Classical first-passage times under restart are used in a wide variety of models, yet the quantum version of the problem still misses key concepts. We study the quantum hitting time with restart ...using a monitored quantum walk. The restart strategy eliminates the problem of dark states, i.e., cases where the particle evades detection, while maintaining the ballistic propagation which is important for a fast search. We find profound effects of quantum oscillations on the restart problem, namely, a type of instability of the mean detection time, and optimal restart times that form staircases, with sudden drops as the rate of sampling is modified. In the absence of restart and in the Zeno limit, the detection of the walker is not possible, and we examine how restart overcomes this well-known problem, showing that the optimal restart time becomes insensitive to the sampling period.
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CMK, CTK, FMFMET, IJS, NUK, PNG, UL, UM
Recent evidence highlights long noncoding RNAs (lncRNAs) as crucial regulators of cancer biology that contribute to tumorigenesis. LncRNA TUG1 was initially detected in a genomic screen for genes ...upregulated in response to taurine treatment in developing mouse retinal cells. Our previous study showed that TUG1 could affect cell proliferation through epigenetically regulating HOXB7 in human non-small cell lung cancer. However, the clinical significance and potential role of TUG1 in GC remains unclear. In this study, we found that TUG1 is significantly increased and is correlated with outcomes in gastric cancer (GC). Further experiments revealed that knockdown of TUG1 repressed GC proliferation both in vitro and in vivo. Mechanistic investigations showed that TUG1 has a key role in G0/G1 arrest. We further demonstrated that TUG1 was associated with PRC2 and that this association was required for epigenetic repression of cyclin-dependent protein kinase inhibitors, including p15, p16, p21, p27 and p57, thus contributing to the regulation of GC cell cycle and proliferation. Together, our results suggest that TUG1, as a regulator of proliferation, may serve as a candidate prognostic biomarker and target for new therapies in human GC.
The rapid development of technology has ushered in a new era of minimally invasive and intelligent surgery.Minimally invasive surgeries, such as small incision, percutaneous surgery, arthroscopic ...surgery, and endoscopic surgery, have contributed to less invasive surgical trauma, better cosmesis, and faster recovery. Furthermore, the recent adoption of artificial intelligence (AI) has introduced new assistances and tools for minimally invasive foot and ankle surgery. By the help of advanced AI algorithms, surgeons can accurately make diagnose and personalized treatment strategies. The application of computer-assisted navigation systems and robotics has facilitated precise surgical procedures and real-time confirmation of surgical outcomes. Foot and ankle surgery has lagged behind other surgical specialties in adopting these advancements. Currently, the integration of various forms of minimally invasive surgery and AI technology stands as the main trend in the development of foot and ankle surgery. It is believ
This study evaluates the utility of sedimentary mercury (Hg) contents as a proxy for fingerprinting ancient massive volcanism, which is often associated with biogeochemical perturbations. Herein we ...present new Hg geochemical data from anoxic marine basins across the Toarcian Oceanic Anoxic Event (T-OAE; ∼183 Ma) as a test of the complex Hg cycle. The T-OAE was likely initiated by the main eruptive phase of the Karoo–Ferrar large igneous province, which caused a subsequent cascade of environmental perturbations and resulting mass extinction. At present the leading interpretation of sedimentary Hg anomalies has been volcanogenic outgassing as the primary source. Our study and compilation results suggest, however, that Hg/TOC anomalies were restricted to shallow-water, and/or proximal environments, while deep-water, more distal depositional settings document no significant Hg-related anomalies. Furthermore, asynchronous stratigraphic deviations in Hg enrichments favor terrestrially sourced materials and local redox variability, rather than direct volcanogenic emissions, as a primary control mechanism. Additionally, Hg isotope signatures from our only study site documenting an Hg anomaly are also consistent with a terrestrial Hg origin during the T-OAE. Therefore, our results suggest that Hg anomalies in the geological record need to be re-evaluated as a “smoking gun” proxy that only infers volcanogenic inputs.
•Mercury concentration and isotopes from anoxic basins across the Toarcian OAE.•Compilation shows mercury anomalies are observed near landmasses.•Compilation suggests that Hg is dominantly delivered via terrestrial sources.•Mercury isotopes from one section agree with terrestrial source delivering Hg.•Sedimentary Hg anomalies are not a direct proxy for past volcanism.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ
This research aimed to isolate β‐glycosidase‐producing endophytic fungus in Panax ginseng to achieve biotransformation of ginsenoside Rb1 to ginsenoside C‐K. Of these 15 β‐glucosidase‐producing ...endophytic fungus isolated from ginseng roots, a β‐glucosidase‐producing endophytic fungi GE 17‐18 could hydrolyse major ginsenosides Rb1 to minor ginsenoside C‐K with metabolic pathways: ginsenoside Rb1→ginsenoside Rd→ginsenoside F2→ginsenoside C‐K. Phylogenetic analysis of ITS gene sequences indicated that the strain GE 17‐18 belongs to the genus Arthrinium and is most closely related to Arthrinium sp. HQ832803.1.
Significance and Impact of the Study
This is the first study to provide information of cultivable β‐glycosidase‐producing Endophytic fungus in Panax ginseng. The strain GE 17‐18 has potential to be applied on the preparation for minor ginsenoside C‐K in pharmaceutical industry.
Significance and Impact of the Study: This is the first study to provide information of cultivable β‐glycosidase‐producing Endophytic fungus in Panax ginseng. The strain GE 17‐18 has potential to be applied on the preparation for minor ginsenoside C‐K in pharmaceutical industry.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
This study evaluated maintenance treatment with niraparib, a potent inhibitor of poly(ADP-ribose) polymerase 1/2, in patients with platinum-sensitive recurrent ovarian cancer.
In this phase III, ...double-blind, placebo-controlled study conducted at 30 centers in China, adults with platinum-sensitive recurrent ovarian cancer who had responded to their most recent platinum-containing chemotherapy were randomized 2 : 1 to receive oral niraparib (300 mg/day) or matched placebo until disease progression or unacceptable toxicity (NCT03705156). Following a protocol amendment, patients with a bodyweight <77 kg or a platelet count <150 × 103/μl received 200 mg/day, and all other patients 300 mg/day, as an individualized starting dose (ISD). Randomization was carried out by an interactive web response system and stratified by BRCA mutation, time to recurrence following penultimate chemotherapy, and response to most recent chemotherapy. The primary endpoint was progression-free survival (PFS) assessed by blinded independent central review.
Between 26 September 2017 and 2 February 2019, 265 patients were randomized to receive niraparib (n = 177) or placebo (n = 88); 249 patients received an ISD (300 mg, n = 14; 200 mg, n = 235) as per protocol. In the intention-to-treat population, median PFS was significantly longer for patients receiving niraparib versus placebo: 18.3 95% confidence interval (CI), 10.9-not evaluable versus 5.4 (95% CI, 3.7-5.7) months hazard ratio (HR) = 0.32; 95% CI, 0.23-0.45; P < 0.0001, and a similar PFS benefit was observed in patients receiving an ISD, regardless of BRCA mutation status. Grade ≥3 treatment-emergent adverse events occurred in 50.8% and 19.3% of patients who received niraparib and placebo, respectively; the most common events were neutrophil count decreased (20.3% versus 8.0%) and anemia (14.7% versus 2.3%).
Niraparib maintenance treatment reduced the risk of disease progression or death by 68% and prolonged PFS compared to placebo in patients with platinum-sensitive recurrent ovarian cancer. Individualized niraparib dosing is effective and safe and should be considered standard practice in this setting.
•Chinese patients with platinum-sensitive recurrent ovarian cancer received maintenance niraparib (n = 177) or placebo (n = 88).•Median PFS was longer for niraparib versus placebo: 18.3 versus 5.4 months (HR = 0.32; 95% CI, 0.23-0.45; P < 0.0001).•Niraparib had a similar PFS benefit for 249 patients receiving individualized dosing based on bodyweight and platelet count.•Grade ≥3 treatment-emergent adverse events occurred in 50.8% and 19.3% of patients who received niraparib and placebo, respectively.•In the niraparib group, Grade ≥3 platelet count decreased/thrombocytopenia occurred in 11.3% of patients.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
We present the results of a systematic review and meta-analysis examining outcomes of endovascular coiling of wide-neck and wide-neck bifurcation aneurysms with and without stent assistance. The aim ...of our study was to assess angiographic and clinical outcomes.
We performed a comprehensive literature search for all articles on the endovascular coiling of wide-neck and wide-neck bifurcation aneurysms. Studies meeting our inclusion criteria and abstracted data were selected by 2 independent reviewers. Primary outcomes were >6-month complete or near-complete angiographic occlusion, aneurysm recanalization, and aneurysm retreatment. Secondary outcomes included initial complete or near-complete occlusion, long-term good neurologic outcome, procedure-related morbidity, and procedure-related mortality. Data were analyzed by using random-effects meta-analysis.
In total, 38 studies including 2446 patients with 2556 aneurysms were included. For all wide-neck aneurysms, immediate complete or near-complete occlusion rate was 57.4% (95% CI, 48.1%-66.8%). Follow-up near-complete occlusion rate was 74.5% (95% CI, 68.0%-81.0%). Recanalization and retreatment rates were 9.4% (95% CI, 7.1%-11.7%) and 5.8% (95% CI, 4.1%-7.5%), respectively. Long-term good neurologic outcome was 91.4% (95% CI, 88.5%-94.2%). For wide-neck bifurcation aneurysms, initial complete or near-complete occlusion rate was 60.0% (95% CI, 42.7%-77.3%), long-term complete or near-complete occlusion rate was 71.9% (95% CI, 52.6%-91.1%), and the recanalization and retreatment rates were 9.8% (95% CI, 7.1%-12.5%) and 5.2% (95% CI, 1.9%-8.4%), respectively.
Our study of angiographic and clinical outcomes for patients with wide-neck aneurysms demonstrates that endovascular coiling with or without stent-assisted coiling is safe, with low rates of perioperative morbidity and mortality. Initial and long-term angiographic outcomes were generally satisfactory, but not ideal. These data provide some baseline comparisons against which emergent technologies can be assessed.
Recent evidence indicates that long noncoding RNAs (lncRNAs) have a critical role in the regulation of cellular processes such as differentiation, proliferation, and metastasis. These lncRNAs are ...dysregulated in a variety of cancers and many function as tumor suppressors; however, the regulatory factors involved in silencing lncRNA transcription are poorly understood. In this study, we showed that epigenetic silencing of lncRNA SPRY4 intronic transcript 1 (SPRY4-IT1) occurs in non-small-cell lung cancer (NSCLC) cells through direct transcriptional repression mediated by the Polycomb group protein enhancer of zeste homolog 2 (EZH2). SPRY4-IT1 is derived from an intron within SPRY4, and is upregulated in melanoma cells; knockdown of its expression leads to cell growth arrest, invasion inhibition, and elevated rates of apoptosis. Upon depletion of EZH2 by RNA interference, SPRY4-IT1 expression was restored, and transfection of SPRY4-IT1 into NSCLC cells resulted in a significant antitumoral effect, both in culture and in xenografted nude mice. Moreover, overexpression of SPRY4-IT1 was found to have a key role in the epithelial-mesenchymal transition through the regulation of E-cadherin and vimentin expression. In EZH2-knockdown cells, which characteristically showed impaired cell proliferation and metastasis, the induction of SPRY4-IT1 depletion partially rescued the oncogenic phenotype, suggesting that SPRY4-IT1 repression has an important role in EZH2 oncogenesis. Of most relevance, translation of these findings into human NSCLC tissue samples demonstrated that patients with low levels of SPRY4-IT1 expression had a shorter overall survival time, suggesting that SPRY4-IT1 could be a biomarker for poor prognosis of NSCLC.
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