Constraints to dark matter annihilation from high-latitude hawc unidentified sources

The ΛCDM cosmological framework predicts the existence of thousands of subhalos in our own Galaxy not massive enough to retain baryons and become visible. Yet, some of them may outshine in gamma rays provided that the dark matter is made of weakly interacting massive particles (WIMPs), which would self-annihilate and would appear as unidentified gamma-ray sources (unIDs) in gamma-ray catalogs. Indeed, unIDs have proven to be competitive targets for dark matter searches with gamma rays. In this work, we focus on the three high-latitude (|b| ≥ 10) sources present in the 2HWC catalog of the High Altitude Water Cherenkov (HAWC) observatory with no clear associations at other wavelengths. Indeed, only one of these sources, 2HWC J1040+308, is found to be above the HAWC detection threshold when considering 760 days of data, i.e., a factor 1.5 more exposure time than in the original 2HWC catalog. Other gamma-ray instruments, such as Fermi-LAT or VERITAS at lower energies, do not detect the source. Also, this unID is reported as spatially extended, making it even more interesting in a dark matter search context. While waiting for more data that may shed further light on the nature of this source, we set competitive upper limits on the annihilation cross section by comparing this HAWC unID to expectations based on state-of-the-art N-body cosmological simulations of the Galactic subhalo population. We find these constraints to be particularly competitive for heavy WIMPs, i.e., masses above ∼25 (40) TeV in the case of the b ¯b (τ +τ −) annihilation channel, reaching velocity-averaged cross section values of 2 × 10−25 (5 × 10−25) cm3 ·s −1 . Although far from testing the thermal relic cross section value, the obtained limits are independent and nicely complementary to those from radically different DM analyses and targets, demonstrating once again the high potential of this DM search approachJ.C.-B. and M.A.S.-C. are supported by the Atracción de Talento contract no. 2016-T1/TIC-1542 granted by the Comunidad de Madrid in Spain, by the Spanish Agencia Estatal de Investigación through the grants PGC2018-095161-B-I00, IFT Centro de Excelencia Severo Ochoa SEV-2016-0597, and Red Consolider MultiDark FPA2017-90566-RED

Bulk autophagy, but not mitophagy, is increased in cellular model of mitochondrial disease

Oxidative phosphorylation system (OXPHOS) deficiencies are rare diseases but constitute the most frequent inborn errors of metabolism. We analyzed the autophagy route in 11 skin fibroblast cultures derived from patients with well characterized and distinct OXPHOS defects. Mitochondrial membrane potential determination revealed a tendency to decrease in 5 patients' cells but reached statistical significance only in 2 of them. The remaining cells showed either no change or a slight increase in this parameter. Colocalization analysis of mitochondria and autophagosomes failed to show evidence of increased selective elimination of mitochondria but revealed more intense autophagosome staining in patients' fibroblasts compared with controls. Despite the absence of increased mitophagy, Parkin recruitment to mitochondria was detected in both controls' and patients' cells and was slightly higher in cells harboring complex I defects. Western blot analysis of the autophagosome marker LC3B, confirmed significantly higher levels of the protein bound to autophagosomes, LC3B-II, in patients' cells, suggesting an increased bulk autophagy in OXPHOS defective fibroblasts. Inhibition of lysosomal proteases caused significant accumulation of LC3B-II in control cells, whereas in patients' cells this phenomenon was less pronounced. Electron microscopy studies showed higher content of late autophagic vacuoles and lysosomes in OXPHOS defective cells, accompanied by higher levels of the lysosomal marker LAMP-1. Our findings suggest that in OXPHOS deficient fibroblasts autophagic flux could be partially hampered leading to an accumulation of autophagic vacuoles and lysosomesThis work was supported by grants PS09/01359, PI12/ 01683, PI11/00182 and CP11/00151 from Instituto de Salud Carlos III- Ministerio de Industria y Competitividad de España (ISCIIIMINECO, Spain), S2010/BMD-2361 and S2010/BMD-2402 from Comunidad de Madrid (CAM, Spain). AD is recipient of a research contract from ISCIII-MINECO (PI12/01683). MM is supported by a research contract ‘Miguel Servet’ ISCIII-MINECO (CP11/00151). AB is supported by a research contract (CIBERER-Spain

Measuring attention of ADHD patients by means of a computer game featuring biometrical data gathering

ADHD is a neurodevelopmental disorder diagnosed mainly in children, marked by inattention and hyperactivity-impulsivity. The symptoms are highly variable, such as different ages of onset and potential comorbidities, contributing to frequent misdiagnoses. Professionals note a gap in modern diagnostic tools, making accurate identification challenging. To address this, recent studies recommend gamification for better ADHD diagnosis and treatment, though further research is essential to confirm its efficacy. This work aims to create a serious game, namely “Attention Slackline", to assess attention levels. The game, designed with expert input, requires players to concentrate on a specific point to recognize specific patterns while managing distractions. A controlled experiment tested its precision, and results were compared with established attention tests by a correlation analysis. Statistical analysis confirmed the game's validity, especially in tracking attention through correct responses and errors. Preliminary evidence suggests that “Attention Slackline" may serve as a credible instrument for the assessment of attentional capacities in individuals with ADHD, given that its outcomes have been empirically shown to correlate with those derived from a well-established attention assessment methodology.This work has been co-funded by the BALLADEER (PROMETEO/2021/088) project, a Big Data analytical plat-form for the diagnosis and treatment of Attention Deficit Hyperactivity Disorder (ADHD) featuring extended reality, funded by the ,Conselleria de Innovación, Universidades Ciencia y Sociedad Digital (Generalitat Valenciana), Grant RED2022-134656-T funded by MCIN/AEI/10.13039/501100011033 and Program for the Promotion of R + D + I (UAIND20-03B) by Vicerrectorado de Investigación y Transferencia de Conocimiento de la Universidad de Alicante, and by the AETHER-UA project (PID2020-112540RB-C43), a smart data holistic approach for context-aware data analytics: smarter machine learning for business modelling and analytics, funded by Spanish Ministry of Science and Innovation

Evaluation of a workshop to teach a new surgical technique in abdominal wall reconstruction.

Purpose Assess the utility of a hands-on workshop on abdominal wall reconstruction for teaching the posterior components separation (PCS) with transversus abdominis release. Methods Our department has been organizing a training course on abdominal wall reconstruction for the last 6 years. It is a 2-day-long course and 10–12 surgeons with experience in abdominal wall surgery attend to every course. The first day is dedicated to theoretical lectures and two simultaneous live surgeries, and the second day there is a cadaver dissection. Feedback from the trainees was collected at the end of the workshop. A survey was sent to all the surgeons who had completed the course at least a year ago, to inquire how the course had improved their surgical practice. Results From 2013 to April 2017, we have made 15 editions of the course. A total of 192 surgeons from Europe, South Africa and Middle East attended. All the surgeons answered the survey that was carried out at the end of the course. It showed a very high level of satisfaction in more than 98% of the cases. The second survey was answered by 79 surgeons (41.15%). 96% of the surgeons had modified, after attending the course, their way of dealing with complex abdominal wall problems. Only 29% of the surgeons had made a TAR before attending the course, while 86% are performing it after attending the course and 60% do it on a regular basis. In fact, 43% of surgeons have performed more than five posterior component separations in the last year. Conclusions A workshop of abdominal wall surgery that combines live surgery, theoretical content and a cadaver lab can be a very useful tool to expand the use of new surgical techniques.pre-print424 K

West Nile Virus Replication Requires Fatty Acid Synthesis but Is Independent on Phosphatidylinositol-4-Phosphate Lipids

West Nile virus (WNV) is a neurovirulent mosquito-borne flavivirus, which main natural hosts are birds but it also infects equines and humans, among other mammals. As in the case of other plus-stranded RNA viruses, WNV replication is associated to intracellular membrane rearrangements. Based on results obtained with a variety of viruses, different cellular processes have been shown to play important roles on these membrane rearrangements for efficient viral replication. As these processes are related to lipid metabolism, fatty acid synthesis, as well as generation of a specific lipid microenvironment enriched in phosphatidylinositol-4-phosphate (PI4P), has been associated to it in other viral models. In this study, intracellular membrane rearrangements following infection with a highly neurovirulent strain of WNV were addressed by means of electron and confocal microscopy. Infection of WNV, and specifically viral RNA replication, were dependent on fatty acid synthesis, as revealed by the inhibitory effect of cerulenin and C75, two pharmacological inhibitors of fatty acid synthase, a key enzyme of this process. However, WNV infection did not induce redistribution of PI4P lipids, and PI4P did not localize at viral replication complex. Even more, WNV multiplication was not inhibited by the use of the phosphatidylinositol-4-kinase inhibitor PIK93, while infection by the enterovirus Coxsackievirus B5 was reduced. Similar features were found when infection by other flavivirus, the Usutu virus (USUV), was analyzed. These features of WNV replication could help to design specific antiviral approaches against WNV and other related flaviviruses

Long-term outcomes after prophylactic use of onlay mesh in midline laparotomy.

Background The prevalence of incisional hernias (IHs) is still high after midline laparotomy (ML). There is an increasing body of evidence that prophylactic mesh placement (PMP) can be safe and efficient in the short-term outcomes, but there still are some concerns about the potential long-term complications of these meshes. This study describes our long-term PMP experience. Methods Observational and prospective study including all patients undergoing the use of prophylactic onlay large-pore polypropylene meshes for the closure of ML since 2008 to 2014. Outcome measures included demographics, perioperative details, wound complications, recurrences, reoperations and chronic complications. Results A cohort of 172 patients was analysed: 75% elective surgery, 25% emergency cases. Mean age was 68 years with mean body mass index (BMI) of 28.6 kg/m2. Wound classification: 6.4% clean; 85% clean-contaminated; 1.2% contaminated and 8.1% dirty. Follow-up of patients was up to 8 years (mean: 5 ± 1.6). Two meshes were removed due to chronic infection in first six postoperative months. Of the 13 patients (9.02%) who developed IH, 5 of them have been reoperated for IH repair without any difficulty related to previous mesh. During follow-up, 8 patients have been reoperated for other reasons and the integrity of abdominal wall was also checked. After the comparative study, higher BMI and emergency surgery were still risk factors for IH despite PMP. Conclusions In our setting, the use of polypropylene prophylactic meshes in MLs is safe, efficient and durable.pre-print977 K

Spectral and spatial analysis of the dark matter subhalo candidates among Fermi Large Area Telescope unidentified sources

Fermi-LAT unidentified sources (unIDs) have proven to be compelling targets for performing indirect dark matter (DM) searches. In a previous work, we found that among the 1235 unIDs in Fermi-LAT catalogs (3FGL, 2FHL and 3FHL) only 44 of those are DM subhalos candidates. We now implement a spectral analysis to test whether these remaining sources are compatible or not with DM origin. This analysis is executed using almost 10 years of Pass 8 Fermi-LAT data. None of the unIDs are found to significantly prefer DM-induced emission compared to other, more conventional, astrophysical sources. In order to discriminate between pulsar and DM sources, we developed a new method which is based on the source's spectral curvature, peak energy, and its detection significance. We also look for spatial extension, which may be a hint for a DM origin according to our N-body simulation studies of the subhalo population. In addition, we used Gaia DR2 data to search for a potential stellar counterpart to our best DM subhalo candidates and, although no firm associations could be found, one of them coincides with the Sagittarius stream. Finally, previous constraints on the DM annihilation cross section are updated with the new number of remaining DM subhalo candidates among unIDs. Our limits now rule out canonical thermal WIMPs up to masses of 10 GeV for $b\bar{b}$ and 20 GeV for $\tau^+\tau^-$ annihilation channels, in this way being as sensitive and complementary to those obtained from other targets and probes.Comment: 27 pages, 10 figures, JCAP accepted. Matches the accepted versio

Identification of Transgene-Free CRISPR-Edited Plants of Rice, Tomato, and Arabidopsis by Monitoring DsRED Fluorescence in Dry Seeds

Efficient elimination of the editing machinery remains a challenge in plant biotechnology after genome editing to minimize the probability of off-target mutations, but it is also important to deliver end users with edited plants free of foreign DNA. Using the modular cloning system Golden Braid, we have included a fluorescence-dependent transgene monitoring module to the genome-editing tool box. We have tested this approach in Solanum lycopersicum, Oryza sativa, and Arabidopsis thaliana. We demonstrate that DsRED fluorescence visualization works efficiently in dry seeds as marker for the detection of the transgene in the three species allowing an efficient method for selecting transgene-free dry seeds. In the first generation of DsRED-free CRISPR/Cas9 null segregants, we detected gene editing of selected targets including homozygous mutants for the plant species tested. We demonstrate that this strategy allows rapid selection of transgene-free homozygous edited crop plants in a single generation after in vitro transformation

Widespread distribution of hepatitis E virus in Spanish pig herds

<p>Abstract</p> <p>Background</p> <p>Hepatitis E virus (HEV) infection is a serious health problem in developing countries and is also increasingly reported in industrialized regions. HEV is considered a zoonotic agent and strains isolated from swine and human sources are genetically similar. Thus, HEV is of increasing importance to both public and animal health. The aim of the present study was to evaluate the distribution of HEV in a large population of pigs from herds located in different autonomous regions throughout Spain.</p> <p>Results</p> <p>The presence of anti-HEV IgG antibodies was analyzed in 1141 swine serum samples (corresponding to 381 pigs younger than 6 months and 760 pigs older than 6 months) collected from 85 herds. Herds were located in 6 provinces in 4 autonomous regions throughout Spain. At least one pig tested positive for anti-HEV IgG in over 80% of herds. Of individual pigs, 20.4% (233/1141) were positive for anti-HEV IgG, with the prevalence being higher in adult pigs than in those under 6 months (30.2% <it>vs. </it>15.5%). A subset of serum samples taken at 2- to 5-week intervals showed that seroprevalence dropped between 3 and 11 weeks of age, and then rose significantly by the 15th week. Pigs were also examined for the presence of HEV-RNA by RT-PCR. Of pigs tested for the presence of HEV-RNA 18.8% (64/341) were positive, with at least one pig in almost half of the herds testing positive. HEV-RNA amplicons from several positive pigs were sequenced and all were of genotype 3.</p> <p>Conclusions</p> <p>HEV was found to be widely distributed among swine farms across Spain, with the prevalence being highest among animals older than 6 months. These results indicate that HEV infection either is or is likely to become endemic in the Spanish swine population.</p