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Computational and Structural... 2020In the past few years, deep learning has been successfully applied to various omics data. However, the applications of deep learning in metabolomics are still relatively... (Review)
Review
In the past few years, deep learning has been successfully applied to various omics data. However, the applications of deep learning in metabolomics are still relatively low compared to others omics. Currently, data pre-processing using convolutional neural network architecture appears to benefit the most from deep learning. Compound/structure identification and quantification using artificial neural network/deep learning performed relatively better than traditional machine learning techniques, whereas only marginally better results are observed in biological interpretations. Before deep learning can be effectively applied to metabolomics, several challenges should be addressed, including metabolome-specific deep learning architectures, dimensionality problems, and model evaluation regimes.
PubMed: 33133423
DOI: 10.1016/j.csbj.2020.09.033 -
Population and Development Review Jun 2022Estimating excess mortality is challenging. The metric depends on the expected mortality level, which can differ based on given choices, such as the method and the time...
Estimating excess mortality is challenging. The metric depends on the expected mortality level, which can differ based on given choices, such as the method and the time series length used to estimate the baseline. However, these choices are often arbitrary, and are not subject to any sensitivity analysis. We bring to light the importance of carefully choosing the inputs and methods used to estimate excess mortality. Drawing on data from 26 countries, we investigate how sensitive excess mortality is to the choice of the mortality index, the number of years included in the reference period, the method, and the time unit of the death series. We employ two mortality indices, three reference periods, two data time units, and four methods for estimating the baseline. We show that excess mortality estimates can vary substantially when these factors are changed, and that the largest variations stem from the choice of the mortality index and the method. We also find that the magnitude of the variation in excess mortality is country-specific, resulting in cross-country rankings changes. Finally, based on our findings, we provide guidelines for estimating excess mortality.
PubMed: 35600716
DOI: 10.1111/padr.12475 -
PLoS Computational Biology Nov 2021We present artificial neural networks as a feasible replacement for a mechanistic model of mosquito abundance. We develop a feed-forward neural network, a long...
We present artificial neural networks as a feasible replacement for a mechanistic model of mosquito abundance. We develop a feed-forward neural network, a long short-term memory recurrent neural network, and a gated recurrent unit network. We evaluate the networks in their ability to replicate the spatiotemporal features of mosquito populations predicted by the mechanistic model, and discuss how augmenting the training data with time series that emphasize specific dynamical behaviors affects model performance. We conclude with an outlook on how such equation-free models may facilitate vector control or the estimation of disease risk at arbitrary spatial scales.
Topics: Aedes; Animals; Computational Biology; Databases, Factual; Humans; Models, Biological; Mosquito Vectors; Neural Networks, Computer; Population Dynamics; Spatio-Temporal Analysis; Stochastic Processes; Systems Analysis; United States; Vector Borne Diseases; Weather
PubMed: 34797822
DOI: 10.1371/journal.pcbi.1009467 -
Frontiers in Genetics 2021This minireview describes the history of the conceptual development of conserved extended haplotypes (CEHs): megabase-length haplotypes that exist at high (≥0.5%)... (Review)
Review
This minireview describes the history of the conceptual development of conserved extended haplotypes (CEHs): megabase-length haplotypes that exist at high (≥0.5%) population frequency. My career began in internal medicine, shifted to pediatrics, and clinical practice changed to research. My research interest was initially in hematology: on plasma proteins, their metabolism, synthesis, and function. This narrowed to a focus on proteins of the human complement system, their role in immunity and their genetics, beginning with polymorphism and deficiency of C3. My group identified genetic polymorphisms and/or inherited deficiencies of C2, C4, C6, and C8. After defining glycine-rich beta glycoprotein as factor B (Bf) in the properdin system, we found that the genes for Bf (), C2, C4A, and C4B were inherited as a single haplotypic unit which we named the "complotype." Complotypes are located within the major histocompatibility complex (MHC) between and and are designated (in arbitrary order) by their , , , and types. Pedigree analysis revealed long stretches (several megabases) of apparently fixed DNA within the MHC that we referred to as "extended haplotypes" (later as "CEHs"). About 10 to 12 common CEHs constitute at least 25 - 30% of MHC haplotypes among European Caucasian populations. These CEHs contain virtually all the most common markers of MHC-associated diseases. In the case of type 1 diabetes, we have proposed a purely genetic and epigenetic model (with a small number of Mendelian recessive disease genes) that explains all the puzzling features of the disease, including its rising incidence.
PubMed: 34422017
DOI: 10.3389/fgene.2021.716603 -
Scientific Reports Jan 2018Architectured materials with rationally designed geometries could be used to create mechanical metamaterials with unprecedented or rare properties and functionalities....
Architectured materials with rationally designed geometries could be used to create mechanical metamaterials with unprecedented or rare properties and functionalities. Here, we introduce "shape-matching" metamaterials where the geometry of cellular structures comprising auxetic and conventional unit cells is designed so as to achieve a pre-defined shape upon deformation. We used computational models to forward-map the space of planar shapes to the space of geometrical designs. The validity of the underlying computational models was first demonstrated by comparing their predictions with experimental observations on specimens fabricated with indirect additive manufacturing. The forward-maps were then used to devise the geometry of cellular structures that approximate the arbitrary shapes described by random Fourier's series. Finally, we show that the presented metamaterials could match the contours of three real objects including a scapula model, a pumpkin, and a Delft Blue pottery piece. Shape-matching materials have potential applications in soft robotics and wearable (medical) devices.
PubMed: 29343772
DOI: 10.1038/s41598-018-19381-3 -
Environmental Science and Pollution... Aug 2021This paper contributes to the environmental literature by (i) demonstrating that the estimated coefficients and the statistical significance of the non-leading terms in...
This paper contributes to the environmental literature by (i) demonstrating that the estimated coefficients and the statistical significance of the non-leading terms in quadratic, cubic, and quartic logarithmic environmental Kuznets curve (EKC) specifications are arbitrary and should therefore not be used to choose the preferred specification and (ii) detailing a proposed general-to-specific type methodology for choosing the appropriate specifications when attempting to estimate higher-order polynomials such as cubic and quartic logarithmic EKC relationships. Testing for the existence and shape of the well-known EKC phenomenon is a hot topic in the environmental economics literature. The conventional approach widely employs quadratic and cubic specifications and more recently also the quartic specification, where the variables are in logarithmic form. However, it is important that researchers understand whether the estimated EKC coefficients, turning points, and elasticities are statistically acceptable, economically interpretable, and comparable. In addition, it is vital that researchers have a clear structured non-arbitrary methodology for determining the preferred specification and hence shape of the estimated EKC. We therefore show mathematically and empirically the arbitrary nature of estimated non-leading coefficients in quadratic, cubic, and quartic logarithmic EKC specifications, being dependent upon the units of measurement chosen for the independent variables (e.g. dependent upon a rescaling of the variables such as moving from $m to $bn). Consequently, the practice followed in many previously papers, whereby the estimates of the non-leading terms are used in the decision to choose the preferred specification of an estimated EKC relationship, is incorrect and should not be followed since it potentially could lead to misleading conclusions. Instead, it should be based upon the sign and statistical significance of the estimated coefficients of the leading terms, the location of turning point(s), and the sign and statistical significance of the estimated elasticities. Furthermore, we suggest that researchers should follow a proposed general-to-specific type methodology for choosing the appropriate order of polynomials when attempting to estimate higher-order polynomial logarithmic EKCs.
Topics: Algorithms; Carbon Dioxide; Economic Development; Humans
PubMed: 33797046
DOI: 10.1007/s11356-021-13463-y -
Physical Review Applied Aug 2022Airy beams are peculiar beams that are non-diffracting, self-accelerating, and self-healing, and they have offered great opportunities for ultrasound beam manipulation....
Airy beams are peculiar beams that are non-diffracting, self-accelerating, and self-healing, and they have offered great opportunities for ultrasound beam manipulation. However, one critical barrier that limits the broad applications of Airy beams in ultrasound is the lack of simply built device to generate Airy beams in water. This work presents a family of Airy beam-enabled binary acoustic metasurfaces (AB-BAMs) to generate Airy beams for underwater ultrasound beam manipulation. AB-BAMs are designed and fabricated by 3D printing with two coding bits: a polylactic acid (which is the commonly used 3D printing material) unit acting as a bit "1" and a water unit acting as a bit "0". The distribution of the binary units on the metasurface is determined by the pattern of Airy beam. To showcase the wavefront engineering capability of the AB-BAMs, several examples of AB-BAMs are designed, 3D printed, and coupled with a planar single-element ultrasound transducer for experimental validation. We demonstrate the capability of AB-BAMs in flexibly tuning the focal region size and beam focusing in 3D space by changing the design of the AB-BAMs. The focal depth of AB-BAMs can be continuous and electronical tuned by adjusting the operating frequency of the planar transducer without replacing the AB-BAMs. The superimposing method is leveraged to enable the generation of complex acoustic fields, e.g., multi-foci and letter patterns (e.g., "W" and "U"). The more complex focal patterns are shown to be also continuously steerable by simply adjusting the operating frequency. Furthermore, the proposed 3D-printed AB-BAMs are simple to design, easy to fabricate, and low-cost to produce with the capabilities to achieve tunable focal size, flexible 3D beam focusing, arbitrary multipoint focusing, and continuous steerability, which creates unprecedented potential for ultrasound beam manipulation.
PubMed: 36600893
DOI: 10.1103/physrevapplied.18.024070 -
JAMA Ophthalmology Feb 2023Tumor necrosis factor inhibitors (TNFis) can induce antidrug antibody (ADA) formation and loss of therapeutic response. However, the utility of ADA testing and the...
IMPORTANCE
Tumor necrosis factor inhibitors (TNFis) can induce antidrug antibody (ADA) formation and loss of therapeutic response. However, the utility of ADA testing and the association between ADAs and treatment response in patients with noninfectious uveitis (NIU) is not well understood.
OBJECTIVE
To assess the frequency of ADAs and their association with drug levels and clinical response in patients with NIU treated with adalimumab or infliximab.
DESIGN, SETTING, AND PARTICIPANTS
This retrospective cross-sectional study included patients diagnosed with NIU who received adalimumab or infliximab and underwent testing for serum drug level and ADAs at the National Eye Institute from September 2017 to July 2021.
EXPOSURES
Serum drug level testing with reflex testing for ADA levels was performed.
MAIN OUTCOMES AND MEASURES
The main outcome was the association between drug levels and ADAs, clinical response, and concurrent antimetabolite use in patients treated with TNFis for NIU.
RESULTS
Of 54 patients included in the study, 42 received adalimumab (mean [SD] age, 43.6 [19.6] years; 25 [59.5%] female) and 12 received infliximab (mean [SD] age, 42.7 [20.4] years; 7 [58.3%] male). In the adalimumab group, mean (SD) drug level was 9.72 (6.82) μg/mL, mean (SD) ADA level was 84.2 (172.9) arbitrary units/mL, and ADA frequency was 35.7% (15 of 42 patients). Mean drug level was lower in those with ADAs compared with those without ADAs (mean [SD], 2.8 [2.6] μg/mL vs 13.6 [5.2] μg/mL; difference: 10.8 μg/mL; 95% CI, 8.3-13.2 μg/mL; P < .001). There was a higher mean drug level with concurrent antimetabolite use compared with monotherapy (mean [SD], 11.0 [7.3] μg/mL vs 6.8 [4.5] μg/mL; difference: -4.2 μg/mL; 95% CI, -8.7 to 0.2 μg/mL; P = .06). Multivariable modeling showed that a 1-arbitrary unit increase in ADAs was associated with a -0.02 μg/mL (95% CI, -0.01 to -0.34 μg/mL) difference in mean drug level (P < .001). Favorable clinical response was associated with a threshold drug level above 2.7 μg/mL or an antibody level below 15.2 μg/mL. The mean (SD) drug level in the infliximab group was 27.02 (18.15) μg/mL, and no ADAs were detected.
CONCLUSIONS AND RELEVANCE
In this study, 35.7% of adalimumab-treated patients with NIU had ADAs. The presence of ADAs was associated with lower drug levels, and higher ADA levels were associated with increased risk of TNFi treatment failure. Although limited by the retrospective design, our results suggest that therapeutic drug monitoring may be considered among patients experiencing therapy failure to help exclude ADAs as a potential cause of treatment failure.
Topics: Humans; Male; Female; Adult; Infliximab; Adalimumab; Tumor Necrosis Factor-alpha; Retrospective Studies; Drug Monitoring; Cross-Sectional Studies; Antibodies; Immunologic Factors; Immunosuppressive Agents; Uveitis; Antimetabolites
PubMed: 36547953
DOI: 10.1001/jamaophthalmol.2022.5584 -
Sports (Basel, Switzerland) May 2019The effects of submaximal performances on critical speed (S) and critical power (P) were studied in 3 protocols: a constant-speed protocol (protocol 1), a constant-time...
The effects of submaximal performances on critical speed (S) and critical power (P) were studied in 3 protocols: a constant-speed protocol (protocol 1), a constant-time protocol (protocol 2) and a constant-distance protocol (protocol 3). The effects of submaximal performances on S and P were studied with the results of two theoretical maximal exercises multiplied by coefficients lower or equal to 1 (from 0.8 to 1 for protocol 1; from 0.95 to 1 for protocols 2 and 3): coefficient C for the shortest exercises and C for the longest exercises. Arbitrary units were used for exhaustion times (t), speeds (or power-output in cycling) and distances (or work in cycling). The submaximal-performance effects on S and P were computed from two ranges of t (1-4 and 1-7). These effects have been compared for a low-endurance athlete (exponent = 0.8 in the power-law model of Kennelly) and a high-endurance athlete (exponent = 0.95). Unexpectedly, the effects of submaximal performances on S and P are lower in protocol 1. For the 3 protocols, the effects of submaximal performances on S, and P, are low in many cases and are lower when the range of t is longer. The results of the present theoretical study confirm the possibility of the computation of S and P from several submaximal exercises performed in the same session.
PubMed: 31159341
DOI: 10.3390/sports7060136 -
Medical Ultrasonography May 2022Contrast-enhanced ultrasound (CEUS) appears to be a promising application for the diagnosis of parotid gland tumours. We aimed to systematically review and meta-analyse... (Meta-Analysis)
Meta-Analysis Review
AIM
Contrast-enhanced ultrasound (CEUS) appears to be a promising application for the diagnosis of parotid gland tumours. We aimed to systematically review and meta-analyse the ability of CEUS in distinguishing benign from malignant parotid gland tumours.
MATERIAL AND METHODS
PubMed was searched for relevant studies. Data on area under time intensity curve (AUC) in arbitrary unit (AU), and mean transit time (MTT) in seconds (sec) were analysed using the Cochrane Review Manager Software.
RESULTS
Nine studies met the eligibility criteria comprising a total number of 498 parotid gland tumours (benign, number (n)=423; malignant, n=75). Descriptive evaluation of parotid gland tumours following CEUS administration showed overlap characteristics in benign and malignancies. Two publications assessed AUC and MTT in 72 and 60 parotid gland tumours, respectively. AUC was significantly lower in benign compared to malignant tumours following contrast administration (AUC, mean difference (MD) -266.77 AU, 95% confidence intervals (CI) -433.22, -100.33, p=0.002). No significant different in MTT between benign and malignant tumours (p=0.12). Heterogeneity was statistically significant in AUC (p=0.04) and MTT (p<0.00001).
CONCLUSION
Descriptive evaluation of parotid gland tumours showed overlap CEUS characteristics. Perfusion related CEUS parameters analysis is promising in differentiating benign parotid tumours from malignancies.
Topics: Contrast Media; Diagnosis, Differential; Humans; Parotid Gland; Parotid Neoplasms; Perfusion; Ultrasonography
PubMed: 34216453
DOI: 10.11152/mu-3119