Good data feature representation and high precision classifiers are the key steps for pattern recognition. However, when the data distributions between testing samples and training samples do not match, the traditional feature extraction methods and classification models usually degrade. In this paper, we propose a domain adaptation approach to handle this problem. In our method, we first introduce cross-domain mean approximation (CDMA) into semi-supervised discriminative analysis (SDA) and design semi-supervised cross-domain mean discriminative analysis (SCDMDA) to extract shared features across domains. Secondly, a kernel extreme learning machine (KELM) is applied as a subsequent classifier for the classification task. Moreover, we design a cross-domain mean constraint term on the source domain into KELM and construct a kernel transfer extreme learning machine (KTELM) to further promote knowledge transfer. Finally, the experimental results from four real-world cross-domain visual datasets prove that the proposed method is more competitive than many other state-of-the-art methods. Traditional classification tasks deal with situations where the distribution of source domain samples and target domain samples are the same, and a classifier trained from source domain samples can be directly applied to the target domain samples. Theoretical studies on classifiers are also based on this assumption . HoweverOne strategy of DA is to find invariant feature representation subspaces between domains to minimize distribution divergence. A large number of existing methods applying this strategy learn a shared feature subspace where the distribution mismatch between the two domains is reduced, and then employ standard classification methods in this subspace . MetricsHuang et al.  proposedTo sum up, there are several challenges to DA. The first issue is the similarity between source domain and target domain. To cope with this issue, suitable distribution distance measurement criteria are found to eliminate this dissimilarity. Secondly, there is class separability and shared feature extraction between source and target domains in the feature subspace. The third challenge is the knowledge transfer ability of the classifier.We believe that a well-developed DA algorithm is able to address these three challenges. Therefore, we want to tackle all these problems simultaneously. We propose a domain adaptation approach which consists of two stages: feature-based adaptation and classifier-based adaptation. At the former stage, we develop semi-supervised cross-domain mean discriminative analysis (SCDMDA). It introduces cross-domain mean approximation (CDMA)  into SDAWe introduce CDMA into SDA and then propose SCDMDA. It extracts shared discriminative features across domains by using CDMA to minimize the marginal and conditional discrepancies between domains and applying SDA to exploit the label information and original structure information.We present KTELM by designing a cross-domain mean approximation constraint into KELM for classification in domain adaptation.We obtain a classifier with the ability of knowledge transfer by combining SCDMDA and KTELM and implement a classification task on public image datasets. The results show the superiority of our approach.In this paper, we make the following contributions: The rest of this paper is as follows: In In this section, we will briefly introduce SDA, ELM, KELM, and DA.As a classical semi-supervised feature extraction algorithm, SDA extends LDA by adding a geometrical regularizer to prevent overfitting. Given a sample set As a high-performance classifier, ELM with a single hidden layer has a fast training process and high classification performance. Given a dataset In Equation (5), We consider Equation (5) to be a regular least square problem and set Then, the output of the trained ELM model corresponding to test sample If the activation function In practical application scenarios, it is difficult to collect enough training samples with the same distribution as the testing samples. For example, in photography, it is hard to avoid changes in pixel distribution caused by changes in lighting, posture, weather, and background. If a large number of samples with the same distribution are selected and manually marked for model training, the cost will be high . The aboThe instance-based adaptation methods seek a strategy which selects “good” samples in the source domain to participate in model training and suppresses “bad” samples to prevent negative transfer. Kernel mean matching (KMM)  minimizeThe feature-based adaptation methods attempt to learn a subspace with a better shared features representation, in which the marginal or conditional distribution divergences between domains are minimized to facilitate knowledge transfer. Transfer component analysis (TCA), joint distribution adaptation (JDA), balanced distribution adaptation (BDA), and multiple kernel variant of maximum mean discrepancy (MK-MMD) apply the maximum mean discrepancy (MMD) strategy to perform distribution matching, thus minimizing the marginal or conditional distribution divergences between domains . In 29]29], WangIn recent years, deep neural networks (DNNs) have performed well in high-level semantic feature extraction with strong expression ability, and have broad application prospects in domain adaptation. Domain adaptation networks (DAN) , faster The goal of the classifier-based adaptation methods is to adjust the parameters of the classifier so that the classifier trained on the source domain has good performance in the target task. Adaptive support vector machine (Adapt-SVM)  introducIn addition, the adaptation model based on the generative adversarial network  ,40,41,42In this paper, our method is a combination of feature- and classifier-based adaptation. SCDMDA belongs to a shallow feature-based adaptation method, and KTELM is a classifier-based adaptation method. At the feature-based adaptation stage, SCDMDA finds domain-invariant features. It not only applies SDA to maximize between-class scatter, minimize within-class scatter, and keep the original structure information by pseudo-labeled target samples and labeled source samples, but it also reduces the distribution differences between domains using CDMA. At the classifier-based adaptation stage, a cross-domain mean constraint term is added to KELM to further enhance its knowledge transfer ability.In a domain adaptation environment, given a source domain with labeled samples At the feature-based adaptation stage, we design SCDMDA, and its goal is to find an optimal transformation matrix At the classifier-based adaptation stage, KTELM is constructed by adding a cross-domain mean constraint term into KELM, which improves the knowledge transfer ability of KELM.From Equation (1) in To enhance the knowledge transfer ability of SDA, we combine Equation (9) and Equation (1) and design the objective function of SCDMDA for shared feature extraction across domains as follows:Furthermore, the above formula is equivalent to:We set Finally, Equation (12) is used to find Algorithm 1. SCDMDAInput: Dataset Output: Projection matrix Step1: According to Equations (1) and (9), construct Step2: Let Step3: Solve Equation (12) or Equation (14) to obtain the projection matrix Step4: Project Step5: Learn a KTELM on Step6: Use Step7: Let Step8: If To address the issue of the nonlinear data, we transform Equations (11) and (12) into a high-dimensional space by kernel mapping, namely ugh Ref. . A complAfter feature adaptation of SCDMADA, we can obtain Similar to ELM, we set We kernelize Equation (17) and let In this paper, our method is proposed for domain adaptation, which includes feature adaptation based on SCDMDA and classifier adaptation based on KTELM. From Equation (11) and Equation (18), it can be seen that, compared with SDA, SCDMDA adopts CDMA to reduce the distribution discrepancy between domains, which is better for domain adaptation than SDA. Moreover, as a semi-supervised feature extraction method, SCDMDA focuses more attention on individual information with the help of the category separability of LDA and the original structure information of graph regularizers.Compared with MMD, CDMA reflects individual differences. In our method, CDMA mines individual information through In the classical ELM, solving the output weight In this section, extensive experiments were conducted on four widely adopted datasets, including Office+Caltech , Office-Office + Caltech: It is a visual domain adaptation benchmark dataset, which contains two sub-datasets of Office and Caltech (C), shown in Office-31: This is a public dataset commonly used to investigate domain adaptation algorithms, which includes three distinct domains: amazon, webcam, and dslr. It contains 4652 images with 31 categories. In our experiments, we carried out a classification task in a 2048-dimensional ResNet-50 feature space and performed six groups of experiments: amazon vs. dslr, amazon vs. webcam, dslr vs. amazon, dslr vs. webcam, webcam vs. amazon, and webcam vs. dslr.PIE: It is a standard facial dataset collected by Carnegie Mellon University, which contains 41,368 face images with a pixel resolution of 32 × 32 from 68 people. These images depict facial postures, lighting, and expressions  outperforms 1-NN in most cases, showing the importance of feature extraction in classification tasks. Most domain adaptation techniques such as JDA, STDA-CMC, W-JDA, JDA-CDMAW, and SCDMDA (0–2) achieve higher accuracy than SDA, due to cross-domain shared feature extraction with few or no same distribution samples in the target domain. The accuracy of JDA, STDA-CMC, W-JDA, JDA-CDMAW, and SCDMDA (0–2) generally improves shared feature extraction through joint distribution adaptation.We applied our method, compared algorithms, and performed classification experiments on the Office+Caltech, USPS+MNIST, PIE, and Office-31 datasets. The results are presented in In addition, results on the Office-31 dataset with ResNet-50 features are shown in In this section, we conducted some experiments to investigate the influence on the accuracy of SCDMDA2, including the number of dimensions of the subspace, the graph tradeoff parameter th iteration, verifying its good convergence.In We ran SCDMDA2 with other parameters fixed Similar situations also occur in We ran SCDMDA with KTELM on A vs. D, MNIST vs. USPS, PIE1 vs. PIE2, and amazon vs. dslr datasets with the optimal parameter settings, and computed the CDMA distance shown in  accordinWe can see that as the iteration number increases, SCDMDA reduces the between-domain marginal and conditional distribution difference, leading to a smaller CDMA distance and higher accuracy. Therefore, SCDMDA can extract better shared features across domains.We further display the t-distributed stochastic neighbor embedding (t-SNE) visualization plots of feature embedding for the PIE1 vs. PIE2 classification task. t-SNE, as a dimension-reduction method, transforms high-dimensional data into a low-dimensional space for visualization. In t-SNE visualization plots, clusters of the same color are closer, clusters of different colors are more distant, and the extracted features are more discriminative. The visualized source and target features derived from raw data, JDA, STDA-CMC, and SCDMA were drawn in the feature scatterplot As we can see from In this paper, we develop a semi-supervised domain adaptation approach which contains feature-based adaptation and classifier-based adaptation. At the feature-based adaptation stage, we introduce CDMA into SDA to reduce the cross-domain distribution discrepancy and develop SCDMDA for domain-invariant feature extraction. At the classifier-based adaptation stage, we select KELM as the baseline classifier. To further enhance knowledge transfer ability of the proposed approach, we design a cross-domain mean constraint term and add it to KELM to construct KTELM for domain adaptation. Through feature and classifier adaptation, we can learn more discriminatory feature representations and obtain higher accuracy. Comprehensive experiments on several visual cross-domain datasets show that SCDMDA with KTELM significantly outperforms many other state-of-the-art shallow and deep domain adaptation methods.In the future, we plan to explore the interdomain metric criterion in more depth. At present, CDMA is superior to MMD in reducing cross-domain distribution differences; however, its computational complexity is greater than that of MMD. To solve this problem, better metrics can be developed to improve the distribution differences between domains.


The receiver operating characteristic curve (ROC) pointed to 326 pg/dL of NT-proBNP as the optimal cutoff level for developing in-hospital systemic complications . Multivariate analyses showed that NT-proBNP > 326 pg/dL was associated with systemic complications , adjusted for confounders. This did not reach statistical significance for neurological complications. NT-proBNP could be a predictor of in-hospital systemic complications in AIS patients. Further studies are needed.Previous studies have shown the relationship between N-terminal pro-brain natriuretic peptide (NT-proBNP) with stroke mortality and functional outcome after an acute ischemic stroke (AIS). Knowledge of its association with systemic and neurological in-hospital complications is scarce. Our objective is to analyze this. We performed an observational, retrospective study that included consecutive AIS patients during a 1-year period (2020). A multivariate analysis was performed to identify if NT-proBNP levels were independently associated with in-hospital complications. 308 patients were included, of whom 96 (31.1%) developed systemic and 62 (20.12%) neurological in-hospital complications. Patients with any complication (39.3%) showed higher NT-proBNP levels than those without (median (IQR): 864 (2556) vs. 142 (623) pg/dL,  In-hospital complications are major causes of death in acute ischemic stroke (AIS) patients ,2,3,4. CBrain natriuretic peptide is a cardiac hormone produced from the cleavage of its precursor pro-BNP and is secreted together with a biologically inactive terminal fragment, the N-terminal pro-brain natriuretic peptide (NT-proBNP) . These tPrevious studies have shown that plasma of NT-proBNP are elevated in two thirds of patients with AIS . This maThere is a lack of studies examining the relationship between blood levels of NT-proBNP and in-hospital complications after stroke, both systemic and neurological. Our hypothesis is that higher NT-proBNP levels could be predictor of a higher risk of in-hospital complications after an AIS. Our objective was to analyze this.A retrospective analysis of consecutive AIS patients admitted to the Torrecárdenas University Hospital  during 2020 was conducted. TUH is the referral Stroke Center for a population of 739,293 inhabitants. Patients in whom NT-proBNP determination could not be performed were excluded from the study.All patients were initially treated in the emergency room by a neurologist. Each patient was examined according to a standard protocol that included routine laboratory analyses, chest X-rays, ECG and neuroimaging.− Systemic complications: RTI , other infections  and other non-infective complications .− Neurological complications: neurological impairment (worsening of previous cognitive level), hemorrhage , malignant edema  or seizures (seizures after the stroke in patients without a previous history of epilepsy).The variables included were: (a) demographic data (sex and age); (b) pre-stroke functional status by modified Rankin Scale (mRS) score, classifying patients in two groups: mRS lower than 2 and greater than or equal to 2; (c) vascular risk factors: arterial hypertension , dyslipidemia (previous diagnosis and/or current treatment with lipid-lowering drugs), diabetes mellitus , smoking, alcohol abuse, previous atrial fibrillation, coronary heart disease , valvular heart disease , renal dysfunction  and previous stroke; (d) prior treatments: antiplatelet agents, anticoagulants, statins, antihypertensives, oral antidiabetics and insulin; (e) stroke severity evaluated by the National Institutes of Health Stroke Scale (NIHSS); (f) acute phase treatments: thrombolysis and mechanical thrombectomy; (g) stroke etiology classified by TOAST classification; (h) stroke unit length of stay; (i) blood pressure on admission ; (j) biochemical markers in peripheric blood tests: NT-proBNP (pg/mL), creatinine (mg/dL), glycaemia (mg/dL); k) systemic complications and (l) neurological complications:Diagnosis of in-hospital complications was made by the physician in charge of the patient, who was blinded to the conduct of this study. The physician in charge was always a stroke neurologist, who clinically assessed the patient daily and checked for in-hospital complications, in accordance with the stroke unit’s protocol. In addition, serum NT-proBNP determination was performed in the central laboratory of the hospital by technicians who were also blinded to the objectives of this study.A peripheral blood sample was taken within 48 h of hospitalization and serum NT-proBNP was measured by a central laboratory on the Roche Elecsys assay .Patients were divided into two groups according to the presence of in-hospital complications, as well as whether these were systemic or neurological.t-test was used for comparing quantitative variables, and the Mann-Whitney test in the case of non-normal data, for dichotomous variables. ANOVA and Kruskal-Wallis tests were used for comparing quantitative variables, in case of polytomous variables, when appropriate. Furthermore, post-hoc analyses, such as Bonferroni test or Kruskal-Wallis H test were carried out to test differences between groups.For the quantitative variables, the mean and standard deviation or the median and the interquartile range, were calculated and, for qualitative data, the absolute and relative frequency was offered. Comparisons between the groups were carried out using parametric or non-parametric tests. In case of homoscedasticity and normality of the samples, 2 or Fisher’s exact test for dichotomous variables. Continuous variables were expressed as mean ± SD or median (interquartile range) and compared with Student’s t test or the Mann-Whitney test, as appropriate. The relationship between NT-proBNP levels and the presence of in-hospital complications was analyzed in three steps. First, a receiver operating characteristic (ROC) curve analysis was conducted to determine the predictive value of the area under the curve (AUC), as well as a cutoff point for NT-proBNP levels. We considered the point at which the sum of the specificity and sensitivity was highest, giving the same weight to false-positives and false-negatives. Second, the relationship between this NT-proBNP cutoff point and the developments of in-hospital complications was assessed using multivariate logistic regression models. Variables with a value of p ≤ 0.2 in the univariate testing were included, as well as those variables which are known to be associated with in-hospital complications and NT-proBNP levels . A backward procedure was followed as the modeling strategy, using the log-likelihood ratio test to assess the correctness of fit and compare nested models. Those variables that, when eliminated, produced a change of ≥15% in the OR (Odds Ratio) were considered as confounding variables. We conducted another ROC curve with the multivariate analysis results. Third, a forward stepwise (likelihood ratio) multivariate logistic analysis that included the variables selected by the backward analysis was developed to test the stability of the model. Comparisons between groups were analyzed with the χp values of 0.05 or less were considered statistically significant. Statistical analysis was performed using IBM SPSS Statistics for Windows, Version 25.0, software  for Windows.Ninety-five percent confidence intervals (CI) are presented. All tests were two-sided and The study was approved by the local ethics committee and patient consent was not sought due to the retrospective nature of the study. The data that support the findings are available from the corresponding author on reasonable request.During the study period, a total of 476 stroke patients were admitted to the Stroke Center. Some were excluded from the study for the following reasons: cerebral hemorrhage (70), transient ischemic attack (18), venous infarction (7), patients did not meet the criteria for admission to the Stroke Unit (28), and incomplete data (45). A total of 308 patients were finally included in the analysis . Of thesp < 0.001). The receiver operating characteristic curve (ROC) pointed to 326 pg/dL of NT-proBNP as the optimal cutoff level for developing systemic complications during hospitalization  .The multivariate analyses  showed tTo our knowledge, this is the first study to analyze the association between blood NT-proBNP levels and post-stroke in-hospital complications, both systemic and neurological, in a cohort of unselected patients with cerebral infarction. Our results suggest that this biomarker is associated with a doubling of the likelihood of systemic complications, although its relationship with neurological complications is unclear.The use of blood biomarkers for the prediction of complications after ischemic stroke has been widely studied in recent years . NT-proBThe results of our study support the use of NT-proBNP levels as a biomarker to predict the occurrence of in-hospital complications in AIS. This could be explained by the ability of the damaged brain to influence the heart through a local and systemic inflammatory response and a dysregulated autonomic activity influenced by the hypothalamic–pituitary–adrenal axis . Some prOther short-term and long-term complications that could be predicted with NT-ptoBNP levels have been studied previously. One study showed that the risk of recurrent stroke was in relation to admission BNP levels . AnotherThe relationship between RANKL gen polymorphins has been recently demonstrated as an independent risk factor for ischemic stroke in a study based on Italian population . It may In this study, the bivariate analysis showed that NT-proBNP levels were associated with a higher frequency of neurological complications, especially hemorrhagic transformation. This association is diluted in the multivariate analysis, which could be due to the lower weight of this biomarker in the development of neurological complications and the small sample size. Indeed, a recent study has shown that NT-proBNP levels are independently associated with hemorrhagic transformation, poor functional outcomes, and 3-month mortality in stroke patients who underwent intravenous thrombolysis . FurtherOur study has several limitations. Firstly, it is a single-center retrospective observational study, although data have been included prospectively. Secondly, the sample size remains relatively small, although it is one of the largest case series published. Finally, the sample included subjects with previous AF and ischemic heart disease, which could produce variations in NT-proBNP values due to their cardiac and non-neurological pathology.Future studies are warranted to establish the role of NT-proBNP levels in the development of post-stroke complications. If a relevant role is confirmed, the inclusion of its measurement in stroke management guidelines could be recommended, since predicting the appearance of complications would help optimize resources and anticipate future clinical complications.In conclusion, NT-proBNP could be a predictor of in-hospital systemic complications in ischemic stroke patients. Its determination in all stroke patients would be useful in order to prevent and treat complications early. Further studies are needed to clarify the role of NT-proBNP as a prognostic marker in these patients.


Multipotent mesenchymal stem cells (MSCs) are widely accepted as a useful tool for cell-based therapy of various diseases including malignancies. The therapeutic effects of MSCs are mainly attributed to their immunomodulatory and immunosuppressive properties. Despite the promising outcomes of MSCs in cancer therapy, a growing body of evidence implies that MSCs also show tumorigenic properties in the tumor microenvironment (TME), which might lead to tumor induction and progression. Owing to the broad-spectrum applications of MSCs, this challenge needs to be tackled so that they can be safely utilized in clinical practice. Herein, we review the diverse activities of MSCs in TME and highlight the potential methods to convert their protumorigenic characteristics into onco-suppressive effects.  Cancer is the major obstacle to improving life expectancy in the 21st century . The morRecently, mesenchymal stem cells (MSCs) have been of great interest in the field of cancer therapy. MSCs are precursor cells that have the ability to self-regulate and proliferate. Under particular circumstances, they can differentiate into numerous mesenchymal tissues . MSCs arImmunomodulatory properties of MSCs are mediated by various cytokines, including transforming growth factor (TGF-β), hepatic growth factors (HGF), prostaglandin E2 (PGE2), interleukins , indolamEffects of MSCs on TME• Investigations have revealed that despite the positive impact of MSCs on tumorigenesis, they can limit tumor growth. These effects may be exerted via different mechanisms.Antitumor properties exerted through signaling pathways• Via their strong proinflammatory properties, the combination of MSCs and tumor cells enhances the infiltration of monocytes, granulocytes, and T lymphocytes. The elevated infiltration of inflammatory cells facilitates interaction between immune cells and the adjacent tissues. These immune cells and the inflamed tissues enclosing them can produce several chemokines that recruit activated lymphocytes with their correlating receptors, hence provoking antitumor immunity  Ohlsson. Researcin vivo by reducing target cell AKT activation in Kaposi’s sarcoma (KS). Nevertheless, they observed that when KS tumor cells were modified to express active AKT constantly, KS tumors were no longer susceptible to MSC treatment. These results imply that MSCs produce significant antitumorigenic properties via blocking AKT signaling. Furthermore, others have found that MSCs decrease breast cancer cell growth through the Wnt pathway, which is critical in oncogenesis  have been shown to attenuate the growth and spread of breast cancer cells, probably by modifying the cell cycle of cancerous cells . AdditioTumorigenic effects of MSCs on TME• in vitro and accelerating tumor growth in vivo , IL-4, indoleamine 2,3-dioxygenase , TGF-β1, in vivo . Tumor c in vivo . As an i in vivo ; on the  in vivo . SDF-1α  in vivo , and HGF in vivo . Besides in vivo   against various cancers in animal models . Severalications . von Einications . Other sications . By way ications . Gene-diications . Adiposeications . In anotications .• PreconMSC-extracellular vesicles (MSC-EVs)• Macrophages, which can be present as pro-inflammatory M1 and alternatively activated M2 cells, contribute to different inflammatory responses. MSCs can steer monocytes to differentiate into anti-inflammatory M2 phenotypes. Thus, MSCs have the ability to inhibit excessive immune response. MSCs feature immunosuppressive effects that need to be promoted by supportive signals. The immunosuppressive properties of MSCs can be affected by certain pro-inflammatory cytokines IFN-γ, TNF-α, and IL-1α. The stimulation of MSCs by these cytokines is essential for the demonstration of their immunosuppressive behavior . Philippin vivo stability and long half-life (in vitro. Kamerkar and co-authors (Manipulating the protumorigenic signaling pathways• Recently, the application of MSC-EVs has been suggested as a potential cell-free therapeutic agent . EVs arealf-life . They plalf-life . Variousalf-life . By way alf-life . The actalf-life  investigalf-life . For insalf-life  enriched-authors  evaluate-authors . MSC-EVs-authors . Hence, Therapeutic blockade of signaling cascade molecules involved in tumorigenesis is another approach to suppress protumorigenic activities of MSCs. In this regard, both chemical and herbal products have been suggested to hinder the protumorigenic properties of MSCs. To give an example, MSCs have been shown to induce ovarian carcinoma STAT3 signaling through IL6 and LIF. A group of researchers used Ruxolitinib to target this signaling and observed increased survival in subjects following this therapy . Recentlin vivo and in vitro (As mentioned earlier, the influence of MSCs on the tumor milieu is extensive and occasionally paradoxical. The majority of studies that have shown antitumorigenic effects for MSCs have applied MSCs with no previous exposure to cancer cells. This may reflect that cancer-naïve MSCs and cancer-educated MSCs have different functions . Moreovein vitro . It is iin vitro . This isin vitro  (Table 4MSCs can be considered the major regulators of tissue homeostasis. Evaluating the level of the inflammatory response to injury, MSCs can adapt effective functions to suppress or promote the response. Pro-tumorigenic effects of MSCs are exerted through various mechanisms in the TME, including differentiation into stromal components of the TME, suppression of immune response, enhancement of angiogenesis, improving tumor cell survival, and promotion of metastasis. On the other hand, many studies have suggested that MSCs have the potential to suppress tumor progression via modulation of the immune system, suppression of angiogenesis, induction of apoptosis, and regulation of cellular signaling pathways. Despite the controversy on the role of MSCs in tumor promotion or inhibition, it is obvious that they have a dynamic role in the TME. Considering the wide range of therapeutic applications of MSCs, numerous studies have tried to identify the anti-cancer properties of different types of MSCs. A great body of evidence shows that cancer-naïve MSCs and UC-MSCs have remarkably higher onco-suppressive effects compared with other subtypes. Additionally, some researchers have taken a step further and proposed techniques to convert the tumorigenic function of MSCs into onco-suppressive effects. The existing methods include the application of GM-MSCs, which can help to transfer anti-cancer agents in a highly effective way compared with systemic administration, using MSC-EVs as biocompatible tools to deliver mRNA, miRNAs, prodrugs, and peptides to the target cells, autologous injection of MSCs, which can be administered in combination with prodrugs, therapeutic blockade of cell signaling, and the use of herbal such as curcumin and ginseng. Further studies are suggested to explain the complex interaction between MSCs and tumor components more precisely. Since different subpopulations of MSCs show varied effects, further research should be conducted to evaluate the role of these subpopulations in the progression of different types of cancer which can help to develop more effective methods to convert these unfavorable activities to onco-suppressive effects.


To identify current and emerging self-care interventions to improve maternity healthcare.Scoping review.MEDLINE, Embase, EmCare, PsycINFO, Cochrane CENTRAL/CDSR, CINAHL Plus (last searched on 17 October 2021).Evidence syntheses, interventional or observational studies describing any tool, resource or strategy to facilitate self-care in women preparing to get pregnant, currently pregnant, giving birth or post partum.Screening and data collection were conducted independently by two reviewers. Self-care interventions were identified based on predefined criteria and inductively organised into 11 categories. Characteristics of study design, interventions, participants and outcomes were recorded.We identified eligible 580 studies. Many included studies evaluated interventions in high-income countries (45%) and during antenatal care (76%). Self-care categories featuring highest numbers of studies were diet and nutrition , physical activity (24%), psychosocial strategies (18%) and other lifestyle adjustments (17%). Few studies featured self-care interventions for sexual health and postpartum family planning (2%), self-management of medication (3%) and self-testing/sampling (3%). Several venues to introduce self-care were described: health facilities (44%), community venues (14%), digital platforms (18%), partner/peer support (7%) or over-the-counter products (13%). Involvement of health and community workers were described in 38% and 8% of studies, who supported self-care interventions by providing therapeutics for home use, training or counselling. The most common categories of outcomes evaluated were neonatal outcomes  (31%), maternal mental health (26%) and labour outcomes  (22%).Self-care interventions in maternal care are diverse in their applications, implementation characteristics and intended outcomes. Many self-care interventions were implemented with support from the health system at initial stages of use and uptake. Some promising self-care interventions require further primary research, though several are matured and up-to-date evidence syntheses are needed. Research on self-care in the preconception period is lacking. Mapping all potential self-care practices across the spectrum of pregnancy care, from preconception, antenatal, intrapartum to postnatal care.Use of the new WHO self-care classification system to organise and categorise findings.Not screening for primary studies reported within an included evidence synthesis.Not including interventions that took place after 42 days post partum, or those that related primarily to care of newborns and breast feeding (which should require dedicated reviews).Search limited to published reports and reports written in English only.Self-care is defined by the WHO as ‘the ability of individuals, families and communities to promote health, prevent disease, maintain health, and to cope with illness and disability with or without the support of a health worker’.8In 2021, WHO published a guideline on self-care interventions for health and well-being, which included 13 recommendations on selected self-care interventions to improve preconception, antenatal, intrapartum and postpartum care.https://doi.org/10.17605/OSF.IO/97X25  first independently screened all titles and abstracts to exclude irrelevant studies, and then independently reviewed potentially eligible full texts based on predetermined eligibility criteria. All stages of screening were conducted using Covidence software.The eligibility criteria for inclusion were: (A) Participants: women preparing to get pregnant, currently pregnant, giving birth or in the postpartum period (up to 42 days after birth), of any age. Studies in which partners or family members carried out self-care for the pregnant woman, were also eligible. Interventions for abortion were not eligible. We also excluded interventions that were only directed at newborns and postnatal breastfeeding interventions for improving neonatal outcomes, though antenatal programmes related to preparation for the postnatal period were eligible. (B) Interventions: for this review, a self-care intervention was defined as any tool, resource or strategy designed to promote or facilitate self-care by a woman intending to get pregnant, or a currently pregnant, labouring or in the postpartum period, for the purpose of improving the quality or coverage of maternity healthcare, and/or improving her health, well-being and care experiences. To be eligible, interventions must have been aimed at reducing risks of pregnancy, childbirth or postpartum complications and/or enabling a positive pregnancy, childbirth or postpartum experience. Each intervention was evaluated independently by two reviewers for inclusion based on a set of prespecified principles . (C) ComTwo reviewers independently extracted data using a standardised extraction form we developed to suit the review . Data exPatients were not included in the design, conduct and plans for dissemination of results of this review.A total of 12 215 records from six databases were retrieved, together with an additional 182 records from manual reference screening . In totaAmong 580 studies, two-thirds were interventional studies , many of which reported results of randomised trials . Evidence syntheses (n=165) accounted for 28% of all studies, out of which 109 were meta-analyses (19%). Observational studies were less common  and were mainly retrospective or prospective cohort studies . Study designs used were largely similar across all self-care categories, with some exceptions . In selfMost studies took place in high-income countries , followed by middle-income  and low-income countries ; 163 studies (28%) were reviews with no geographical restriction, and usually included studies from multiple countries. Countries with the most studies were the USA , Iran , UK  and Australia . Self-care interventions most commonly took place in the antenatal  and postpartum periods . Few studies related to the preconception  or intrapartum periods  .Thirty-eight studies (7%) included women under the age of 18. One-third of included studies  included women with high-risk pregnancies. High-risk pregnancies were variably defined—the most common definitions included pregnant women with gestational or existing diabetes , obesity or overweight  and ex-smokers/current smokers .Among included studies, 35 studies (6%) described a complex intervention involving more than three different self-care activities . The remThe identified interventions correspond to a range of categories from WHO’s classification of self-care interventions . The mosAmong 545 studies under analysis, self-care was accessible through several avenues as described in the WHO classification framework.Across the self-care categories, provision of information and demonstration of self-care were most commonly done in health facilities, especially for self-testing (94% of studies in this category) and self-monitoring (58%). Provision of similar services outside health facilities, such as via community health workers or at community-based venues, was mainly for the support of self-management of medication (41%) and physical activity (28%). Home-based self-care  was less frequent, mainly in the categories of breast or nipple care (23%) and lifestyle adjustments (20%). Digital platforms were popular in some categories, notably self-monitoring (51%). Use of OTC products was common in complementary/alternative therapies (39%) and breast and nipple care (27%). Lastly, peer or partner support was relatively less common across categories (7%), and we observed that partner support (1%) was relatively less frequent than support from peers  (6%) .A large number of studies described the involvement of health workers in promoting or facilitating self-care , especially for sexual health and family planning (67% of studies in this category), psychosocial strategies (45%) or physical activity (44%) . Few stuIncluded studies used a diverse range of outcomes, including both maternal and neonatal outcomes . The mos10.1136/bmjopen-2022-068713.supp2Supplementary dataIn this scoping review, 580 studies were identified pertaining to 112 self-care interventions across preconception, antenatal, intrapartum and postpartum periods. These interventions encompassed multiple modalities, settings and levels of provider involvement. Most self-care interventions required close engagement with health facilities, in which healthcare workers or community health workers would teach self-care skills or provide therapeutics for home use. Previous studies also suggest that healthcare services are a critical starting point for successful self-care approaches.26Most studies concentrated on self-care interventions related to lifestyle modification—such as diet, nutrition/supplement intake, physical activity and sleep habits—as well as strategies to optimise mental and social well-being. The established evidence base for lifestyle interventions was also reflected in previous systematic reviews on self-care for pre-eclampsia and gestational diabetes.We identified studies describing self-testing options for urinary tract infections and HIV, but few or no studies on malaria, syphilis or chlamydia self-testing, for which rapid test technologies are available but not yet scaled up or tested in pregnancy.38Last but not least, we found no eligible studies on traditional and Indigenous self-care practices. While important qualitative research has been conducted on this topic,While there are systematic reviews for some self-care practices, this is the first scoping review that maps all potential self-care practices across the spectrum of pregnancy care, from preconception, antenatal, intrapartum to postnatal care. This scoping review provides a comprehensive summary of the state of research on this topic, and lays the foundation for future systematic reviews and primary research. We analysed studies based on multiple characteristics, as well as applying the new WHO self-care classification system to organise, categorise and facilitate interpretation of findings.This scoping review was intended to present an overview of the research landscape, and not to critically appraise or meta-analyse available evidence. The total number of studies identified for a given self-care intervention may not correlate with evidence quality, or its effectiveness. We reported the results for complex interventions  separately , since s41 42Some limitations must nonetheless be acknowledged. We did not formally screen those primary studies reported within an included evidence synthesis, and we assessed intervention and outcomes characteristics based on the review’s summary description of the included studies. It is possible that the number of primary studies was there underestimated, or the characteristics of individual primary studies might differ. Our assessment found 45 primary studies  that were also included within an evidence synthesis included in this review. Given their small number, we consider it unlikely that these overlapping studies would substantively affect the overall results. Hence, the distribution of study designs  should bThis review was conducted for the purpose of guiding further evidence synthesis activities and assisting the WHO with guideline development in this research area. This scoping review identified two distinct groups of self-care interventions, which have different pathways forward. The first group are those interventions with a substantial number of primary studies, where no systematic review has been conducted or only outdated systematic reviews exist. For these interventions—such as use of clean cookstoves to reduce adverse birth outcomes associated with indoor air pollution, self-care interventions to reduce postpartum depression, or self-collection of vaginal samples to test for sexually transmitted diseases—up-to-date systematic reviews are warranted to inform guidelines, clinical practice and self-care programmes. The second group are interventions with limited or no primary studies, or where available primary studies were not designed to fully deliver the intervention in a self-care approach. For these interventions, well-designed primary studies that compare a self-care approach with standard care are needed. Examples include self-testing for proteinuria, or self-measurement of vaginal pH to detect early signs of bacterial vaginosis. Some self-care interventions may be particularly useful in limited-resource settings, and thus should be evaluated in such settings.Self-care interventions during preconception, antepartum, intrapartum and postpartum periods are diverse in scope and implementation characteristics. Many self-care interventions were implemented with support from the health system at initial stages of use and uptake. Some promising self-care interventions require further primary research, though several are more matured and up-to-date evidence syntheses are needed. Research on self-care in the preconception period is lacking. Future research should explore task-sharing from clinical care to home or community settings, or effective self-management of complications where access to care is unavailable.


We aimed to compare the HRQOL of CRC survivors 14–24 years post-diagnosis to that of age- and sex-matched non-cancer controls, stratified by demographic and clinical factors. (2) Methods: We used data from 506 long-term CRC survivors and 1489 controls recruited from German population-based multi-regional studies. HRQOL was assessed with the European Organization for Research and Treatment of Cancer Quality of Life Core-30 (EORTC QLQ-C30) questionnaire. We estimated differences in the HRQOL of CRC survivors and controls with multiple regression, adjusted for age at survey, sex, and education, where appropriate. (3) Results: CRC survivors reported poorer social functioning but better health status/QOL than controls. CRC survivors, in general, had higher levels of symptom burden, and in particular diarrhea and constipation, regardless of demographic or clinical factors. In stratified analyses, HRQOL differed by age, sex, cancer type, and having a permanent stoma. (4) Conclusions: Although CRC survivors may have a comparable health status/QOL to controls 14–24 years after diagnosis, they still live with persistent bowel dysfunction that can negatively impact aspects of functioning. Healthcare providers should provide timely and adapted follow-up care to ameliorate potential long-term suffering. Earlier detection and better treatment have improved the relative 5-year survival after colorectal cancer (CRC) ,2,3,4, eBesides survival, health-related quality of life (HRQOL) is now considered an important outcome of cancer treatments . For mosIn our previous study on long-term CRC survivors 5–16 years post-diagnosis, we noted that survivors reported a global health/quality of life (QOL) comparable to that of age-matched non-cancer controls . NeverthThere is a paucity of research on the HRQOL of CRC survivors extending >10 years post-diagnosis ,14,15,16Our main study objectives were to compare the HRQOL of CRC survivors 14–24 years post-diagnosis to that of non-cancer controls. Furthermore, we were interested in whether HRQOL was associated with demographic  and clinical  factors.The population-based CAncEr Survivorship—A multi-Regional (CAESAR) study aimed to describe the long-term HRQOL of colorectal, breast, and prostate cancer survivors. The German Cancer Research Center  conducted the study in collaboration with six epidemiologic cancer registries in Germany . This study used data from five cancer registries as no CRC survivors were recruited from Schleswig-Holstein for logistical reasons. Cancer survivors diagnosed between January 1994 and June 2004, as registered in the participating cancer registries, and aged between 20 and 75 years at diagnosis, were eligible. Details of the initial study have been described elsewhere . InitialAn individual level HRQOL from a representative sample of the German population was accessed from the Lebensqualität in DEutschland  study . EligiblHRQOL and financial difficulty were assessed with the European Organization for Research and Treatment of Cancer Quality of Life Core-30 (EORTC QLQ-C30) questionnaire . This 30The CAESAR questionnaire contained questions concerning sociodemographic factors and clinical history. Self-reported data include primary treatment received, disease recurrence since index cancer , and comorbid conditions. Participating cancer registries provided clinical data such as date of diagnosis and the tumor stage . Other self-reported data collected in the initial data survey include monthly household income, education, type of employment , and work situation . The classification of cancer site was according to the International Classification of Diseases-10 codes. Relevant data from surveys in 2008–2010 and 2018–2019 were combined for this analysis.We compared sociodemographic differences between CRC survivors and population controls with Cochran–Mantel–Haenszel tests. Although the age distribution of the population controls reflected a stratified sampling scheme, controls were significantly younger than CRC survivors. Therefore, we used direct standardization for further comparisons of sample characteristics, using the age and sex distribution of CRC survivors as standard.We used multiple linear regression to derive least square mean HRQOL scores of CRC survivors and controls. In models stratified by disease status, we categorized CRC survivors accordingly: stage I–III at diagnosis and with no reports of recurrence/metastasis/new cancer at follow-up (‘disease-free’); stage IV at diagnosis or self-report of subsequent recurrence/metastasis/new cancer after CRC diagnosis (’active disease’). Linear regression models were adjusted for age , sex, and education at the time of the survey, where appropriate. Covariates included for adjustment in the models were selected a priori, based on previous associations with HRQOL reported in the literature ,22. Althp < 0.05 (two-sided). The p-values were not adjusted for multiple testing, referring to the individual tests rather than a global test for differences.Missing data were imputed using the Markov chain Monte Carlo method with 25 repetitions to reduce possible bias due to missing values . All analyses were conducted with SAS . Statistical significance is determined at n = 924), 506 (55%) returned a completed questionnaire  had died before follow-up. Of the survivors eligible for the follow-up survey , and role and social functioning in comparison with colon cancer survivors and controls . In contCRC survivors with a permanent stoma reported significantly lower levels of physical, role, and social functioning when compared with stoma-free CRC survivors or controls . Stoma-fCRC survivors with active disease reported lower levels of emotional functioning when compared with disease-free survivors or controls . SurvivoWith CRC survivors living longer, it is important to have a better understanding of the quality of this prolonged survival. We found that CRC survivors 14–24 years after diagnosis, in general, had comparable levels of functioning and global health/QOL to age- and sex-matched population controls. Nevertheless, we see persistent deficits in aspects of functioning and a higher symptom burden in subgroup analyses. We observed a consistent pattern of lower levels of social functioning among CRC survivors, most prominent among survivors who were <75 years old, with 10–11 years of education, male rectal cancer survivors, and survivors with a permanent stoma. In addition, constipation and diarrhea remain as problems of significance among survivors in comparison with controls, irrespective of age, sex, education, cancer type, and disease status. Treatments for CRC have been associated with chronic bowel dysfunction , of whicMale rectal cancer survivors and survivors with permanent stoma reported similar patterns of deficits, namely poorer levels of physical, role, and social functioning, and higher levels of fatigue, dyspnea, and diarrhea than comparison groups. These results are consistent with concerns commonly shared by individuals living with a stoma . ProblemSurvivors younger than 75 years at survey were more likely to have deficits in emotional, cognitive, and social functioning. Keeping in mind that our study involved survivors who were diagnosed up to 24 years previously, this would suggest that poorer emotional and social functioning scores observed closer to the time since diagnosis can persist in survivors who were diagnosed at a younger age . FurtherDespite the improved prognosis after CRC diagnosis, a significant proportion of survivors are living with long-term symptoms and functioning impairments. Existing clinical guidelines on CRC follow-up care tend to focus on the detection of early recurrences, the timing of follow-ups, and appropriate diagnostic tools, but few guidelines provide adequate recommendations for the management of long-term symptoms . For exaOur population-based study focused on the long-term HRQOL of CRC survivors 14–24 years after diagnosis, a group that is currently understudied. Another strength is the adequate sample size that allowed for subgroup analyses. However, our study has several limitations to consider. Although our sample size is adequate, nevertheless with a response rate of 55%, our results may not be generalizable to CRC survivors of a similar vintage. There were significant differences in characteristics between respondents and non-respondents. This potential participation bias may influence the reported mean HRQOL estimates. Participants provided clinical data in the context of the initial study round in 2008–2010. As some participants were diagnosed up to 16 years before the initial survey, the possibility of under-reporting or problem with recall  has to be discussed. It is unlikely that almost 20% of all participants did not undergo surgery for primary treatment. In addition, the participants who were classified as stoma-free could have had a temporary stoma although we do not know the duration and when the stoma was removed. We reported on the cross-sectional associations of clinical and demographic factors with HRQOL, and therefore the results should not be interpreted as causal associations. In conclusion, while CRC survivors 14–24 years after diagnosis may have a comparable health status/QOL to age- and sex-matched controls, they still live with persistent bowel dysfunction that can negatively impact aspects of functioning. Health care providers should regularly screen for potential unmet needs and provide timely follow-up care that is adapted to the needs of CRC survivors, to ameliorate potential long-term suffering.


With increasing health awareness worldwide, lactose intolerance has become a major concern of consumers, creating new market opportunities for low-lactose/lactose-free dairy foods. In recent years, through innovating processes and technologies, dairy manufacturers have significantly improved the variety, and functional and sensory qualities of low-lactose and lactose-free dairy products. Based on this, this paper first covers the pathology and epidemiology of lactose intolerance and market trends. Then, we focus on current advantages and disadvantages of different lactose hydrolysis technologies and improvements in these technologies to enhance nutritional value, and functional, sensory, and quality properties of lactose-free dairy products. We found that more and more cutting-edge technologies are being applied to the production of lactose-free dairy products, and that these technologies greatly improve the quality and production efficiency of lactose-free dairy products. Hopefully, our review can provide a theoretical basis for the marketing expansion and consumption guidance for low-lactose/lactose-free dairy products. There is improving awareness of lactose intolerance in both research and dairy consumers. Generally, lactose intolerance is caused by primary lactose malabsorption. Lactase activity is highest at birth and declines after weaning. Undigested lactose is metabolized by intestinal microflora and converted into short-chain fatty acids  and gases , causing gastrointestinal discomfort such as diarrhea, bloating and other symptoms. Long-term avoidance of dairy products due to lactose malabsorption or lactose intolerance may lead to malnutrition and skeletal disorders. Epidemiological surveys of lactose intolerance showed that approximately 70% of the world’s population was affected by lactose malabsorption, with prevalence as high as 95% to 100% in some Asian and African countries [Current managements for lactose-intolerant people are mainly to replace regular dairy products with low-lactose and lactose-free products  and consThe requirements for developing low/lactose-free dairy products are avoiding lactose sources, ensuring the nutritional value and sensory properties of the product, and controlling production costs ,8. GenerLactose intolerance is a widespread worldwide problem. The ability of adults to digest lactose (lactase persistence) has become an important topic in genetics, medicine, and evolution. In recent years, the in-depth study of genetic mechanisms of lactase has provided a new theoretical basis for the epidemiological investigation and prevention of lactose intolerance. Storhaug, Fosse and Fadnes  presenteThe distribution of LP genotypes shows significant national and regional differences, e.g., −13910C/T mostly occurrs in European and American countries. For northern Europeans, their endogenous lactase activity is still at a high level with increasing age. Anguita-Ruiz et al.  reportedIt is now clear that lactase gene SNPs plays an important role in lactose metabolism . The MCMBifidobacterium genus is widely identified [Bifidobacterium abundance. Goodrich et al. [Bifidobacterium and the lactase gene locus, and the direction of the genetic association showed lactase non-persisters harbored higher levels of Bifidobacterium. In addition, the latest study reported [Bifidobacteria compared to lactose-intolerant adults (AA/AG). There was a significant interaction between milk intake and LCT variant on Bifidobacterium, with a positive association between milk intake, and Bifidobacterium was observed only in lactose-intolerant but not in tolerant people.Lactase genotypes of hosts are known to influence the gut microbiome, and the influence seems to be modulated by lactose intake . It is rentified . Kurilshentified  conducteh et al.  reportedreported  that aduGenerally, lactose intolerance is considered to be a risk factor for reduced milk/calcium intake. According to a survey conducted by Cargill, 61 percent of US consumers avoided dairy products due to lactose intolerance or allergy to milk protein . ObermayLactose-intolerant consumers need nutritional products that they can utilize. It is known that 25% of consumers in India are motivated to buy or have started to buy lactose-free drinks. The lactose-free dairy products market in Vietnam is also booming, and relevant surveys showed that consumers preferred dairy products that are easy to digest . The larLactose-free dairy products have become the fastest-growing part of the dairy industry. The compound annual growth rate of global lactose-free dairy products from 2017 to 2022 was about 7% and accounted for 80% of the total lactose-free products  . In the The development of lactose-free and low-lactose dairy products made it possible for lactose-intolerant people to utilize the rich nutrients in milk, which is one of the effective ways to improve lactose malabsorption and lactase intolerance. Currently, there are three processes commonly used to reduce lactose content: enzymatic hydrolysis of lactose, membrane filtration, and fermentation. Studies have tried to combine several of above processes. Lactose-free milk can be further processed into lactose-free/low-lactose yogurt, cheese, milk powder, ice cream and other dairy products  Figure . Many st−1 feed flow rate. Graphene oxide membrane allowed lactose to diffuse through the nanochannel and exhibit higher lactose permeation flux (2.87 kg m−2 day−1) than commercial nanofiltration (0.57 kg m−2 day−1) and ultrafiltration (1.61 kg m−2 day−1). In addition, the fouling layers on graphene oxide membrane were porous, facilitating higher permeation flux and water flux recovery. Graphene oxide membrane is very promising for lactose separation of lactose-free milk [Among methods of separating lactose, the most well-known and widely used are methods of membrane separation, including ultrafiltration, nanofiltration, reverse osmosis, and electrodialysis. In different fields of the dairy industry, membranes are applied to shelf life extension of milk, whey processing, cheese industry, milk protein processing, fractionation of milk fat and desalting or demineralization . The keyree milk .Generally, ultrafiltration membranes have low permeability and high protein rejection, whereas microfiltration membranes have higher permeability, but higher protein losses . AnotherBrosimum gaudichaudii and immobilized onto polyaniline. The system removed 47% of lactose from skim bovine milk.Several studies explored methods to separate lactose by chromatography and freeze concentration. For example, lactose-free milk produced by Valio Ltd.  employed chromatography, membrane separation and enzymatic hydrolysis. Freeze concentration is a widely accepted technology and is able to preserve thermosensitive food with high nutritional value. In this process, the temperature of food liquid decreases below its freezing point, and the concentration of liquid is reached by removing water in the form of ice crystals. A new type of lactose-free dairy product was developed by combining progressive freeze concentration with vacuum-assisted block freeze concentration, because carbohydrates accumulated more during progressive freeze concentration, while in block freeze concentration, protein is more likely to enter concentrated liquid . BatistaThe process of lactose hydrolysis does minimal damage to the nutritional components in milk and is highly specific. Two processes, batch and aseptic, are used in producing lactose-free milk. In the batch process, neutral lactase is added to milk under slow stirring until lactose is fully hydrolyzed, after which the milk is pasteurized, homogenized, and packaged. The batch process lacks pasteurization during the hydrolysis phase, and enzyme dosage is relatively high because the reaction occurs at low temperatures to prevent microbial spoilage . ResearcAspergillus oryzae, Aspergillus niger, Escherichia coli, Kluyveromyces lactis and Kluyveromyces fragilis [Kluyveromyces lactis, the most reported microorganism in the literature, showed high hydrolytic performance that was relevant with an exclusive insertion in loop 420–443 of its catalytic site, which enhanced affinity of lactase to lactose [The most plentiful resource of β-galactosidase  are microorganisms, which have advantages of a short production cycle and high production yield. Research has been conducted on the optimization of reaction conditions, purification and characterization of β-galactosidase. Commercially available β-galactosidase mainly includes fragilis . β-galac lactose .E. coli, Lactococcus and Pichia pastoris, et al.). As presented in M) and low product inhibition (KI) by galactose, which is adverse for hydrolysis reaction. Engineering technology is used to get satisfactory lactose affinity (KM) and product inhibition (KI) [Isolation and characterization of β-galactosidase that fulfill the demands of production of low-lactose dairy products remains a hot topic. Genetic engineering technology was used to express the lactase with good enzymatic characteristics in heterologous expression (ion (KI) . The option (KI) . Furtherion (KI)  used theGalactose oligosaccharides (GOSs) can be applied as prebiotics in a variety of dairy products. The global prebiotics market size exceeded US$ 2.90 billion in 2015, with an expected growth of about 12.7% and a profit of about $10.55 billion by 2025 . TransglImmobilization is widely applied in production of lactose-free products because of operational stability, reusability and easy recovery of β-galactosidase in continuous process. Absence of the enzyme in the final product increases its stability. Retained activity of β-galactosidase after recyclable use is critical when deciding whether the immobilized enzyme is suitable for manufacturing. The performance of lactase is greatly influenced by the sources and purity of the enzyme, as well as the type of immobilization method and support materials used. Immobilization methods include adsorption, covalent binding, cross-linking, encapsulation and entrapment. Support materials significantly affect properties  of immobilized enzymes  Table 3Table 3. Lactobacillus bulgaricus and Streptococcus thermophilus. The lactose content of the fermented milk decreased and ranged between 4.6% and 3.7%. Moreover, the yogurt strains produce few β-galactolactases, which further hydrolyze lactose. A systematic review by Savaiano et al. [Fermentation hydrolyzes 20–30% of the lactose of milk, and protein and fat into peptides, amino acids, fatty acids, which makes it easy for human to digest and absorb nutrients. Traditional yogurt is fermented by o et al.  concludeo et al. . Greek-so et al.  and prodo et al. . The laco et al. . Cheese o et al.  detectedo et al. . The lacLactobacillus bulgaricus, extracellular polysaccharide synthesis and viscosity of pre-hydrolyzed milk significantly increased, which may be related to the decrease in dissolved oxygen and the increase in formic acid concentration caused by utilization of glucose. Martins et al. [Bifidobacterium animalis, Lactobacillus acidophilus and typical microorganisms of yogurt and co-hydrolyzed reduced from 4.55 h to 3.68 h. Lactose conversion increased from 15.2% to 97.9%.The lactose content of traditional fermented dairy products still does not meet the needs of lactose-intolerant people. Lactase can be added to further hydrolyze lactose before (pre-hydrolysis) or during (co-hydrolysis) fermentation. These two hydrolysis methods will affect the fermentation characteristics of yogurt to some extent. Generally, lactose is hydrolyzed into glucose and galactose by lactase, and lactic acid bacteria can directly utilize glucose to produce lactic acid, thus shortening the fermentation time. In the meantime, lactic acid bacteria produce more exopolysaccharides and possibly result in higher viscosity. During storage, a large number of flavor substances such as acetaldehyde and 2,3-butanedione were synthesized at higher levels in low-lactose yogurt than in regular yogurt. For example, Yamamoto et al.  found ths et al.  found thPre-hydrolysis to control the lactose content in the final product relatively easily. For example, Raza et al.  producedTraditionally, detection of lactose in dairy products is carried out using different methods, such as gravimetry, polarimetry, enzymatic methods and high-performance liquid chromatography (HPLC). These methods have been proven to perform well in the un-hydrolyzed milk system. However, when it comes to low-lactose/lactose-free dairy products, they suffer from various drawbacks . The forChromatography includes a wide range of improved and coupled methods, such as gas chromatography (GC) , ultrahiOther methods include nuclear magnetic resonance (NMR) , capillaLactobacillus , Bifidobacterium and Saccharomyces and other probiotics are often used in the production and preparation of fermented milk. A systematic review by Oak et al. [Bifidobacterium longum BB536, Lactobacillus rhamnosus HN001, and vitamin B6 together significantly improved bloating and constipation in lactose-intolerant patients. Compared with placebo, probiotics drove the enrichment of bacteria involved in lactose digestion in the gut and also produced a few lactases to promote the hydrolysis of lactose in the human body.More and more clinical studies report that probiotics can assist in relieving lactose intolerance ,101,102.k et al.  evaluatek et al.  showed tLactobacillus acidophilus LA-5, Bifidobacterium lactis Bb-12 and inulin to produce fermented milk with lactose below 0.1%, and this product had a high sensory score and probiotic activity. 6 CFU/g at least) to promote lactose digestion and absorption.Prebiotics are also functionally beneficial for gut health. However, compared with probiotics, there are few studies on improving lactose intolerance using prebiotics alone . At presMilk is a good source of calcium, vitamin B2, vitamin A, and vitamin D. Consumption of 250 mL milk provides 26–40%, 23–52%, 10–24% and about 5% of mineral and vitamins US RDA  recommendations, respectively. However, lactose-intolerant people often avoid eating dairy products. It is also difficult for them to effectively utilize the rich minerals, vitamins and other nutrients in milk, thus resulting in osteoporosis and other adverse health consequences. Although human clinical trials cannot confirm the effect of lactose on enhancing calcium bioavailability , there aIn addition, many lactose-intolerant consumers turn to plant-based alternatives after finding it hard to digest dairy products. Many plant-based beverages have even higher levels of fortified calcium than dairy products. A review compared nutrient density in milk and 17 plant-based beverages, with milk containing 120 mg/100 mL calcium and fortified plant-based beverages containing 42–197 mg/100 mL calcium . HoweverApart from direct addition of calcium, phosphorus, and vitamin D, there are other ways to increase the nutritional value of lactose-free dairy products. For example, Dantas et al.  increaseSince consumers are easily driven by the senses, lactose-free dairy products manufacturers attached great importance to sensory properties. Lactose-free dairy products similar to skim milk are believed to be more popular. However, commercially available lactose-free milk typically utilizes lactase to hydrolyze lactose into galactose and glucose, so it tends to taste sweeter than regular milk. Commercial lactase can also have proteolytic activity that releases peptides and free amino acids generating nonenzymic browning and “off” flavors during the shelf life. The extent of proteolysis and product deterioration identified depended on the lactase preparation used and its purity . HoweverCeratonia siliqua L.) with content of 1.16–1.44 g/100 g, which had good acceptability. Synthesis of GOS using lactase with high trans-glycosylation activity is another common method to increase the added value and improve the flavor of dairy products. For example, Raza et al. [Kluveromyces lactis. Lactose content decreased to 56.25%. The prebiotic cheese has a similar appearance and overall acceptability, as does the control cheese, except for taste and texture, which were improved by trans-glycosylation.It is generally believed that fermentation can not only improve the flavor of products but also increase functional substances or the content of nutrients in products . The sena et al.  producedHydrolyzed milk can further produce lactose-free milk powder, but there are still many problems in the production of lactose-free milk powder. Lactose-free milk powder is more hygroscopic, which is related to the fact that there are more molecules in the amorphous state  during drying. Shrestha et al.  showed tIn the production of lactose-free ice cream, since the solubility of lactose at room temperature is only 20% of that of sucrose, there are difficulties, including crystallization of α-lactose during freezing and formation of sandy texture. Another problem in lactose-free ice cream production is the low sweetness of lactose, which is about 20% of sucrose. Membrane was combined with enzymatic method to solve the problem of the high sweetness of lactose-free milk . FurtherWith the awakening of consumer health awareness, lactose-intolerant people tend to choose healthier and safer lactose-free dairy products. Dairy enterprises and manufacturers have improved processes and technologies, using immobilized enzymes, genetic engineering, membrane filtration, and fermentation to remove lactose. Different methods have their own advantages and disadvantages. The right choices and combination of several methods can improve sensory properties, decrease the cost of production, and increase the nutritional value and functional effect under the premise of low lactose content. Research in the future will focus on the improvement in production and development of lactose-free dairy products of high quality, so as to provide more choices for lactose-intolerant patients.


The existence of Type 2 Diabetes Mellitus (DM) in tuberculosis (TB) patients is very dangerous for the health of patients. One of the major concerns is the emergence of MDR-TB in such patients. It is suspected that the development of MDR-TB further worsens the treatment outcomes of TB such as treatment failure and thus, causes disease progression.To investigate the impact of DM on the Emergence of MDR-TB and Treatment Failure in TB-DM comorbid patients.The PubMed database was systematically searched until April 03, 2022 (date last searched). Thirty studies met the inclusion criteria and were included in this study after a proper selection process.p < 0.001). Heterogeneity observed among included studies was moderate (I2 = 38%). No significant change was observed in the results after sub-group analysis by study design . In the case of treatment failure, TB-DM patients were at higher risk to experience treatment failure rates as compared to TB-non-DM patients .Tuberculosis-Diabetes Mellitus patients were at higher risk to develop MDR-TB as compared to TB-non-DM patients (HR 0.81, 95% CI: 0.60–0.96, The results showed that DM had a significant impact on the emergence of MDR-TB in TB-diabetes comorbid patients as compared to TB-non-DM patients. DM enhanced the risk of TB treatment failure rates in TB-diabetes patients as compared to TB-non-DM patients. Our study highlights the need for earlier screening of MDR-TB, thorough MDR-TB monitoring, and designing proper and effective treatment strategies to prevent disease progression. The existence of Type 2 Diabetes Mellitus (DM) in tuberculosis (TB) patients causes serious public health concerns . People One of the challenges in controlling this TB-DM comorbid condition is the development of MDR-TB, in which resistance develops for both Isoniazid and Rifampicin . The preThe “WHO Collaborative Framework for Care and Control of Tuberculosis and Diabetes” helps to guide healthcare professionals in the effective management of both diseases at administrative and clinical levels . The linThe Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines were being followed by this study .In this review, the PubMed database was systematically searched until April 15, 2023 (the last date of searching). For PubMed Search terms used were as follows: “Diabetes Mellitus” [Mesh]) OR “Diabetes Mellitus, Type 2” [Mesh]) AND “Tuberculosis” [Mesh]) OR “Tuberculosis, Pulmonary” [Mesh]) AND “Treatment Outcome” [Mesh]) AND “Drug resistance” [Mesh]) OR “Multidrug resistance” [Mesh]). The studies that were fulfilling the criteria were also searched from the references of the included studies. The review was only performed on English-language published papers.The inclusion criteria for this study are as follows: the research articles  reporting the association of DM with both MDR-TB and treatment failure rates with adjusted covariates data, studies involving human subjects receiving anti-TB therapy, clinical outcome studies, studies investigating diabetes mellitus’s impact on tuberculosis treatment failure results in tuberculosis patients, and articles published in the English language. The study excluded non-research articles, non-human studies, reports, editorials, studies not analyzing the MDR-TB and treatment failure rates in patients, studies involving pre-DM and type-1 DM patients, and studies for which full text could not be retrieved. Three reviewers independently reviewed papers that fulfilled the selection process. If there were any conflicts between the reviewers, then those were clarified through discussion or the involvement of fourth reviewer.The first step performed was to screen the studies by reading their title and abstracts. The entire content of the selected studies was further retrieved for additional review. For the evaluation of the quality of the individual research articles in the study and to assess the possible risk of bias among studies, the Newcastle-Ottawa Quality Assessment Scale (NOS) was used. The scale comprises of three parts: selection, comparability, and exposure  or measurement of outcome (for cohort studies). It is a nine-score quality assessment scale. A score of <3 means having poor quality and high risk of bias, ≥3 means having median quality and moderate risk of bias and a score of ≥7 means having high quality study and a low risk of bias .p values were the data of the included studies extracted. The relevant data were extracted independently by two reviewers. The data of included studies extracted were reviewed by a third reviewer. Any conflicts were sorted out through discussion until a final decision was taken.From the research articles included in this meta-analysis, the relevant information was collected using a data collection form. Author information, year, country of study, study design, participants, inclusion criteria, treatment regimen, covariates, TB treatment outcomes, and regression results with 95% CI and 2 test. The pooled HR (95% CI) were calculated using the fixed effects model. Subgroup analyses were performed by study design to assess the impact of study design on results. p < 0.01 was considered statistically significant. All statistical analyses were conducted by the meta program in STATA version 12.0 .Heterogeneity among studies was assessed by using IWhen searching the databases, 2,690 results were retrieved. A total of 1,257 articles qualified for the preliminary screening after 1,433 duplicates were removed. Based on their titles and abstracts, 1,208 studies were irrelevant to our study objective and were excluded. Out of 49 studies that were available for full-text review, 19 studies were excluded out of which seven studies were review articles, two studies were editorials, and eight studies did not use multivariable analysis for adjustment of covariates. Thirty studies were selected for inclusion in this meta-analysis after a complete article overview. Among the included studies, 23 were cohort studies including 13 retrospective and 10 prospective and seven were case–control studies. There were six studies conducted in China , six in p < 0.001). There was 19% reduced risk in TB-non-DM patients for MDR-TB emergence as compared to TB-DM patients. Heterogeneity observed among included studies was moderate (I2 = 38%). To check the impact of the study design on the results, the subgroup analysis was conducted. Only studies that were prospective were included in the sub-group analysis. No significant change was observed in the results  as shown in 2 = 23%). The 95% CI was overlapping in both major analysis and subgroup analysis . TB-non-DM patients were at 46% reduced risk for experiencing treatment failure rates as compared to TB-DM patients. The heterogeneity observed among included studies was (I2 = 61%).The included studies showed NOS score range of 6–9. Out of 30 studies, the quality of 21 studies was high. The criteria for selection domain were fully met by all studies except five studies. The age factor was not adjusted in multivariable analysis in five studies in section of confounding bias. For bias in exposure measurement, the non-response rate was not reported in seven studies by the cases as well as controls. The overall NOS mean score of included studies was seven, indicating low biasness risk and high quality of the included studies. The TB-DM comorbidity has become more prevalent worldwide and it has become a major challenge for healthcare organizations to control this comorbid condition . As it ip < 0.001). Our results were found comparable to the previous studies and meta-analyses that found a significant association between DM and MDR-TB . Diabetics are more prone to TB treatment failure rates. The TB treatment failure results in our study were found similar with previous studies .Most of the information was based only on self-reporting or health records of patients, which can lead to assessment error. There should be complete reporting of non-response rates among cases as well as controls to assess reporting-based bias properly. There was moderate heterogeneity across all studies. We performed subgroup analysis by study design, the heterogeneity was reduced. With sub-group analysis by study design for MDR-TB, no change in results was noted when we included prospective studies (HR 0.81, 95% CI: 0.61–0.96, There are some limitations present in our study. The studies with different study designs were included that may lead to heterogeneity in results. The heterogeneity in control groups can affect the association to be determined. We assessed overall MDR-TB patients not by primary and secondary subtypes, which may cause differences in risk factors and outcomes. Moreover, there may be the possibility of publication bias, even though the study included a comprehensive set of studies. The statistical techniques used to address the variability in the study design may introduce some uncertainty in the findings. Despite few limitations, the study has several strengths. The main findings of this study given us a valuable understanding of how DM affects emergence of MDR-TB in TB-Diabetes comorbid patients. The strengths of our results lie in comprehensive analysis of a significant number of studies, focusing on a specific patient population. We focused on specific subtypes of DM and TB, providing a more refined understanding of their interaction. The screening for MDR-TB should be prioritized at an earlier stage in TB-DM comorbid patients, which could reduce the economic burden on these patients. There should also be thorough MDR-TB monitoring and necessary steps should be taken to design a proper treatment strategy to prevent the disease progression in these patients. For future concern, this study highlights the importance of conducting more thorough research with large groups of people, using consistent methods, and considering variables that might affect the results. This would help gain a better understanding of how Type 2 DM affects TB-DM comorbid patients.The results showed that DM had significant impact on emergence of MDR-TB in TB-Diabetes comorbid patients as compared to TB-non-DM patients. DM enhanced the risk of experiencing TB treatment failure rates in TB-Diabetes patients as compared to TB-non-DM patients. Our study highlights the need for earlier screening of MDR-TB, thorough MDR-TB monitoring and designing proper and effective treatment strategies to prevent disease progression.MK, AR, UM, ML, IA, MR, SS, KH, RH, GA, AA, MA, SAlg, MI, SAlm, SK, and AH made substantial contributions to the conception and design of the study, and analysis and interpretation of the data, and drafted the work or revised it critically for important intellectual content. MK and AR made substantial contributions to the analysis and interpretation of the data. All authors contributed to the article and approved the submitted version.


Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) was used to assess the control group. Meanwhile, the FA-BCID group was evaluated using both FA-BCID and MALDI-TOF, and the results were compared. The identification results from 73% (44/60) of the blood samples demonstrated agreement between FA-BCID and MALDI-TOF. The FA-BCID panel detected mecA genes in seven Staphylococcus species; six cases were confirmed using antimicrobial susceptibility testing. In addition, KPC genes were detected in one Escherichia coli and one Klebsiella pneumoniae, although only the latter corresponded with the result from antimicrobial susceptibility testing. The turnaround time (TAT) for identification through FA-BCID was shorter, with a median of 3.6 [2.4–4.6] hours (p < 0.05). No significant differences in the clinical and microbial outcomes following the ASP were observed between FA-BCID and MALDI-TOF. These results suggest that the FA-BCID panel provides an identification result that is as reliable as that provided by the routine identification procedure but with shorter TAT; thus, the FA-BCID method is considered an effective and beneficial method for therapeutic decision making and the improvement of the ASP for patients with bloodstream infection.We analyzed the accuracy and time efficiency of the FilmArray blood culture identification (FA-BCID) panel in identifying the pathogens in positive blood cultures. Two-hundred and seventy-two individuals were randomly assigned as the control ( Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection . It caus® 2 , also require approximately two to three days before the results are available [E test, bioMérieux), or automated AST systems such as VITEK® 2, are generally required. The additional assessment in conventional blood culture identification undoubtedly adds to the length of time in which the results are available [Since sepsis is related to the infection of bacteria, fungi, or other pathogens, detecting and identifying the related pathogen in the blood is crucial for treating sepsis patients. Among diagnosis methods, blood culture is considered the gold standard for detecting that bacteria or fungi that cause sepsis in the blood . Neverthvailable . Moreovevailable . In addivailable ,9.mecA, yanA/B, and blaKPC) [The FilmArray blood culture identification panel  is a closed diagnostic system using high-order multiplex PCR analysis and is approved by the U.S. Food and Drug Administration (FDA) for use on positive blood cultures . FA-BCID blaKPC) . Several blaKPC) ,14; howeIn this study, we evaluated the clinical benefit of the FA-BCID panel by assessing its accuracy in prospective clinical samples and determining its turnaround time compared to routine identification methods. We also defined the benefits of FA-BCID when implemented in the antimicrobial stewardship program (ASP) by evaluating the clinical and microbial outcomes compared to the conventional method.n = 212) and FA-BCID (n = 60) groups. Samples obtained from patients admitted to the emergency department in GNUCH that were suspected of a positive blood culture were included in the study. The samples from patients who died between blood culture sampling and positivity detection were excluded from the study.We conducted a prospective study at the Gyeongsang National University Changwon Hospital, Republic of Korea. Two-hundred and seventy-two positive blood cultures were collected between November 2018 and April 2019 and included as study subjects. The study subjects were randomly assigned to the control (The experiment was conducted during the same period as sample collection (November 2018 and April 2019). Only individuals who conducted investigation and data analysis have access to information that could identify individual participants during and after data collection. The identification of microorganisms in the positive blood cultures was conducted using the FA-BCID panel and MALDI-TOF . This stAccording to the manufacturer’s instructions, the blood cultures were processed using BACT/ALERT Virtuo  . Two bloFA-BCID combines nucleic acid extraction, high-order nested multiplex PCR, and post-PCR DNA melting curve analysis within one system. The assessment was conducted according to the manufacturer’s instructions and as described previously . Briefly® MS v3.0 (bioMérieux). This automated mass spectrometry microbial identification system uses matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) technology [Following Gram staining, microorganisms from the positive blood cultures were sub-cultured on the proper agar plate (MacConkey agar plate for Gram-negative bacteria and blood agar plate for Gram-positive bacteria). The microorganisms that grew on the plates were identified using VITEKchnology . The ass® 2 AST Cards (bioMérieux) with pure microorganisms one day after the empirical antimicrobial therapy was implemented. The AST was performed according to the manufacturer’s instructions. Briefly, for each isolate, the suspensions were prepared and used to inoculate the AST card. The results were read and interpreted automatically using software  provided by bioMérieux [The antimicrobial susceptibility test (AST) was conducted using VITEKoMérieux .We determined several clinical and microbial factors to evaluate the FA-BCID outcomes of the antimicrobial stewardship program (ASP). We observed their outcomes following the ASP that was performed based on the FA-BCID result. Subsequently, the results were compared with those from the control group, in which the implementation of the ASP was based on the MALDI-TOF result. Three infectious disease physicians reviewed the medical records and consulted regarding escalating/de-escalating antibiotics usage.p < 0.05 was considered significant. The two groups were compared using the t-test for continuous variables and the chi-squared test for categorical variablesAll statistical analyses were performed using MedCalc for Windows, version 18.5 , and n = 212) and FA-BCID (n = 60) groups. Analysis of participants’ demographic and clinical characteristics demonstrated no significant differences between the two groups  were differentially identified using the FA-BCID panel  and MALDI-TOF , respectively. The FA-BCID panel was used to detect mecA genes in seven Staphylococcus species; six were confirmed with antimicrobial susceptibility testing. The KPC genes were also detected in one Escherichia coli and one Klebsiella pneumoniae, although only the latter agreed with antimicrobial susceptibility testing  . The median turnaround time (TAT) in the FA-BCID group was 3.6 h, whereas the TAT in the control group was 28.5 h ( 0.0001) . Subsequp = 0.0274). Correspondingly, the time for the antimicrobial susceptibility test (AST) and the de-escalation of antibiotics was also shorter in the FA-BCID group than in the control  than in the control group (50.2 h) ( control .p = 0.7201). There were also no significant differences in 30-day mortality  and 30-day readmission for infection of the same organism  between the FA-BCID and control groups. Similarly, we did not observe any statistical difference in microbiologic outcomes between the two groups. The acquisition of C. difficile or multidrug-resistant organisms appeared comparable for both groups, with a p-value of 0.7503.Furthermore, observation of the clinical and microbial outcomes in the patients following the ASP demonstrated a comparable result between the FA-BCID and control groups. The clinical outcomes, including disposition, length of stay, and mortality, were not statistically different between the two groups . The numEscherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Enterobacter cloacae, Proteus sp., Pseudomonas aeruginosa, Serratia marcescens, Haemophilus influenza, Neisseria meningitides, Candida albicans, Candida glabrata, Candida parapsilosis, Candida krusei, and Candida tropicalis [In this study, we presented a prospective study to evaluate the advantage of microorganism identification in blood cultures using FA-BCID, a multiplex PCR-based system. According to the published research, FA-BCID demonstrated high sensitivity and specificity for pathogen identification: up to 96.5%  and 99.7% , respectively . The taropicalis ,19.The result from this study demonstrated that the FA-BCID panel was 97% (58/60) reliable when used to detect the presence of microorganisms in positive blood samples; 77% (46/60) of these microorganisms demonstrated monomicrobial growth. This suggests that the FA-BCID panel could be used to cover the majority of microorganisms encountered in the positive blood cultures during the study period. The results of this study are consistent with a previous study that reported 91% of all assessed cases could be identified with FA-BCID .Proteus sp. in the FA-BCID assessment is the main reason for this discrepancy. As already informed by bioMérieux, the manufacturer of FA-BCID, Proteus sp. was likely detected in the blood culture sample due to the increased level of nucleic acid from nonviable Proteus sp. bacteria in the BACT/ALERT® blood culture bottles [Proteus sp. using the FA-BCID panel and the BACT/ALERT® blood culture bottles. Additionally, there were three other positive blood cultures with discrepancies between FA-BCID and MALDI-TOF in their identified microorganism, likely due to the limited number of target organisms in FA-BCID, as it only covered 24 different target organisms. The Shewanella algae, Clostridium tertium, and Bacteroides fragilis detected using MALDI-TOF are not target organisms in the FA-BCID panel. The limited number of target organisms in the FA-BCID panel may constitute a disadvantage of FA-BCID implementation compared to the conventional procedure that enables the detection of limitless organisms. However, unlike the traditional procedure, which requires a separate assessment for the detection of antimicrobial resistance genes, FA-BCID is used not only to detect and identify the microorganism, but also to distinguish the isolates with antimicrobial resistance genes [In this study, microorganisms identified in 73% (44/60) of positive blood cultures demonstrated an agreement between FA-BCID and MALDI-TOF. Microorganisms from six positive blood cultures that showed discrepancy were identified as polymicrobial using FA-BCID and monomicrobial using MALDI-TOF. The presence of  bottles . This coce genes ,19,22, mStaphylococcus sp. and one as Klebsiella pneumoniae, showed the presence of antimicrobial resistance genes; these were identified as mecA and KPC, respectively. An antimicrobial susceptibility test confirmed that all six Staphylococcus sp. isolates were resistant to methicillin. Similarly, the Klebsiella pneumoniae isolate identified as carrying KPC was resistant to a variety of β-lactam and non-β-lactam antibiotics, as reported in a previous study [ESBL) or NDM resistance genes is essential; thus, the target antimicrobial resistance in the FA-BCID panel, which is limited to KPC, mecA, and vanA/B, may reduce the clinical benefit and implementation of FA-BCID in hospitals in Korea.Seven of the nine identified isolates, six identified as us study . IdentifThe timing of antibiotic therapy is considered a crucial determinant for the survival of patients with a blood infection or sepsis. The mortality rate may be double or more in patients with severe infections who experience delays in the administration of antibiotic therapy . TherefoThe usage of broad-spectrum antibiotics may contribute to antimicrobial resistance. Hence, reassessing the possibility of any antibiotic resistance following the escalation of antimicrobial therapy is necessary for optimizing the ASP. The de-escalation of antimicrobial therapy is conducted, based on microbiological assessment results, around the third day from the escalation point . AdjustiConsidering the rapidity and accuracy of FA-BCID in detecting microbial pathogens in positive blood cultures, we expected that implementing FA-BCID may improve the clinical outcomes of patients. However, this study found no significant differences in the clinical outcomes observed between the two groups. The percentage of clinical outcomes, such as recovery period, length of stays, and mortality rates, were very much alike between the FA-BCID and control groups. These findings show that using FA-BCID may not be advantageous for managing patients with blood infections. We assumed that the relatively small sample size in the FA-BCID group and the unequal distribution of patients with chronic and nonchronic diseases were the main reasons for this finding. Additionally, although FA-BCID may provide rapid and accurate identification of microbial pathogens and detection of antimicrobial resistance genes, the clinical value of FA-BCID also depends on the actual application of the identification results on managing the patients. Hence, effective communication between the diagnosis department and attending physician is crucial to improving the management of patients with blood infections.The relatively small number of study subjects in the FA-BCID group may constitute a limitation of this study. Additionally, FA-BCID may be less favorable as a bloodborne pathogen detection method due to its high cost and limited targets compared to the conventional method. Nevertheless, as a microbial pathogen detection tool, the FA-BCID panel demonstrated rapid and accurate detection and identification of microbial pathogens and antimicrobial resistance genes; thus, it may constitute a promising AST tool that can be implemented, along with the ASP, to improve management of patients with blood infections.