Prostate cancer is the second leading cause of cancer death in men in the developed world. A more sensitive and specific detection strategy for lethal prostate cancer beyond serum prostate specific ...antigen (PSA) population screening is urgently needed. Diagnosis by canine olfaction, using dogs trained to detect cancer by smell, has been shown to be both specific and sensitive. While dogs themselves are impractical as scalable diagnostic sensors, machine olfaction for cancer detection is testable. However, studies bridging the divide between clinical diagnostic techniques, artificial intelligence, and molecular analysis remains difficult due to the significant divide between these disciplines. We tested the clinical feasibility of a cross-disciplinary, integrative approach to early prostate cancer biosensing in urine using trained canine olfaction, volatile organic compound (VOC) analysis by gas chromatography-mass spectroscopy (GC-MS) artificial neural network (ANN)-assisted examination, and microbial profiling in a double-blinded pilot study. Two dogs were trained to detect Gleason 9 prostate cancer in urine collected from biopsy-confirmed patients. Biopsy-negative controls were used to assess canine specificity as prostate cancer biodetectors. Urine samples were simultaneously analyzed for their VOC content in headspace via GC-MS and urinary microbiota content via 16S rDNA Illumina sequencing. In addition, the dogs' diagnoses were used to train an ANN to detect significant peaks in the GC-MS data. The canine olfaction system was 71% sensitive and between 70-76% specific at detecting Gleason 9 prostate cancer. We have also confirmed VOC differences by GC-MS and microbiota differences by 16S rDNA sequencing between cancer positive and biopsy-negative controls. Furthermore, the trained ANN identified regions of interest in the GC-MS data, informed by the canine diagnoses. Methodology and feasibility are established to inform larger-scale studies using canine olfaction, urinary VOCs, and urinary microbiota profiling to develop machine olfaction diagnostic tools. Scalable multi-disciplinary tools may then be compared to PSA screening for earlier, non-invasive, more specific and sensitive detection of clinically aggressive prostate cancers in urine samples.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
Background
A rapid, accurate, non-invasive diagnostic screen is needed to identify people with SARS-CoV-2 infection. We investigated whether organic semi-conducting (OSC) sensors and trained ...dogs could distinguish between people infected with asymptomatic or mild symptoms, and uninfected individuals, and the impact of screening at ports-of-entry.
Methods
Odour samples were collected from adults, and SARS-CoV-2 infection status confirmed using RT-PCR. OSC sensors captured the volatile organic compound (VOC) profile of odour samples. Trained dogs were tested in a double-blind trial to determine their ability to detect differences in VOCs between infected and uninfected individuals, with sensitivity and specificity as the primary outcome. Mathematical modelling was used to investigate the impact of bio-detection dogs for screening.
Results
About, 3921 adults were enrolled in the study and odour samples collected from 1097 SARS-CoV-2 infected and 2031 uninfected individuals. OSC sensors were able to distinguish between SARS-CoV-2 infected individuals and uninfected, with sensitivity from 98% (95% CI 95–100) to 100% and specificity from 99% (95% CI 97–100) to 100%. Six dogs were able to distinguish between samples with sensitivity ranging from 82% (95% CI 76–87) to 94% (95% CI 89–98) and specificity ranging from 76% (95% CI 70–82) to 92% (95% CI 88–96). Mathematical modelling suggests that dog screening plus a confirmatory PCR test could detect up to 89% of SARS-CoV-2 infections, averting up to 2.2 times as much transmission compared to isolation of symptomatic individuals only.
Conclusions
People infected with SARS-CoV-2, with asymptomatic or mild symptoms, have a distinct odour that can be identified by sensors and trained dogs with a high degree of accuracy. Odour-based diagnostics using sensors and/or dogs may prove a rapid and effective tool for screening large numbers of people.
Trial Registration NCT04509713 (clinicaltrials.gov).
The omicron variant (B.1.1.529) of SARS-CoV-2 has demonstrated partial vaccine escape and high transmissibility, with early studies indicating lower severity of infection than that of the delta ...variant (B.1.617.2). We aimed to better characterise omicron severity relative to delta by assessing the relative risk of hospital attendance, hospital admission, or death in a large national cohort.
Individual-level data on laboratory-confirmed COVID-19 cases resident in England between Nov 29, 2021, and Jan 9, 2022, were linked to routine datasets on vaccination status, hospital attendance and admission, and mortality. The relative risk of hospital attendance or admission within 14 days, or death within 28 days after confirmed infection, was estimated using proportional hazards regression. Analyses were stratified by test date, 10-year age band, ethnicity, residential region, and vaccination status, and were further adjusted for sex, index of multiple deprivation decile, evidence of a previous infection, and year of age within each age band. A secondary analysis estimated variant-specific and vaccine-specific vaccine effectiveness and the intrinsic relative severity of omicron infection compared with delta (ie, the relative risk in unvaccinated cases).
The adjusted hazard ratio (HR) of hospital attendance (not necessarily resulting in admission) with omicron compared with delta was 0·56 (95% CI 0·54–0·58); for hospital admission and death, HR estimates were 0·41 (0·39–0·43) and 0·31 (0·26–0·37), respectively. Omicron versus delta HR estimates varied with age for all endpoints examined. The adjusted HR for hospital admission was 1·10 (0·85–1·42) in those younger than 10 years, decreasing to 0·25 (0·21–0·30) in 60–69-year-olds, and then increasing to 0·47 (0·40–0·56) in those aged at least 80 years. For both variants, past infection gave some protection against death both in vaccinated (HR 0·47 0·32–0·68) and unvaccinated (0·18 0·06–0·57) cases. In vaccinated cases, past infection offered no additional protection against hospital admission beyond that provided by vaccination (HR 0·96 0·88–1·04); however, for unvaccinated cases, past infection gave moderate protection (HR 0·55 0·48–0·63). Omicron versus delta HR estimates were lower for hospital admission (0·30 0·28–0·32) in unvaccinated cases than the corresponding HR estimated for all cases in the primary analysis. Booster vaccination with an mRNA vaccine was highly protective against hospitalisation and death in omicron cases (HR for hospital admission 8–11 weeks post-booster vs unvaccinated: 0·22 0·20–0·24), with the protection afforded after a booster not being affected by the vaccine used for doses 1 and 2.
The risk of severe outcomes following SARS-CoV-2 infection is substantially lower for omicron than for delta, with higher reductions for more severe endpoints and significant variation with age. Underlying the observed risks is a larger reduction in intrinsic severity (in unvaccinated individuals) counterbalanced by a reduction in vaccine effectiveness. Documented previous SARS-CoV-2 infection offered some protection against hospitalisation and high protection against death in unvaccinated individuals, but only offered additional protection in vaccinated individuals for the death endpoint. Booster vaccination with mRNA vaccines maintains over 70% protection against hospitalisation and death in breakthrough confirmed omicron infections.
Medical Research Council, UK Research and Innovation, Department of Health and Social Care, National Institute for Health Research, Community Jameel, and Engineering and Physical Sciences Research Council.
In this randomized trial involving 438 hospitalized patients with severe Covid-19 pneumonia, the use of the monoclonal antibody tocilizumab did not result in significantly better clinical status or ...lower mortality than placebo at 28 days.
In a large case–control study in England, immunity to the omicron variant was very low and less than that to the delta variant 20 weeks after the second vaccine dose, regardless of the initial ...vaccine type. A booster dose of one of the mRNA vaccines improved efficacy to approximately 65 to 70%, but protection waned over a 10-week period.
Sophorolipids are one of the most important microbial biosurfactants, because of their large-scale production and applications developed so far in the fields of detergency, microbiology, cosmetics or ...environmental science. However, the structural variety of native sophorolipids is limited/restricted, a limiting fact for the development of new properties and their potential applications. In their open acidic form, C18:1 sophorolipids (SL) are classically composed of a sophorose headgroup and a carboxylic acid (COOH) end-group. The carboxyl group gives them unique pH-responsive properties, but it is a poorly reactive group and its charge can only be negative. To develop a new generation of pH-responsive, positively charged, SL and to improve their reactivity for further functionalization, we develop here SL with an amine (-NH
2
) or terminal alkyne (-C&z.tbd;CH) end-group analogues. The amine group generates positively charged SL and is more reactive than carboxylic acids,
e.g.
towards aldehydes; the alkyne group provides access to copper-based click chemistry. In this work, we synthesized (C18:1) and (C18:0) -NH
2
and (C18:1) -C&z.tbd;CH sophorolipid derivatives and we study their self-assembly properties in response to pH and/or temperature changes by means of static and dynamic light scattering, small angle (X-ray, neutron) scattering and cryogenic electron microscopy. Monounsaturated aminyl SL-C18:1-NH
2
sophorolipids form a micellar phase in their neutral form at high pH and a mixed micellar-bilayer phase in their positively charged form at low pH. Saturated aminyl SL-C18:0-NH
2
sophorolipids form a micellar phase in their charged form at low pH and a twisted ribbon phase in their neutral form at high pH and monounsaturated alkynyl SL-C18:1-C&z.tbd;CH sophorolipids form a main micellar phase at
T
> 51.8 °C and a twisted ribbon phase at
T
< 51.8 °C.
Sophorolipids are one of the most important microbial biosurfactants, because of their large-scale production and applications developed so far in the fields of detergency, microbiology, cosmetics or environmental science.
This document is a summary of the French Intergroup guidelines regarding the management of gastric cancer published in October 2016, available on the website of the French Society of Gastroenterology ...(SNFGE) (www.tncd.org), updated in October 2017.
This collaborative work was realized under the auspices of several French medical societies involved in management of gastric cancer. Recommendations are graded in three categories (A–C), according to the amount of evidence found in the literature until July 2017.
There are several known risk factors for gastric cancer, including Helicobacter pylori and genetic predispositions, both requiring a specific screening for patients and their relatives. The diagnosis and staging evaluation are essentially based on gastroscopy plus biopsies and computed tomography scan. The endoscopic ultrasonography can be used for superficial tumors in case of discussion for endoscopic resection (T1N0). For local disease (N+ and/or T > T1), the strategic therapy is based on surgery associated with perioperative chemotherapy. In the absence of preoperative treatment (for any raison), the postoperative chemoradiotherapy (or chemotherapy) should be discussed for patients with stage II or III tumor. For metastatic disease, the treatment is based on “palliative” chemotherapy consisting in a doublet or triplet regimens depending of age, performance status and HER2 tumor status. For patients with limited metastatic disease, surgical resection could be discussed in multidisciplinary meeting in case of stable disease after chemotherapy.
These guidelines in gastric cancer are done to help decision for daily clinical practice. These recommendations are permanently being reviewed. Each individual case must be discussed within a multidisciplinary team.
Gold nanoparticles (AuNPs) with unique physicochemical properties have received a great deal of interest in the field of biological, chemical and biomedical implementations. Despite the widespread ...use of AuNPs in chemical and biological sensing, catalysis, imaging and diagnosis, and more recently in therapy, no comprehensive summary has been provided to explain how AuNPs could aid in developing improved sensing and catalysts systems as well as medical settings.
The chemistry of Au-based nanosystems was followed by reviewing different applications of Au nanomaterials in biological and chemical sensing, catalysis, imaging and diagnosis by a number of approaches, and finally synergistic combination therapy of different cancers. Afterwards, the clinical impacts of AuNPs, future application of AuNPs, and opportunities and challenges of AuNPs application were also discussed.
AuNPs show exclusive colloidal stability and are considered as ideal candidates for colorimetric detection, catalysis, imaging, and photothermal transducers, because their physicochemical properties can be tuned by adjusting their structural dimensions achieved by the different manufacturing methods.
This review provides some details about using AuNPs in sensing and catalysis applications as well as promising theranostic nanoplatforms for cancer imaging and diagnosis, and sensitive, non-invasive, and synergistic methods for cancer treatment in an almost comprehensive manner.
•We listed different applications of AuNPs as biological and chemical sensing, catalysis, imaging and diagnosis by various techniques.•Moreover, we tried to cover all aspects of Au nanosystems (AuNPs, AuNRs, AuNC, and Au nanoshells) in cancer therapeutics.•Finally, the clinical impact of AuNPs, future application of AuNPs, and opportunities and challenges of AuNPs application were also discussed.
Abstract
Background
Typhoid fever contributes to approximately 135 000 deaths annually. Achievable improvements in household water, sanitation, and hygiene (WASH) combined with vaccination using ...typhoid conjugate vaccines (TCVs) may be an effective preventive strategy. However, little is known about how improved WASH and vaccination interact to lower the risk of typhoid.
Methods
A total of 61 654 urban Bangladeshi children aged 9 months to <16 years, residing in 150 clusters with a baseline population of 205 760 residents, were randomized 1:1 by cluster to Vi-tetanus toxoid TCV or Japanese encephalitis (JE) vaccine. Surveillance for blood culture–confirmed typhoid fever was conducted over 2 years. Existing household WASH status was assessed at baseline as Better or Not Better using previously validated criteria. The reduction in typhoid risk among all residents associated with living in TCV clusters, Better WASH households, or both was evaluated using mixed-effects Poisson regression models.
Results
The adjusted reduced risk of typhoid among all residents living in the clusters assigned to TCV was 55% (95% confidence interval CI, 43%–65%; P < .001), and that of living in Better WASH households, regardless of cluster, was 37% (95% CI, 24%–48%; P < .001). The highest risk of typhoid was observed in persons living in households with Not Better WASH in the JE clusters. In comparison with these persons, those living in households with Better WASH in the TCV clusters had an adjusted reduced risk of 71% (95% CI, 59%–80%; P < .001).
Conclusions
Implementation of TCV programs combined with achievable and culturally acceptable household WASH practices were independently associated with a significant reduction in typhoid risk.
Clinical Trials Registration
ISRCTN11643110.
Better preexisting household water, sanitation, and hygiene and delivering Vi-TT vaccine act independently to reduce typhoid risk, so that the combination of both yields greater protection against typhoid at the population level (71%) than either vaccination (55%) or improved WASH alone (37%).
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