Artificial intelligence (AI) is here to stay. It is not a future anymore, and there are many particular problems in cardiology that are already being solved via machine learning (ML), and many more ...are to come. AI cannot solve complex tasks yet, and probably this will not change in the upcoming years. Therefore, cardiologists do not have to be afraid that computers will replace them. However, cardiologists who will not be able to use ML algorithms in their clinical practice will be replaced by those who will. (Fig. 2, Ref. 50). Keywords: artificial intelligence, cardiology, potential machine learning, survival models, classification algorithms, computer vision, automated analysis of various imaging examinations, ECG interpretation, phenotype clustering, pathophysiological mechanisms.
This paper estimates cost functions for both municipal solid waste collection and disposal services and curbside recycling programs. Cost data are obtained from a national survey of randomly selected ...municipalities. Results suggest, perhaps unsurprisingly, that both marginal and average costs of recycling systems exceed those of waste collection and disposal systems. Economies of scale are estimated for all observed quantities of waste collection and disposal. Economies of scale for recycling disappear at high levels of recycling—marginal and average cost curves for recycling take on the usual U-shape. Waste and recycling costs are also estimated as functions of factor costs and program attributes.
The presented multi-method was developed for the confirmation of 37 antibiotic substances from the six antibiotic groups: macrolides, lincosamides, quinolones, tetracyclines, pleuromutilines and ...diamino-pyrimidine derivatives. All substances were analysed simultaneously in a single analytical run with the same procedure, including an extraction with buffer, a clean-up by solid-phase extraction, and the measurement by liquid chromatography tandem mass spectrometry in ESI+ mode. The method was validated on the basis of an in-house validation concept with factorial design by combination of seven factors to check the robustness in a concentration range of 5–50 μg kg
−1
. The honeys used were of different types with regard to colour and origin. The values calculated for the validation parameters—decision limit CCα (range, 7.5–12.9 μg kg
−1
), detection capability CCβ (range, 9.4–19.9 μg kg
−1
), within-laboratory reproducibility RSD
wR
(<20% except for tulathromycin with 23.5% and tylvalosin with 21.4 %), repeatability RSD
r
(<20% except for tylvalosin with 21.1%), and recovery (range, 92–106%)—were acceptable and in agreement with the criteria of Commission Decision 2002/657/EC. The validation results showed that the method was applicable for the residue analysis of antibiotics in honey to substances with and without recommended concentrations, although some changes had been tested during validation to determine the robustness of the method.
The presented method is able to analyse 47 substances of the antibiotic groups tetracyclines, quinolones, macrolides, sulfonamides, diamino-pyrimidine derivatives and lincosamides simultaneously in a ...single analytical run. Applying an in-house validation concept, the validation of the multi-method was successfully accomplished with a low number of experiments. Each substance was validated at least at the concentrations 0.5, 1.0 and 1.5
MRL (maximum residue limit), or respectively, at concentrations as low as possible for substances without MRL. The calculated relevant validation parameters, e.g. the decision limit CCα, the detection capability CCβ, the repeatability, the within-laboratory reproducibility and the recovery, are in an acceptable range and in compliance with the requirements of Commission Decision 2002/657/EC. A proficiency test and the implementation of the method by other laboratories were performed successfully.
Somatic mutations in skin cancers and other ultraviolet (UV)-exposed cells are typified by C>T and CC>TT substitutions at dipyrimidine sequences; however, many oncogenic “driver” mutations in ...melanoma do not fit this UV signature. Here, we use genome sequencing to characterize mutations in yeast repeatedly irradiated with UV light. Analysis of ~50,000 UV-induced mutations reveals abundant non-canonical mutations, including T>C, T>A, and AC>TT substitutions. These mutations display transcriptional asymmetry that is modulated by nucleotide excision repair (NER), indicating that they are caused by UV photoproducts. Using a sequencing method called UV DNA endonuclease sequencing (UVDE-seq), we confirm the existence of an atypical thymine-adenine photoproduct likely responsible for UV-induced T>A substitutions. Similar non-canonical mutations are present in skin cancers, which also display transcriptional asymmetry and dependence on NER. These include multiple driver mutations, most prominently the recurrent BRAF V600E and V600K substitutions, suggesting that mutations arising from rare, atypical UV photoproducts may play a role in melanomagenesis.
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•Genome sequencing of UV-irradiated yeast reveals non-canonical mutation classes•Non-canonical mutations are likely caused by atypical UV photoproducts•UV induces an atypical thymine-adenine (TA) photoproduct in vitro and in yeast cells•Non-canonical UV mutation classes can explain many driver mutations in melanoma
UV mutagenesis has been well studied, but many driver mutations in melanoma do not fit the canonical UV signature. Using whole-genome sequencing, Laughery et al. show that UV induces a broader spectrum of mutations than anticipated. Non-canonical UV mutations are likely caused by atypical photoproducts, which may contribute to melanomagenesis.
Purpose
The incidence of acute myocardial infarctions (AMI) shows circadian variation typically peaking during morning hours with a decline at night. However, this variation does not occur in ...patients with diabetes mellitus (DM). The night’s decline of AMI may be partially explained by melatonin-related platelet inhibition. Whether this effect is absent in diabetic patients is unknown. The aim was to study the effect of melatonin on in-vitro platelet aggregation in healthy individuals and patients with type 2 DM.
Methods
Platelet aggregation was measured in blood samples from healthy individuals (
n
= 15) and type 2 DM patients (
n
= 15) using multiple electrode aggregometry. Adenosine diphosphate (ADP), arachidonic acid (ASPI) and thrombin (TRAP) were used as agonists. Aggregability for each subject was tested after adding melatonin in two concentrations.
Results
In healthy individuals, melatonin inhibited platelet aggregation in both higher (10–5 M) and lower concentrations (10–9 M) induced by ADP, ASPI, and TRAP (
p
< 0.001,
p
= 0.002,
p
= 0.029, respectively). In DM patients, melatonin did not affect platelet aggregation in both concentrations induced by ADP, ASPI, and TRAP. Melatonin decreased platelet aggregation induced by ADP, ASPI, and TRAP significantly more in healthy individuals compared to patients with DM. (
p
= 0.005,
p
= 0.045 and
p
= 0.048, respectively).
Conclusion
Platelet aggregation was inhibited by melatonin in healthy individuals.
In-vitro
antiplatelet effect of melatonin in type 2 DM patients is significantly attenuated.
Transgenic manipulation of subsets of brain cells is increasingly used for studying behaviors and their underlying neural circuits. In Drosophila, the GAL4-upstream activating sequence (UAS) binary ...system is powerful for gene manipulation, but GAL4 expression is often too broad for fine mapping of neural circuits. Here, we describe the development of unique molecular genetic tools to restrict GAL4 expression patterns. Building on the GAL4-UAS system, our method adds two components: a collection of enhancer-trap recombinase, Flippase (ET-FLP), transgenic lines that provide inheritable, reproducible, and tissue-specific FLP and an FRT-dependent GAL80 "flip-in" construct that converts FLP expression into tissue-specific repression of GAL4 by GAL80. By including a UAS-encoded fluorescent protein, circuit morphology can be simultaneously marked while the circuit function is assessed using another UAS transgene. In a proof-of-principle analysis, we applied this ET-FLP-induced intersectional GAL80/GAL4 repression (FINGR) method to map the neural circuitry underlying fly wing inflation. The FINGR system is versatile and powerful in combination with the vast collection of GAL4 lines for neural circuit mapping as well as for clonal analysis based on the infusion of the yeast-derived FRT/FLP system of mitotic recombination into DROSOPHILA: The strategies and tactics underlying our FINGR system are also applicable to other genetically amenable organisms in which transgenes including the GAL4, UAS, GAL80, and FLP factors can be applied.
Exposure to ultraviolet (UV) light induces DNA damage, predominantly cyclobutane pyrimidine dimers (CPD) and 6,4-photoproducts (6,4-PP), as well as rare, atypical photoproducts at thymidine-adenine ...(TA) sequences. We have recently shown ‘TA’ photoproducts are induced in UV-irradiated oligonucleotides and across the budding yeast genome. Here, we describe a protocol for mapping atypical ‘TA’ photoproducts in vitro and in vivo. This protocol overcomes the technical challenges involved in accurately mapping such rare photoproducts by using ultraviolet damage endonuclease (UVDE) enzymes.
For complete details on the use and execution of this protocol, please refer to Laughery et al. (2020).
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•UVDE enzyme cleaves ‘TA’ photoproducts in UV-irradiated oligos and the yeast genome•CPD photolyase treatment ensures only 6,4-PPs and atypical lesions are mapped•Bioinformatic pipelines precisely locate where these ‘TA’ lesions formed in vivo
Exposure to ultraviolet (UV) light induces DNA damage, predominantly cyclobutane pyrimidine dimers (CPD) and 6,4-photoproducts (6,4-PP), as well as rare, atypical photoproducts at thymidine-adenine (TA) sequences. We have recently shown ‘TA’ photoproducts are induced in UV-irradiated oligonucleotides and across the budding yeast genome. Here, we describe a protocol for mapping atypical ‘TA’ photoproducts in vitro and in vivo. This protocol overcomes the technical challenges involved in accurately mapping such rare photoproducts by using ultraviolet damage endonuclease (UVDE) enzymes.
Chronic graft-versus-host disease (GVHD) remains a serious complication after allogeneic hematopoietic stem cell transplantation (HCT). In 2005 the National Institutes of Health (NIH) established new ...criteria for chronic GVHD based on retrospective data and expert recommendations. We prospectively evaluated the incidence of NIH-defined chronic GVHD and its prognostic impact in 178 consecutive patients. The cumulative incidence of chronic GVHD at 3 years was 64, 48 and 16% for chronic classic GVHD and overlap syndrome. Prior acute GVHD and myeloablative conditioning were significantly associated with increased risk of chronic GVHD. Three-year survival (overall survival (OS)) for late-acute GVHD, chronic classic and overlap chronic GVHD when assigned on day 100 were 69, 83 and 73%. OS was significantly worse for patients with platelet counts below 100 g/l at onset of chronic GVHD (35% versus 86%, P<0.0001) and progressive as compared with de novo and quiescent onset of chronic GVHD (54.5% versus 89.5% versus 84%, P = 0.022 and 0.001). Peak severity of chronic GVHD had no impact on non-relapse mortality (NRM) and OS. Recurrent acute GVHD, platelet counts below 100 g/l at diagnosis of chronic GVHD, progressive onset of chronic GVHD and advanced disease stage prior to HCT were significantly associated with increased NRM. This prospective analysis provides for the first-time data on the incidence rates of NIH-defined chronic GVHD categories and identified risk factors for the occurrence of chronic GVHD. A prognostic value of thrombocytopenia and progressive onset type of chronic GVHD for survival after HCT was observed in NIH-defined chronic GVHD.
Bioelectrical impedance analysis (BIA) is a relatively simple, inexpensive and non-invasive technique to measure body composition and is therefore suitable in field studies and larger surveys.
We ...performed an overview of BIA-derived body fat percentages (BF%) from 55 published studies of healthy populations aged 6-80 years. In addition, the relationship between body mass index (BMI) and body composition is documented in the context of BIA as a good alternative to closely differentiate which composition of the body better relates to the risk of cardiovascular diseases (CVDs)and all-cause mortality.
BIA-estimated percentage of BF varies greatly with population and age. BIA-estimated BF% is directly and closely related to various health outcomes such as CVDs, which is in contrast to BMI where both high and low BMIs are associated with increased risk of developing chronic diseases. Studies, among others using BIA, suggest that low BMI may reflect low muscle and high BMI fat mass (FM). BIA-derived lean and FM is directly associated with morbidity and mortality. To the contrary, BMI is rather of limited use for measuring BF% in epidemiological studies.
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