The finding that sequence-specific gene silencing occurs in response to the presence of double-stranded RNAs has had an enormous impact on biology, uncovering an unsuspected level of regulation of ...gene expression. This process, known as RNA interference (RNAi) or RNA silencing, involves small non-coding RNAs, which associate with nuclease-containing regulatory complexes and then pair with complementary messenger RNA targets, thereby preventing the expression of these mRNAs. Remarkable progress has been made towards understanding the underlying mechanisms of RNAi, raising the prospect of deciphering the 'RNAi code' that, like transcription factors, allows the fine-tuning and networking of complex suites of gene activity, thereby specifying cellular physiology and development.
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DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background
Neoadjuvant chemotherapy (NAC) represents a promising alternative to pancreatic ductal adenocarcinoma (PDAC) planned resection, but the survival impact remains undefined. To assess the ...feasibility and survival outcomes of NAC with gemcitabine and S1 (GS) for PDAC planned resection by prospective study.
Methods
Patients with resectable or borderline resectable PDAC received 2 cycles of NAC-GS and were offered curative resection followed by gemcitabine adjuvant. The primary endpoint was 2-year overall survival (OS). Adverse events during NAC, radiological and tumor marker responses, resection rate, and surgical safety were evaluated as secondary endpoints (UMIN000004148).
Results
We enrolled 104 patients between 2010 and 2012, with 101 patients treated using NAC-GS as the full analysis set (FAS). Of the 101 patients, 88% received the planned 2 cycles of NAC. Grade 3 neutropenia was common (35%). Radiological partial response and decreased carbohydrate antigen 19-9 concentration (> 50% decrease) were noted in 13% and 41%, respectively. R0/1 resections with M0 were performed in 65 patients without surgical mortality. Of the 65 patients, 44 received planned gemcitabine adjuvant for 6 months as the on-protocol cohort. The primary endpoint for the 2-year OS rate was 55.9% in the FAS (
n
= 101) and 74.6% in the on-protocol cohort (
n
= 44).
Conclusions
NAC-GS was feasible and actively prolonged survival following PDAC planned resection. Randomized control trials are needed to further clarify the survival benefit of NAC-GS in addition to surgery followed by adjuvant therapy.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Summary
Background
Pre‐operative tissue diagnosis for suspected malignant biliary strictures remains challenging.
Aim
To develop evidence‐based consensus statements on endoscopic tissue acquisition ...for biliary strictures.
Methods
The initial draft of statements was prepared following a systematic literature review. A committee of 20 experts from Asia‐Pacific region then reviewed, discussed, and modified the statements. Two rounds of independent voting were conducted to reach a final version. Consensus was considered to be achieved when 80% or more of voting members voted “agree completely” or “agree with some reservation.”
Results
Eleven statements achieved consensus. The choice of tissue sampling modalities for biliary strictures depends on the clinical setting, the location of lesion, and availability of expertise. Detailed radiological and endoscopic evaluation is useful to guide the selection of appropriate tissue acquisition technique. Standard intraductal biliary brushing and/or forceps biopsy is the first option when endoscopic biliary drainage is required with an overall (range) sensitivity and specificity of 45% (26%‐72%) and 99% (98%‐100%), and 48% (15%‐100%) and 99% (97%‐100%), respectively, in diagnosing malignant biliary strictures. Probe‐based confocal laser endomicroscopy and fluorescence in situ hybridisation using 4 fluorescent‐labelled probes targeting chromosomes 3, 7, 17 and 9p21 locus may be added to improve the diagnostic yield. Cholangioscopy‐guided biopsy and EUS‐guided tissue acquisition can be considered after prior negative conventional tissue sampling with an overall (range) sensitivity and specificity of 60% (38%‐88%) and 98% (83%‐100%), and 80% (46%‐100%) and 97% (92%‐100%), respectively, in diagnosing malignant biliary strictures.
Conclusion
These consensus statements provide evidence‐based recommendations for endoscopic tissue acquisition of biliary strictures.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Purpose
This study sought to discern the clinical outcomes of intensity-modulated radiation therapy (IMRT) administered to the spine in patients who had undergone previous radiotherapy.
Methods
A ...total of 81 sites of 74 patients who underwent previous radiotherapy administered to the spine or peri-spine and subsequently received IMRT for the spine were analyzed in this study. The prescribed dose of 80 Gy in a biologically effective dose (BED) of
α
/
β
= 10 (BED
10
) was set as the planning target volume. The constraint for the spinal cord and cauda equine was
D
0.1 cc
≤ 100 Gy and ≤ 150 Gy of BED for re-irradiation alone and the total irradiation dose, respectively.
Results
The median follow-up period was 10.1 (0.9–92.1) months after re-irradiation, while the median interval from the last day of the previous radiotherapy to the time of re-irradiation was 15.6 (0.4–210.1) months. Separately, the median prescript dose of re-irradiation was 78.0 (28.0–104.9) of BED
10
. The median survival time in this study was 13.9 months, with 1-, 3-, and 5-year overall survival rates of 53.7%, 29.3%, and 26.6%, respectively. The 1-, 3-, and 5-year local control rates were 90.8%, 84.0%, and 84.0%, respectively. Neurotoxicity was observed in two of 72 treatments (2.8%) assessed after re-irradiation.
Conclusion
Re-irradiation for the spine using IMRT seems well-tolerated. Definitive re-irradiation can be a feasible treatment option in patients with the potential for a good prognosis.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Observing wear debris during friction is crucial for comprehending the wear behavior of lubrication systems. Despite various techniques attempted for observation, a persistent challenge is the ...oversight of wear debris with a diameter less than 1 μm, mainly due to limitations in measurement systems. Consequently, we still lack a comprehensive understanding of whether these small particles can infiltrate contact points and serve as abrasives. In this study, we conducted in-situ friction tests to investigate the entrainment of imitation wear particles at the contact point under boundary lubrication conditions. These imitation wear particles were glass beads with diameters of approximately 0.8 μm, 1.0 μm, and 3.0 μm, respectively. To address optical limitations, we stained these particles using silane coupling to attach Rhodamine B to the glass beads. We examined the effect of particle diameter on entrainment numbers under varying outside oil film thicknesses. The results showed that the entrainment number was highest when the outside oil film thickness matched the particle diameter. This clearly indicated that the outside oil film thickness significantly influenced the entrainment of particles.