Classification of kinematic and electromyographic signals associated with pathological tremor using machine and deep learning.

Peripheral Electrical Stimulation (PES) of afferent pathways has received increased interest as a solution to reduce pathological tremors with minimal side effects. Closed-loop PES systems might present some advantages in reducing tremors, but further developments are required in order to reliably detect pathological tremors to accurately enable the stimulation only if a tremor is present. This study explores different machine learning (K-Nearest Neighbors, Random Forest and Support Vector Machines) and deep learning (Long Short-Term Memory neural networks) models in order to provide a binary (Tremor; No Tremor) classification of kinematic (angle displacement) and electromyography (EMG) signals recorded from patients diagnosed with essential tremors and healthy subjects. Three types of signal sequences without any feature extraction were used as inputs for the classifiers: kinematics (wrist flexion-extension angle), raw EMG and EMG envelopes from wrist flexor and extensor muscles. All the models showed high classification scores (Tremor vs. No Tremor) for the different input data modalities, ranging from 0.8 to 0.99 for the f1 score. The LSTM models achieved 0.98 f1 scores for the classification of raw EMG signals, showing high potential to detect tremors without any processed features or preliminary information. These models may be explored in real-time closed-loop PES strategies to detect tremors and enable stimulation with minimal signal processing steps

Unveiling the nature of the "Green Pea" galaxies

We review recent results on the oxygen and nitrogen chemical abundances in extremely compact, low-mass starburst galaxies at redshifts between 0.1-0.3 recently named to as "Green Pea" galaxies. These galaxies are genuine metal-poor galaxies ($\sim$ one fifth solar) with N/O ratios unusually high for galaxies of the same metallicity. In combination with their known general properties, i.e., size, stellar mass and star-formation rate, these findings suggest that these objects could be experiencing a short and extreme phase in their evolution. The possible action of both recent and massive inflow of gas, as well as stellar feedback mechanisms are discussed here as main drivers of the starburst activity and their oxygen and nitrogen abundances.Comment: To appear in JENAM Symposium "Dwarf Galaxies: Keys to Galaxy Formation and Evolution", P. Papaderos, G. Hensler, S. Recchi (eds.). Lisbon, September 2010, Springer Verlag, in pres

First-line eradication rates comparing two shortened non-bismuth quadruple regimens against Helicobacter pylori: an open-label, randomized, multicentre clinical trial

OBJECTIVES: Helicobacter pylori eradication remains a challenge. Non-bismuth-based quadruple regimens (NBQR) have shown high eradication rates (ER) elsewhere that need to be locally confirmed. The objective of this study was to compare the first-line ER of a hybrid therapy (20 mg of omeprazole twice daily and 1 g of amoxicillin twice daily for 10 days, adding 500 mg of clarithromycin twice daily and 500 mg of metronidazole every 8 h for the last 5 days; OA-OACM) with that of a 10 day concomitant regimen consisting of taking all four drugs twice daily every day (including 500 mg of metronidazole every 12 h; OACM). A 10 day arm with standard triple therapy (OAC; 20 mg of omeprazole/12 h, 1 g of amoxicillin/12 h and 500 mg of clarithromycin/12 h) was included. PATIENTS AND METHODS: Three hundred consecutive patients were randomized (1: 2: 2) into one of the three following regimens: (i) OAC (60); (ii) OA-OACM (120); and (iii) OACM (120). Eradication was generally confirmed by a [(13)C]urea breath test at least 4 weeks after the end of treatment. Adverse events and compliance were assessed. EudraCT: 2011-006258-99. RESULTS: ITT cure rates were: OAC, 70.0% (42/60) (95% CI: 58.3-81.7); OA-OACM, 90.8% (109/120) (95% CI: 85.6-96.0); and OACM, 90.0% (107/119) (95% CI: 84.6-95.4). PP rates were: OAC, 72.4% (42/58) (95% CI: 60.8-84.1); OA-OACM, 93.9% (108/115) (95% CI: 89.5-98.3); and OACM, 90.3% (102/113) (95% CI: 84.8-95.8). Both NBQR significantly improved ER compared with OAC (P < 0.01), but no differences were seen between them. Mean compliance was elevated [98.0% (SD = 9.8)] with no differences between groups. There were more adverse events in the quadruple arms (OACM, 65.8%; OA-OACM, 68.6%; OAC, 46.6%; P < 0.05), but no significant differences between groups in terms of severity were seen. CONCLUSIONS: Hybrid and concomitant regimens show good ER against H. pylori infection with an acceptable safety profile. They clearly displace OAC as first-line regimen in our area

FUS-DDIT3 Prevents the Development of Adipocytic Precursors in Liposarcoma by Repressing PPARγ and C/EBPα and Activating eIF4E

FUS-DDIT3 is a chimeric protein generated by the most common chromosomal translocation t(12;16)(q13;p11) linked to liposarcomas, which are characterized by the accumulation of early adipocytic precursors. Current studies indicate that FUS-DDIT3- liposarcoma develops from uncommitted progenitors. However, the precise mechanism whereby FUS-DDIT3 contributes to the differentiation arrest remains to be elucidated. METHODOLOGY/PRINCIPAL FINDINGS: Here we have characterized the adipocyte regulatory protein network in liposarcomas of FUS-DITT3 transgenic mice and showed that PPARgamma2 and C/EBPalpha expression was altered. Consistent with in vivo data, FUS-DDIT3 MEFs and human liposarcoma cell lines showed a similar downregulation of both PPARgamma2 and C/EBPalpha expression. Complementation studies with PPARgamma but not C/EBPalpha rescued the differentiation block in committed adipocytic precursors expressing FUS-DDIT3. Our results further show that FUS-DDIT3 interferes with the control of initiation of translation by upregulation of the eukaryotic translation initiation factors eIF2 and eIF4E both in FUS-DDIT3 mice and human liposarcomas cell lines, explaining the shift towards the truncated p30 isoform of C/EBPalpha in liposarcomas. Suppression of the FUS-DDIT3 transgene did rescue this adipocyte differentiation block. Moreover, eIF4E was also strongly upregulated in normal adipose tissue of FUS-DDIT3 transgenic mice, suggesting that overexpression of eIF4E may be a primary event in the initiation of liposarcomas. Reporter assays showed FUS-DDIT3 is involved in the upregulation of eIF4E in liposarcomas and that both domains of the fusion protein are required for affecting eIF4E expression. CONCLUSIONS/SIGNIFICANCE: Taken together, this study provides evidence of the molecular mechanisms involve in the disruption of normal adipocyte differentiation program in liposarcoma harbouring the chimeric gene FUS-DDIT3.Research in ISG group is supported partially by FEDER and by MEC (SAF2006-03726), Junta de Castilla y León (CSI03A05), FIS (PI050087, PI050116), Fundación de Investigación MMA, Federación de Cajas de Ahorro Castilla y León (I Convocatoria de Ayudas para Proyectos de Investigación Biosanitaria con Células Madre), CDTEAM project (CENIT-Ingenio 2010) and MEC Consolider-Ingenio 2010 (Ref. CSD2007-0017).Research in ISG group is supported partially by FEDER and by MEC (SAF2006-03726 and PETRI N° 95-0913.OP), Junta de Castilla y León (CSI03A05), FIS (PI050087, PI050116), Fundación de Investigación MMA, Federación de Cajas de Ahorro Castilla y León (I Convocatoria de Ayudas para Proyectos de Investigación Biosanitaria con Células Madre), CDTEAM project (CENIT-Ingenio 2010) and MEC Consolider-Ingenio 2010 (Ref. CSD2007-0017). MSM is supported by the Ramon y Cajal Scientific Spanish Program, Fondo Investigacion Sanitaria (FIS PI04-1271), Junta de Castilla y León (SA085A06) and Fundación Manuel Solorzano, University of Salamanca.Peer reviewe

Response of the photosynthetic apparatus to a flowering-inductive period by water stress in Citrus

The photosynthetic responses to a flowering-inductive water-stress period and recovery were studied and compared in two Citrus species. Under greenhouse conditions, Fino lemon and Owari satsuma trees were subjected to moderate (-2 MPa at predawn) and severe (-3 MPa) water stress levels and were re-watered after 60 days. Vegetative growth was inhibited during the stress assays, and strong defoliation levels were reported, especially in Fino lemon. In both species, bud sprouting was induced after re-watering. Flowers and vegetative shoots developed in Owari satsuma after a drought period, and the development was independent of the stress level. In Fino lemon, vegetative shoots and flowers were primarily formed after moderate and severe stress, respectively. The photosynthetic rate and stomatal conductance were reduced by water stress, and a marked increase in water-use efficiency at the moderate water deficit level was observed. Nevertheless, the photosynthetic apparatus was not damaged, since the maximum quantum yield, photosynthetic pigment concentrations and Rubisco level and activity did not change. Furthermore, the measured malonyldialdehyde (MDA) and peroxidase activity indicated that oxidative stress was not specifically triggered by water stress in our study. Therefore, the gas exchange, fluorescence and biochemical parameters suggested that diffusional limitations to photosynthesis predominated in both of the studied Citrus species, and explained the rapid recovery of the photosynthetic parameters after rehydration. The net CO 2 fixation rate and stomatal conductance were recovered within 24 h in Fino lemon, whereas 3 days were required in Owari satsuma. This suggests the presence of some metabolic limitations in the latter species. Furthermore, the sensibility of the defoliation rates, the accumulation of proline and the stomatal behaviour in response to water stress indicated a higher drought tolerance of Fino lemon, according to its better acclimation to hot climates. © 2011 Springer-Verlag.The authors thank Dr. J. Moreno and co-workers from the Departamento de Bioquimica of the Universidad de Valencia for his help and support in the Rubisco assays, and Dr. F. Fornes, Dr. A. Calatayud and Dr. E. Primo-Millo for the critical review of the manuscript. This work was funded by the Universitat Politecnica de Valencia, Spain (Ayudas para primeros proyectos de investigacion PAID06-06).Ávila Reséndiz, C.; Guardiola Barcena, JL.; González Nebauer, S. (2012). Response of the photosynthetic apparatus to a flowering-inductive period by water stress in Citrus. Trees - Structure and Function. 26(3):833-840. https://doi.org/10.1007/s00468-011-0657-4S833840263Addicott FT (1982) Abscission. University of California Press, BerkeleyBajji M, Kinet JM, Lutts S (1998) Salt stress effects on roots and leaves of Atriplex halimus L. and their corresponding callus. Plant Sci 137:131–142Barbera G, Fatta-del-Bosco G, Lo-Cascio B (1985) Effect of water stress on lemon summer bloom: the Forzatura technique in the Sicilian citrus industry. Acta Hortic 171:391–397Bates LS, Waldren RP, Teare ID (1973) Rapid determination of free proline for water stress studies. Plant Soil 39:205–207Bota J, Medrano H, Flexas J (2004) Is photosynthesis limited by decreased Rubisco activity and RuBP content under progressive water stress? New Phytol 162:671–681Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248–254Cassin J, Bourdeaut A, Fougue V, Furon V, Gaillard JP, LeBourdelles J, Montagut G, Moreuil C (1969) The influence of climate upon blooming of Citrus in tropical areas. Proc Int Soc Citrus 1:315–323Castel JR, Buj A (1990) Response of Salustiana oranges to high frequency deficit irrigation. Irrig Sci 11:121–127Chaikiatitiyos S, Menzel CM, Rasmussen TS (1994) Floral induction in tropical fruit trees: effects of temperature and water supply. J Hortic Sci 69:397–415Chaves MM, Flexas J, Pinheiro C (2009) Photosynthesis under drought and salt stress: regulation mechanisms from whole plant to cell. Ann Bot 103:551–560Costa JM, Ortuño MF, Chaves M (2007) Deficit irrigation as a strategy to save water: physiology and potential application to horticulture. J Integr Plant Biol 49:1421–1434Davenport TL (1990) Citrus flowering. Hortic Rev 12:249–408Davies FS, Albrigo LG (1994) Citrus. CAB International, Wallingford, pp 126–134Domingo R, Ruiz-Sánchez MC, Sánchez-Blanco MJ, Torrecillas A (1996) Water relations, growth and yield of Fino lemon trees under regulated deficit irrigation. Irrig Sci 16:115–123Erismann ND, Machado EC, Tucci MLS (2008) Photosynthetic limitation by CO2 diffusion in drought stressed orange leaves on three rootstocks. Photosynth Res 96:163–172Flexas J, Bota J, Galmés J, Medrano H, Ribas-Carbó M (2006) Keeping a positive carbon balance under adverse conditions: responses of photosynthesis and respiration to water stress. Physiol Plant 127:343–352Gallé A, Florez-Sarasa I, Tomas M, Pou A, Medrano H, Ribas-Carbó M, Flexas J (2009) The role of mesophyll conductance during water stress and recovery in tobacco (Nicotiana sylvestris): acclimation or limitation? J Exp Bot 60:2379–2390Galmés J, Medrano H, Flexas J (2007) Photosynthetic limitations in response to water stress and recovery in Mediterrenean plants with different growth forms. New Phytol 175:81–93García-Luis A, Kanduser M, Santamarina P, Guardiola JL (1992) Low temperature influence on flowering in Citrus. The separation of inductive and bud dormancy releasing effects. Physiol Plant 86:648–652García-Sánchez F, Syvertsen JP, Gimeno V, Botía P, Pérez-Pérez JG (2007) Responses to flooding and drought stress by two citrus rootstock seedlings with different water-use efficiency. Physiol Plant 130:532–542Genty B, Briantais JM, Baker NR (1989) The relationship between quantum yield of photosynthetic electron transport and quenching of chlorophyll fluorescence. Biochim Biophys Acta 990:87–92Gómez-Cadenas A, Tadeo FR, Talon M, Primo-Millo E (1996) Leaf abscission induced by ethylene in water-stressed intact seedlings of Cleopatra mandarin requires previous abscisic acid accumulation in roots. Plant Physiol 112:401–408Gordo O, Sanz JJ (2010) Impact of climate change on plant phenology in Mediterranean ecosystems. Glob Chang Biol 16:1082–1106Heath RL, Packer L (1968) Photoperoxidation in isolated chloroplasts. I. Kinetics and stoichiometry of fatty acid peroxidation. Arch Biochem Biophys 125:189–190Hoagland DR, Arnon DI (1950) The water culture method for growing plants without soil. California Agricultural Experiment Station Circular no. 347, p 32IPCC (2001) Climate change 2001. In: Houghton JT (ed) The scientific basis. Cambridge University Press, CambridgeLawlor DW (1995) The effects of water deficit on photosynthesis. In: Smirnoff N (ed) Environment and plant metabolism. Bios Scientific Publishers, Oxford, pp 129–160Lichtenthaler HK, Buschmann C (2001) Current protocols in food analytical chemistry, F4.2.1 and F4.3.1. John Wiley and Sons, Inc, NJLorimer GH, Badger MR, Andrews TJ (1977) D-Ribulose-1, 5-bisphosphate carboxilase-oxigenase. Improved methods for activation and assay of catalytic activities. Anal Biochem 78:66–75Miyashita K, Tanakamaru S, Maitani T, Kimura K (2005) Recovery responses of photosynthesis, transpiration, and stomatal conductance in kidney bean following drought stress. Environ Exp Bot 53:205–214Nir I, Leshem B, Goren R (1972) Effects of water stress, gibberellic acid and 2-chloroethylammoniumchloride (CCC) ob flower differentiation in Eureka lemon trees. J Am Soc Hortic Sci 97:774–778Peñarrubia L, Moreno J (1988) Ribulose 1, 5-bisphosphate carboxylase oxygenase from citrus leaves. Phytochemistry 27:1999–2004Pérez-Pérez JG, Syvertsen JP, Botía P, García-Sánchez F (2007) Leaf water relations and net gas exchange responses of salinized carrizo citrange seedlings during drought stress and recovery. Ann Bot 100:335–345Pérez-Pérez JG, Robles JM, Tovar JC, Botía P (2009) Response to drought and salt stress of lemon ‘Fino 49’ under field conditions: water relations, osmotic adjustment and gas Exchange. Sci Hortic 122:83–90Reynolds M, Tuberosa R (2008) Translational research impacting on crop productivity in drought-prone environments. Curr Opin Plant Biol 11:171–179Ruiz-Sánchez MC, Domingo R, Savé R, Biel C, Torrecillas A (1997) Effects of water stress and rewatering on leaf water relations of lemon plants. Biol Plant 39:623–631Sarris D, Christodoulakis D, Körner C (2007) Recent decline in precipitation and tree growth in the eastern Mediterranean. Glob Chang Biol 13:1187–1200Sharkey TD (1990) Water-stress effects on photosynthesis. Photosynthetica 24:651Southwick SM, Davenport TL (1986) Characterization of water stress and low temperature effects on flower induction in Citrus. Plant Physiol 81:26–29Spiegel-Roy P, Goldschmidt EE (1996) Biology of Citrus. Cambridge University Press, Cambridge, pp 131–136Syvertsen JP, Lloyd J (1994) Citrus. In: Schaffer BA, Andersen PC (eds) Handbook of environmental physiology of fruit crops. Vol II Subtropical and tropical crops. CRC Press, Boca Raton, pp 65–99Syvertsen JP (1996) Water stress and carbon budgets. Proc Int Soc Citrus 1:46–50Valladares F, Arrieta S, Aranda I, Lorenzo D, Sánchez-Gómez D, Tena D, Suarez F, Pardos JA (2005) Shade tolerance, photoinhibition sensitivity and phenotypic plasticity of Illex aquifolium in continental Mediterranean sites. Tree Physiol 25:1041–1052Vu JCV, Yelenosky G (1988) Solar irradiance and drought stress effects on the activity and concentration of ribulose bisphosphate carboxylase in ‘Valencia’ orange leaves. Isr J Bot 37:245–25

Transcriptional portrait of M. bovis BCG during biofilm production shows genes differentially expressed during intercellular aggregation and substrate attachment.

Mycobacterium tuberculosis and M. smegmatis form drug-tolerant biofilms through dedicated genetic programs. In support of a stepwise process regulating biofilm production in mycobacteria, it was shown elsewhere that lsr2 participates in intercellular aggregation, while groEL1 was required for biofilm maturation in M. smegmatis. Here, by means of RNA-Seq, we monitored the early steps of biofilm production in M. bovis BCG, to distinguish intercellular aggregation from attachment to a surface. Genes encoding for the transcriptional regulators dosR and BCG0114 (Rv0081) were significantly regulated and responded differently to intercellular aggregation and surface attachment. Moreover, a M. tuberculosis H37Rv deletion mutant in the Rv3134c-dosS-dosR regulon, formed less biofilm than wild type M. tuberculosis, a phenotype reverted upon reintroduction of this operon into the mutant. Combining RT-qPCR with microbiological assays (colony and surface pellicle morphologies, biofilm quantification, Ziehl-Neelsen staining, growth curve and replication of planktonic cells), we found that BCG0642c affected biofilm production and replication of planktonic BCG, whereas ethR affected only phenotypes linked to planktonic cells despite its downregulation at the intercellular aggregation step. Our results provide evidence for a stage-dependent expression of genes that contribute to biofilm production in slow-growing mycobacteria

State of emergency medicine in Spain

Spain has universal public health care coverage. Emergency care provisions are offered to patients in different modalities and levels according to the characteristics of the medical complaint: at primary care centers (PCC), in an extrahospital setting by emergency medical services (EMS) and at hospital emergency departments (ED). We have more than 3,000 PCCs, which are run by family doctors (general practitioners) and pediatricians. On average, there is 1 PCC for every 15,000 to 20,000 inhabitants, and every family doctor is in charge of 1,500 to 2,000 citizens, although less populated zones tend to have lower ratios. Doctors spend part of their duty time in providing emergency care to their own patients. While not fully devoted to emergency medicine (EM) practice, they do manage minor emergencies. However, Spanish EMSs contribute hugely to guarantee population coverage in all situations. These EMS are run by EM technicians (EMT), nurses and doctors, who usually work exclusively in the emergency arena. EDs dealt with more than 25 million consultations in 2008, which implies, on average, that one out of two Spaniards visited an ED during this time. They are usually equipped with a wide range of diagnostic tools, most including ultrasonography and computerized tomography scans. The academic and training background of doctors working in the ED varies: nearly half lack any structured specialty residence training, but many have done specific master or postgraduate studies within the EM field. The demand for emergency care has grown at an annual rate of over 4% during the last decade. This percentage, which was greater than the 2% population increase during the same period, has outpaced the growth in ED capacity. Therefore, Spanish EDs become overcrowded when the system exerts minimal stress. Despite the high EM caseload and the potential severity of the conditions, training in EM is still unregulated in Spain. However, in April 2009 the Spanish Minister of Health announced the imminent approval of an EM specialty, allowing the first EM resident to officially start in 2011. Spanish emergency physicians look forward to the final approval, which will complete the modernization of emergency health care provision in Spain

Gas Accretion and Star Formation Rates

Cosmological numerical simulations of galaxy evolution show that accretion of metal-poor gas from the cosmic web drives the star formation in galaxy disks. Unfortunately, the observational support for this theoretical prediction is still indirect, and modeling and analysis are required to identify hints as actual signs of star-formation feeding from metal-poor gas accretion. Thus, a meticulous interpretation of the observations is crucial, and this observational review begins with a simple theoretical description of the physical process and the key ingredients it involves, including the properties of the accreted gas and of the star-formation that it induces. A number of observations pointing out the connection between metal-poor gas accretion and star-formation are analyzed, specifically, the short gas consumption time-scale compared to the age of the stellar populations, the fundamental metallicity relationship, the relationship between disk morphology and gas metallicity, the existence of metallicity drops in starbursts of star-forming galaxies, the so-called G dwarf problem, the existence of a minimum metallicity for the star-forming gas in the local universe, the origin of the alpha-enhanced gas forming stars in the local universe, the metallicity of the quiescent BCDs, and the direct measurements of gas accretion onto galaxies. A final section discusses intrinsic difficulties to obtain direct observational evidence, and points out alternative observational pathways to further consolidate the current ideas.Comment: Invited review to appear in Gas Accretion onto Galaxies, Astrophysics and Space Science Library, eds. A. J. Fox & R. Dav\'e, to be published by Springe

Aggregation Pheromone of Coconut Rhinoceros Beetle, Oryctes rhinoceros (L.) (Coleoptera: Scarabaeidae)

Male coconut rhinoceros beetles,Oryctes rhinoceros (L.), produce three sex-specific compounds, ethyl 4-methyloctanoate, ethyl 4-methylheptanoate, and 4-methyloctanoic acid, the first of which is an aggregation pheromone. Synthesis of these compounds involving conjugate addition of organocuprates to ethyl acrylate is reported. In field trapping experiments, (4S)-ethyl 4-methyloctanoate and the racemic mixture were equally attractive and 10 times more effective in attracting beetles than ethyl chrysanthemumate, a previously recommended attractant. Ethyl 4-methylheptanoate was as attractive as ethyl chrysanthemumate and more attractive than 4-methyloctanoic acid, but further studies are required before it can be classed as an aggregation pheromone. Compared to ethyl 4-methyloctanoate alone, combinations of the three male-produced compounds did not increase attraction, whereas addition of freshly rotting oil palm fruit bunches to pheromone-baited traps significantly enhanced attraction. With increasing dose, captures of O. rhinoceros increased, but doses of 6, 9, and 18 mg/day were competitive with 30 mg/day lures. Newly designed vane traps were more effective in capturing beetles than were barrier or pitfall traps. Results of this study indicate that there is potential for using ethyl 4-methyloctanoate in operational programs to control O. rhinoceros in oil palm plantations.Chem Tica InternationalUCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias Básicas::Centro de Investigaciones en Productos Naturales (CIPRONA

Exploiting oxidative phosphorylation to promote the stem and immunoevasive properties of pancreatic cancer stem cells

© The Author(s) 2020Pancreatic ductal adenocarcinoma (PDAC), the fourth leading cause of cancer death, has a 5-year survival rate of approximately 7–9%. The ineffectiveness of anti-PDAC therapies is believed to be due to the existence of a subpopulation of tumor cells known as cancer stem cells (CSCs), which are functionally plastic, and have exclusive tumorigenic, chemoresistant and metastatic capacities. Herein, we describe a 2D in vitro system for long-term enrichment of pancreatic CSCs that is amenable to biological and CSC-specific studies. By changing the carbon source from glucose to galactose in vitro, we force PDAC cells to utilize OXPHOS, resulting in enrichment of CSCs defined by increased CSC biomarker and pluripotency gene expression, greater tumorigenic potential, induced but reversible quiescence, increased OXPHOS activity, enhanced invasiveness, and upregulated immune evasion properties. This CSC enrichment method can facilitate the discovery of new CSC-specific hallmarks for future development into targets for PDAC-based therapies.We acknowledge and thank Dr. Nuria Malats and Jaime Villarreal from the Spanish National Cancer Research Center (CNIO) for RNA sequencing and analysis, funded by Fondo de Investigaciones Sanitarias (FIS) grant PI18/01347. We thank Patricia Sánchez-Tomero and Marina Ochando-Garmendia for technical assistance and support and Dr. Raúl Sánchez Lanzas for assistance with autophagy experiments. We want to particularly acknowledge the patients and the BioBank Hospital Ramón y Cajal-IRYCIS (PT13/0010/0002) integrated in the Spanish National Biobanks Network for its collaboration and, in particular, Adrián Povo Retana for macrophage isolation. We would also like to thank the Transmission Electron Microscopy Unit Laboratory, part of the UAM Interdepartmental Investigation Service (SIdI); Coral Pedrero for exceptional help with in vivo experiments; and the laboratories of Dr. Amparo Cano and Dr. José González Castaño for reagents and helpful discussions. S.V. was a recipient of an Ayuda de Movilidad del Personal Investigador del IRYCIS, a mobility grant from the Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain, and a pre-doctoral fellowship from the Comunidad de Madrid, Ayudas Para La Contratación De Investigadores Predoctorales Y Posdoctorales (PEJD-2017-PRE/BMD-5062), Madrid, Spain. This study was supported by a Rámon y Cajal Merit Award (RYC-2012-12104) from the Ministerio de Economía y Competitividad, Spain (to B.S.); funding from la Beca Carmen Delgado/Miguel Pérez-Mateo from AESPANC-ACANPAN Spain (to B.S.); a Conquer Cancer Now Grant from the Concern Foundation (Los Angeles, CA, USA) (to B.S.); a Coordinated grant (GC16173694BARB) from the Fundación Asociación Española Contra el Cáncer (AECC) (to B.S.); FIS grants PI18/00757 (to B.S.), PI16/00789 (to M.A.F.-M.), PI18/00267 (to L.G.-B.; co-financed through Fondo Europeo de Desarrollo Regional (FEDER) “Una manera de hacer Europa”); a Miguel Servet award (CP16/00121) (to P.S.); a Max Eder Fellowship of the German Cancer Aid (111746) (to P.C.H.); and the German Research Foundation (DFG, CRC 1279 “Exploiting the human peptidome for Novel Antimicrobial and Anticancer Agents”; to P.C.H.)