Using contex-awarenes to foster active lifestyles

This paper describes a context-aware mobile application which aims at adaptively motivating its users to assume active lifestyles. The application is built on a model which combines ‘motion patterns’ with ‘activity profiles’, in order to evaluate the user’s real level of activity and decide which actions to take to give advice or provide feedback. In particular, a ‘move-to-uncover’ wallpaper puzzle interface is employed as motivating interface; at the same time, context-aware notifications are triggered when low activity levels are detected. In order to accelerate the application’s design and development cycle, a mobile service oriented framework – CASanDRA Mobile - has been used and improved. CASanDRA Mobile provides standard features to facilitate context acquisition, fusion and reasoning in mobile devices, making easier access to sensors and context-aware applications cohabitatio

Downscaling CMIP6 climate projections to classify the future offshore wind energy resource in the Spanish territorial waters

The Spanish government has established a Maritime Spatial Planning including areas for wind farms, with the aim of contributing up to 40% of European floating offshore wind power by 2030. Thus, it is crucial to assess the current and future offshore wind energy resource in these areas, and classify the near future resource by considering wind power density and other relevant factors like resource stability, environmental risks, and installation costs. To attain the necessary high spatial resolution, a dynamic downscaling of a multi-model ensemble from the 6th phase of the Coupled Model Intercomparison Project was conducted using the Weather Research and Forecasting model in Spanish territorial waters, including the Iberian Peninsula, Balearic Islands, and Canary Islands. Future projections were considered under the Shared Socioeconomic Pathways 2–4.5 and 5–8.5 scenarios. According to the results, Spain’s offshore wind energy potential is projected to grow in the upcoming years, particularly in the Atlantic Ocean and surrounding the Canary Islands. Wind resource classification in the potential offshore wind farm areas reveals noteworthy diversity, with ratings ranging from “fair” (3/7) to “outstanding” (6/7). The most promising areas for offshore wind farm development in the near future are located in the northwest of the Iberian Peninsula and the Canary Islands.Xunta de Galicia | Ref. ED431C 2021/44Agencia Estatal de Investigación | Ref. TED2021-129479A-I00Agencia Estatal de Investigación | Ref. PID2021-128510OB-I00Agencia Estatal de Investigación | Ref. IJC2020-043745-

The Prevalence of Fatigue Following Deep Brain Stimulation Surgery in Parkinson's Disease and Association with Quality of Life

Fatigue is a common and disabling nonmotor symptom seen in Parkinson's disease (PD). While deep brain stimulation surgery (DBS) improves motor symptoms, it has also been associated with non-motor side effects. To date no study has utilized standardized instruments to evaluate fatigue following DBS surgery. Our objective was to determine the prevalence of fatigue following DBS surgery in PD its impact on quality of life and explore predictive factors. We recruited 44 PD subjects. At least one year following DBS placement, we administered the Fatigue Severity Scale (FSS), the Parkinson's Disease Questionnaire (PDQ-39), the Beck Depression Inventory, the Beck Anxiety Inventory, the UPDRS, and a neuropsychological battery. Fifty-eight percent of subjects had moderate to severe fatigue. Fatigue was significantly associated with quality of life, depression, and anxiety. Depression preoperatively was the only predictive factor of fatigue. Fatigue is common following DBS surgery and significantly impacts quality of life

Telomere Dynamics in Human Cells Reprogrammed to Pluripotency

BACKGROUND:Human induced pluripotent stem cells (IPSCs) have enormous potential in the development of cellular models of human disease and represent a potential source of autologous cells and tissues for therapeutic use. A question remains as to the biological age of IPSCs, in particular when isolated from older subjects. Studies of cloned animals indicate that somatic cells reprogrammed to pluripotency variably display telomere elongation, a common indicator of cell "rejuvenation." METHODOLOGY/PRINCIPAL FINDINGS:We examined telomere lengths in human skin fibroblasts isolated from younger and older subjects, fibroblasts converted to IPSCs, and IPSCs redifferentiated through teratoma formation and explant culture. In IPSCs analyzed at passage five (P5), telomeres were significantly elongated in 6/7 lines by >40% and approximated telomere lengths in human embryonic stem cells (hESCs). In cell lines derived from three IPSC-teratoma explants cultured to P5, two displayed telomeres shortened to lengths similar to input fibroblasts while the third line retained elongated telomeres. CONCLUSIONS/SIGNIFICANCE:While these results reveal some heterogeneity in the reprogramming process with respect to telomere length, human somatic cells reprogrammed to pluripotency generally displayed elongated telomeres that suggest that they will not age prematurely when isolated from subjects of essentially any age

FGFR1 amplification or overexpression and hormonal resistance in luminal breast cancer: rationale for a triple blockade of ER, CDK4/6, and FGFR1.

BACKGROUND: FGFR1 amplification, but not overexpression, has been related to adverse prognosis in hormone-positive breast cancer (HRPBC). Whether FGFR1 overexpression and amplification are correlated, what is their distribution among luminal A or B HRPBC, and if there is a potential different prognostic role for amplification and overexpression are currently unknown features. The role of FGFR1 inhibitors in HRPBC is also unclear. METHODS: FGFR1 amplification (FISH) and overexpression (RNAscope) were investigated in a N = 251 HRPBC patients cohort and the METABRIC cohort; effects on survival and FISH-RNAscope concordance were determined. We generated hormonal deprivation resistant (LTED-R) and FGFR1-overexpressing cell line variants of the ER+ MCF7 and T47-D and the ER+, FGFR1-amplified HCC1428 cell lines. The role of ER, CDK4/6, and/or FGFR1 blockade alone or in combinations in Rb phosphorylation, cell cycle, and survival were studied. RESULTS: FGFR1 overexpression and amplification was non-concordant in > 20% of the patients, but both were associated to a similar relapse risk (~ 2.5-fold; P < 0.05). FGFR1 amplification or overexpression occurred regardless of the luminal subtype, but the incidence was higher in luminal B (16.3%) than A (6.6%) tumors; P < 0.05. The Kappa index for overexpression and amplification was 0.69 (P < 0.001). Twenty-four per cent of the patients showed either amplification and/or overexpression of FGFR1, what was associated to a hazard ratio for relapse of 2.6 (95% CI 1.44-4.62, P < 0.001). In vitro, hormonal deprivation led to FGFR1 overexpression. Primary FGFR1 amplification, engineered mRNA overexpression, or LTED-R-acquired FGFR1 overexpression led to resistance against hormonotherapy alone or in combination with the CDK4/6 inhibitor palbociclib. Blocking FGFR1 with the kinase-inhibitor rogaratinib led to suppression of Rb phosphorylation, abrogation of the cell cycle, and resistance-reversion in all FGFR1 models. CONCLUSIONS: FGFR1 amplification and overexpression are associated to similar adverse prognosis in hormone-positive breast cancer. Capturing all the patients with adverse prognosis-linked FGFR1 aberrations requires assessing both features. Hormonal deprivation leads to FGFR1 overexpression, and FGFR1 overexpression and/or amplification are associated with resistance to hormonal monotherapy or in combination with palbociclib. Both resistances are reverted with triple ER, CDK4/6, and FGFR1 blockade

Phosphoproteomic Landscape of AML Cells Treated with the ATP-Competitive CK2 Inhibitor CX-4945

Casein kinase 2 (CK2) regulates a plethora of proteins with pivotal roles in solid and hematological neoplasia. Particularly, in acute myeloid leukemia (AML) CK2 has been pointed as an attractive therapeutic target and prognostic marker. Here, we explored the impact of CK2 inhibition over the phosphoproteome of two cell lines representing major AML subtypes. Quantitative phosphoproteomic analysis was conducted to evaluate changes in phosphorylation levels after incubation with the ATP-competitive CK2 inhibitor CX-4945. Functional enrichment, network analysis, and database mining were performed to identify biological processes, signaling pathways, and CK2 substrates that are responsive to CX-4945. A total of 273 and 1310 phosphopeptides were found differentially modulated in HL-60 and OCI-AML3 cells, respectively. Despite regulated phosphopeptides belong to proteins involved in multiple biological processes and signaling pathways, most of these perturbations can be explain by direct CK2 inhibition rather than off-target effects. Furthermore, CK2 substrates regulated by CX-4945 are mainly related to mRNA processing, translation, DNA repair, and cell cycle. Overall, we evidenced that CK2 inhibitor CX-4945 impinge on mediators of signaling pathways and biological processes essential for primary AML cells survival and chemosensitivity, reinforcing the rationale behind the pharmacologic blockade of protein kinase CK2 for AML targeted therapy

Studying the non-thermal lobes of IRAS 16547-4247 through a multi-wavelength approach

In recent years, massive protostars have turned out to be a possible population of high-energy emitters. Among the best candidates is IRAS 16547-4247, a protostar that presents a powerful outflow with clear signatures of interaction with its environment. This source has been revealed to be a potential high-energy source because it displays non-thermal radio emission of synchrotron origin, which is evidence of relativistic particles. To improve our understanding of IRAS 16547-4247 as a high-energy source, we analyzed XMM-Newton archival data and found that IRAS 16547-4247 is a hard X-ray source. We discuss these results in the context of a refined one-zone model and previous radio observations. From our study we find that it may be difficult to explain the X-ray emission as non-thermal radiation coming from the interaction region, but it might be produced by thermal Bremsstrahlung (plus photo-electric absorption) by a fast shock at the jet end. In the high-energy range, the source might be detectable by the present generation of Cherenkov telescopes, and may eventually be detected by Fermi in the GeV range

Increased aridity drives post‐fire recovery of Mediterranean forests towards open shrublands

Recent observations suggest that repeated fires could drive Mediterranean forests to shrublands, hosting flammable vegetation that regrows quickly after fire. This feedback supposedly favours shrubland persistence and may be strengthened in the future by predicted increased aridity. An assessment was made of how fires and aridity in combination modulated the dynamics of Mediterranean ecosystems and whether the feedback could be strong enough to maintain shrubland as an alternative stable state to forest. A model was developed for vegetation dynamics, including stochastic fires and different plant fire‐responses. Parameters were calibrated using observational data from a period up to 100 yr ago, from 77 sites with and without fires in Southeast Spain and Southern France. The forest state was resilient to the separate impact of fires and increased aridity. However, water stress could convert forests into open shrublands by hampering post‐fire recovery, with a possible tipping point at intermediate aridity. Projected increases in aridity may reduce the resilience of Mediterranean forests against fires and drive post‐fire ecosystem dynamics toward open shrubland. The main effect of increased aridity is the limitation of post‐fire recovery. Including plant fire‐responses is thus fundamental when modelling the fate of Mediterranean‐type vegetation under climate‐change scenarios

Pharmacokinetics in morbid obesity: influence of two bariatric surgery techniques on paracetamol and caffeine metabolism

The purpose of the study was to study the impact of the two most common bariatric surgery techniques on paracetamol pharmacokinetics (a marker of gastric emptying) and caffeine metabolism (a marker of liver function). In the present prospective study, we studied 24 morbid obese patients before, at 4 weeks, and 6 months after having undergone sleeve gastrectomy (n = 10) or Roux-en-Y gastric bypass (n = 14). For comparative purposes, 28 healthy controls (14 normal weights and 14 overweights) were also included in the study. Paracetamol pharmacokinetics was altered in the obese participants leading to lower bioavailability. Bariatric surgery resulted in faster absorption and normalized pharmacokinetic parameters, prompting an increase in paracetamol bioavailability. No differences were found between surgical procedures. In the case of caffeine, the ratio paraxanthine/caffeine did not differ between morbid obese and healthy individuals. This ratio remained unmodified after surgery, indicating that the liver function (assessed by cytochrome P450 1A2 activity) was unaffected by obesity or bariatric surgery. Paracetamol pharmacokinetics and caffeine plasma levels are altered in severely obese patients. The two studied bariatric surgical techniques normalize paracetamol oral bioavailability without impairing the liver function (measured by cytochrome P450 1A2 activity).Peer ReviewedPostprint (author's final draft