Nevin Manimala

Neural Netw. 2021 Jun 15;143:230-245. doi: 10.1016/j.neunet.2021.06.013. Online ahead of print.

ABSTRACT

This paper discusses the periodicity and multi-periodicity in delayed Cohen-Grossberg-type neural networks (CGNNs) possessing impulsive effects, whose activation functions possess discontinuities and are allowed to be unbounded or nonmonotonic. Based on differential inclusion and cone expansion-compression fixed-point theory of set-valued mapping, several improved criteria are given to derive the positive solution with ω-periodicity and ω-multi-periodicity for delayed CGNNs under impulsive control. These ω-periodicity/ω-multi-periodicity orbits are produced by impulses control. The analytical method and theoretical results presented in this paper are of certain significance to the design of neural network models or circuits possessing discontinuous neuron activation and impulsive effects in periodic environment.

PMID:34157647 | DOI:10.1016/j.neunet.2021.06.013

Eur J Radiol. 2021 Jun 11;141:109816. doi: 10.1016/j.ejrad.2021.109816. Online ahead of print.

ABSTRACT

OBJECTIVES: Rapid communication of CT exams positive for pulmonary embolism (PE) is crucial for timely initiation of anticoagulation and patient outcome. It is unknown if deep learning automated detection of PE on CT Pulmonary Angiograms (CTPA) in combination with worklist prioritization and an electronic notification system (ENS) can improve communication times and patient turnaround in the Emergency Department (ED).

METHODS: In 01/2019, an ENS allowing direct communication between radiology and ED was installed. Starting in 10/2019, CTPAs were processed by a deep learning (DL)-powered algorithm for detection of PE. CTPAs acquired between 04/2018 and 06/2020 (n = 1808) were analysed. To assess the impact of the ENS and the DL-algorithm, radiology report reading times (RRT), radiology report communication time (RCT), time to anticoagulation (TTA), and patient turnaround times (TAT) in the ED were compared for three consecutive time periods. Performance measures of the algorithm were calculated on a per exam level (sensitivity, specificity, PPV, NPV, F1-score), with written reports and exam review as ground truth.

RESULTS: Sensitivity of the algorithm was 79.6 % (95 %CI:70.8-87.2%), specificity 95.0 % (95 %CI:92.0-97.1%), PPV 82.2 % (95 %CI:73.9-88.3), and NPV 94.1 % (95 %CI:91.4-96 %). There was no statistically significant reduction of any of the observed times (RRT, RCT, TTA, TAT).

CONCLUSION: DL-assisted detection of PE in CTPAs and ENS-assisted communication of results to referring physicians technically work. However, the mere clinical introduction of these tools, even if they exhibit a good performance, is not sufficient to achieve significant effects on clinical performance measures.

PMID:34157638 | DOI:10.1016/j.ejrad.2021.109816

Eur J Cancer. 2021 Jun 19;153:142-152. doi: 10.1016/j.ejca.2021.05.023. Online ahead of print.

ABSTRACT

BACKGROUND: This phase 1 study evaluated safety, pharmacokinetics (PK), maximum tolerated dose (MTD), and antitumour activity of regorafenib in paediatric patients with solid tumours.

PATIENTS AND METHODS: Patients (aged 6 months to <18 years) with recurrent/refractory solid tumours received oral regorafenib once daily for 3 weeks on/1 week off. The starting dose (60 mg/m²) was derived from an adult physiology-based PK model and scaled to children; dose escalation was followed by safety expansion of the MTD cohort. Treatment-emergent adverse events (TEAEs) were evaluated using National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. Regorafenib PK was evaluated using a population PK model.

RESULTS: Forty-one patients (median age 13 years) received regorafenib (four cohorts: 60-93 mg/m²). Five of 23 evaluable patients experienced dose-limiting toxicities (Grade 4 thrombocytopenia, Grade 3 maculopapular rash, pyrexia, hypertension, and exfoliative dermatitis [each n = 1]). The MTD was defined as 82 mg/m². The most common Grade ≥3 drug-related TEAE was thrombocytopenia (10%). The incidence and severity of hypertension, diarrhoea, fatigue, hypothyroidism, and hand-foot skin reaction were lower than reported in adults. Regorafenib exposure increased with dose, with substantial overlap because of moderate-to-high interpatient variability. One patient with rhabdomyosarcoma experienced an unconfirmed partial response; 15 patients had stable disease, five for >16 weeks.

CONCLUSIONS: The recommended phase 2 dose of single-agent regorafenib in paediatric patients with solid malignancies is 82 mg/m². Regorafenib demonstrated acceptable tolerability and preliminary antitumour activity, supporting further investigation in paediatric patients.

CLINICAL TRIAL NUMBER: NCT02085148.

PMID:34157616 | DOI:10.1016/j.ejca.2021.05.023

Plant Physiol Biochem. 2021 Jun 16;166:427-436. doi: 10.1016/j.plaphy.2021.06.012. Online ahead of print.

ABSTRACT

Hotness or pungency is the major trait of genetically diverse and economically valuable chili (Capsicum sp.) cultivars. However, little is known about the influence of soil characteristics on genetic regulation of pungency vis-à-vis capsaicin formation in endemic chilies. Hence, the present work was conducted by growing two endemic chili cultivars in two types (alluvial and lateritic) of soil. Capsaicin content, pungency, and capsaicin synthase activity were significantly greater in chilies grown in alluvial soil than in lateritic soil. Correspondingly, Csy1, the gene that encodes capsaicin synthase, was significantly upregulated in alluvial soil grown plants. Interestingly, upregulation of Pun1, the gene responsible for capsaicin accumulation in fruits, was more in lateritic soil than in alluvial soil; but pungency was inhibited in lateritic soil by the overexpression of Pun1², a recessive allele of Pun1 locus. Statistical analyses revealed that high organic C, microbial activity, and NPK status in alluvial soil were responsible for high pungency, capsaicin synthase activity, capsaicin accumulation, and suppression of Pun1². Fruit yield, dry matter, crude protein, titratable acidity, and soluble solids were also significantly high in chilies grown in alluvial soil. Therefore, we postulate that soil quality attributes play vital roles in genetic regulation of pungency, capsaicin biosynthesis, fruit yield, and produce quality of endemic chili cultivars.

PMID:34157605 | DOI:10.1016/j.plaphy.2021.06.012

Food Chem. 2021 Jun 16;364:130381. doi: 10.1016/j.foodchem.2021.130381. Online ahead of print.

ABSTRACT

The objective of this study was to explore the potentiality and mechanism of visible and near-infrared (Vis-NIR) spectroscopy in estimating the freshness of komatsuna. We monitored the cumulative CO₂ production of komatsuna stored under different conditions as a freshness indicator and measured the Vis-NIR spectra of komatsuna as the predictor. Using the informative wavelengths (IW) selected using the stepwise selectivity ratio method, we constructed an accurate freshness prediction model through PLSR analysis. The IW in the visible region were attributed to pigments such as chlorophyll. In the NIR region, ten amino acids were identified as directly or indirectly contributing to the IW and were highly related to freshness. They were confirmed on the basis of the strong correlations between the informative NIR signals and NMR signals, which were determined using statistical heterospectroscopy. The results demonstrate the feasibility of Vis-NIR spectroscopy in estimating the freshness of komatsuna using the IW.

PMID:34157592 | DOI:10.1016/j.foodchem.2021.130381

Hum Mov Sci. 2021 Jun 19;78:102832. doi: 10.1016/j.humov.2021.102832. Online ahead of print.

ABSTRACT

Among adults, persons in control of a vehicle (i.e., drivers) are less likely to experience motion sickness compared to persons in the same vehicle who do not control it (i.e., passengers). This “driver-passenger effect” is well-known in adults, but has not been evaluated in children. Using a yoked-control design with seated pre-adolescent children, we exposed dyads to a driving video game. In each dyad, one child (the driver) drove the virtual vehicle. Their performance was recorded, and later shown to the other child (the passenger). Thus, visual motion stimuli were identical for the members of each dyad. During exposure to the video game, we monitored the quantitative kinematics of head and torso movements. Participants were instructed to discontinue participation immediately if they experienced any symptoms of motion sickness, however mild. Accordingly, the movements that we recorded preceded the onset of motion sickness. Results revealed that Passengers (73.08%) were more likely than Drivers (42.31%) to state that they were motion sick. Drivers tended to move more than passengers, and with a greater degree of multifractality. The magnitude of movement was greater among participants who later reported motion sickness than among those who did not. In addition, for the multifractality of movement a statistically significant interaction revealed that postural precursors of motion sickness differed qualitatively between Drivers and Passengers. Overall, the results reveal that control of a virtual vehicle reduces the risk of motion sickness among pre-adolescent children.

PMID:34157576 | DOI:10.1016/j.humov.2021.102832

J Environ Manage. 2021 Jun 19;295:113019. doi: 10.1016/j.jenvman.2021.113019. Online ahead of print.

ABSTRACT

Urban soils’ health is important to the community because of the soils’ potential use for recreational activities. A data quality-oriented approach to sampling design is proposed for performing soil representative surveys that gives support to defensible and statistically-based decisions. Krowoderski park in Cracow (Poland) was selected as a study case to investigate heavy metals (HMs) accumulation and to assess human risk exposure according to simulated scenarios. Statistical power was computed for optimizing the number of samples to compare HMs concentration against legal upper tolerance levels (LUTL). The samples’ location was iteratively designed as random spatial distribution throughout the study area, followed by K Ripley’s test for selecting the best sampling scheme and avoiding points of clustering or dispersion at several ranges. The total content of Cd, Cu, Pb, Zn, coarse size particles fraction and fine size particles texture, bulk density, pH, total C and S were measured in topsoil at each location using composite sampling. The hydraulic properties were estimated using pedotransfer functions. Statistical analysis of topsoil data shows low correlation between heavy metals, whereas high correlation was found between total S with Cu and Pb as well as total C with Cu and Pb. The concentration of all the HMs analysed was found to be under LUTL in all locations in the park, except for one point that is an outlier for Pb, although the values of several indexes for pooled HMs categorize the park as medium to highly polluted. Spatial autocorrelation was explored for every heavy metal and for elaborated pollution indexes, then maps were drawn using geostatistics. A human health risk assessment (HHRA) was computed for several simulated scenarios finding that risk exists for children from Pb through high ingestion of soil particles.

PMID:34157543 | DOI:10.1016/j.jenvman.2021.113019

Sci Total Environ. 2021 Jun 10;792:148406. doi: 10.1016/j.scitotenv.2021.148406. Online ahead of print.

ABSTRACT

BACKGROUND: Dengue is an endemic vector-borne disease influenced by environmental factors such as landscape and climate. Previous studies separately assessed the effects of landscape and climate factors on mosquito occurrence and dengue incidence. However, both factors concurrently coexist in time and space and can interact, affecting mosquito development and dengue disease transmission. For example, eggs laid in a suitable environment can hatch after being submerged in rain water. It has been difficult for conventional statistical modeling approaches to demonstrate these combined influences due to mathematical constraints.

OBJECTIVES: To investigate the combined influences of landscape and climate factors on mosquito occurrence and dengue incidence.

METHODS: Entomological, epidemiological, and landscape data from the rainy season (July-December) were obtained from respective government agencies in Metropolitan Manila, Philippines, from 2012 to 2014. Temperature, precipitation and vegetation data were obtained through remote sensing. A random forest algorithm was used to select the landscape and climate variables. Afterward, using the identified key variables, a model-based (MOB) recursive partitioning was implemented to test the combined influences of landscape and climate factors on ovitrap index (vector mosquito occurrence) and dengue incidence.

RESULTS: The MOB recursive partitioning for ovitrap index indicated a high sensitivity of vector mosquito occurrence on environmental conditions generated by a combination of high residential density areas with low precipitation. Moreover, the MOB recursive partitioning indicated high sensitivity of dengue incidence to the effects of precipitation in areas with high proportions of residential density and commercial areas.

CONCLUSIONS: Dengue dynamics are not solely influenced by individual effects of either climate or landscape, but rather by their synergistic or combined effects. The presented findings have the potential to target vector surveillance in areas identified as suitable for mosquito occurrence under specific climatic conditions and may be relevant as part of urban planning strategies to control dengue.

PMID:34157535 | DOI:10.1016/j.scitotenv.2021.148406

Clin Neurol Neurosurg. 2021 Jun 8;207:106739. doi: 10.1016/j.clineuro.2021.106739. Online ahead of print.

ABSTRACT

BACKGROUND: Non-Epileptic Paroxysmal Events (NEPE) are common clinical manifestations in pediatric age presenting with dysfunction of motor and behavioral activity mimicking features of epileptic seizures.

OBJECTIVE: To present and analyze number and clinical characteristic of a group of children/adolescents presenting with various types of NEPE; to compare clinical data of this group of NEPE affected children/adolescents with a group of children/adolescents affected by Epileptic Seizures (ES).

METHODS: The retrospective study was conducted at the Pediatric Clinic of University of Catania, Catania, Italy, in a period ranging from January 2005 and January 2018. Two groups of children/adolescents, aged from 1 month to 15 years, were selected: 312 affected by NEPE and 192 by ES. Number and percentage of the single type of NEPE were reported. Then, demographic characteristics, clinical manifestations, duration of the events, time of diagnosis, and age of onset of each type of NEPE and ES affected children/adolescents were analyzed and compared. Results of statistical analysis of the data were carried out between ES and some type of NEPEs including Sandifer syndrome, breath-holding spells, paroxysmal tremors, vertigo, and syncope.

RESULTS: Among the group of NEPE, vertigo, type of paroxysmal event clinically not classifiable, syncope, and Sandifer syndrome were the most common events; In the comparative analyzed samples, variability between NEPE and ES was found in the duration of the paroxysmal events, in number of episodes, in lag-time between the onset of symptoms and the diagnosis, and in age of onset. Analyzing clinical data of ES with some type of NEPE, statistical significant results were obtained in vertigo as regards the duration and average duration event, in paroxysmal tremors as number of events, in Sandifer syndrome as lag-time of diagnosis, and finally in all the types of NEPE as regards the age of onset, and loss of consciousness.

CONCLUSIONS: Analyzing the clinical features of each type of NEPE differences with ES are found. However, globally considered diagnostic differences between NEPE and ES remain difficult, questionable, and unrealizable without the support of correct parental report, direct clinical observations, and video-EEG monitoring.

PMID:34157509 | DOI:10.1016/j.clineuro.2021.106739

EBioMedicine. 2021 Jun 19;69:103436. doi: 10.1016/j.ebiom.2021.103436. Online ahead of print.

ABSTRACT

BACKGROUND: Due to the molecular mechanism complexity and heterogeneity of gastric cancer (GC), mechanistically interpretable biomarkers were required for predicting prognosis and discovering therapeutic targets for GC patients.

METHODS: Based on a total of 824 GC-specific fitness genes from the Project Score database, LASSOCox regression was performed in TCGA-STAD cohort to construct a GC Prognostic (GCP) model which was then evaluated on 7 independent GC datasets. Targets prioritization was performed in GC organoids. ARGLU1 was selected to further explore the biological function and molecular mechanism. We evaluated the potential of ARGLU1 serving as a promising therapeutic target for GC using patients derived xenograft (PDX) model.

FINDINGS: The 9-gene GCP model showed a statistically significant prognostic performance for GC patients in 7 validation cohorts. Perturbation of SSX4, DDX24, ARGLU1 and TTF2 inhibited GC organoids tumor growth. The results of tissue microarray indicated lower expression of ARGLU1 was correlated with advanced TNM stage and worse overall survival. Over-expression ARGLU1 significantly inhibited GC cells viability in vitro and in vivo. ARGLU1 could enhance the transcriptional level of mismatch repair genes including MLH3, MSH2, MSH3 and MSH6 by potentiating the recruitment of SP1 and YY1 on their promoters. Moreover, inducing ARGLU1 by LNP-formulated saRNA significantly inhibited tumor growth in PDX model.

INTERPRETATION: Based on genome-wide functional screening data, we constructed a 9-gene GCP model with satisfactory predictive accuracy and mechanistic interpretability. Out of nine prognostic genes, ARGLU1 was verified to be a potential therapeutic target for GC.

FUNDING: National Natural Science Foundation of China.

PMID:34157484 | DOI:10.1016/j.ebiom.2021.103436