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Around 40–50% of all triple-negative breast cancer (TNBC) patients achieve a pathological complete response (pCR) after treatment with neoadjuvant chemotherapy (NAC). The identification of biomarkers predicting the response to NAC could be helpful for personalized treatment. This systematic review provides an overview of putative biomarkers at baseline that are predictive for a pCR following NAC. Embase, Medline and Web of Science were searched for articles published between January 2010 and August 2022. The articles had to meet the following criteria: patients with primary invasive TNBC without distant metastases and patients must have received NAC. In total, 2045 articles were screened by two reviewers resulting in the inclusion of 92 articles. Overall, the most frequently reported biomarkers associated with a pCR were a high expression of Ki-67, an expression of PD-L1 and the abundance of tumor-infiltrating lymphocytes, particularly CD8+ T cells, and corresponding immune gene signatures. In addition, our review reveals proteomic, genomic and transcriptomic markers that relate to cancer cells, the tumor microenvironment and the peripheral blood, which also affect chemo-sensitivity. We conclude that a prediction model based on a combination of tumor and immune markers is likely to better stratify TNBC patients with respect to NAC response.

This paper analyzes the importance of credit self-rationing for borrowers with lower levels of education using a survey of Vietnamese SMEs from 2004 to 2014. We show that entrepreneurs not only refrain from using formal credit because of burdensome application procedures but also because they are inherently debtaverse. Both factors are more prevalent in entrepreneurs with lower educational levels. Consistently, borrowers with lower education have a lower propensity of using formal credit, are more likely to perceive financial constraints, and are more likely to report difficulties during the loan application process. However, we find no evidence of higher supply-side rationing by banks for entrepreneurs with lower educational levels. Our results imply that efforts targeted at alleviating actual financial constraints will have limited results if debt aversion and apprehension towards formal finance are not properly addressed. The best way to do this is to favor better education.

The purpose of this review is to assess the state-of-the-art fabrication methods, advances in genome editing, and the use of machine learning to shape the prospective growth in cardiac tissue engineering. Those interdisciplinary emerging innovations would move forward basic research in this field and their clinical applications. The long-entrenched challenges in this field could be addressed by novel 3-dimensional (3D) scaffold substrates for cardiomyocyte (CM) growth and maturation. Stem cell-based therapy through genome editing techniques can repair gene mutation, control better maturation of CMs or even reveal its molecular clock. Finally, machine learning and precision control for improvements of the construct fabrication process and optimization in tissue-specific clonal selections with an outlook of cardiac tissue engineering are also presented.

Detection of bacterial pathogens is significant in the fields of food safety, medicine, and public health, just to name a few. If bacterial pathogens are not properly identified and treated promptly, they can lead to morbidity and mortality, also possibly contribute to antimicrobial resistance. Current bacterial detection methodologies rely solely on laboratory-based techniques, which are limited by long turnaround detection times, expensive costs, and risks of inadequate accuracy; also, the work requires trained specialists. Here, we describe a cost-effective and portable 3D-printed electrochemical biosensor that facilitates rapid detection of certain Escherichia coli (E. coli) strains (DH5α, BL21, TOP10, and JM109) within 15 min using 500 μL of sample, and costs only USD 2.50 per test. The sensor displayed an excellent limit of detection (LOD) of 53 cfu, limit of quantification (LOQ) of 270 cfu, and showed cross-reactivity with strains BL21 and JM109 due to shared epitopes. This advantageous diagnostic device is a strong candidate for frequent testing at point of care; it also has application in various fields and industries where pathogen detection is of interest.

Chronic methamphetamine use, a widespread drug epidemic, has been associated with cardiac morphological and electrical remodeling, leading to the development of numerous cardiovascular diseases. While methamphetamine has been documented to induce arrhythmia, most results originate from clinical trials from users who experienced different durations of methamphetamine abuse, providing no documentation on the use of methamphetamine in standardized settings. Additionally, the underlying molecular mechanism on how methamphetamine affects the cardiovascular system remains elusive. A relationship was sought between cardiotoxicity and arrhythmia with associated methamphetamine abuse in zebrafish to identify and to understand the adverse cardiac symptoms associated with methamphetamine. Zebrafish were first treated with methamphetamine 3 times a week over a 2-week duration. Immediately after treatment, zebrafish underwent electrocardiogram (ECG) measurement using an in-house developed acquisition system for electrophysiological analysis. Subsequent analyses of cAMP expression and Ca 2+ regulation in zebrafish cardiomyocytes were conducted. cAMP is vital to development of myocardial fibrosis and arrhythmia, prominent symptoms in the development of cardiovascular diseases. Ca 2+ dysregulation is also a factor in inducing arrhythmias. During the first week of treatment, zebrafish that were administered with methamphetamine displayed a decrease in heart rate, which persisted throughout the second week and remained significantly lower than the heart rate of untreated fish. Results also indicate an increased heart rate variability during the early stage of treatment followed by a decrease in the late stage for methamphetamine-treated fish over the duration of the experiment, suggesting a biphasic response to methamphetamine exposure. Methamphetamine-treated fish also exhibited reduced QTc intervals throughout the experiment. Results from the cAMP and Ca 2+ assays demonstrate that cAMP was upregulated and Ca 2+ was dysregulated in response to methamphetamine treatment. Collagenic assays indicated significant fibrotic response to methamphetamine treatment. These results provide potential insight into the role of methamphetamine in the development of fibrosis and arrhythmia due to downstream effectors of cAMP.

Most patients with triple-negative breast cancer (TNBC) are not candidates for targeted therapy, leaving chemotherapy as the primary treatment option. Recently, immunotherapy has demonstrated promising results in TNBC, due to its immunogenicity. In addition, a novel antibody–drug conjugate, namely, trastuzumab-deruxtecan, has shown effectiveness in TNBC patients with low-HER2 expression (HER2-low). These novel treatment options raise the question about the potential association between the density of stromal tumor-infiltrating lymphocytes (sTILs) and the level of HER2 expression. We aimed to evaluate the association between the level of HER2 expression (HER2-low versus HER2-0) and density of sTILs in TNBC patients, and how they impact the response to neoadjuvant chemotherapy (NAC). This was a retrospective multicenter study including all TNBC patients diagnosed between 2018 and 2022. Central pathology review included sTILs percentages and level of HER2 expression. Tumors were reclassified as either HER2-0 (HER2 IHC 0) or HER2-low (IHC 1 + or 2 + with negative reflex test). Various clinicopathologic characteristics, including sTILs density, and response to NAC were compared between HER2-0 and HER2-low cases. In total, 753 TNBC patients were included in this study, of which 292 patients received NAC. Interobserver agreement between the original pathology report and central review was moderate (77% had the same IHC status after reclassification in either HER2-0 or HER2-low; k  = 0.45). HER2-low TNBC represented about one third (36%) of the tumors. No significant difference in sTILs density or complete pathologic response rate was found between HER2-0 and HER2-low cases ( p  = 0.476 and p  = 0.339, respectively). The density of sTILs (≥ 10% sTILs vs. < 10%) was independently associated with achieving a pCR ( p  = 0.011). In conclusion, no significant association was found between HER2-low status and density of sTILs nor response to NAC. Nonetheless, sTILs could be an independent biomarker for predicting NAC response in TNBC patients.

Background Anaplasmosis, an animal disease caused by rickettsial bacteria in the genus Anaplasma , is of considerable economic importance in livestock animals in many countries worldwide. The objectives of this study were to determine the identity, prevalence, and geographic distribution of Ehrlichia and Anaplasma in naturally infected water buffalo in Thailand using PCR amplification and sequencing of the 16S ribosomal RNA and heat shock protein groEL genes. A total of 456 buffalo blood samples from Thailand were investigated. Species identification and genetic differentiation of intra-population and inter-population with the global isolates were conducted based on nucleotide sequences. Interplay between the infection and host factors was also assessed. Results Overall, 41% of water buffalo were found to be infected with rickettsial organisms in the family Anaplasmataceae , but Ehrlichia spp. , Neorickettsia spp., and Wolbachia spp. were not found in any of the sequenced samples in this study. Female buffalo were more frequently infected with bacteria in the family Anaplasmataceae than males [71 out of 176 females (40.3%) versus 11 out of 47 males (23.4%)]. The Odds Ratio value indicated that the risk of infection for female buffalo was 2.2-fold higher than that for males ( p  < 0.05). We detected three haplotypes of A. marginale 16S rRNA gene and they were placed in a clade that was closely related to the A. marginale in buffalo in China; and cattle in Thailand, Uganda, and China. Homology searching of groEL sequences against the GenBank™ database using the BLASTn algorithm revealed that the obtained sequences had a high percentage similarity (98.36–99.62%) to A. platys sequences. The groEL sequences of three A. platys -like isolates were clustered in the same clade as the A. platys from the tick Rhipicephalus microplus in China . Conclusions Our data showed that the apparently healthy buffalo were naturally infected by bacteria in the family Anaplasmataceae at a relatively high prevalence. We also report the finding of A. platys -like infections in water buffalo in Thailand for the first time. Water buffalo serving as the reservoir host of anaplasmosis is of concern for managing the disease control and prevention in ruminants.

This study develops and tests an integrated framework to explain how tourism firms in an emerging economy translate strategic and environmental capabilities into competitive advantage under sustainability pressures. Drawing on the Resource-Based View (RBV), Natural Resource-Based View (NRBV), innovation theory, and dynamic capabilities, each offering a distinct perspective, we focus on four capabilities: strategic orientation, innovation governance, climate-action orientation, and environmental responsibility. The research problem addressed is how these capabilities interact under resource constraints and institutional voids in emerging economies, where pathways to competitiveness remain unclear. These operate through incremental and breakthrough innovation pathways, with top management support and dynamic capabilities as enabling conditions. Using survey data from 209 Vietnamese tourism firms and moderated mediation analysis, we find that environmental responsibility and innovation governance enhance competitiveness primarily through incremental innovation, offering a reliable pathway in resource-constrained contexts. Strategic and climate-action orientations influence competitiveness indirectly through breakthrough innovation, though these effects are conditional and weakened by institutional voids. The study contributes by (1) clearly distinguishing the roles of RBV, NRBV, and dynamic capabilities in shaping innovation pathways, (2) demonstrating the substitution of dynamic capabilities for breakthrough innovation under uncertainty, and (3) highlighting incremental innovation as the dominant and practical pathway to sustainable competitiveness in emerging markets.

Background: This study aimed to evaluate different Bayesian algorithms and the first-order pharmacokinetics (PK) equation approach for forecasting vancomycin concentrations in critically ill pediatric patients and to identify influencing factors. Methods: A cohort of 110 patients with 568 therapeutic drug monitoring (TDM) blood samples was included. Three Bayesian algorithms, i.e., conventional, flattened, and weighted-flattened, using one or two historical values of either blood concentrations measured at the peak, trough, or middle (mid) of the dosing interval, were applied to forecast the concentrations of the next TDM occasion. The first-order PK approach, according to the Sawchuk–Zaske method, was used with two levels. The forecasting performance was assessed via relative bias (rBias) and relative root mean squared error (rRMSE) between the forecasted and observed levels. A linearmixed-effects model was employed to identify potential influencing factors on the rBias and rRMSE. Results: All methods showed negative rBias values of less than −20% and had relatively similar rRMSE of about 40%. First-order PK had lower bias than the conventional and flattened Bayesian algorithm (−10% vs. −15%), but higher bias than the weighted-flattened Bayesian algorithm (rBias −5%). Multivariate analysis using the linear mixed-effects model revealed that the type of forecasting algorithms significantly impacted the predictability. The weighted-flattened Bayesian algorithm significantly improved the rBias by 12.660% (95% CI: 10.131–15.194, p-value < 0.001) and decreased the rRMSE by 2.099% (CI 95% 3.779–0.418, p-value = 0.014) compared to the conventional Bayesian model. Either using one (mid or trough) or two concentrations in Bayesian forecasting yielded comparable rBias and rRMSE. Conclusion: The weighted-flattened Bayesian estimation method with solely one blood level is appropriate for forecasting the vancomycin concentration during therapeutic drug monitoring in critically ill children.

IntroductionThe global prevalence of chronic obstructive pulmonary disease (COPD) is increasing, and it has become a major public health burden worldwide, including in Vietnam. A large body of preclinical and clinical studies supports the safety of mesenchymal stem/stromal cells (MSCs) in the treatment of lung injury, including COPD. The aim of this trial is to investigate the safety and potential therapeutic efficacy of allogeneic administration of umbilical cord-derived MSCs (UC-MSCs) as a supplementary intervention in combination with standard COPD medication treatments in patients with moderate-to-severe COPD based on the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2019 and Vietnam Ministry of Health’s guidelines.Methods and analysisThis matched case–control phase I/II trial is conducted at Vinmec Times City International Hospital, Hanoi, Vietnam between June 2020 and December 2021. In this study, 40 patients will be enrolled and assigned into two age-matched, gender-matched and COPD condition-matched groups, including a UC-MSC group and a control group. Both groups will receive standard COPD medication treatment based on the GOLD 2019 guidelines and the Vietnam Ministry of Health protocol. The UC-MSC group will receive two doses of thawed UC-MSC product with an intervention interval of 3 months. The primary outcome measures will include the incidence of prespecified administration-associated adverse events and serious adverse events. The efficacy will be evaluated based on the absolute changes in the number of admissions, arterial blood gas analysis, lung function and lung fibrosis via CT scan and chest X-ray. The clinical evaluation will be conducted at baseline and 3, 6 and 12 months postintervention.Ethics and disseminationEthical approval was secured from the Ethical Committee of Vinmec International Hospital (number:166/2019/QĐ-VMEC) and Vietnam Ministry of Health (number:2002/QĐ-BYT). The results will be reported to trial collaborators, publication in peer-reviewed academic journals.Trial registration numberNCT04433104.