Pruning deep neural networks generates a sparse, bio-inspired nonlinear controller for insect flight.

Insect flight is a strongly nonlinear and actuated dynamical system. As such, strategies for understanding its control have typically relied on either model-based methods or linearizations thereof. Here we develop a framework that combines model predictive control on an established flight dynamics model and deep neural networks (DNN) to create an efficient method for solving the inverse problem of flight control. We turn to natural systems for inspiration since they inherently demonstrate network pruning with the consequence of yielding more efficient networks for a specific set of tasks. This bio-inspired approach allows us to leverage network pruning to optimally sparsify a DNN architecture in order to perform flight tasks with as few neural connections as possible, however, there are limits to sparsification. Specifically, as the number of connections falls below a critical threshold, flight performance drops considerably. We develop sparsification paradigms and explore their limits for control tasks. Monte Carlo simulations also quantify the statistical distribution of network weights during pruning given initial random weights of the DNNs. We demonstrate that on average, the network can be pruned to retain a small amount of original network weights and still perform comparably to its fully-connected counterpart. The relative number of remaining weights, however, is highly dependent on the initial architecture and size of the network. Overall, this work shows that sparsely connected DNNs are capable of predicting the forces required to follow flight trajectories. Additionally, sparsification has sharp performance limits.

Is there autochthonous strongyloidiasis in Spanish children?

Strongyloidiasis, a neglected helminthiasis, is more prevalent in tropical/subtropical areas. However, sporadic autochthonous cases have been described around the Mediterranean coast. We performed a retrospective descriptive study in a referral Spanish Center for Pediatric Tropical diseases. All patients below 18 years of age diagnosed with probable strongyloidiasis between January 2014 and December 2019, born in Spain and with no history of travel abroad, were included. Epidemiological, clinical, and follow-up data were recorded, as well as all microbiology results. Five children met the inclusion criteria and were included in the study. Three males and two females, with a median age of 6.7 years (IQR: 5.8-9.1). All patients had previous medical conditions and used to spend holidays on the Mediterranean coast of Spain. All but one were mildly symptomatic at diagnosis but only four presented peripheral eosinophilia, which was the main reason for referral. First-line treatment was ivermectin in all but one, who was treated with albendazole. Reinfection was suspected in two during follow-up. At 12 months of follow-up 3/5 (60%) children presented negative serology.Conclusion: Although more prevalent in tropical areas, strongyloidiasis should be included among differential diagnosis in children presenting with eosinophilia. Screening for strongyloidiasis should be considered in all children candidate to immunosuppressive therapy. What is Known: • Strongyloidiasis is more prevalent in tropical/subtropical areas. • Strongyloidiasis can be life-threatening in immunosuppressed patients What is New: • Spanish children can be affected by autochthonous strongyloidiasis. • Screening for strongiloidiasis should be performed in all candidates to immunosuppresive therapies, including children.

Intra- and extradural anterior clinoidectomy: anatomy review and surgical technique step by step.

PURPOSE: The complex relations of the paraclinoid area make the surgical management of the pathology of this region a challenge. The anterior clinoid process (ACP) is an anatomical landmark that hinders the visualization and manipulation of the surrounding neurovascular structures, hence in certain surgical interventions might be necessary to remove it. We reviewed the anatomical relationships that involve the paraclinoid area and detailed the step-by-step techniques of intra and extradural clinoidectomy in cadaveric specimens. MATERIALS AND METHODS: A literature review was done describing the most relevant anatomic relationships regarding the anterior clinoid process. Extradural and intradural clinoidectomy techniques were performed in six dry bone heads and in ten previously injected cadaverous specimens with colored latex (Sanan et al. in Neurosurgery 45:1267-1274, 1999) and each step of the procedure was recorded using photographic material. Finally, an analysis of the anatomical exposure achieved in each of the techniques used was performed. RESULTS: The main advantage of the intradural clinoidectomy technique is the direct visualization of the neurovascular structures adjacent to the ACP when drilling, at the same time, opening the Sylvian fissure will allow the direct visualization of the ACP variants. The main advantage offered by the extradural technique is that the dura protects adjacent eloquent structures while drilling. Among the disadvantages, it is noted that the same dura that would protect the underlying structures also prevents the direct visualization of these neurovascular structures adjacent to the ACP. CONCLUSION: We reviewed the anatomy of the paraclinoid area and made a step-by-step description of the technique of the anterior clinoidectomy in its intra- and extradural variants in cadaveric preparations for a better understanding.

Loss of p53 enhances the tumor-initiating potential and drug resistance of clonogenic multiple myeloma cells.

Tumor relapse and drug resistance are major factors that limit the curability of multiple myeloma (MM). New regimens have improved overall MM survival rates, but patients with high-risk features continue to have inferior outcomes. Chromosome 17p13 deletion (del17p) that includes the loss of the TP53 gene is a high-risk cytogenetic abnormality and is associated with poor clinical outcomes owing to relatively short remissions and the development of pan-drug resistant disease. Increased relapse rates suggest that del17p enhances clonogenic growth, and we found that the loss of p53 increased both the frequency and drug resistance of tumor-initiating MM cells (TICs). Subsequent RNA sequencing (RNA-seq) studies demonstrated significant activation of the Notch signaling pathway and upregulation of inhibitor of DNA binding (ID1/ID2) genes in p53-knock out (p53-KO) cells. We found that the loss of ID1 or HES-1 expression or treatment with a gamma-secretase inhibitor (GSI) significantly decreased the clonogenic growth of p53-KO but not p53 wild-type cells. GSI treatment in a small set of MM specimens also reduced the clonogenic growth in del17p samples but not in non-del17p samples. This effect was specific as overexpression of the Notch intracellular domain (NICD) rescued the effects of GSI treatment. Our study demonstrates that the Notch signaling and ID1 expression are required for TIC expansion in p53-KO MM cells. These findings also suggest that GSI may be specifically active in patients with p53 mutant MM.

Robust, functional nanocrystal solids by infilling with atomic layer deposition.

Thin films of colloidal semiconductor nanocrystals (NCs) are inherently metatstable materials prone to oxidative and photothermal degradation driven by their large surface-to-volume ratios and high surface energies. (1) The fabrication of practical electronic devices based on NC solids hinges on preventing oxidation, surface diffusion, ripening, sintering, and other unwanted physicochemical changes that can plague these materials. Here we use low-temperature atomic layer deposition (ALD) to infill conductive PbSe NC solids with metal oxides to produce inorganic nanocomposites in which the NCs are locked in place and protected against oxidative and photothermal damage. Infilling NC field-effect transistors and solar cells with amorphous alumina yields devices that operate with enhanced and stable performance for at least months in air. Furthermore, ALD infilling with ZnO lowers the height of the inter-NC tunnel barrier for electron transport, yielding PbSe NC films with electron mobilities of 1 cm2 V(-1) s(-1). Our ALD technique is a versatile means to fabricate robust NC solids for optoelectronic devices.

Abdominal Movements in Insect Flight Reshape the Role of Non-Aerodynamic Structures for Flight Maneuverability I: Model Predictive Control for Flower Tracking.

Research on insect flight control has focused primarily on the role of wings. Yet abdominal deflections during flight can potentially influence the dynamics of flight. This paper assesses the role of airframe deformations in flight, and asks to what extent the abdomen contributes to flight maneuverability. To address this, we use a combination of both a Model Predictive Control (MPC)-inspired computational inertial dynamics model, and free flight experiments in the hawkmoth, Manduca sexta. We explored both underactuated (i.e., number of outputs are greater than the number of inputs) and fully actuated (equal number of outputs and inputs) systems. Using metrics such as the non-dimensionalized tracking error and cost of transport to evaluate flight performance of the inertial dynamics model, we show that fully actuated simulations minimized the tracking error and cost of transport. Additionally, we tested the effect of restricted abdomen movement on free flight in live hawkmoths by fixing a carbon fiber rod over the thoracic-abdomen joint. Moths with a restricted abdomen performed worse than sham treatment moths. This study finds that abdominal motions contribute to flight control and maneuverability. Such motions of non-aerodynamic structures, found in all flying taxa, can inform the development of multi-actuated micro air vehicles.

Screening for parasites in migrant children.

BACKGROUND: Globalization has pushed population movements in the last decades, turning imported diseases into the focus. Due to behavioral habits, children are at higher risk of acquiring parasitosis. This study aims to investigate the prevalence of parasites in migrant children and factors associated with parasitic diseases. METHOD: Retrospective cross-sectional study (2014-2018) including children diagnosed with parasitosis. The diagnosis was based on serology and/or microscopic stool-sample evaluation. Epidemiological and clinical data were recorded. RESULTS: Out of 813 migrant children screened, 241 (29.6%) presented at least one parasite, and 89 (10.9%) more than one. The median age was 6.6 years (IQR: 3.1-11.9) and 58.9% were males. Most cases were referred for a health exam; only 52.3% of children were symptomatic, but 43.6% had eosinophilia. The most common diagnosis were giardiasis (35.3%), schistosomiasis (19.1%), toxocariasis (15.4%), and strongyloidiasis (9.1%). After the multivariate analysis, African origin and presenting with eosinophilia were the main risk factors for parasitism. CONCLUSIONS: parasitosis are frequent among migrant children. Children are often asymptomatic, and thus active screening for parasitosis should be considered among high-risk populations. Eosinophilia can be useful to guide complimentary tests, as well as geographical origin, but normal eosinophil count does not exclude parasitosis.

Eosinophilia in Migrant Children: How Should We Proceed?

BACKGROUND: The diagnostic approach to eosinophilia is complex, given the numerous reported etiologies. Intestinal parasites (especially helminths) are a concern in children from high-burden settings. We describe the diagnostic approach and clinical management of eosinophilia in a cohort of migrant children. METHODS: We conducted a retrospective observational study that included children diagnosed with eosinophilia at a reference center for pediatric tropical diseases from 2014 to 2018. All patients were screened according to a unified protocol, including direct microbiologic and serologic tests. RESULTS: A total of 163 children presented with eosinophilia during the study period [median age, 7.7 years (4.1-12.2); 57.1% boys], mostly from Asia (27.6%) and South America (22.1%). Most were internationally adopted children (43.6%) or migrants (26.4%). Only 34.4% of the children were symptomatic, and the main etiology for eosinophilia was helminths (56.4%). After a sequential diagnostic approach, no etiology was found for 40.5% of the patients. The independent risk factors for an unexplained etiology were younger age (≤2 years: odds ratio, 3.6; 95% CI, 1.3-10.2; P = 0.015), absence of symptoms (odds ratio, 4.8; 95% CI, 1.8-12.5; P = 0.001) and mild eosinophilia (<1000/µL: odds ratio, 4.2; 95% CI, 4.5-11.7; P = 0.005). Only 6 children were treated empirically. In those children with an identified cause and in those treated empirically, the eosinophilia resolved in 52% in a median of 7 months (5-9). CONCLUSIONS: Helminths are the main cause of eosinophilia in migrant children and need to be hunted, especially in older children with eosinophil counts >1000 eosinophils/µL.

Covalent JNK Inhibitor, JNK-IN-8, Suppresses Tumor Growth in Triple-Negative Breast Cancer by Activating TFEB- and TFE3-Mediated Lysosome Biogenesis and Autophagy.

The heterogeneity and aggressiveness of triple-negative breast cancer (TNBC) contribute to its early recurrence and metastasis. Despite substantial research to identify effective therapeutic targets, TNBC remains elusive in terms of improving patient outcomes. Here, we report that a covalent JNK inhibitor, JNK-IN-8, suppresses TNBC growth both in vitro and in vivo. JNK-IN-8 reduced colony formation, cell viability, and organoid growth in vitro and slowed patient-derived xenograft and syngeneic tumor growth in vivo. Cells treated with JNK-IN-8 exhibited large, cytoplasmic vacuoles with lysosomal markers. To examine the molecular mechanism of this phenotype, we looked at the master regulators of lysosome biogenesis and autophagy transcription factor EB (TFEB) and TFE3. JNK-IN-8 inhibited TFEB phosphorylation and induced nuclear translocation of unphosphorylated TFEB and TFE3. This was accompanied by an upregulation of TFEB/TFE3 target genes associated with lysosome biogenesis and autophagy. Depletion of both TFEB and TFE3 diminished the JNK-IN-8-driven upregulation of lysosome biogenesis and/or autophagy markers. TFEB and TFE3 are phosphorylated by a number of kinases, including mTOR. JNK-IN-8 reduced phosphorylation of mTOR targets in a concentration-dependent manner. Knockout of JNK1 and/or JNK2 had no impact on TFEB/TFE3 activation or mTOR inhibition by JNK-IN-8 but inhibited colony formation. Similarly, reexpression of either wildtype or drug-nonbinding JNK (C116S) in JNK knockout cells did not reverse JNK-IN-8-induced TFEB dephosphorylation. In summary, JNK-IN-8 induced lysosome biogenesis and autophagy by activating TFEB/TFE3 via mTOR inhibition independently of JNK. Together, these findings demonstrate the efficacy of JNK-IN-8 as a targeted therapy for TNBC and reveal its novel lysosome- and autophagy-mediated mechanism of action.