Notes

Composition, De-oxidizing Action as well as in Vitro Hypoglycemic Action of a Polysaccharide Purified coming from Tricholoma matsutake.
This demonstrated high-throughput material discovery pipeline presents a paradigm for facile and accelerated exploration of MMNCs for a broad range of applications. Copyright © 2020 the Author(s). Published by PNAS.BACKGROUND The success of multi-site collaborative research relies on effective data collection, harmonization and aggregation strategies. Data Coordination Centers (DCCs) serve to facilitate the implementation of these strategies. The utility of a DCC can be particularly relevant for research on rare diseases where collaboration from multiple sites to amass large aggregate data sets is essential. However, approaches to building a DCC have been scarcely documented. METHODS AND MATERIALS The Li-Fraumeni Exploration (LiFE) Consortium's DCC was created using multiple open source packages, including LAM/G Application (Linux, Apache, MySQL, Grails), Extraction-Transformation-Loading (ETL) Pentaho Data Integration Tool, and the Saiku-Mondrian client. PD 0332991 manufacturer This document serves as a resource for building a rare disease DCC for multi-institutional collaborative research. RESULTS The primary scientific and technological objective to create an online central repository into which data from all participating sites could be deposited, harmonized, aggregated, disseminated, and analyzed was completed. The cohort now include 2,193 participants from 6 contributing sites, including 1,354 individuals from families with a pathogenic or likely variant in TP53. Data on cancer diagnoses are also available. Challenges and lessons learned are summarized. CONCLUSION The methods leveraged mitigate challenges associated with successfully developing a DCC's technical infrastructure, data harmonization efforts, communications, and software development and applications. IMPACT These methods can serve as a framework in establishing other collaborative research efforts. Data from the consortium will serve as a great resource for collaborative research to improve knowledge on, and the ability to care for, individuals and families with Li-Fraumeni Syndrome. Copyright ©2020, American Association for Cancer Research.BACKGROUND We aimed to evaluate the utility of p16/Ki-67 dual-stained cytology for triaging HPV-positive women. METHODS HPV-positive women aged ≥ 21 years were recruited in a multicenter prospective observational study between May 2016 and May 2017. The clinical performance of dual-stained cytology, with or without HPV16/18 genotyping, were evaluated for all HPV-positive women to detect cervical intraepithelial neoplasia grade 2 or worse (CIN2+). RESULTS Eight hundred and forty-six HPV-positive women aged ≥ 21 years with valid cervical biopsies were enrolled for this study. For CIN2+ detection, dual-stained cytology showed statistically higher specificity (85.28%) than Pap cytology (80.00%, P less then 0.001) and HPV16/18 genotyping (72.36%, P less then 0.001), while the sensitivity of dual-stained cytology (63.49%) remained comparable to that of Pap cytology (61.90%, P=0.832) and HPV16/18 genotyping (61.90%, P=0.897). HPV16/18 genotyping in combination with dual-stained cytology was more specific (62.50% vs. 58.06%, P less then 0.001), while showed similar sensitivity (86.51% vs. 85.71%, P=1.000), as compared to HPV16/18 genotyping in combination with Pap cytology. Similar patterns were also observed for CIN3+. CONCLUSIONS p16/Ki-67 dual-stained cytology, either alone or in combination with HPV16/18 genotyping, showed a good stratification with high specificity and comparable sensitivity for HPV-positive women. IMPACT This is one of the few studies that has evaluated the performance of dual-stained cytology for triaging HPV-positive women in China. The higher specificity and comparable sensitivity of dual-stained cytology in comparison to Pap cytology in the detection of CIN2+ or CIN3+ is of vital importance to developing countries, where Pap cytology faces many challenges. Copyright ©2020, American Association for Cancer Research.Neutrophil extracellular traps (NETs) are one of the most intriguing discoveries in immunological research of the past few years. After their first description in 2004, the number of research articles on how NETs affect immunodefense, and also how they contribute to an ever-growing number of diseases, has skyrocketed. However, tempting as it may seem to plunge into pharmaceutical approaches to tamper with NET formation, our understanding of this complex process is still incomplete. Important concepts such as the context-dependent dual functions of NETs, in that they are both inflammatory and anti-inflammatory, or the major intra- and extracellular forces driving NET formation, are only emerging. In this Review, we summarize key aspects of our current understanding of NET formation (also termed NETosis), emphasize biophysical aspects and focus on three key principles - rearrangement and destabilization of the plasma membrane and the cytoskeleton, alterations and disassembly of the nuclear envelope, and chromatin decondensation as a driving force of intracellular reorganization. © 2020. Published by The Company of Biologists Ltd.Inhibition of acid sphingomyelinase (ASM), a lysosomal enzyme that catalyzes the hydrolysis of sphingomyelin into ceramide and phosphorylcholine, may serve as an investigational tool or a therapeutic intervention to control many diseases. Specific ASM inhibitors are currently not sufficiently characterized. Here, we found that 1-aminodecylidene bis-phosphonic acid (ARC39) specifically and efficiently (>90%) inhibits both lysosomal and secretory ASM in vitro. Results from investigating sphingomyelin phosphodiesterase 1 (SMPD1/Smpd1) mRNA and ASM protein levels suggested that ARC39 directly inhibits ASM's catalytic activity in cultured cells, a mechanism which differs from that of functional inhibitors of ASM (FIASMAs). We further provide evidence that ARC39 dose- and time-dependently inhibits lysosomal ASM in intact cells, and we show that ARC39 also reduces platelet- and ASMpromoted adhesion of tumor cells. The observed toxicity of ARC39 is low at concentrations relevant for ASM inhibition in vitro, and it does not strongly alter the lysosomal compartment or induce phospholipidosis in vitro When applied intraperitoneally in vivo, even subtoxic high doses administered short-term induced sphingomyelin accumulation only locally in the peritoneal lavage without significant accumulation in plasma, liver, spleen or brain. These findings require further investigation with other possible chemical modifications. In conclusion, our results indicate that ARC39 potently and selectively inhibits ASM in vitro and highlight the need for developing compounds that can reach tissue concentrations sufficient for ASM inhibition in vivo. link2 Published under license by The American Society for Biochemistry and Molecular Biology, Inc.Gram-negative bacteria possess an asymmetric outer membrane (OM) composed primarily of lipopolysaccharides (LPS) on the outer leaflet and phospholipids (PLs) on the inner leaflet. Loss of this asymmetry due to mutations in the lipopolysaccharide (LPS) biosynthesis or transport pathways causes externalization of PLs to the outer leaflet of the OM and leads to OM permeability defects. Here, we employed metabolic labeling to detect a compromised OM in intact bacteria. Phosphatidylcholine synthase (Pcs) expression in Escherichia coli allowed for incorporation of exogenous propargylcholine (PCho) into phosphatidyl(propargyl)choline (PPC) and for incorporation of exogenous 1-azidoethyl-choline (AECho) into phosphatidyl(azidoethyl)choline (AEPC) as confirmed by LC-MS analyses. A fluorescent copper-free click reagent poorly labeled AEPC in intact wild-type cells, but readily labeled AEPC from lysed cells. Fluorescence microscopy and flow cytometry analyses confirmed the absence of significant AEPC labeling from intact wild-type E. coli strains, and revealed significant AEPC labeling in an E. coli LPS transport mutant (lptD4213) and an LPS biosynthesis mutant (E. coli lpxC101). Our results suggest that metabolic PL labeling with AECho is a promising tool to detect a compromised bacterial OM, reveal aberrant PL externalization, and identify or characterize novel cell-active inhibitors of LPS biosynthesis or transport. Published under license by The American Society for Biochemistry and Molecular Biology, Inc.OBJECTIVE Patient understanding of angiography and angioplasty is often incomplete at the time of consent. Language barriers and time constraints are significant obstacles, particularly in the urgent setting. We introduced digital animations to support consent and assessed the effect on patient understanding. METHODS Multi-language animations explaining angiography and angioplasty (www.explainmyprocedure.com/heart) were introduced at nine district hospitals for patients with acute coronary syndrome before urgent transfer to a cardiac centre for their procedure. Reported understanding of the reason for transfer, the procedure, its benefits and risks in 100 consecutive patients were recorded before introduction of the animations into practice (no animation group) and in 100 consecutive patients after their introduction (animation group). Patient understanding in the two groups was compared. RESULTS Following introduction, 83/100 patients reported they had watched the animation before inter-hospital transfer (3 declined and 14 were overlooked). The proportions of patients who understood the reason for transfer, the procedure, its benefits and risks in the no animation group were 58%, 38%, 25% and 7% and in the animation group, 85%, 81%, 73% and 61%, respectively. The relative improvement (ratio of proportions) was 1.5 (95% CI 1.2 to 1.8), 2.1 (1.6 to 2.8), 2.9 (2.0 to 4.2) and 8.7 (4.2 to 18.1), respectively (p less then 0.001 for all comparisons). link3 CONCLUSION Use of animations explaining angiography and angioplasty is feasible before urgent inter-hospital transfer and was associated with substantial improvement in reported understanding of the procedure, its risks and its benefits. The approach is not limited to cardiology and has the potential to be applied to all specialties in medicine. © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.OBJECTIVE Post-operative concurrent chemoradiotherapy has become the standard treatment for patients with positive lymph nodes after radical surgery. The aim of this study was to explore the efficiency and safety of consolidation chemotherapy in early-stage cervical cancer patients with lymph node metastasis after radical hysterectomy. METHOD We reviewed the medical records of patients with early-stage cervical cancer with lymph node metastasis after radical hysterectomy from January 2010 to January 2017. All patients underwent adjuvant concurrent chemoradiotherapy (n=49) or three cycles of platinum-based consolidation chemotherapy following concurrent chemoradiotherapy (n=89). The primary end points of the study were disease-free survival and overall survival. RESULTS The median follow-up time was 51 months (range 10-109). No significant difference was noted in disease-free survival, overall survival, or grade 3/4 gastrointestinal disorder between the consolidation chemotherapy group (78.1% vs 83.1% vs 6.7%) and the concurrent chemoradiotherapy alone group (75.
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