Mammalian sirtuin 1 (SIRT1) has connected to an ever widening circle of activities that encompass cellular stress resistance, energy metabolism and tumorigenesis. However, underlying mechanisms ...leading to oncogenic SIRT1 overexpression are less understood. In this study, we identified SIRT1 regulatory microRNA (miRNA) and its function in hepatocellular carcinoma (HCC). Aberrant SIRT1 overexpression was demonstrated in a subset of human HCCs. SIRT1 knockdown suppressed HCC cell growth by transcriptional deregulation of cell cycle proteins. This led to hypophosphorylation of pRb, which inactivated E2F/DP1 target gene transcription, and thereby caused significant increase of HCC cells to remain in the G1/S phase. A comprehensive miRNA profiling analysis indentified five putative endogenous miRNAs that are significantly downregulated in HCC. Ectopic expression of miRNA mimics evidenced miR-29c to suppress SIRT1 in HCC cells. Notably, ectopic miR-29c expression repressed cancer cell growth and proliferation, and it recapitulated SIRT1 knockdown effects in HCC cells. In addition, miR-29c expression was downregulated in a large cohort of HCC patients, and low expression of miR-29c was significantly associated with poor prognosis of HCC patients. Taken together, we demonstrated that miR-29c suppresses oncogenic SIRT1 by way of binding to 3'-untranslated region of SIRT1 mRNA causing translational inhibition in liver cancer cells. The loss or suppression of miR-29c may cause aberrant SIRT1 overexpression and promotes liver tumorigenesis. Overall, we suggest that miR-29c functions as a tumor suppressor by regulating abnormal SIRT1 activity in liver.
Deep neural networks, especially convolutional neural networks, have been successfully applied to image denoising tasks. Along with advances in network architectures, many attempts have been made to ...find an alternative loss function to the widely used L1-loss and L2-loss. However, the perception-distortion tradeoff was recently demonstrated; thus, advanced loss functions such as adversarial loss from generative adversarial networks can only improve the perceptual image quality at the expense of distortion. This Letter shows that distortion can be further decreased when an image denoising network is trained using modified versions of ground-truth (GT) (defined as pseudo-ground-truth (PGT)) images that are obtained by combining the original GT images and initially denoised images. Experimental results show that the proposed denoising network that is trained to predict both PGT and GT images produces denoised images closer to GT images.
mTORC2 phosphorylates AKT in a hydrophobic motif site that is a biomarker of insulin sensitivity. In brown adipocytes, mTORC2 regulates glucose and lipid metabolism, however the mechanism has been ...unclear because downstream AKT signaling appears unaffected by mTORC2 loss. Here, by applying immunoblotting, targeted phosphoproteomics and metabolite profiling, we identify ATP-citrate lyase (ACLY) as a distinctly mTORC2-sensitive AKT substrate in brown preadipocytes. mTORC2 appears dispensable for most other AKT actions examined, indicating a previously unappreciated selectivity in mTORC2-AKT signaling. Rescue experiments suggest brown preadipocytes require the mTORC2/AKT/ACLY pathway to induce PPAR-gamma and establish the epigenetic landscape during differentiation. Evidence in mature brown adipocytes also suggests mTORC2 acts through ACLY to increase carbohydrate response element binding protein (ChREBP) activity, histone acetylation, and gluco-lipogenic gene expression. Substrate utilization studies additionally implicate mTORC2 in promoting acetyl-CoA synthesis from acetate through acetyl-CoA synthetase 2 (ACSS2). These data suggest that a principal mTORC2 action is controlling nuclear-cytoplasmic acetyl-CoA synthesis.
Accurate diagnosis of Helicobacter pylori(H. pylori) infection is a crucial part in the effective management of many gastroduodenal diseases. Several invasive and non-invasive diagnostic tests are ...available for the detection of H. pylori and each test has its usefulness and limitations in different clinical situations. Although none can be considered as a single gold standard in clinical practice,several techniques have been developed to give the more reliable results. Invasive tests are performed via endoscopic biopsy specimens and these tests include histology,culture,rapid urease test as well as molecular methods. Developments of endoscopic equipment also contribute to the real-time diagnosis of H. pylori during endoscopy. Urea breathingtest and stool antigen test are most widely used noninvasive tests,whereas serology is useful in screening and epidemiological studies. Molecular methods have been used in variable specimens other than gastric mucosa. More than detection of H. pylori infection,several tests are introduced into the evaluation of virulence factors and antibiotic sensitivity of H. pylori,as well as screening precancerous lesions and gastric cancer. The aim of this article is to review the current options and novel developments of diagnostic tests and their applications in different clinical conditions or for specific purposes.
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.
Background
The fate of the portal vein (PV) after pancreatoduodenectomy, especially its long‐term patency and associated complications, has received little attention. The aim of this study was to ...explore the long‐term patency rate of the PV after pancreatoduodenectomy, focusing on risk factors for PV stenosis/occlusion and associated complications.
Methods
Serial CT images of patients who underwent pancreatoduodenectomy for periampullary cancer between January 2000 and June 2012 in a single institution were evaluated for PV stenosis or occlusion.
Results
A total of 826 patients were enrolled. The PV stenosis/occlusion rate after pancreatoduodenectomy was 19·6 per cent and the 5‐year patency rate 69·9 per cent. The most frequent cause of PV stenosis/occlusion was local recurrence followed by postoperative change and PV thrombosis. Patients who underwent PV resection had a higher PV stenosis/occlusion rate than those who did not (51 versus 17·4 per cent; P < 0·001). The 3‐year patency rate was highest in patients with cancer of the ampulla of Vater and lowest in patients with pancreatic cancer (91·9 versus 55·5 per cent respectively; P < 0·001). Multivariable analysis showed that risk factors for PV stenosis/occlusion included primary tumour location, chemoradiotherapy and PV resection. PV stenosis or occlusion without disease recurrence was observed in 17·3 per cent of the patients. PV resection and grade B or C pancreatic fistula were independent risk factors for PV stenosis/occlusion. Among 162 patients with PV stenosis or occlusion, five (3·1 per cent) had fatal recurrent gastrointestinal bleeding.
Conclusion
PV stenosis or occlusion is common after pancreatoduodenectomy, particularly if the PV has been resected and/or chemoradiotherapy was given after surgery. Although recurrence is the most frequent cause of PV stenosis/occlusion, this complication is found in a significant proportion of patients without disease recurrence.
Occlusion common with or without recurrence
Abstract
Topological superconductors (TSCs) are unconventional superconductors with bulk superconducting gap and in-gap Majorana states on the boundary that may be used as topological qubits for ...quantum computation. Despite their importance in both fundamental research and applications, natural TSCs are very rare. Here, combining state of the art synchrotron and laser-based angle-resolved photoemission spectroscopy, we investigated a stoichiometric transition metal dichalcogenide (TMD), 2M-WS
2
with a superconducting transition temperature of 8.8 K (the highest among all TMDs in the natural form up to date) and observed distinctive topological surface states (TSSs). Furthermore, in the superconducting state, we found that the TSSs acquired a nodeless superconducting gap with similar magnitude as that of the bulk states. These discoveries not only evidence 2M-WS
2
as an intrinsic TSC without the need of sensitive composition tuning or sophisticated heterostructures fabrication, but also provide an ideal platform for device applications thanks to its van der Waals layered structure.
Summary
Background
Non‐alcoholic fatty liver disease (NAFLD) is associated with colorectal neoplasia. Yet, NAFLD ranges from simple steatosis to steatohepatitis with advanced fibrosis.
Aim
To ...investigate the risk of colorectal neoplasia according to the presence and severity of NAFLD.
Methods
A total of 26 540 asymptomatic adults who underwent same day first‐time colonoscopy and abdominal ultrasonography as a health check‐up programme were analysed. NAFLD was diagnosed by ultrasonography. Advanced colorectal neoplasia was defined as an invasive cancer or adenoma that was at least 10 mm in diameter, had high‐grade dysplasia, or had villous histological characteristics or any combination thereof.
Results
NAFLD patients had a higher prevalence of any colorectal neoplasia (38.0% vs. 28.9%) and advanced colorectal neoplasia (2.8% vs. 1.9%) compared to those without NAFLD. In a multivariable model adjusted for age, sex, smoking, alcohol, body mass index, first‐degree family history of colorectal cancer, aspirin use and metabolic factors, the odd ratios comparing patients with NAFLD to those without were 1.10 95% confidence interval (CI): 1.03–1.17 for any colorectal neoplasia and 1.21 (95% CI: 0.99–1.47) for advanced colorectal neoplasia. When NAFLD patients were further stratified according to the non‐invasive parameters of liver disease severity, the risk of any colorectal neoplasia or advanced colorectal neoplasia was higher for those with severe liver diseases than those with mild liver diseases.
Conclusions
The presence and severity of NAFLD were closely associated with any colorectal neoplasia and advanced colorectal neoplasia, suggesting that clinicians should be aware of the increased risk of colorectal neoplasia in patients with NAFLD.
Linked ContentThis article is linked to Ahn et al, and Kountouras et al papers. To view these articles visit https://doi.org/10.1111/apt.13911 and https://doi.org/10.1111/apt.13900.
Background and purpose
We investigated the effect of celecoxib, a selective inhibitor of cyclo‐oxygenase 2, in patients with intracerebral hemorrhage (ICH).
Methods
We conducted a multicenter, ...randomized, controlled, and open with blinded end‐point trial of 44 Korean patients 18 years or older with ICH within 24 h of onset. The intervention group (n = 20) received celecoxib (400 mg twice a day) for 14 days. The control group (n = 24) received the standard medical treatment for ICH. The primary end‐point was the number of patients with a change in the volume of perihematomal edema (PHE) from the 1st to the 7th ± 1 day (cut‐off value, 20%).
Results
The time from onset to computed tomography scan slightly differed between groups (177 ± 160 min for control vs. 297 ± 305 min for the celecoxib group; P = 0.10). In the primary end‐point analysis using cut‐off values, there was a significant shift to reduced expansion of PHE in the celecoxib group (P = 0.005). With respect to the secondary end‐points, there was also a significant shift to reduced expansion of ICH in the celecoxib group (P = 0.046). In addition, the expansion rate of PHE at follow‐up tended to be higher in the control group than in the celecoxib group (90.6 ± 91.7% vs. 44.4 ± 64.9%; P = 0.058).
Conclusions
In our small, pilot trial, administration of celecoxib in the acute stage of ICH was associated with a smaller expansion of PHE than that observed in controls.
We compared late thoracic radiotherapy (TRT) with early TRT in the treatment of limited-disease small-cell lung cancer (LD-SCLC).
Patients with LD-SCLC received four cycles of etoposide plus ...cisplatin every 21 days. Patients were randomly assigned to receive either TRT administered concurrently with the first cycle (early TRT) or the third cycle (late TRT) of chemotherapy. The primary end point was complete response rate.
Two hundred twenty-two patients were randomly assigned. Late TRT was not inferior to early TRT in terms of the complete response rate (early versus late; 36.0% versus 38.0%). Other efficacy measures including overall survival median, 24.1 versus 26.8 months; hazard ratio (HR) 0.90; 95% CI 0.18–1.62 and progression-free survival (median, 12.4 versus 11.2 months; HR 1.10; 95% CI 0.37–1.84) were not different between two arms. No statistical difference was noted in the pattern of treatment failures. However, neutropenic fever occurred more commonly in the early TRT arm than the late TRT arm (21.6% versus 10.2%; P = 0.02).
In LD-SCLC treatment, TRT starting in the third cycle of chemotherapy seemed to be noninferior to early TRT, and had a more favorable profile with regard to neutropenic fever.
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