Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease with an increasing case number and extensive geographical expansion, raising concerns locally and globally; ...however, the description of its clinical features needs to be addressed by large studies. We aimed to determine all the clinical features of SFTS in a large population of patients in an endemic area.
In this prospective observational study, data were collected on patients admitted to the People's Liberation Army Hospital in Xinyang, Henan Province, China, with laboratory-diagnosed SFTS. Demographic, clinical, laboratory, and treatment data were collected for each patient, and patients were followed up within 2 weeks after discharge or discontinuation of treatment. The association between each demographic, clinical, and laboratory variable with a fatal outcome was assessed. A clinical scoring model was designed for the early prediction of a fatal outcome, and the effect of treatment on outcome was analysed.
Between April 1, 2011, and Oct 31, 2017, 2096 patients with laboratory-confirmed SFTS were admitted. Mean age at admission was 61·4 years (SD 12·2) and 1239 (59%) patients were female. The case fatality rate (CFR) was 16·2% (95% CI 14·6–17·8). A higher risk was associated with being male (unadjusted odds ratio OR 1·45, 95% CI 1·15–1·83; p=0·002), older age (for a 10-year increase, unadjusted OR 1·82, 95% CI 1·62–2·04; p<0·0001), longer delay in admission (for every extra day taken before admission to hospital, unadjusted OR 1·18, 1·12–1·24; p<0·0001), presence of diarrhoea (adjusted OR 1·44, 1·12–1·87; p=0·005) or dyspnoea (adjusted OR 8·35, 5·97–11·69; p<0·0001), and development of haemorrhagic signs (adjusted OR 2·79, 95% CI 2·18–3·57; p<0·0001) or neurological symptoms (adjusted OR 30·26, 21·39–42·81; p<0·0001). Laboratory variables that were associated with death included abnormal concentrations of lactate dehydrogenase, aspartate aminotransferase, and blood urea nitrogen, and abnormal neutrophil percentage, which together with age and neurological symptoms were combined in the clinical scoring system. A total score of more than 8 was the optimal threshold to predict risk of death for patients who were evaluated within 6 days after symptom onset (area under the curve 0·879, 95% CI 0·855–0·902). For all participants, viraemia was a strong predictor of fatal outcome (all p<0·0001). Ribavirin therapy was effective in reducing CFR from 6·25% (15 of 240 participants) to 1·16% (two of 173 participants), but only in patients with a viral load below 1×106 copies per mL (hazard ratio 9·72, 95% CI 1·30–72·87; p=0·027).
The changing epidemiological features and high CFR of SFTS underscore the necessity of continued surveillance. Early prediction of fatal outcome can be attained by monitoring of clinical and laboratory data. Ribavirin should be applied early, with best results achieved before the viral load reaches 1 × 106 copies per mL.
National Natural Science Foundation of China.
Whether ultra‐processed food consumption is associated with the risk of pancreatic cancer has not been determined. We performed a prospective study to fill this gap. A population‐based cohort of 98 ...265 American adults was identified from the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Ultra‐processed foods were defined by the NOVA classification. Cox regression was used to estimate hazard ratios (HRs) for pancreatic cancer incidence. Subgroup analysis was performed to identify the potential effect modifiers. During a mean follow‐up of 8.86 years, 387 pancreatic cancer cases occurred. High consumption of ultra‐processed foods was found to be associated with an increased risk of pancreatic cancer (fully adjusted HRquartile 4 vs 1:1.49; 95% confidence interval CI: 1.07‐2.07; Ptrend = .021) in a linear dose‐response manner (Pnonlinearity = .075). Subgroup analysis further found that the positive association of ultra‐processed food consumption with the risk of pancreatic cancer was more pronounced in subjects aged <65 years (HRquartile 4 vs 1:2.17; 95% CI: 1.14‐4.15) than in those aged ≥65 years (HRquartile 4 vs 1:1.32; 95% CI: 0.88‐1.94), though the interaction test failed to achieve the statistical significance (Pinteraction = .061). These findings suggest that reducing ultra‐processed food consumption may be beneficial in decreasing pancreatic cancer incidence.
What's new?
“Ultra‐processed” foods, industrially formulated products consisting of ingredients extracted from foods, but no intact foods, now make up as much as 58.5% of Americans' daily calorie intake. Think frozen meals, hot dogs and packaged snacks. Here, the authors investigate the relationship between ultra‐processed foods and pancreatic cancer in a cohort of 98 265 American adults. High consumption of ultra‐processed foods was associated with increased risk of pancreatic cancer, and the association was more pronounced for those under age 65.
Bioinspired electronics are rapidly promoting advances in artificial intelligence. Emerging AI applications, e.g., autopilot and robotics, increasingly spur the development of power devices with new ...forms. Here, we present a strain-controlled power device that can directly modulate the output power responses to external strain at a rapid speed, as inspired by human reflex. By using the cantilever-structured AlGaN/AlN/GaN-based high electron mobility transistor, the device can control significant output power modulation (2.30-2.72 × 10
W cm
) with weak mechanical stimuli (0-16 mN) at a gate bias of 1 V. We further demonstrate the acceleration-feedback-controlled power application, and prove that the output power can be effectively adjusted at real-time in response to acceleration changes, i.e., ▵P of 72.78-132.89 W cm
at an acceleration of 1-5 G at a supply voltage of 15 V. Looking forward, the device will have great significance in a wide range of AI applications, including autopilot, robotics, and human-machine interfaces.
We demonstrate maintenance and transmission of severe fever with thrombocytopenia syndrome virus by Haemaphysalis longicornis ticks in the larva, nymph, and adult stages with dissemination in ...salivary gland, midgut, and ovarian tissues. The H. longicornis tick is a competent vector to transmit this virus in both transovarial and transstadial modes.
Metal‐based thermally activated delayed fluorescence (TADF) is conceived to inherit the advantages of both phosphorescent metal complexes and purely organic TADF compounds for high‐performance ...electroluminescence. Herein a panel of new TADF Au(I) emitters has been designed and synthesized by using carbazole and pyrazine‐fused nitrogen‐heterocyclic carbene (NHC) as the donor and acceptor ligands, respectively. Single‐crystal X‐ray structures show linear molecular shape and coplanar arrangement of the donor and acceptor with small dihedral angles of <6.5°. The coplanar orientation and appropriate separation of the HOMO and LUMO in this type of molecules favour the formation of charge‐transfer excited state with appreciable oscillator strength. Together with a minor but essential heavy atom effect of Au ion, the complexes in doped films exhibit highly efficient (Φ∼0.9) and short‐lived (<1 μs) green emissions via TADF. Computational studies on this class of emitters have been performed to decipher the key reverse intersystem crossing (RISC) pathway. In addition to a small energy splitting between the lowest singlet and triplet excited states (ΔEST), the spin‐orbit coupling (SOC) effect is found to be larger at a specific torsion angle between the donor and acceptor planes which favours the RISC process the most. This work provides an alternative molecular design to TADF Au(I) carbene emitters for OLED application.
A novel gold(I)‐carbene complex shows high efficiency thermally activated delayed fluorescence (TADF) and sub‐microsecond emission lifetime. The use of conventional pyrazine‐fused nitrogen‐heterocyclic carbene (NHC) ligand as the acceptor provides an alternative molecular design to TADF Au(I) carbene emitters.
Epithelial-mesenchymal transition of tubular epithelial cells, which is characterized by a loss of epithelial cell characteristics and a gain of ECM-producing myofibroblast characteristics, is an ...essential mechanism that is involved in tubulointerstitial fibrosis, an important component of the renal injury that is associated with diabetic nephropathy. Under diabetic conditions, p38 MAPK activation has been reported in glomeruli and mesangial cells; however, studies on p38 MAPK in TECs are lacking. In this study, the role of p38 MAPK in AP-1 activation and in the EMT in the human proximal tubular epithelial cell line (HK-2) under high glucose concentration conditions is investigated.
A vector for small interfering RNA that targets p38 MAPK was constructed; the cells were then either transfected with p38 siRNA or pretreated with a chemical inhibitor of AP-1 and incubated with low glucose plus TGF-β1 or high glucose for 48 h. Cells that were not transfected or pretreated and were exposed to low glucose with or without TGF-β1 or high glucose for 48 h were considered to be the controls. We found that high glucose induced an increase in TGF-β1. And high glucose-induced p38 MAPK activation was inhibited by p38 siRNA (P<0.05). A significant decline in E-cadherin and CK expression and a notable increase in vimentin and α-SMA were detected when exposed to low glucose with TGF-β1 or high glucose, and a significant raise of secreted fibronectin were detected when exposed to high glucose; whereas these changes were reversed when the cells were treated with p38 siRNA or AP-1 inhibitor (P<0.05). AP-1 activity levels and Snail expression were up-regulated under high glucose conditions but were markedly down-regulated through knockdown of p38 MAPK with p38 siRNA or pretreatment with AP-1 inhibitor (P<0.05).
This study suggests that p38 MAPK may play an important role in the high glucose-induced EMT by activating AP-1 in tubular epithelial cells.
We aim to evaluate the relationship between the use of metformin and the risk of pancreatic cancer in type 2 diabetes patients.
We systematically searched the observational studies on PubMed, Embase, ...Web of Science, Cochrane Library, clinicalrials.gov, and CNKI databases, extracted relevant data, combined the OR value and 95% CI using the random effect model, and conducted a sensitivity analysis, subgroup analysis, and meta-regression to evaluate the size and stability of this relationship.
Twenty-nine studies from twenty-four articles met our inclusion criteria, including more than 2 million subjects. Overall analysis showed that compared with no use of metformin, the use of metformin could reduce the risk of pancreatic cancer in patients with type 2 diabetes (OR = 0.82, 95% CI (0.69, 0.98)). Subgroup analysis showed that compared with the use of hypoglycemic drugs, the use of metformin could reduce the risk of pancreatic cancer in patients with type 2 diabetes (OR = 0.79, 95% CI (0.66, 0.94)). However, compared with no drugs or only diet therapy, metformin users might increase the risk of pancreatic cancer (OR = 2.19, 95% CI (1.08, 4.44)). Sensitivity analysis confirmed the stability of the study, and there was no significant publication bias.
Compared with the no-use of metformin, metformin users with diabetes can reduce the risk of pancreatic cancer. More research is needed to prove it works.
Nonalcoholic fatty liver disease (NAFLD) is the second major chronic liver disease world-wide and growing. Current medical treatment of NAFLD is not effective, and there is an urgent need to find new ...effective drugs. Liraglutide is now the first-line treatment for type 2 diabetes mellitus (T2DM) with promise, according to recent reports, to mitigate the fatty degeneration of the liver. The investigators of the current study discern if liraglutide reduces non-alcoholic fatty liver disease (NAFLD) induced by a high-fat diet using mice via modulating Kupffer cells M2 polarization in the liver. The mice underwent four weeks of intraperitoneal injections of liraglutide (0.6 mg/kg body weight). In the NAFLD model used in this study, the liver index, the body weight, and the serum levels of ALT, AST, total cholesterol, and triglycerides were meaningfully improved. In sections using H&E and Oil Red O staining, hepatic steatosis was significantly improved. Liraglutide decreased liver inflammation and the inflammatory properties of Kupffer cells in the NAFLD mouse model and there was a higher ratio of M2/M1 Kupffer cells. In vitro studies found that Liraglutide treatment modulates Kupffer cells to M2-like activation via the cAMP-PKA-STAT3 signaling pathway. The perilous effects of a high-fat diet were alleviated by liraglutide, including hepatic steatosis, by modulating Kupffer cells M2 polarization via the cAMP-PKA-STAT3 signaling pathway. Liraglutide can indeed reverse the negative effects of NAFLD.
•Current medical treatment of NAFLD is not effective, and there is an urgent need to find new effective drugs.•In our study, Liraglutide, now the first-line treatment for type 2 diabetes mellitus, reduces high-fat diet-induced NAFLD in a mice model.•Liraglutide alleviated hepatic steatosis induced by a high-fat diet by modulating Kupffer cells M2 polarization via the cAMP-PKA-STAT3 signaling pathway.
ABSTRACT
Subduction recycling of sediments plays a key role in the geochemical evolution of Earth. The presence of recycled terrigenous sediments in upwelling plumes has been cited to explain the EM2 ...signature in ocean island volcanics, characterized by particularly high 87Sr/86Sr (>0.706). However, the origin of such isotopic anomalies in continental regions and the role of subducted sediments in the subcontinental lithospheric mantle (SCLM) remain unclear. The Himalaya–Tibet orogen is one of the world’s best places for deciphering continental subduction and the fate of subducted crustal materials in the mantle. Here we present a systematic study of the geochronology, mineral chemistry (especially clinopyroxene), whole-rock chemistry and Sr–Nd–Pb–Hf–O isotopic compositions of Cenozoic potassic–ultrapotassic lavas from the western Kunlun area of northwestern Tibet. New secondary ion mass spectrometry (SIMS) zircon U–Pb dating, coupled with published age results, constrain the timing of volcanism from ~8.3 Ma to the present. These lavas show geochemical characteristics that closely resemble the EM2 mantle end-member represented by the Samoan hotspot. Both whole rocks and individual magmatic clinopyroxenes display arc-like trace-element patterns and remarkably enriched Sr–Nd–Pb–Hf isotope compositions (87Sr/86Sr ≥ 0.7080; εNd ≤ −4.8; 206Pb/204Pb ≥ 18.704; εHf ≤ −2.6). Together with high zircon δ18O values (6.3–10.4‰), the data point to a mantle source enriched by recycled sedimentary materials. Geochemical modeling and geophysical evidence further indicate that the sediments were directly derived from the subducted Indian continental lithosphere during India–Eurasia collision. Partial melting models assuming a hybridized mantle source that contains ~5% Indian continental crust suggest that the primary melts of the potassic–ultrapotassic lavas could be formed by melting of a phlogopite-bearing garnet lherzolite at low melting degrees (1–5%). The magma geochemistry is consistent with the model of mélange melting, implying that the subducted sediments may detach from the downgoing Indian slab and rise up diapirically into the overlying mantle lithosphere. Unlike traditional models of subducted sediments entering the deep mantle, the western Kunlun EM2-like lavas reveal that subducted sediments can be rapidly recycled into the SCLM during continental subduction (probably <50 Myr). We suggest that the SCLM could be an important reservoir for subducted sediments. The findings are important to our understanding of mantle circulation rates and chemical heterogeneities.
Most subspace-based algorithms need exact array manifold for direction of arrival (DOA) estimation, while, in practical applications, the gain-phases of different array elements are usually ...inconsistent, degrading their estimation performance. In this paper, a novel low-complexity 2D DOA and gain-phase error estimation algorithm is proposed by adding auxiliary array elements in a uniform rectangular array (URA). Firstly, the URA is modeled as the Kronecker product of two uniform linear arrays (ULAs) to decouple the 2D DOA estimation. Then, several well-calibrated auxiliary array elements are added in the two ULAs, based on which the rotation invariant factor of the URA destroyed by the gain-phase error is reconstructed by solving constrained optimization problems. Lastly, ESPRIT is used to estimate the 2-D DOA and the gain-phase error coefficients. The closed-form expressions of the estimation CRBs are also derived, providing insight into the impact of gain-phase error on DOA estimation. Simulation results are used to validate the effectiveness of the proposed algorithm and the correctness of the theoretical analysis.
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