those scoring between 60% and 80% were classified as possessing average levels in these dimensions. Scoring < 60% of the total suggested inadequate knowledge, negative attitudes, and passive behaviors.23

    The questionnaire was generated using the “Questionnaire Star” platform, after which a QR code was obtained, printed, and placed in the endoscopy room. After patients completed their endoscopy and fully regained consciousness, two specially trained nurses invited them to the endoscopy room to scan the QR code and complete the questionnaire. Patients scanned the QR code and completed the questionnaire using their phone, with each phone allowing only one submission of responses. Researchers will only provide clarifications about the questions without offering any hints for the answers. For elderly patients who cannot use a mobile phone, the nurses will record the patients’ answers and fill out the questionnaire on their behalf.

    To further evaluate the validity of the questionnaire, both content validity and construct validity were assessed. Content validity was established through expert review by two gastroenterologists and two endoscopy nurses. Construct validity was examined using confirmatory factor analysis (CFA) (Supplementary Table 1). The Kaiser-Meyer-Olkin (KMO) test yielded a value of 0.913 (P < 0.001), indicating sampling adequacy. Model fit indices demonstrated good construct validity (CMIN/DF = 4.487; RMSEA = 0.076; IFI = 0.937; TLI = 0.929; CFI = 0.937), and all standardized factor loadings were statistically significant (P < 0.001). A CFA path diagram is presented in Supplementary Figure 1 to illustrate the measurement structure.

    Statistical Analysis

    Statistical analysis was conducted using SPSS 22.0 (IBM, Armonk, NY, USA). Continuous data are reported as mean ± standard deviation (SD), and categorical data are expressed as n (%). Continuous data that were confirmed to follow a normal distribution were analyzed using independent-sample t-tests or one-way ANOVA. The Wilcoxon Mann–Whitney test or Kruskal–Wallis test was used to compare continuous data with skewed distribution. The correlation among KAP was analyzed using Pearson correlation analysis, and interactions among KAP were explored using structural equation modeling (SEM) performed with AMOS version 26.0. A two-sided P-value less than 0.05 was considered statistically significant.

    Results

    Patients’ Characteristics

    Among a total of 744 collected questionnaires, 20 refused to participate in the study, 9 had a short response time (< 90 seconds), 13 had a logical conflict, and 80 were incomplete, resulting in 612 valid questionnaires, with a validity rate of 82.26%.

    Out of these 612 participants, 308 (50.33%) were filled out by males; the mean age of participants was 51.11 ± 12.61 years; 363 (62.42%) had a BMI in the normal range; 152 (24.84%) had poor dietary habits, 250 (40.85%) had heavy taste preference in their diets and 147 (24.02%) were frequently constipated. Meanwhile, 355 (58.01%) had their first gastroscopy, 561 (91.67%) opted for a painless procedure, and 308 (50.33%) had gastrointestinal polyps (Table 1). Among the 308 patients with polyps, the majority (225 cases, 73.1%) underwent painless enteroscopy alone, followed by 33 cases (10.7%) who received both painless enteroscopy and painless gastroscopy, and 29 cases (9.4%) with painless gastroscopy alone. This distribution, as visualized in the UpSet plot (Figure 1), indicates that painless colonoscopy was the predominant modality associated with polyp detection in this study. The reason for the endoscopy examination and results are shown in Figure 2. “Life stage screening” refers to routine health check-ups commonly recommended based on age or risk factors, such as colorectal cancer screening in adults over 50.

    Table 1 Demographic Characteristics, Knowledge, Attitude, and Practice

    Figure 1 UpSet plot showing the distribution of gastrointestinal endoscopic procedures among the 308 patients diagnosed with polyps.

    Figure 2 (A) Reasons for undergoing digestive endoscopy (including upper and lower GI procedures); “Life stage screening” refers to routine health check-ups. (B) Results of endoscopic examinations.

    Knowledge, Attitude, and Practice

    The mean scores for knowledge, attitude, and practice were 11.66 ± 3.95 (possible range: 0–18), 29.79 ± 3.27 (possible range: 7–35), and 36.69 ± 4.99 (possible range: 8–40), separately. Knowledge scores varied depending on education (P < 0.001), monthly income (P = 0.010), alcohol consumption (P = 0.047), family history of gastric or colorectal cancer (immediate family) (P = 0.008), unexplained changes in bowel habits or fecal abnormalities (P = 0.002), number of gastroscopies (P < 0.001), and the number of polyps (P = 0.015). Attitude scores were more likely to vary depending on unexplained changes in bowel habits or fecal abnormalities (P = 0.049), number of gastroscopies (P = 0.047), presence of polyps (P = 0.015), and whether the polyp was >5 mm (P = 0.030). Practice scores varied depending on education (P = 0.020), monthly income (P < 0.010), number of gastroscopies (P = 0.015), and type of the current gastroenteroscopy (P < 0.001) (Table 1).

    For all the knowledge items, no more than 40% of the participants answered “Very well known”, while more than 60% chose “Heard of it”, indicating that while progress has been made, there remains ample opportunity for further improvement. Specifically, for “ Endoscopic examinations can assess different areas of the gastrointestinal tract, such as the esophagus, stomach, duodenum, and colon.”, 70.1% chose “Heard of it” (K3). As for “This examination is typically used to diagnose gastrointestinal diseases such as ulcers, tumors, and inflammation.”, 69.77% chose “Heard of it” (K2) (Table 2).

    Table 2 Responses to the Knowledge Section

    For the attitude dimension, more than 90% of participants chose either “strongly agree” or “agree”, except for A1 and A3. Specifically, 23.37% and 23.53% were neutral on whether they felt nervous or anxious before the examination (A1) and whether they were worried about the safety and side effects of endoscopy (A3), respectively (Table 3).

    Table 3 Responses to the Attitude Section

    Responses on the practice revealed that > 70% of the participants chose “always” for all items except P2 and P3. Specifically, 68.63% of the participants were always fully aware of the endoscopy procedure and possible discomfort before the examination (P2), and 61.44% of the participants always raised concerns and questions about the procedure with the doctor prior to the examination (P3) (Table 4).

    Table 4 Responses to the Practice Section

    The Correlation and Interaction Among KAP

    The correlation analyses revealed statistically significant, weak to moderate positive correlations: knowledge was weakly correlated with attitude (r = 0.281, P < 0.001) and with practice (r = 0.148, P < 0.001), while attitude demonstrated a moderate correlation with practice (r = 0.370, P < 0.001) (Table 5).

    Table 5 Correlation Analysis

    The SEM model showed that the questionnaire fit the KAP model well (Figure 3 and Supplementary Table 2), and the analysis of direct and indirect effects showed that knowledge directly affected attitude (β = 0.397, P = 0.026) and attitude directly affected practice (β = 0.402, P = 0.007). Although the direct effect of knowledge on practice is not significant (β = 0.032, P = 0.568), knowledge has an indirect effect on practice through attitude (β = 0.159, P = 0.014) (Table 6).

    Table 6 Direct and Indirect Effects in SEM

    Figure 3 Structural Equation Model.

    Discussion

    Our findings reveal important knowledge gaps among patients undergoing diagnostic endoscopy, despite their generally positive attitudes and adherence to recommended practices. Notably, over 60% of participants reported only partially understanding basic endoscopic concepts, highlighting a critical need for enhanced pre-procedure education. Healthcare providers in the Endoscopy Unit should prioritize patient education to enhance their understanding of gastrointestinal endoscopy, ultimately improving their overall experience and outcomes.

    This study investigates the KAP of patients undergoing gastrointestinal endoscopy, unveiling a paradoxical scenario in which patients display inadequate knowledge yet exhibit positive attitudes and proactive practices towards the procedure. Previous studies have explored patient involvement in gastrointestinal endoscopy from the patients’ viewpoints, revealing that patient participation typically varied from minimal to basic levels, it occasionally reached higher levels when staff actively involved patients in decision-making processes.24 These findings underscore the significant responsibility of endoscopy staff to recognize individual patient needs and enhance patient engagement. The results of the current study resonate with these observations, suggesting a consistent pattern across different settings.

    Significant disparities in KAP scores were noted across demographic and clinical variables. Notably, education level emerged as a pivotal factor, aligning with existing literature suggesting a positive association between higher education and health literacy.25,26 Individuals with higher levels of education typically exhibited better knowledge and practice scores, highlighting the essential part that education has in enhancing patient understanding and involvement in medical procedures. This highlights the necessity for focused educational initiatives designed for different backgrounds to effectively bridge knowledge gaps. Similarly, income level emerged as a significant determinant of KAP, corroborating prior research linking socioeconomic status with health outcomes.27,28 Higher-income groups exhibited better knowledge and practices, possibly because of enhanced access to healthcare resources and information dissemination channels. This highlights the significance of addressing socioeconomic disparities in healthcare delivery and designing interventions that are accessible and affordable for socioeconomically disadvantaged groups.

    Patients with a family member diagnosed with stomach or colon cancer exhibited higher knowledge scores, likely due to several interconnected factors. Familial experiences of cancer diagnosis and treatment may have heightened awareness and understanding of gastrointestinal health conditions among these individuals. Additionally, the perceived susceptibility to similar health issues within the family may have motivated proactive information-seeking behaviors. Open communication patterns within families about health concerns, including genetic predispositions and disease experiences, likely facilitated the exchange of knowledge and support, contributing to greater awareness among patients. Moreover, the familial context may have increased exposure to healthcare services and screening programs, encouraging individuals to actively engage in preventive healthcare practices.29,30 Additionally, the positive relationship between the number of gastroscopies a patient underwent and KAP scores highlights how previous experiences influence patient engagement and empowerment. Patients undergoing repeated procedures demonstrated superior knowledge and practices, possibly attributed to familiarity with the process and ongoing education through healthcare interactions.31 This highlights the importance of continuity of care and patient-provider communication in fostering health literacy and promoting proactive healthcare behaviors over time.

    In the correlation analyses and SEM, the interaction among knowledge, attitudes, and practices was elucidated, revealing a pathway through which knowledge influences attitude, which in turn impacts practice. Although the direct impact of knowledge on practice was not significant, the indirect effect mediated by attitude highlights the crucial influence of patient perceptions and beliefs in shaping health-related behaviors. This underscores the importance of addressing not only factual knowledge but also attitudinal barriers in promoting behavior change and adherence to medical recommendations.32

    The results from the knowledge section reveal a substantial awareness of gastrointestinal endoscopy but also highlight specific gaps in understanding. Remarkably, the highest familiarity is with the requirement for patients to fast before the examination, which reflects a basic understanding that might stem from general pre-procedure instructions given in various medical contexts. Conversely, the concept of endoscopic examinations covering various parts of the gastrointestinal tract was among the least recognized. This could indicate a lack of detailed communication about the procedure’s scope, which is often not elaborated on unless directly relevant to the patient’s condition. Recommendations to improve patient knowledge could include providing comprehensive pre-procedural education materials covering all aspects of the endoscopic process, including detailed instructions on preparatory measures and post-examination care. Interactive educational sessions led by healthcare providers could also address patient queries and concerns in real-time, enhancing understanding and adherence to pre-procedural instructions.15,33

    The attitudes section illustrates a strong recognition of the importance of gastrointestinal endoscopy in detecting potential health issues, with significant agreement observed. This positive attitude is pivotal for patient compliance and procedural success. However, the results also show a notable percentage of respondents feeling nervous or anxious before the examination. This anxiety can adversely affect the preparation and cooperation needed during the procedure. To address these concerns, healthcare providers could implement pre-procedural counseling sessions focusing on anxiety management techniques and addressing patient-specific fears. Creating a supportive and reassuring environment during the examination through clear communication and empathetic care practices can also alleviate patient anxiety and enhance overall satisfaction with the procedure.33

    In the practice section, adherence to pre-examination preparations like dietary restrictions is notably high, indicating effective communication of these requirements. However, the least compliance was observed in discussing personal concerns and questions about the examination with doctors, which could hinder personalized care and lead to increased anxiety. These findings highlight the crucial need to enhance patient education and enable individuals to actively participate in their healthcare journey. Implementing personalized care plans and follow-up protocols tailored to individual patient needs can promote sustained engagement in recommended practices and enhance long-term health outcomes. Moreover, incorporating technology-based solutions like mobile apps or telehealth platforms can enhance communication between patients and healthcare providers, enabling ongoing support and monitoring outside of the clinical environment.34,35

    This study has important practical implications for routine clinical practice. Incorporating KAP assessments into standard pre-endoscopy evaluations may help identify patients with limited understanding or elevated anxiety, allowing for targeted educational interventions. Tailored communication strategies, such as illustrated booklets or video-based tools, could be developed to address specific knowledge gaps and improve psychological preparedness. To maximize impact, these efforts should go beyond conveying factual information and also aim to reinforce positive attitudes and encourage proactive health behaviors. Enhancing public awareness of the indications, diagnostic and therapeutic roles of endoscopy—and its value in the early detection of malignancies—may ultimately support more timely diagnoses and improved long-term outcomes in gastrointestinal health. Future research should focus on evaluating the effectiveness of these approaches in improving patient comprehension, satisfaction, and procedural outcomes.

    Several limitations warrant consideration. First, our post-procedure questionnaire timing may have introduced recall bias and potentially overestimated patient knowledge due to pre-procedure education. Second, the heterogeneous study population, including both diagnostic and screening patients, limits the generalizability of our findings to specific patient subgroups. Third, our single-center design and convenience sampling method may not fully represent the broader patient population. Finally, self-reported data collection could introduce social desirability bias. Furthermore, the cross-sectional design of the study prevents the establishment of causality and temporal relationships between variables. Notwithstanding these limitations, the strengths of this paper are found in its thorough evaluation of knowledge, attitudes, and practices regarding gastrointestinal endoscopy among patients, as well as its utilization of both correlation and structural equation modeling analyses to explore the relationships between these variables, providing valuable insights for enhancing patient care and education within Endoscopy Units. In addition, while we analyzed the relationship between KAP and the number of gastroscopies, we did not assess colonoscopy frequency separately. Considering the high proportion of patients with polyps, this may have limited our ability to fully explore associations related to lower gastrointestinal endoscopy. Additionally, indications and findings for upper and lower gastrointestinal endoscopies were not collected separately. This may have limited the interpretability of certain result distributions.

    Conclusion

    To conclude, patients in the Endoscopy Unit demonstrated limited knowledge, favorable attitudes, and proactive practices regarding gastrointestinal endoscopy. Specifically, knowledge gaps were most prominent in understanding the scope of endoscopic examination-including the anatomical regions visualized (eg, esophagus, stomach, duodenum, and colon) and its diagnostic capabilities for conditions such as ulcers, tumors, and inflammation. These findings highlight the need for targeted educational interventions that address these fundamental concepts to enhance patient comprehension, informed consent, and overall procedural cooperation, thereby improving clinical outcomes and satisfaction.

    Data Sharing Statement

    All data generated or analysed during this study are included in this published article.

    Ethics Approval and Consent to Participate

    All procedures were performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. The study was approved by the Medical Ethics Committee of Dongying People’s Hospital (DYYX-2023-182) All participants provided written informed consent prior to enrollment. For elderly participants requiring assistance with questionnaire completion, trained research nurses provided support while ensuring participant privacy and autonomy. The study was carried out in accordance with the applicable guidelines and regulations.

    Author Contributions

    All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

    Disclosure

    Lianmin Wei and Qing Niu are co-first authors for this study. The authors report no other conflicts of interest in this work.

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    11. Pourshams A, Sepanlou SG, Ikuta KS. The global, regional, and national burden of pancreatic cancer and its attributable risk factors in 195 countries and territories, 1990-2017: a systematic analysis for the global burden of disease study 2017. Lancet Gastroenterol Hepatol. 2019;4(12):934–947. doi:10.1016/S2468-1253(19)30347-4

    12. Alatab S, Sepanlou SG, Ikuta K. The global, regional, and national burden of inflammatory bowel disease in 195 countries and territories, 1990-2017: a systematic analysis for the global burden of disease study 2017. Lancet Gastroenterol Hepatol. 2020;5(1):17–30. doi:10.1016/S2468-1253(19)30333-4

    13. Koni A, Taha S, Daifallah A, et al. A cross-sectional evaluation of knowledge, attitudes, practices, and perceived challenges among Palestinian pharmacists regarding COVID-19. SAGE Open Med. 2022;10:20503121211069278. doi:10.1177/20503121211069278

    14. Shubayr MA, Kruger E, Tennant M. Oral health providers’ views of oral health promotion in Jazan, Saudi Arabia: a qualitative study. BMC Health Serv Res. 2023;23(1):214. doi:10.1186/s12913-023-09170-8

    15. Berry P, Kotha S, Tritto G, et al. A three-tiered approach to investigating patient safety incidents in endoscopy: 4-year experience in a teaching hospital. Endosc Int Open. 2021;9(8):E1188–e1195. doi:10.1055/a-1479-2556

    16. Bazerbachi F, Chahal P, Shaukat A. Improving upper gastrointestinal endoscopy quality. Clin Gastroenterol Hepatol. 2023;21(10):2457–2461. doi:10.1016/j.cgh.2023.04.002

    17. Libânio D, Pimentel-Nunes P, Bastiaansen B, et al. Endoscopic submucosal dissection techniques and technology: European society of gastrointestinal endoscopy (ESGE. Technical Rev Endoscopy. 2023;55(4):361–389. doi:10.1055/a-2031-0874

    18. Nassani N, Alsheikh M, Carroll B, et al. Theranostic gastrointestinal endoscopy: bringing healing light to the lumen. Clin Transl Gastroenterol. 2020;11(3):e00119. doi:10.14309/ctg.0000000000000119

    19. Minciullo A, Filomeno L. Assessment of patient satisfaction in digestive endoscopy: a narrative review of the literature. Gastroenterol Nurs. 2022;45(1):43–51. doi:10.1097/SGA.0000000000000605

    20. Charan J, Biswas T. How to calculate sample size for different study designs in medical research? Indian J Psychol Med. 2013;35(2):121–126. doi:10.4103/0253-7176.116232

    21. Kuzhively J, Pandit JJ. Anesthesia and airway management for gastrointestinal endoscopic procedures outside the operating room. Curr Opin Anaesthesiol. 2019;32(4):517–522. doi:10.1097/ACO.0000000000000745

    22. Sidhu R, Turnbull D, Haboubi H, et al. British society of gastroenterology guidelines on sedation in gastrointestinal endoscopy. Gut. 2024;73(2):219–245. doi:10.1136/gutjnl-2023-330396

    23. Bloom BS. Learning for mastery. instruction and curriculum. regional education laboratory for the Carolinas and Virginia, topical papers and reprints Number 1. Eval Comment. 1968;1(2):n2.

    24. Dubois H, Creutzfeldt J, Törnqvist M, et al. Patient participation in gastrointestinal endoscopy – from patients’ perspectives. Health Expect. 2020;23(4):893–903. doi:10.1111/hex.13066

    25. Abheiden H, Teut M, Berghöfer A. Predictors of the use and approval of CAM: results from the German general social survey (ALLBUS). BMC Complement Med Ther. 2020;20(1):183. doi:10.1186/s12906-020-02966-9

    26. Irigoyen-Camacho ME, Velazquez-Alva MC, Zepeda-Zepeda MA, et al. Effect of income level and perception of susceptibility and severity of COVID-19 on stay-at-home preventive behavior in a group of older adults in Mexico City. Int J Environ Res Public Health. 2020;17(20):7418. doi:10.3390/ijerph17207418

    27. Atri SB, Sahebihagh M, Jafarabadi M, et al. The relationship between health literacy and stages of change in smoking behavior among employees of educational health centers of tabriz university of medical sciences (2016). Int J Prev Med. 2018;9(1):91. doi:10.4103/ijpvm.IJPVM_259_17

    28. Mularczyk-Tomczewska P, Zarnowski A, Gujski M, et al. Barriers to accessing health services during the COVID-19 pandemic in Poland: a nationwide cross-sectional survey among 109,928 adults in Poland. Front Public Health. 2022;10:986996. doi:10.3389/fpubh.2022.986996

    29. Bai Y, Cho Lee W, Li G, et al. Development and feasibility of an evidence-based and theory-driven tailored mHealth communication intervention to increase colonoscopy screening rate in first-degree relatives of people with colorectal cancer. Eur J Oncol Nurs. 2022;56:102063. doi:10.1016/j.ejon.2021.102063

    30. Bisschops R, Rutter MD, Areia M, et al. Overcoming the barriers to dissemination and implementation of quality measures for gastrointestinal endoscopy: European society of gastrointestinal endoscopy (ESGE) and United European gastroenterology (UEG) position statement. United Europ Gastroenterol J. 2021;9(1):120–126. doi:10.1177/2050640620981366

    31. Sato S, Shiozawa M, Uchiyama M, et al. Correlation between endoscopic features of the anastomosis after low anterior resection and postsurgical anorectal function. J Gastrointest Oncol. 2019;10(2):188–193. doi:10.21037/jgo.2018.11.09

    32. Hashemiparast M, Sharma M, Asghari Jafarabadi M, et al. Still careless: findings from a cross-sectional study of young pedestrians’ risky road crossing behaviors. Arch Public Health. 2020;78(1):44. doi:10.1186/s13690-020-00421-2

    33. Broder E, Davies A, Alrubaiy L. Using information videos to improve patient satisfaction in endoscopy: a prospective service improvement project. Cureus. 2022;14(4):e24108. doi:10.7759/cureus.24108

    34. Kutyla MJ, Gray MA, von Hippel C, et al. Improving the quality of bowel preparation: rewarding patients for success or intensive patient education? Dig Dis. 2021;39(2):113–118. doi:10.1159/000510461

    35. Walter B, Klare P, Strehle K, et al. Improving the quality and acceptance of colonoscopy preparation by reinforced patient education with short message service: results from a randomized, multicenter study (PERICLES-II). Gastrointest Endosc. 2019;89(3):506–13.e4. doi:10.1016/j.gie.2018.08.014

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  • How to manage your money in turbulent times, from savings to mortgages | Money

    How to manage your money in turbulent times, from savings to mortgages | Money

    It is understandable to be worried about your finances. The world seems to be lurching from one political crisis to the next, and each one has an impact on stock markets and prices.

    A recent survey found UK consumers are worried about a slowing economy, possible tax increases in the next budget and rising food costs. We asked experts how you should manage your money in an uncertain world.

    Investments

    Stock markets around the world, especially in the US, were in flux earlier this year over Donald Trump’s tariff plans. Things have settled down now but it is impossible to predict what shocks may be around the corner.

    If you hold stocks and shares – in an Isa or pension, perhaps – you may have been nervously checking their value. UK fund managers have been increasing their holdings in US companies over recent years, largely fuelled by the boom in tech stocks, so big moves over there have an impact here.

    However, experts say the most important thing to do is to not sell up out of panic. The analyst Dan Coatsworth of the financial advisers AJ Bell says: “The worst thing people can do is to see troubling things in the news and then suddenly try to shift around their portfolio.” Markets have recovered in the past, he says, so patience is key.

    Gold has tripled in price over the past decade. Photograph: Denys Rudyi/Alamy

    Where this advice may differ is if you need your money for something in less than five years – such as a wedding, university fees or a house purchase. Then you should look at how much risk you are taking, he says.

    Andrew Oxlade, an investment director at the fund management company Fidelity International, says this could mean switching some of your money away from the markets and into bonds. Bonds are issued by a corporation or country – the investor loans it money in exchange for a fixed rate of interest.

    They are typically bought through a fund. Many investment management companies offer funds that have a split between equities and bonds, such as Vanguard’s Lifestrategy 80%.

    Gold, an investment that is often seen as a safe bet during times of crisis, has tripled in price over the past decade, and many investors now hold a small amount in their portfolios, Oxlade says, after years of poor performance. Investing does not have to mean buying bars or coins – Fidelity says the most direct way for most is through an exchange traded fund that tracks the price of gold.

    Mortgages

    Interest rates in the UK can be affected by what goes on globally. The Bank of England is tasked with keeping inflation down. Before the war in Ukraine started, it had begun to put up rates, and as prices increased, it continued, raising them from 0.25% at the start of 2022 to 5.25% by August 2023, before holding them there for another year.

    The Bank has been reducing rates and is expected to make more cuts later this year, but the question is when. If you are planning to take out a new mortgage – either to buy a home or as a remortgage – you face a decision about whether to fix for the short or long term, choose a tracker or even to go on a bank’s standard variable rate (SVR).

    Currently, the best-priced two- and five-year fixed deals have a rate of just below 4%.

    Nick Mendes of the brokers John Charcol says lenders are reducing rates at present largely because of falling swap rates, a key factor in how mortgages are priced. Swap rates reflect what the money markets expect to happen to interest rates in future.

    “Fixed mortgage rates are more influenced by swap rates than the base rate itself, which means they are shaped by what markets think might happen in the future rather than what is happening today,” he says.

    If you want to take out a mortgage you face a decision about whether to fix for the short or long term, choose a tracker or go on a bank’s SVR. Photograph: Ian Nolan/Getty Images/Image Source

    Going on to a lender’s SVR in the hope that fixed rates will improve later in the year is a risky strategy as the rates are high, at about 6.5%, and can change at any time and increase your monthly repayments.

    Tracker mortgages are also worth considering, Mendes says. These are linked to the Bank base rate. “They tend to start lower than SVRs and often come without early repayment charges, which means borrowers can move on to a fixed deal later,” he says.

    Mendes says people who are remortgaging should not “sit back and wait. Most lenders allow you to secure a new deal up to six months in advance, which is a smart way to hedge your bets,” he says. “You can lock in a deal now as a safety net and still switch to something better if rates improve before the new deal begins.”

    For new buyers, Mendes says they should base decisions on what is affordable now rather than making assumptions about what may or may not happen in the future. “The last position anyone wants to be in is having overstretched themselves on the assumption that they will be able to refinance on to something cheaper at the end of their fixed-rate period,” he adds.

    You are not tied to a rate until completion, so you should be able to switch if a better deal comes along.

    Savings

    Savings rates could fall even before the Bank reduces the base rate, says Rachel Springall of the financial information site Moneyfacts, as account providers may decide that they have enough deposits for a certain product. “If the whole market starts moving in one direction, you’ll find that other peers will do the same because they don’t want to put themselves too high up [in best buy tables],” she says.

    Until then, easy access and fixed-term rates are competitive, Springall says.

    The best rates this week for fixed one-year and two-year bonds are from Cynergy Bank (4.55% for the one-year and 4.45% for the two-year), while an easy access account from Chase offers 5%, although this includes a 12-month bonus and is a variable rate, so it could go down.

    There have been increases in the interest paid on fixed-rate bonds in recent weeks, she says.

    Anna Bowes of the financial advisers The Private Office says “now is a really good time for a saver who has not been paying attention to their savings” as there is good competition in the market.

    If you have money in a variable-rate account it may be a good time to move it to a fixed rate.

    Pensions

    The tumultuous times that stock markets have been having since the start of the year will have had a direct effect on many people in the UK through their pensions. Often funds are heavily invested in US stocks, so the ups and downs there could be affecting your retirement saving.

    It is understandable if you are considering shifting money in your pension into other safer options such as bonds, says Helen Morrissey, the head of retirement analysis at the financial advice company Hargreaves Lansdown. However, unless you are cashing in your pension within the next five years, you should avoid reactions based on the international turmoil, she says.

    The tumultuous times that stock markets have been having this year will affect many people in the UK through their pensions. Photograph: Alamy/PA

    “Over the course of your saving journey, you will hit several periods of market volatility and it’s important to keep in mind that markets do recover over time,” she says. “Making kneejerk reactions such as changing investment strategy has the potential to lock in losses as you miss out when markets do recover.”

    Workplace pensions are often invested in “lifestyling” funds, which reduce the amount of risk as the holder gets older by shifting from equities to bonds. So if you are approaching retirement this may be happening automatically.

    If your fund has been hit by turbulence in the markets and you intend on retiring soon, Morrissey says that you may want to start to take a lower amount out from your fund than you had planned in order to allow the rest to recover from any losses caused by market turbulence.

    “We suggest that people in [income] drawdown keep between one and three years’ worth of essential expenditure [from their savings] in an easy access account that they can use to supplement their income during times of turbulence,” she adds.

    Another option, on retirement, is to invest some or all of your fund in an annuity, where returns are close to all-time highs. Annuities convert a lump sum from your pension into a regular guaranteed income for the rest of your life or a fixed term. A healthy 65-year-old can now get an annuity rate of 7.72% on average, according to the pension provider Standard Life – that means that for every £100,000 invested, they would get an annual income of £7,720.

    Energy bills

    About 21 million households will see their bills decrease after the price cap was reduced this week. For a household with typical usage, the cap has dropped by £129, to £1,720 a year. The good news may not last too long, however, as there are predictions of increases in October.

    After the recent conflict between Iran and Israel, oil prices went up because of concerns that supplies could be affected by threats of a blockade of the strait of Hormuz. Prices later reduced after a ceasefire deal was agreed.

    The energy price cap has dropped, but that may not be for long. Photograph: Christopher Thomond/The Guardian

    Will Owen of the price comparison website Uswitch says the volatility of the international economy has led to uncertainty. “We are now seeing predictions from various organisations and energy suppliers that the price cap from October onwards will probably go up,” he says.

    To protect yourself against a rise you could considered a fixed-rate tariff – with these each unit of energy and the standing charges are set for a certain length of time.

    The MoneySavingExpert site advises that you are “very likely” to save if you can find a fixed-rate deal priced at least 5% below the current price cap, which is predicted to fluctuate.

    The current best deals are a 12-month fix from E.ON Next that is 8.8% below the cap, another from Outfox Energy that is 8.1% less and then a fix from EDF Energy that is 7.2% less, according to the site.

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  • Butter’s Global Price Surge Hits Croissants and Kitchens Alike

    Butter’s Global Price Surge Hits Croissants and Kitchens Alike

    (Bloomberg) — At the Mamiche bakeries in the 9th and 10th arrondissements of Paris, their famous pains au chocolat and croissants depend on an essential but increasingly scarce ingredient — butter.

    Most Read from Bloomberg

    The bakery’s regular supplier can no longer provide a steady flow of French beurre de tourage, a type of flat butter used to make the pastries. Mamiche has gone searching elsewhere to ensure the steady flow of sweet treats from its ovens, but it’s coming with a cost.

    Butter prices in most of the world are lingering near record highs, with little end in sight to the surge. It’s the result of a complex interplay of factors — challenges faced by dairy farmers from France to New Zealand, changes in Asian consumers’ appetites that’s spurring global demand, and commercial decisions by milk processors defending their bottom line.

    The end result is more cost pressure on consumers’ favorite foods.

    “When we have to change supplier, we can really see the difference” said Robin Orsoni, commercial operator for Mamiche. Other providers are charging prices 25% to 30% higher but Mamiche has to absorb the cost because “we want to make our customers happy, we need the butter.”

    Around 70% of the butter exported around the world comes from two places — Europe and New Zealand. Each began 2025 with historically low stockpiles, and this supply tightness has caused prices to spike to a record, according to the Food and Agriculture Organization.

    The roots of the squeeze can be traced back to 2022, when the price of milk in Europe peaked as inflation and fuel costs hit farmers hard, pushing dairy processors to look at the best way to maximize profits.

    Butter is made by removing cream from raw milk and churning it. Once the process is complete, you are left with butter and buttermilk, the latter of which “has some industrial uses, but those are relatively limited,” said Monika Tothova, an economist at the FAO. It’s used for some cooking, to make other dairy products, and for livestock feed.

    In contrast, “if you make cheese, you process the entire volume of milk,” said Tothova. Even the by-product from cheese-making, called whey, is in high demand from commercial food makers for flavoring and nutrition, or gym enthusiasts to bulk out the protein in their diets.

    European Union dairy processors have making more and more cheese. As a result, the bloc’s butter production has steadily declined and is expected to hit an eight-year low this season, according to estimates from the US Department of Agriculture.

    Milk production itself is also becoming more challenging. In Europe, farmers’ herd sizes are shrinking due to financial pressures, and they now face added risks to their cows from bluetongue virus, said Jose Saiz, a dairy market analyst at price reporting agency Expana. Lumpy skin disease, which can curb an infected cows’ milk yields, is also making its way into Italy and France.

    Just as butter has fallen out of favor with dairy processors, consumers are developing a stronger taste for it, particularly in Asia.

    Global consumption of butter is expected to grow 2.7% in 2025, outpacing production, according to the USDA. In China demand has already grown by 6% in just one year. Usage in Taiwan between 2024 and 2025 rose 4%, while in India, the world’s largest consumer, it is up 3%.

    Hong Kong’s French bakery chain, Bakehouse, has been tapping into Asian consumers changing tastes. Its annual butter use is currently about 180 tons, an increase of 96 tons from the prior year after they opened two new stores, in addition to another 180 tons of cream, according to co-founder Gregoire Michaud. The firm only buys from well established suppliers — New Zealand has a top-tier reputation but China isn’t good enough yet, he said.

    In New Zealand, which is a major dairy exporter and produces about 2.5% of global milk supply, butter production has yet to return to pre-pandemic levels, fluctuating around 500,000 tons a year since 2020.

    As in Paris, supply scarcity and high butter prices have forced Hong Kong’s Bakehouse to cycle through three different providers in just a short period – from Australia, to New Zealand and then Belgium. Now they’re potentially looking for a fourth.

    Western consumers are also eating more butter, which for years was shunned for being unhealthy, as they look to cut ultra-processed foods out of their diets.

    Purchases of pure block butter in the UK have grown, said Susie Stannard, lead dairy analyst at the UK Agriculture and Horticulture Development Board. “Consumers who can afford it will still buy butter,”she said, but they aren’t immune from price pressures.

    At the newly opened Morchella restaurant in London’s Clerkenwell district, the brown butter and bread that was so popular at its sister eatery, Perilla in Newington Green, has been replaced with olive oil.

    Before the recent price hikes “you’d put a lot of butter into the pan to base that piece of fish and meat,” said Ben Marks, who heads up the kitchens at Perilla. “Now you’ve just got be much cleverer.”

    Relief for consumers isn’t expected to come any time soon. Butter prices are also affected by the global conflicts, supply chain disruptions and tariff wars that have roiled every other commodity.

    Amid this “very hot market,” Hong Kong’s Bakehouse is now prioritizing butter from closer providers to avoid a loss of supply, said Michaud.

    Orsoni said Mamiche will absorb the higher cost of butter to keep French staples affordable for its customers, but Perilla’s Marks said it’s “inevitable” that diners will face higher prices.

    The heat wave seen in Europe in recent weeks could also exacerbate the situation. High temperatures can reduce yields from diary cows, while also pushing up demand for other products that compete with butter for the fatty cream taken off the top of milk.

    Tennis fans reaching for cream to accompany their strawberries as they watch Wimbledon, or workers cooling down with an ice cream in city plazas, “can only hold butter prices up,” said Stannard.

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  • UAE Dirham moves up against Pak rupee – 5 July 2025

    UAE Dirham moves up against Pak rupee – 5 July 2025

    KARACHI – The buying rate of UAE Dirham (AED) recorded upward trend and now stood at Rs77.31 against Pakistani rupee in open market on Saturday.

    Similarly, the selling rate of the Dirham also increased and stood at Rs77 91, according to the forex.pk.

    AED to PKR Rate Today

    Buying Rs77.31

    Selling Rs77.91

    The UAE Dirham (AED) to Pakistani Rupee exchange rate holds great significance as millions of Pakistanis work in the UAE. Its stability ensures consistent remittance value, bolstering Pakistan’s foreign reserves and household incomes.Currency exchange helps determine the value of the Pakistani rupee against foreign currencies like the US dollar or UAE dirham. A strong exchange rate boosts imports and lowers inflation, while a weak rate can increase export competitiveness.

    It is also crucial for overseas Pakistanis who send remittances. Monitoring exchange rates helps businesses, travelers, and policymakers make informed financial decisions and manage economic stability effectively.

    Overseas Pakistanis residing in the UAE sent $754.2 million in wake of remittances in May 2025, securing second top position in the chart of the workers’ remittances as the first spot is held by Saudi Arabia.

    Meanwhile, the workers’ remittances from overseas to Pakistan, recording a significant growth of 28.8 percent during eleven months of fiscal year 2024-25, reached nearly $ 35 billion in the period from July to May while monthly inflows in May increased to $ 3.69 billion.

    “Cumulatively, with an inflow of US$ 34.9 billion, workers’ remittances increased by 28.8 percent during Jul-May FY25 compared to US$ 27.1 billion received during Jul-May FY24,” the State Bank of Pakistan reported on Wednesday.

    During May 2025, the workers’ remittances recorded an inflow of US$ 3.686 billion, depicting 16 percent growth over April 25 and 13.7 percent yearly increase against May 2024, the statistics showed.

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  • Small Chance $8.6B Bitcoin Transfer Was a Hack

    Small Chance $8.6B Bitcoin Transfer Was a Hack

    Conor Grogan, Coinbase’s head of product, says there’s a slight chance the $8.6 billion worth of Bitcoin moved on Thursday — from eight wallets that had held the Bitcoin for over 14 years — was caused by a hack, and if so, it could be the largest robbery ever.

    “If true (again, I’m speculating on straws here), this would be by far the largest heist in human history,” Grogan said in an X post on Friday, after raising the slim chance that the $8.6 billion worth of Bitcoin (BTC) moved from eight separate wallets was the work of bad actors.

    Suspicious BCH transaction has Grogan scratching his head

    “There is a small possibility that the $8B in BTC that recently woke up were hacked or compromised private keys,” Grogan said, pointing out a suspicious Bitcoin Cash (BCH) transaction made before the significant transfers on Thursday involving 10,000 Bitcoin at a time.

    “I found a single BCH test transaction from one of the BTC whale clusters 14 hours ago, followed by the full amount. An hour later, the BTC wallets began to move,” he said.

    Coinbase’s Conor Grogan highlighted a single Bitcoin Cash transaction. Source: Conor Grogan

    Grogan said it is possible that the wallet owner may have been quietly testing the private key, since Bitcoin Cash transactions don’t attract as much attention from whale tracking services. However, he reiterated he found the behavior unusual:

    “What makes me say this is the other BCH wallets have not been touched at all; why wouldn’t they also sweep these?”

    In a post on the same day, blockchain intelligence firm Arkham said it was a single entity that moved $8.6 billion worth of Bitcoin from eight separate wallets. 

    $8.6 billion Bitcoin is now sitting in eight new wallets

    Arkham said that all the Bitcoin was transferred into the original wallets on either April 2 or May 4, 2011, and had remained on the wallets for more than 14 years.

    Cryptocurrencies, Bitcoin Price
    Source: Arkham

    Related: Brazil’s central bank service provider hacked, $140M stolen

    Arkham said the Bitcoin is now stored in eight new wallets and hasn’t been moved since.

    Despite the uncertainty, Bitcoin’s price has stayed relatively stable, dipping 1.02% in the last 24 hours and trading at $108,150 at the time of publication, according to CoinMarketCap data.

    Magazine: Bitcoin vs stablecoins showdown looms as GENIUS Act nears