We conducted a systemic evaluation to describe the effect of minimal residual disease (MRD) kinetics on long-term allogeneic transplantation outcome by analyzing 95 adult transplants with ...Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph-positive ALL) who received first-line two courses of imatinib-based chemotherapy (median follow-up 5 years). MRD monitoring was centrally evaluated by real-time quantitative PCR (4.5 log sensitivity). After the first course of imatinib-based chemotherapy, 33 patients (34.7%) achieved at least major molecular response. On the basis of MRD kinetics by the end of two courses of imatinib-based chemotherapy, we stratified entire patients into four subgroups: early-stable molecular responders (EMRs, n=33), late molecular responders (LMRs, n=35), intermediate molecular responders (IMRs, n=9) and poor molecular responders (PMRs, n=18). Multivariate analysis showed that the most powerful factor affecting long-term transplantation outcome was MRD kinetics. Compared with EMRs, IMRs or PMRs had significantly higher risk of treatment failure in terms of relapse and disease-free survival (DFS). LMRs had a tendency toward a lower DFS. Quantitative monitoring of MRD kinetics during the first-line imatinib-based chemotherapy course is useful in identifying subgroups of Ph-positive ALL transplants at a high risk of relapse.
A novel illumination normalisation (IN) method using a convolutional neural network (CNN) is proposed. The proposed network is composed of the local pattern extraction (LPE) and illumination ...elimination (IE) layers. The LPE layers model the relationships between the pixels in each local region in order to handle various types of local shadow and shading in the face image. Based on the commonly used assumption about the illumination field, the IE layers generate illumination-insensitive ratio images by calculating the ratio between the output pairs produced from the LPE layers. The final feature map obtained by combining the ratio images can possess an improved discriminative ability for face recognition (FR). For training the proposed network, the results produced by the Weber fraction-based IN methods as ground truths are utilised. The experimental results demonstrate that the proposed network performs better in terms of FR accuracy compared with the conventional non-CNN-based method and it can be combined with any CNN-based face classifier.
The cancer stem cell (CSC) hypothesis has important clinical implications for cancer therapeutics because of the proposed role of CSCs in chemoresistance. The aim of this study was to investigate ...changes in the CSC populations before and after primary systemic therapy (PST) and their prognostic role in human breast cancer.
Paired samples (before and after PST) of breast cancer tissue were obtained from clinical stage II or III patients (n=92) undergoing PST with the regimen of doxorubicin plus docetaxel (AD) (n=50) or doxorubicin plus cyclophosphamide (AC) (n=42) and subsequent breast resection. The proportions of putative CSCs with CD44+/CD24- or aldehyde dehydrogenase 1+ (ALDH1+) phenotypes were determined by immunohistochemistry.
A higher proportion of CD44+/CD24- tumour cells and ALDH1 positivity in pre-chemotherapy tissue was correlated with higher histologic grade, oestrogen receptor (ER) negativity, high Ki-67 proliferation index and basal-like subtype of breast cancer. Aldehyde dehydrogenase 1 positivity in pre-chemotherapy biopsy was also associated with a higher rate of pathologic complete response following PST. In comparisons of putative CSC populations before and after PST, the proportions of CD44+/CD24- and ALDH1+ tumour cells were significantly increased after PST. The cases with increased CD44+/CD24- tumour cell populations after PST showed high Ki-67 proliferation index in post-chemotherapy specimens and those with increased ALDH1+ tumour cell population after PST were associated with ER negativity and p53 overexpression. Furthermore, cases showing such an increase had significantly shorter disease-free survival time than those with no change or a reduced number of CSCs, and the survival difference was most notable with regard to the changes of ALDH1+ tumour cell population in the patients who received AC regimen.
The present study provides the clinical evidence that the putative CSCs in breast cancer are chemoresistant and are associated with tumour progression, emphasising the need for targeting of CSCs in the breast cancer therapeutics.
Gene fusion is involved in the development of various types of malignancies. Recent advances in sequencing technology have facilitated identification of gene fusions and have stimulated the research ...of this field in cancer. In the present study, we performed next-generation transcriptome sequencing in order to discover novel gene fusions in gastric cancer. A total of 282 fusion transcript candidates were detected from 12 gastric cancer cell lines by bioinformatic filtering. Among the candidates, we have validated 19 fusion transcripts, which are 7 inter-chromosomal and 12 intra-chromosomal fusions. A novel DUS4L-BCAP29 fusion transcript was found in 2 out of 12 cell lines and 10 out of 13 gastric cancer tissues. Knockdown of DUS4L-BCAP29 transcript using siRNA inhibited cell proliferation. Soft agar assay further confirmed that this novel fusion transcript has tumorigenic potential. We also identified that microRNA-coding gene PVT1, which is amplified in double minute chromosomes in SNU-16 cells, is recurrently involved in gene fusion. PVT1 produced six different fusion transcripts involving four different genes as fusion partners. Our findings provide better insight into transcriptional and genetic alterations of gastric cancer: namely, the tumorigenic effects of transcriptional read-through and a candidate region for genetic instability.
Summary
Background Subungual haemorrhages are characterized by well‐circumscribed dots or blotches with a red to red–black pigmentation, but some cases can be difficult to distinguish from subungual ...melanoma by the naked eye alone. Dermoscopy has proven to be a useful, noninvasive tool in the diagnosis of pigmented lesions in the nail; however, few dermoscopic studies of subungual haemorrhages have been reported.
Objectives To investigate characteristic dermoscopic patterns of subungual haemorrhages, and to find distinctive features that can differentiate them from nail‐unit melanomas.
Methods Patients with a confirmed diagnosis of either subungual haemorrhage or nail‐unit melanoma at a tertiary university hospital were included in the study. Clinical features and dermoscopic patterns were evaluated.
Results Sixty‐four patients with a total of 90 lesions of subungual haemorrhage were enrolled in the study. The majority of cases (84%) showed combinations of more than one colour, while 16% had only one colour. The most common colour of the subungual haemorrhages was purple–black, in 37% of cases. A homogeneous pattern was observed in 92% of cases, globular patterns in 42% and streaks in 39%. Peripheral fading and periungual haemorrhages were found in 54% and 22% of cases, respectively. Destruction or dystrophy of the nail plate was observed in 16% of cases. In the 16 cases of nail‐unit melanomas, Hutchinson sign, longitudinal irregular bands or lines, triangular shape of bands, vascular pattern, and ulcerations were found in 100%, 81%, 25%, 6% and 81% of cases, respectively. In contrast, these features were not found in subungual haemorrhages.
Conclusions Dermoscopy provides valuable information for the diagnosis of subungual haemorrhage and aids in the differential diagnosis from nail‐unit melanoma.
What’s already known about this topic?
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Subungual haemorrhage is a common imitator of subungual melanoma, and thus subungual melanoma should always be included in the differential diagnosis of subungual haemorrhage.
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Dermoscopy is a helpful, noninvasive diagnostic tool that has been reported to improve diagnostic accuracy in pigmented nail lesions.
What does this study add?
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The results of our study show that the characteristic dermoscopic findings of subungual haemorrhage can be summarized as homogeneous patterns, globular patterns, streaks, peripheral fading and periungual haemorrhages.
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This study shows that dermoscopy provides valuable information for the diagnosis of subungual haemorrhages and assists in its differential diagnosis from nail‐unit melanomas.
Given the mode of transmission of Middle East respiratory syndrome (MERS), healthcare workers (HCWs) in contact with MERS patients are expected to be at risk of MERS infections. We evaluated the ...prevalence of MERS coronavirus (CoV) immunoglobulin (Ig) G in HCWs exposed to MERS patients and calculated the incidence of MERS-affected cases in HCWs. We enrolled HCWs from hospitals where confirmed MERS patients had visited. Serum was collected 4 to 6 weeks after the last contact with a confirmed MERS patient. We performed an enzyme-linked immunosorbent assay (ELISA) to screen for the presence of MERS-CoV IgG and an indirect immunofluorescence test (IIFT) to confirm MERS-CoV IgG. We used a questionnaire to collect information regarding the exposure. We calculated the incidence of MERS-affected cases by dividing the sum of PCR-confirmed and serology-confirmed cases by the number of exposed HCWs in participating hospitals. In total, 1169 HCWs in 31 hospitals had contact with 114 MERS patients, and among the HCWs, 15 were PCR-confirmed MERS cases in study hospitals. Serologic analysis was performed for 737 participants. ELISA was positive in five participants and borderline for seven. IIFT was positive for two (0.3%) of these 12 participants. Among the participants who did not use appropriate personal protective equipment (PPE), seropositivity was 0.7% (2/294) compared to 0% (0/443) in cases with appropriate PPE use. The incidence of MERS infection in HCWs was 1.5% (17/1169). The seroprevalence of MERS-CoV IgG among HCWs was higher among participants who did not use appropriate PPE.
Gene delivery systems are essentially necessary for the gene therapy of human genetic diseases. Gene therapy is the unique way that is able to use the adjustable gene to cure any disease. The gene ...therapy is one of promising therapies for a number of diseases such as inherited disorders, viral infection and cancers. The useful results of gene delivery systems depend open the adjustable targeting gene delivery systems. Some of successful gene delivery systems have recently reported for the practical application of gene therapy.
The recent developments of viral gene delivery systems and non-viral gene delivery systems for gene therapy have briefly reviewed. The viral gene delivery systems have discussed for the viral vectors based on DNA, RNA and oncolytic viral vectors. The non-viral gene delivery systems have also treated for the physicochemical approaches such as physical methods and chemical methods. Several kinds of successful gene delivery systems have briefly discussed on the bases of the gene delivery systems such as cationic polymers, poly(L-lysine), polysaccharides, and poly(ethylenimine)s.
The goal of the research for gene delivery system is to develop the clinically relevant vectors such as viral and non-viral vectors that use to combat elusive diseases such as AIDS, cancer, Alzheimer, etc. Next step research will focus on advancing DNA and RNA molecular technologies to become the standard treatment options in the clinical area of biomedical application.
Patients with advanced non–small-cell lung cancer with a PD-L1 expression level of 1% or more of tumor cells were randomly assigned to receive nivolumab plus ipilimumab, nivolumab alone, or ...chemotherapy. Overall survival was significantly longer among the patients who received nivolumab plus ipilimumab than among those who received chemotherapy.
Background
In the eighth edition of the AJCC staging system for differentiated thyroid carcinoma (DTC), minimal extrathyroidal extension (ETE) is no longer a determinant of T3 category. Instead, ...gross ETE invading only strap muscles has been designated as a new T3b category. The long‐term prognosis of patients with DTC and gross ETE invading only strap muscles was investigated.
Methods
This was a retrospective analysis of patients who underwent thyroidectomy between 1996 and 2005. Differences in cancer‐specific and recurrence‐free survival according to extent of ETE were assessed.
Results
A total of 3174 patients with DTC were included. No significant differences were observed in 10‐year cancer‐specific survival among patients with no ETE (98·6 per cent), microscopic ETE (98·3 per cent) and gross ETE invading only strap muscles (98·9 per cent) (P = 0·375). The 10‐year recurrence‐free survival rate for patients with gross ETE invading only strap muscles (89·2 per cent) was shorter than that for patients with no ETE (93·7 per cent; P = 0·016), but similar to that of patients with microscopic ETE (90·3 per cent). In univariable analysis, patients with gross ETE invading only strap muscles had a significantly higher risk of recurrence than those with no ETE (hazard ratio (HR) 1·67, 95 per cent c.i. 1·10 to 2·55; P = 0·017). In multivariable analysis, gross ETE invading only strap muscles was not an independent predictor of recurrence (HR 1·09, 0·71 to 1·69; P = 0·685).
Conclusion
Although gross ETE invading only strap muscles may provide prognostic information about long‐term recurrence, it does not affect mortality. The actual impact of gross ETE invading only strap muscles will be important in revising the staging system in the future.
None, for survival
This study is an epidemiologic investigation of nosocomial severe fever with thrombocytopenia syndrome virus (SFTSV) transmission among healthcare workers (HCWs) after contact with an index patient. ...The aim of this study was to determine whether exposure to blood or bloody respiratory secretion is associated with human-to-human transmission of SFTSV.
Eleven days after the index patient died, two HCWs who had close exposure to the patient presented with typical symptoms of SFTS. An epidemiological investigation was conducted on all 25 HCWs who had been in close contact with the index patient. Clinical and laboratory data were collected, and transmission rate before and after the index patient had haemorrhagic manifestations was analysed.
Among 25 HCWs who had direct contact with the index patient, five HCWs were confirmed to have SFTS. All five HCWs had contact to blood or bloody respiratory secretions of the index patient without adequate use of personal protective equipment (PPE). No HCW with contact before haemorrhagic manifestations of the index patient contracted SFTS. Overall, the transmission rate was higher for HCWs who had contact after the index patient had haemorrhagic manifestations (33.3%, five of 15 HCWs, vs. 0%, zero of ten HCWs, p 0.041).
In HCWs who are inadequately protected, person-to-person transmission of SFTSV may be associated with contact with blood or bloody respiratory secretions. Therefore, universal precaution and full PPE is highly recommended for protection against SFTSV when there are signs of bleeding.
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