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Purpose – Effective and efficient supply chain coordination requires the integration of all product flow processes. However, inconsistent empirical results have been obtained with respect to the relationships between supply chain integration (SCI) and performance. Drawing on efficiency-flexibility arguments, this paper seeks to develop a SCI model that includes buyer-supplier-supplier relationships, and proposes a contingency framework for reexamining the SCI-supplier performance relationship under demand and technological uncertainties. Design/methodology/approach – A two-stage data collection process was conducted, and a total of 878 suppliers that listed in the Taiwanese “Center-Satellite Production System” with supply contract were contacted for this study. Finally 164 suppliers were gathered and screened as valid responses. Hierarchical regression analysis was used to test the hypotheses in this study. Findings – Evidence indicates that SCI has a significant positive effect on the suppliers' performance. The positive SCI-performance relationship can be moderately weakened by demand uncertainty; however, this positive SCI-performance relationship will be strengthened by technological uncertainty. Originality/value – While supply chain management is needed to manage the vertical and horizontal relationships simultaneously, this study offers a framework to solve efficiency-flexibility dilemma arguments when dealing with “exploitation” and “exploration” alternatives to help to reexamine the inconsistent SCI-performance relationship. Furthermore, based on transaction cost theory, this paper takes the nature of uncertainty into account for improving the theoretical background of the SCI-performance relationship arguments. Empirical results indicate the existence of an ambidextrous supply chain integration strategy which justifies the choice of which one is preferable in efficiency-flexibility dilemma arguments.

Background Initial symptoms of dengue fever are non-specific, and thus definite diagnosis requires laboratory confirmation. Detection of IgM against dengue virus (DENV) has become widely used for dengue diagnosis. Understanding the persistence of anti-DENV IgM in subjects after acute infection is essential in order to interpret test results correctly. Although the longevity of anti-DENV IgM has been vehemently investigated in symptomatic children, anti-DENV IgM persistence in adults and in asymptomatically infected people have seldom been reported. Methods We prospectively investigated 44 adults with detectable anti-DENV IgM in a serosurvey conducted in the 2015 dengue epidemic in Tainan, Taiwan. Among subjects within the cohort, 17 were classified to be symptomatic and 27 were asymptomatic. The enzyme-linked immunosorbent assay (ELISA) from Standard Diagnostic (SD) and Focus Diagnostic were used to detect anti-DENV IgM for specimens collected initially, at 6 and 12 months. Regression analyses were used to estimate the duration of anti-DENV IgM fell below the detectable level. Rapid dengue tests from Standard Diagnostics had been widely adopted to detect anti-DENV IgM in Taiwan during the 2015 dengue outbreak. As such, collected specimens were also evaluated with the SD rapid dengue test in parallel. Results Anti-DENV IgM was detectable in 70.5 and 46.2% of the 44 subjects at 6 months and 12 months by the SD ELISA, respectively, while 13.6 and 7.7%, respectively, by the Focus ELISA. There was no significant difference in anti-DENV IgM detection for the follow-up specimens between subjects with symptomatic and asymptomatic infections. The regression analysis estimated that anti-DENV IgM persistence fell to the undetectable level at 338.3 days (95% CI 279.7–446.9) by SD ELISA, while at 175.7 days (95% CI 121.9–221.1) by Focus ELISA. The detectable frequency of anti-DENV IgM by rapid tests was 86.4%, 68.2 and 35.9% at initial, 6 and 12 months, respectively. Conclusion Anti-DENV IgM was found to persist much longer than previously thought, suggesting a necessity of re-evaluation of the use of anti-DENV IgM for both the diagnosis of dengue and serological surveillance, especially when large outbreaks have occurred in the preceding year.

Chronic myeloid leukemia (CML) is a myeloproliferative disorder associated with the Philadelphia chromosome, and the current standard of care is the use of tyrosine kinase inhibitors (TKI). However, some patients will not achieve a molecular response and may progress to blast crisis, and the underlying mechanisms remain to be clarified. In this study, next-generation sequencing was used to explore endogenous miRNAs in CML patients versus healthy volunteers, and miR-342-5p was identified as the primary target. We found that miR-342-5p was downregulated in CML patients and had a significant inhibitory effect on cell proliferation in CML. Through a luciferase reporter system, miR-342-5p was reported to target the 3’-UTR domain of CCND1 and downregulated its expression. Furthermore, overexpression of miR-342-5p enhanced imatinib-induced DNA double-strand breaks and apoptosis. Finally, by analyzing clinical databases, we further confirmed that miR-342-5p was associated with predicted molecular responses in CML patients. In conclusion, we found that both in vivo and in vitro experiments and database cohorts showed that miR-342-5p plays a key role in CML patients, indicating that miR-342-5p may be a potential target for future CML treatment or prognostic evaluation.

Bone marrow aspiration and biopsy remain the gold standard for the diagnosis of hematological diseases despite the development of flow cytometry (FCM) and molecular and gene analyses. However, the interpretation of the results is laborious and operator dependent. Furthermore, the obtained results exhibit inter- and intravariations among specialists. Therefore, it is important to develop a more objective and automated analysis system. Several deep learning models have been developed and applied in medical image analysis but not in the field of hematological histology, especially for bone marrow smear applications. The aim of this study was to develop a deep learning model (BMSNet) for assisting hematologists in the interpretation of bone marrow smears for faster diagnosis and disease monitoring. From January 1, 2016, to December 31, 2018, 122 bone marrow smears were photographed and divided into a development cohort (N=42), a validation cohort (N=70), and a competition cohort (N=10). The development cohort included 17,319 annotated cells from 291 high-resolution photos. In total, 20 photos were taken for each patient in the validation cohort and the competition cohort. This study included eight annotation categories: erythroid, blasts, myeloid, lymphoid, plasma cells, monocyte, megakaryocyte, and unable to identify. BMSNet is a convolutional neural network with the YOLO v3 architecture, which detects and classifies single cells in a single model. Six visiting staff members participated in a human-machine competition, and the results from the FCM were regarded as the ground truth. In the development cohort, according to 6-fold cross-validation, the average precision of the bounding box prediction without consideration of the classification is 67.4%. After removing the bounding box prediction error, the precision and recall of BMSNet were similar to those of the hematologists in most categories. In detecting more than 5% of blasts in the validation cohort, the area under the curve (AUC) of BMSNet (0.948) was higher than the AUC of the hematologists (0.929) but lower than the AUC of the pathologists (0.985). In detecting more than 20% of blasts, the AUCs of the hematologists (0.981) and pathologists (0.980) were similar and were higher than the AUC of BMSNet (0.942). Further analysis showed that the performance difference could be attributed to the myelodysplastic syndrome cases. In the competition cohort, the mean value of the correlations between BMSNet and FCM was 0.960, and the mean values of the correlations between the visiting staff and FCM ranged between 0.952 and 0.990. Our deep learning model can assist hematologists in interpreting bone marrow smears by facilitating and accelerating the detection of hematopoietic cells. However, a detailed morphological interpretation still requires trained hematologists.

In a retrospective cohort study, we report the current epidemiology of patients with multiple myeloma (MM) and analyze the real-world clinical outcomes of bortezomib-based therapy. This retrospective study was mainly designed to evaluate the characteristics, treatment outcomes, and prognostic factors of patients with MM who received bortezomib-based therapy. We identified 5,726 patients in Taiwan with MM newly diagnosed between 2007 and 2015. Confidential data from the National Health Insurance Research Database (NHIRD) was used under strict guidelines, as it was made available in an electronic format for research purposes. In addition, we analyzed 96 patients who have been diagnosed with MM and were treated at the Tri-Service General Hospital (TSGH) between January 1, 2002, and December 31, 2018. Patients receiving first-line treatment with bortezomib had longer overall survival (OS) compared to those who received non-first-line treatment (p<0.001). In addition, the statistically lowest risk of mortality was when patients received first-line bortezomib followed by an autologous hematopoietic stem cell transplant (adjusted hazard ratio = 0.39, p<0.001). In the TSGH study, the patients were enrolled between January 1, 2002, and December 31, 2018, with an initial diagnosis of MM; there were 96 individuals treated with bortezomib. There was no statistically significant difference in the OS or progression-free survival (PFS) according to the gender, myeloma type, International Staging System stage, or treatment regimen. There was a significant difference in the PFS in patients receiving first-line bortezomib treatment with transplantation compared to those without transplantation (p = 0.021). Bortezomib as a first-line treatment extended the OS in four-year mortality tracking and lowered the mortality risk according to the NHIRD analysis. In the TSGH analysis, the results indicated that the initial conditions of patients with MM have a lower influence on the OS and PFS after bortezomib-based therapy was administered.

Background: Combination therapy with the administration of GW5074 and sorafenib significantly induced necrotic death in various cancer cells in vivo, as well as prolonging the survival of an animal disease model due to significant suppression of the primary and metastatic lesions. We sought to determine the safety, tolerability, pharmacokinetics, and anti-tumor activity of this co-administration therapy in patients with refractory advanced solid cancers. Methods: Twelve patients were enrolled. Eligible subjects received different dosages of GW5074 in one of the three dose cohorts (Cohort 1: 750 mg daily, Cohort 2: 1500 mg daily, Cohort 3: 750 mg twice daily) plus 200 mg of sorafenib daily to determine the maximum tolerated dose (MTD) and dose limiting toxicities (DLT) at phase 1. Furthermore, the expression level of phosphorylated DAPKS308 in primary tumor, metastatic tumor, and circulating tumor cells (CTC) were evaluated to investigate the relationship between biomarker and the efficacy profile. Results: Among the 12 enrolled patients in this phase 1 trial, most adverse effects (AE) were grade 1, with two being grade 3. The most frequent AE of all grades were weight loss and hypertension, occurring in 16.7% of participants. Eight patients (66.7%) had the disease controlled by receiving co-administration therapy of GW5074 and sorafenib. GW5074 was found to have poor absorption, as increasing the dosage did not result in a significant increase in the bioavailability of GW5074 in subjects. Furthermore, the expression level of phosphorylated DAPKS308 in tumor and CTCs were correlated with the disease control rate (DCR) and duration of response (DOR). Conclusions: Co-administration therapy of GW5074 and sorafenib demonstrated a favorable safety profile and showed anti-tumor activity in a variety of tumor types. However, the solubility of GW5074 is not satisfactory. A future phase 2a trial will be carried out using the new salted form that has been proven to be more effective.

EW02, a polysaccharide-enriched crude extract from black soybean, has been shown to assist hematopoiesis in chemotherapy-treated animals. The present study aimed to clarify the safety, quality of life (QOL) and efficacy for myelopoiesis of EW02 administration in early breast cancer (EBC) patients receiving adjuvant chemotherapy. A total of 60 eligible EBC patients were enrolled in a randomized, double-blinded trial, 40 of whom were prescribed 700 mg oral EW02 three times daily for 15 days in chemotherapy cycle (C)2. The remainder were prescribed a placebo. All subjects took EW02 in C3 for 15 days. Blood samples were collected at different time-points for determining the blood cell count, and the serum level of granulocyte colony-stimulating factor (G-CSF) and interleukin (IL)-6. All patients tolerated EW02 well without severe side-effects. QOL evaluation showed that only the score of one questionnaire section (QLQ-C30) was significantly increased at C1 day (D)8 to C2D8 when the EW02 and placebo groups were compared (P=0.045). No significant myelopoiesis recovery, and no incremental change in IL-6 and G-CSF levels were found in C2. Subgroup analysis showed a slightly lower decrease in absolute neutrophil count (ANC) in the EW02 patients who underwent Adriamycin + cyclophosphamide treatment compared with the placebo group. Although EW02 failed to show efficacy for myelopoiesis in the present study, EW02 was still well tolerated in EBC patients who underwent adjuvant chemotherapy.

In response to the introduction of new generation technology into rehabilitation therapy, new methods and effective management approaches specifically for rehabilitation therapy are in urgent need presently. Our lab has developed a 3D virtual game environment for training which mainly integrates 3D images, active touch, and other related information. Mainly consisting of a motor rehabilitation system and a series of 3D simulated flight games, the system aims to achieve rehabilitation of pronation and supination of the arms through the patient’s control and continuous exercise. In this study, social psychological variables are used to evaluate the human-computer interaction process.

This study describes an exercise training case after stroke that can be remotely controlled by a therapiest, and the pilot clinical test result of rehabilitation platform. We have developed a set of training mission with graual difficulty in the virtual environment game, and the process includes delicate hand action and entire upper limb action, meanwhile, the operation patient and the therapist will stay at different room for the training. In the study, social psychology variable is used to assess the process of human machine interaction, thue result shows that after using this rehabilitation system, the negative feeling is significantly reduced (Confused feeking, t(13)=2.54, p<0.05, anxiety feeling t(13)=2.58, p<0.05, pressure feeling, t(13)=2, p<0.1). The entire satisfaction shows positive relationship with the feeling cooperating with the therapist (r(8)=0.770, p<0.05). Using this rehabilitation system case, it was found that the active emotion before carrying of rehabilitation therapy shows positive relationship with the continuous participation of therapy after rehabilitation therapy process (r(14)=0.699,p<0.05), that is, the research shows that rehabilitation significantly enhance the psychological state of the stroke case.