Deoxy sugars represent an important class of carbohydrates, present in a large number of biomolecules involved in multiple biological processes. In various antibiotics, antimicrobials, and ...therapeutic agents the presence of deoxygenated units has been recognized as responsible for biological roles, such as adhesion or great affinity to receptors, or improved efficacy. The characterization of glycosidases and glycosyltranferases requires substrates, inhibitors and analogous compounds. Deoxygenated sugars are useful for carrying out specific studies for these enzymes. Deoxy sugars, analogs of natural substrates, may behave as substrates or inhibitors, or may not interact with the enzyme. They are also important for glycodiversification studies of bioactive natural products and glycobiological processes, which could contribute to discovering new therapeutic agents with greater efficacy by modification or replacement of sugar units. Deoxygenation of carbohydrates is, thus, of great interest and numerous efforts have been dedicated to the development of methods for the reduction of sugar hydroxyl groups. Given that carbohydrates are the most important renewable chemicals and are more oxidized than fossil raw materials, it is also important to have methods to selectively remove oxygen from certain atoms of these renewable raw materials. The different methods for removal of OH groups of carbohydrates and representative or recent applications of them are presented in this chapter. Glycosidic bonds in general, and 2-deoxy glycosidic linkages, are included. It is not the scope of this survey to cover all reports for each specific technique.
Monitoring the Greenland mass balance (GMB) is crucial in the context of global sea level rise. Currently, three main methods are used to measure GMB, with the primary source of uncertainty arising ...from the glacial isostatic adjustment (GIA) contribution. Here, we propose a novel approach based on a simple methodology that uses the entire Greenland GNSS network (GNET) as an instrument to monitor the present‐day mass changes. Our method is validated against GRACE‐derived GMB, and we find a very good agreement. This leads to an independent methodology for estimating present‐day mass changes from GNSS, bridging the gap between GRACE and GRACE‐FO in GMB estimates. Through a combined analysis of GMB from GRACE and GNET, we identify a consistency relation between the gravity and uplift signature of GIA, providing a new robust constraint for GIA models.
Plain Language Summary
The rate of Greenland ice mass change is constantly monitored by satellites measuring gravity and surface elevation variations, airborne surveys, and a growing network of GNSS stations on the ground. Each technique has its strengths and weaknesses and spatial/temporal resolution. We developed an approach that uses the whole GNSS network as a “virtual instrument”, capable of measuring the total ice loss from Greenland. Comparing this with more standard mass balance estimate techniques, we validate the method, and, by combining these techniques, we find a novel constraint on both the mass variations and glacial isostatic adjustment models.
Key Points
New methodology for monitoring daily estimates of the Greenland Mass Balance (GMB) derived from the GNSS network
New glacial isostatic adjustment constraint from combined GRACE and GNSS observations
Filling the gap in the GMB between GRACE and GRACE‐FO using GNSS data
Although known for more than 40 years in the polymer chemistry field, the photochemical radical thiol-ene addition (PRTEA) has been recently recognized as a chemical reaction with click ...characteristics. Photoinitiation enables spatial and temporal control of this highly efficient reaction, bridging simple organic chemistry with high-end materials synthesis and surfaces functionalization. In this minireview, we focus on the latest contributions based on the PRTEA for the synthesis of chemical precursors for silica and transition metal oxides (TMO) based materials. We summarize the mechanism of the PRTEA, the development of new families of photoinitiators and how this extremely simple approach has spilled over into the materials science arena with clear success. In particular, PRTEA adds to the collective efforts for building a reliable and straightforward chemical toolbox for surface modification and the production of sol-gel precursors, nanoparticles and thin films. The excellent perspectives for simple molecular and supramolecular building block synthesis opens up a rational synthetic route for the design and integration of these components in multipurpose platforms.
The photochemical radical thiol-ene addition reaction (PRTEA) is a highly powerful synthetic technique for surface modification.
Summary Background The risk of recurrence of gastrointestinal stromal tumour (GIST) after surgery needs to be estimated when considering adjuvant systemic therapy. We assessed prognostic factors of ...patients with operable GIST, to compare widely used risk-stratification schemes and to develop a new method for risk estimation. Methods Population-based cohorts of patients diagnosed with operable GIST, who were not given adjuvant therapy, were identified from the literature. Data from ten series and 2560 patients were pooled. Risk of tumour recurrence was stratified using the National Institute of Health (NIH) consensus criteria, the modified consensus criteria, and the Armed Forces Institute of Pathology (AFIP) criteria. Prognostic factors were examined using proportional hazards and non-linear models. The results were validated in an independent centre-based cohort consisting of 920 patients with GIST. Findings Estimated 15-year recurrence-free survival (RFS) after surgery was 59·9% (95% CI 56·2–63·6); few recurrences occurred after the first 10 years of follow-up. Large tumour size, high mitosis count, non-gastric location, presence of rupture, and male sex were independent adverse prognostic factors. In receiver operating characteristics curve analysis of 10-year RFS, the NIH consensus criteria, modified consensus criteria, and AFIP criteria resulted in an area under the curve (AUC) of 0·79 (95% CI 0·76–0·81), 0·78 (0·75–0·80), and 0·82 (0·80–0·85), respectively. The modified consensus criteria identified a single high-risk group. Since tumour size and mitosis count had a non-linear association with the risk of GIST recurrence, novel prognostic contour maps were generated using non-linear modelling of tumour size and mitosis count, and taking into account tumour site and rupture. The non-linear model accurately predicted the risk of recurrence (AUC 0·88, 0·86–0·90). Interpretation The risk-stratification schemes assessed identify patients who are likely to be cured by surgery alone. Although the modified NIH classification is the best criteria to identify a single high-risk group for consideration of adjuvant therapy, the prognostic contour maps resulting from non-linear modelling are appropriate for estimation of individualised outcomes. Funding Academy of Finland, Cancer Society of Finland, Sigrid Juselius Foundation and Helsinki University Research Funds.
More people than ever before are currently living with a diagnosis of cancer and the number of people concerned is likely to continue to rise. Cancer survivors are at risk of developing a second ...primary cancer (SPC). This study aims to investigate the risk of SPC in Switzerland.
The study cohort included all patients with a first primary cancer recorded in 9 Swiss population-based cancer registries 1981-2009 who had a minimum survival of 6 months, and a potential follow-up until the end of 2014. We calculated standardized incidence ratios (SIR) to estimate relative risks (RR) of SPC in cancer survivors compared with the cancer risk of the general population. SIR were stratified by type of first cancer, sex, age and period of first diagnosis, survival period and site of SPC.
A total of 33,793 SPC were observed in 310,113 cancer patients. Both male (SIR 1.18, 95%CI 1.16-1.19) and female (SIR 1.20, 95%CI 1.18-1.22) cancer survivors had an elevated risk of developing a SPC. Risk estimates varied substantially according to type of first cancer and were highest in patients initially diagnosed with cancer of the oral cavity and pharynx, Hodgkin lymphoma, laryngeal, oesophageal, or lung cancer. Age-stratified analyses revealed a tendency towards higher RR in patients first diagnosed at younger ages. Stratified by survival period, risk estimates showed a rising trend with increasing time from the initial diagnosis. We observed strong associations between particular types of first and SPC, i.e. cancer types sharing common risk factors such as smoking or alcohol consumption (e.g. repeated cancer of the oral cavity and pharynx (SIR
20.12, 95%CI 17.91-22.33; SIR
37.87, 95%CI 30.27-45.48).
Swiss cancer survivors have an increased risk of developing a SPC compared to the general population, particularly patients first diagnosed before age 50 and those surviving more than 10 years. Cancer patients should remain under continued surveillance not only for recurrent cancers but also for new cancers. Some first and SPCs share lifestyle associated risk factors making it important to promote healthier lifestyles in both the general population and cancer survivors.
Simplifying the synthetic methods to produce metallic gold nanoparticles (AuNPs) is a key point to increment their applicability in multiple fields. In this work, we present a new, simple and fast ...method that ensures the one-pot production of AuNPs in less than two minutes, at room temperature. The proposed methodology is based on the use of a mixture of two usual reductants (ascorbic acid – H2Asc – and sodium citrate) and polyvinylpyrrolidone as stabilizing agent. The particles were obtained by adequately controlling the reductants concentrations and the mixture pH (using citric/citrate-based buffers). Interestingly, two different results were observed, depending on the initial buffer solution. At citric-rich conditions, both buffer and H2Asc did not significantly affect the synthesis outcome and spherical AuNPs of around 25 nm were obtained in all cases. However, at citrate-rich conditions, varying the ascorbic acid concentration provoked marked changes in the size and shape of the AuNPs ranging from spherical (at low H2Asc) to spiked ones (at high H2Asc). Finally, and as a proof of concept, we show that both kinds of AuNPs could be useful for different applications. The small spherical ones can be used as stable seeds for the overgrowth of anisotropic AuNPs, whose characteristics depend on the chosen growth solution. On the other hand, the spiked ones can be employed for both refractive index or Raman spectroscopy-based sensing, with interesting prospects. As a whole, the results presented in this work demonstrate that pH control and combination of several reductants can be used as a tool to develop new synthetic procedures for simpler and faster AuNPs production, in comparison with the currently available methods
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•New one-pot straightforward method to obtain gold nanoparticles is presented.•Solution pH and the reductants concentration define size and shape of the particles.•The particles are useful as seeds for overgrowth and for sensing applications.
Mutated KIT and platelet-derived growth factor alpha gene (PDGFRA) drive GI stromal tumor (GIST) oncogenesis, but the clinical significance of their single mutations is known incompletely.
We ...identified 11 population-based series of patients with GIST through a literature search and pooled individual data from 3,067 patients treated with macroscopically complete tumor excision. Mutation analysis was done from 1,505 tumors. We analyzed associations between KIT and PDGFRA mutations and recurrence-free survival (RFS) in the subsets in which patients were treated with surgery alone.
We identified 301 different single mutations in KIT and 33 in PDGFRA. Patients with PDGFRA mutations had more favorable RFS than those with KIT mutations (hazard ratio, 0.34; P = .004). Only one of the 35 GISTs with KIT exon 11 duplication mutations recurred. Patients with deletions of only one codon of KIT exon 11 had better RFS than those with another deletion type, and some KIT exon 11 substitution mutations (Trp557Arg, Val559Ala, and Leu576Pro) were also associated with favorable RFS. Patients with an identical mutation had greatly variable outcomes depending on the standard prognostic factors, notably, mitotic count. Commonly used risk stratification schemes tended to overestimate the risk for recurrence in subgroups with prognostically favorable mutations.
GISTs with an identical KIT or PDGFRA mutation may have widely varying risks for recurrence. Most of the patients with PDGFRA mutations and those with KIT exon 11 duplication mutation or deletion of one codon have favorable RFS with surgery alone and are usually not candidates for adjuvant therapy.
Quality of cancer care (QoCC) has become an important item for providers, regulators and purchasers of care worldwide. Aim of this study is to present the results of some evidence-based quality ...indicators (QI) for prostate cancer (PC) at the population-based level and to compare the outcomes with data available in the literature.
The study included all PC diagnosed on a three years period analysis (01.01.2011-31.12.2013) in the population of Canton Ticino (Southern Switzerland) extracted from the Ticino Cancer Registry database. 13 QI, approved through the validated Delphi methodology, were calculated using the "available case" approach: 2 for diagnosis, 4 for pathology, 6 for treatment and 1 for outcome. The selection of the computed QI was based on the availability of medical documentation. QI are presented as proportion (%) with the corresponding 95% confidence interval.
700 PC were detected during the three-year period 2011-2013: 78.3% of them were diagnosed through a prostatic biopsy and for 72.5% 8 or more biopsy cores were taken. 46.5% of the low risk PC patients underwent active surveillance, while 69.2% of high risk PC underwent a radical treatment (radical prostatectomy, radiotherapy or brachytherapy) and 73.5% of patients with metastatic PC were treated with hormonal therapy. The overall 30-day postoperative mortality was 0.5%.
Results emerging from this study on the QoCC for PC in Canton Ticino are encouraging: the choice of treatment modalities seems to respect the international guidelines and our results are comparable to the scarce number of available international studies. Additional national and international standardisation of the QI and further QI population-based studies are needed in order to get a real picture of the PC diagnostic-therapeutic process progress through the definition of thresholds of minimal standard of care.
Gastrointestinal stromal tumors (GIST) are characterized by gain-of-function mutations in KIT/PDGFRA genes leading to a constitutive receptor activation which is well counteracted by imatinib. ...However, cases in which imatinib as first-line treatment has no effects are reported (primary resistance). Our purpose is to investigate alterations in downstream effectors, not reported so far in mutated GIST, possibly explaining the primary resistance to targeted treatments.
Two independent naive GIST cohorts have been analyzed for KIT, PDGFRA, KRAS, and BRAF mutations by direct sequencing. Cell lines expressing a constitutively activated and imatinib-responding KIT, alone or in combination with activated KRAS and BRAF, were produced and treated with imatinib. KIT receptor and its downstream effectors were analyzed by direct Western blotting.
In naive GISTs carrying activating mutations in KIT or PDGFRA a concomitant activating mutation was detected in KRAS (5%) or BRAF (about 2%) genes. In vitro experiments showed that imatinib was able to switch off the mutated receptor KIT but not the downstream signaling triggered by RAS-RAF effectors.
These data suggest the activation of mitogen-activated protein kinase pathway as a possible novel mechanism of primary resistance to imatinib in GISTs and could explain the survival curves obtained from several clinical studies where 2% to 4% of patients with GIST treated with imatinib, despite carrying KIT-sensitive mutations, do not respond to the treatment.
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•Pores in mesoporous titania are functionalized with carboxylates and complex Sr ions.•Sr is released from the mesoporous with an initial burst and then slowly over weeks.•Sr release ...from mesoporous improves MC3T3-E1 cell adhesion and proliferation rate.
The release of bioactive Strontium ions (Sr2+) from titanium implants has a positive impact on osseointegration. It is however challenging to achieve a slow Sr2+ release over weeks until tissue regeneration. A hybrid mesoporous titania film (MTF) displaying carboxylic moieties in pore walls has been developed here for encapsulation and slow delivery of Sr2+. Mesoporous films are prepared by Evaporation Induced Self-Assembly. Vinyltrimethoxysilanes are co-condensed during film assembly and vinyl groups of silanes are reacted with mercaptosuccinic acid resulting in pores displaying carboxylic groups. Modified MTFs are loaded with Sr2+, which is retained both as non-complexed ion in the pores and complexed to the carboxylic acid groups. The complexation of Sr2+ to the carboxylic groups is proven by X-ray Photoelectron Spectroscopy and Infrared Spectroscopy. Inductively Coupled Plasma Mass Spectrometry shows that the non-complexed Sr2+ is released from the pores in approximately one day while complexed Sr2+ is released slowly over one week. The released Sr2+ has a positive effect on MC3T3-E1 pre-osteoblastic cell proliferation and the Alkaline Phosphatase test shows that at 15 days of culture in osteogenic medium the differentiation is enhanced due to the slow release of Sr2+ complexed to carboxylates.
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