A study of longitudinal mobile health data through fuzzy clustering methods for functional data: The case of allergic rhinoconjunctivitis in childhood

The use of mobile communication devices in health care is spreading worldwide. A huge amount of health data collected by these devices (mobile health data) is nowadays available. Mobile health data may allow for real-time monitoring of patients and delivering ad-hoc treatment recommendations. This paper aims at showing how this may be done by exploiting the potentialities of fuzzy clustering techniques. In fact, such techniques can be fruitfully applied to mobile health data in order to identify clusters of patients for diagnostic classification and cluster-specific therapies. However, since mobile health data are full of noise, fuzzy clustering methods cannot be directly applied to mobile health data. Such data must be denoised prior to analyzing them. When longitudinal mobile health data are available, functional data analysis represents a powerful tool for filtering out the noise in the data. Fuzzy clustering methods for functional data can then be used to determine groups of patients. In this work we develop a fuzzy clustering method, based on the concept of medoid, for functional data and we apply it to longitudinal mHealth data on daily symptoms and consumptions of anti-symptomatic drugs collected by two sets of patients in Berlin (Germany) and Ascoli Piceno (Italy) suffering from allergic rhinoconjunctivitis. The studies showed that clusters of patients with similar changes in symptoms were identified opening the possibility of precision medicine

An Updated Algorithm Integrated With Patient Data for the Differentiation of Atypical Nevi From Early Melanomas: the idScore 2021

Introduction: It is well known that multiple patient-related risk factors contribute to the development of cutaneous melanoma, including demographic, phenotypic and anamnestic factors. Objectives: We aimed to investigate which MM risk factors were relevant to be incorporated in a risk scoring-classifier based clinico-dermoscopic algorithm. Methods: This retrospective study was performed on a monocentric dataset of 374 atypical melanocytic skin lesions sharing equivocal dermoscopic features, excised in the suspicion of malignancy. Dermoscopic standardized images of 258 atypical nevi (aN) and 116 early melanomas (eMM) were collected along with objective lesional data (i.e., maximum diameter, specific body site and body area) and 7 dermoscopic data. All cases were combined with a series of 10 MM risk factors, including demographic (2), phenotypic (5) and anamnestic (3) ones. Results: The proposed iDScore 2021 algorithm is composed by 9 variables (age, skin phototype I/II, personal/familiar history of MM, maximum diameter, location on the lower extremities (thighs/legs/ ankles/back of the feet) and 4 dermoscopic features (irregular dots and globules, irregular streaks, blue gray peppering, blue white veil). The algorithm assigned to each lesion a score from 0 to 18, reached an area under the ROC curve of 92% and, with a score threshold ≥ 6, a sensitivity (SE) of 98.2% and a specificity (SP) of 50.4%, surpassing the experts in SE (+13%) and SP (+9%).Conclusions: An integrated checklist combining multiple anamnestic data with selected relevant dermoscopic features can be useful in the differential diagnosis and management of eMM and aN exhibiting with equivocal features

Comparing home and parcel lockers’ delivery systems: a math-heuristic approach

E-commerce is a continuously growing sector worldwide, with important repercussions on the delivery system in urban area and especially in the Business to Consumer (B2C) sector. The delivery of a package to a consumer's address involves not only high costs for couriers (greater number of kilometres travelled), but also increased congestion and greater environmental pollution (greater volume of pollutants released into the air). To rationalize deliveries in urban areas the use of collection points, equipped with lockers, to store the goods that users have ordered has been considered in literature. This work compares two alternative delivery options: deliveries to the consumer's home versus to Lockers. To make this comparison we used a cluster first route second math-heuristic approach. In the clustering phase, we experimented a new clustering function, while the routing phase consists in solving an instance of the Traveling Salesman Problem for each generated cluster. Finally, we applied the math-heuristic to a real case (the Italian municipality of Dolo near Venice) and compared the two delivery alternatives. We evaluate the performance considering two different fleets of vehicles, with small and medium capacity. In addition, since additional trips might be performed by consumers to pick up parcels at Lockers, a sensitivity analysis was carried out to analyse the sustainability of the proposed city logistics scheme

Could hair-lichens of high-elevation forests help detect the impact of global change in the Alps?

Climate change and the anthropic emission of pollutants are likely to have an accelerated impact in high-elevation mountain areas. This phenomenon could have negative consequences on alpine habitats and for species of conservation in relative proximity to dense human populations. This premise implies that the crucial task is in the early detection of warning signals of ecological changes. In alpine landscapes, high-elevation forests provide a unique environment for taking full advantage of epiphytic lichens as sensitive indicators of climate change and air pollution. This literature reviewis intended to provide a starting point for developing practical biomonitoring tools that elucidate the potential of hair-lichens, associated with high-elevation forests, as ecological indicators of global change in the European Alps. We found support for the practical use of hair-lichens to detect the impact of climate change and nitrogen pollution in high-elevation forest habitats. The use of these organisms as ecological indicators presents an opportunity to expand monitoring activities and develop predictive tools that support decisions on how to mitigate the effects of global change in the Alps

The trypanocidal benzoxaborole AN7973 inhibits trypanosome mRNA processing

Kinetoplastid parasites—trypanosomes and leishmanias—infect millions of humans and cause economically devastating diseases of livestock, and the few existing drugs have serious deficiencies. Benzoxaborole-based compounds are very promising potential novel anti-trypanosomal therapies, with candidates already in human and animal clinical trials. We investigated the mechanism of action of several benzoxaboroles, including AN7973, an early candidate for veterinary trypanosomosis. In all kinetoplastids, transcription is polycistronic. Individual mRNA 5'-ends are created by trans splicing of a short leader sequence, with coupled polyadenylation of the preceding mRNA. Treatment of Trypanosoma brucei with AN7973 inhibited trans splicing within 1h, as judged by loss of the Y-structure splicing intermediate, reduced levels of mRNA, and accumulation of peri-nuclear granules. Methylation of the spliced leader precursor RNA was not affected, but more prolonged AN7973 treatment caused an increase in S-adenosyl methionine and methylated lysine. Together, the results indicate that mRNA processing is a primary target of AN7973. Polyadenylation is required for kinetoplastid trans splicing, and the EC50 for AN7973 in T. brucei was increased three-fold by over-expression of the T. brucei cleavage and polyadenylation factor CPSF3, identifying CPSF3 as a potential molecular target. Molecular modeling results suggested that inhibition of CPSF3 by AN7973 is feasible. Our results thus chemically validate mRNA processing as a viable drug target in trypanosomes. Several other benzoxaboroles showed metabolomic and splicing effects that were similar to those of AN7973, identifying splicing inhibition as a common mode of action and suggesting that it might be linked to subsequent changes in methylated metabolites. Granule formation, splicing inhibition and resistance after CPSF3 expression did not, however, always correlate and prolonged selection of trypanosomes in AN7973 resulted in only 1.5-fold resistance. It is therefore possible that the modes of action of oxaboroles that target trypanosome mRNA processing might extend beyond CPSF3 inhibition

FFF-based high-throughput sequence shortlisting to support the development of aptamer-based analytical strategies

Aptamers are biomimetic receptors that are increasingly exploited for the development of optical and electrochemical aptasensors. They are selected in vitro by the SELEX (Systematic Evolution of Ligands by Exponential Enrichment) procedure, but although they are promising recognition elements, for their reliable applicability for analytical purposes, one cannot ignore sample components that cause matrix effects. This particularly applies when different SELEX-selected aptamers and related truncated sequences are available for a certain target, and the choice of the aptamer should be driven by the specific downstream application. In this context, the present work aimed at investigating the potentialities of asymmetrical flow field-flow fractionation (AF4) with UV detection for the development of a screening method of a large number of anti-lysozyme aptamers towards lysozyme, including randomized sequences and an interfering agent (serum albumin). The possibility to work in native conditions and selectively monitor the evolution of untagged aptamer signal as a result of aptamer-protein binding makes the devised method effective as a strategy for shortlisting the most promising aptamers both in terms of affinity and in terms of selectivity, to support subsequent development of aptamer-based analytical devices. Graphical abstract: [Figure not available: see fulltext.

Kinematic bidimensional analysis of the propulsion technique in wheelchair rugby athletes

Wheelchair rugby is a sport ideated for individuals with cervical spinal cord injury (CSCI) which is extremely important for maintaining their neuromuscular abilities and improving their social and psychological wellbeing. However, due to the frequent changes in direction and speed it considerably stresses the players' upper limbs. 13 athletes have undergone two sports-related tests on an inertial drum bench and several kinematic parameters have been registered. Most athletes use a semi-circular pattern which is considered protective for the upper limb. With increasing speed, range of motion (ROM) increases. Release angles increment and contact angles reduce, displacing the push angle forward to increase speed. Instead, the more anterior late push angle used to increase velocity is a factor which further loads the shoulder joint. However, other factors affecting propulsion technique, such as posture and wheelchair set up should be studied to further reduce loading on the upper limb

A fuzzy multi-criteria decision making approach for managing performance and risk in integrated procurement-production planning

Nowadays in Supply Chain (SC) networks, a high level of risk comes from SC partners. An effective risk management process becomes as a consequence mandatory, especially at the tactical planning level. The aim of this article is to present a risk-oriented integrated procurement–production approach for tactical planning in a multi-echelon SC network involving multiple suppliers, multiple parallel manufacturing plants, multiple subcontractors and several customers. An originality of the work is to combine an analytical model allowing to build feasible scenarios and a multi-criteria approach for assessing these scenarios. The literature has mainly addressed the problem through cost or profit-based optimisation and seldom considers more qualitative yet important criteria linked to risk, like trust in the supplier, flexibility or resilience. Unlike the traditional approaches, we present a method evaluating each possible supply scenario through performance-based and risk-based decision criteria, involving both qualitative and quantitative factors, in order to clearly separate the performance of a scenario and the risk taken if it is adopted. Since the decision-maker often cannot provide crisp values for some critical data, fuzzy sets theory is suggested in order to model vague information based on subjective expertise. Fuzzy Technique for Order of Preference by Similarity to Ideal Solution is used to determine both the performance and risk measures correlated to each possible tactical plan. The applicability and tractability of the proposed approach is shown on an illustrative example and a sensitivity analysis is performed to investigate the influence of criteria weights on the selection of the procurement–production plan

Structural analysis and corrosion studies on an ISO 5832-9 biomedical alloy with TiO2 sol–gel layers

The aim of this study was to demonstrate the relationship between the structural and corrosion properties of an ISO 5832-9 biomedical alloy modified with titanium dioxide (TiO2) layers. These layers were obtained via the sol–gel method by acid-catalyzed hydrolysis of titanium isopropoxide in isopropanol solution. To obtain TiO2 layers with different structural properties, the coated samples were annealed at temperatures of 200, 300, 400, 450, 500, 600 and 800 C for 2 h. For all the prepared samples, accelerated corrosion measurements were performed in Tyrode’s physiological solution using electrochemical methods. The most important corrosion parameters were determined: corrosion potential, polarization resistance, corrosion rate, breakdown and repassivation potentials. Corrosion damage was analyzed using scanning electron microscopy. Structural analysis was carried out for selected TiO2 coatings annealed at 200, 400, 600 and 800 C. In addition, the morphology, chemical composition, crystallinity, thickness and density of the deposited TiO2 layers were determined using suitable electron and X-ray measurement methods. It was shown that the structure and character of interactions between substrate and deposited TiO2 layers depended on annealing temperature. All the obtained TiO2 coatings exhibit anticorrosion properties, but these properties are related to the crystalline structure and character of substrate–layer interaction. From the point of view of corrosion, the best TiO2 sol–gel coatings for stainless steel intended for biomedical applications seem to be those obtained at 400 C.This study was supported by Grant No. N N507 501339 of the National Science Centre. The authors wish to express their thanks to J. Borowski (MEDGAL, Poland) for the Rex 734 alloy