Assessing the quality of chest compressions with a DIY low-cost manikin (LoCoMan) versus a standard manikin: a quasi-experimental study in primary education.

Extending the access to cardiopulmonary resuscitation (CPR) training to a wider public is an important step in increasing survivability of out-of-hospital cardiac arrest. However, often price and maintenance of CPR manikins are barriers that prevent training at schools. This study aims to evaluate the learning of hands-only (HO) CPR by practicing with a low-cost manikin (LoCoMan) with visual qualitative feedback and to compare the results with the skills acquired by practice on a conventional manikin. A quasi-experimental study with 193 schoolchildren (10 to 12 years old) who were allocated to two groups: the LoCoMan group was taught via an integrative approach (science combined with physical education (PE)) and practiced on a handmade manikin, and a control group practiced in a traditional setting with a commercial manikin (Resusci Junior, Laerdal, Norway). All participants practiced for 1 hands-on skill session before performing a post-test on an instrumented CPR manikin. The outcomes including HO-CPR performance variables were compared between groups. The LoCoMan and control groups both achieved acceptable percentage of HO-CPR quality (57% and 71%, p = 0.004). Among 6th-graders, there were no significant differences in HO-CPR quality between LoCoMan 68% and control 71%, p = 0.66. The control group achieved better chest compression depth while the LoCoMan group showed more compressions with adequate chest recoil.     Conclusion: Schoolchildren are able to build and use a low-cost manikin with visual feedback. The integrative learning approach used in this study may be a feasible alternative methodology for training and learning HO-CPR in schools when commercial manikins are not available. What is Known: • Access to CPR training should be universal and independent of age, location, financial means, or access to qualified instructors. • Scientific societies promote the implementation of CPR in schools, so that teachers and schoolchildren can play a multiplier role in their environment, but the gap in CPR learning is related to cultural, economic factors or access to resources and materials. What is New: • LoCoMan may be a useful device for teaching and learning CPR in schoolchildren from the age of 10 and upwards. • LOCOMAN shows that it is feasible and possible to build a low-cost manikin (about €5 in the European Region) and to integrate it into an integrative educational project, and outlines how this could be done. this approach can be an incentive for teachers to attempt teaching CPR, but also for education outside the formal environment.

Concurrent Encoding of Sequence Predictability and Event-Evoked Prediction Error in Unfolding Auditory Patterns.

Human listeners possess an innate capacity to discern patterns within rapidly unfolding sensory input. Core questions, guiding ongoing research, focus on the mechanisms through which these representations are acquired and whether the brain prioritizes or suppresses predictable sensory signals. Previous work, using fast auditory sequences (tone-pips presented at a rate of 20 Hz), revealed sustained response effects that appear to track the dynamic predictability of the sequence. Here, we extend the investigation to slower sequences (4 Hz), permitting the isolation of responses to individual tones. Stimuli were 50 ms tone-pips, ordered into random (RND) and regular (REG; a repeating pattern of 10 frequencies) sequences; Two timing profiles were created: in "fast" sequences, tone-pips were presented in direct succession (20 Hz); in "slow" sequences, tone-pips were separated by a 200 ms silent gap (4 Hz). Naive participants (N = 22; both sexes) passively listened to these sequences, while brain responses were recorded using magnetoencephalography (MEG). Results unveiled a heightened magnitude of sustained brain responses in REG when compared to RND patterns. This manifested from three tones after the onset of the pattern repetition, even in the context of slower sequences characterized by extended pattern durations (2,500 ms). This observation underscores the remarkable implicit sensitivity of the auditory brain to acoustic regularities. Importantly, brain responses evoked by single tones exhibited the opposite pattern-stronger responses to tones in RND than REG sequences. The demonstration of simultaneous but opposing sustained and evoked response effects reveals concurrent processes that shape the representation of unfolding auditory patterns.

Understanding the salt overly sensitive pathway in Prunus: Identification and characterization of NHX, CIPK, and CBL genes.

Salinity is a major abiotic stress factor that can significantly impact crop growth, and productivity. In response to salt stress, the plant Salt Overly Sensitive (SOS) signaling pathway regulates the homeostasis of intracellular sodium ion concentration. The SOS1, SOS2, and SOS3 genes play critical roles in the SOS pathway, which belongs to the members of Na+/H+ exchanger (NHX), CBL-interacting protein kinase (CIPK), and calcineurin B-like (CBL) gene families, respectively. In this study, we performed genome-wide identifications and phylogenetic analyses of NHX, CIPK, and CBL genes in six Rosaceae species: Prunus persica, Prunus dulcis, Prunus mume, Prunus armeniaca, Pyrus ussuriensis × Pyrus communis, and Rosa chinensis. NHX, CIPK, and CBL genes of Arabidopsis thaliana were used as controls for phylogenetic analyses. Our analysis revealed the lineage-specific and adaptive evolutions of Rosaceae genes. Our observations indicated the existence of two primary classes of CIPK genes: those that are intron-rich and those that are intron-less. Intron-rich CIPKs in Rosaceae and Arabidopsis can be traced back to algae CIPKs and CIPKs found in early plants, suggesting that intron-less CIPKs evolved from their intron-rich counterparts. This study identified one gene for each member of the SOS signaling pathway in P. persica: PpSOS1, PpSOS2, and PpSOS3. Gene expression analyses indicated that all three genes of P. persica were expressed in roots and leaves. Yeast two-hybrid-based protein-protein interaction analyses revealed a direct interaction between PpSOS3 and PpSOS2; and between PpSOS2 and PpSOS1C-terminus region. Our findings indicate that the SOS signaling pathway is highly conserved in P. persica.

Potentially toxic element bioaccumulation in consumed indoor shrimp farming associated with diet, water and sediment levels.

Shrimp production is an important industry for many countries and shrimp consumption is increasing worldwide. Shrimps are a highly nutritional food, but can pose a risk for human health if subject to high levels of environmental contaminants. This work studies the presence of As, Cd, Co, Cr, Cu, Hg, Ni, Pb and Zn in shrimps from Ecuador and compares them to such contents noted in other shrimp-production areas in the world to evaluate the possible risks associated with these elements for consumer health, and to relate them to potentially toxic element (PTE) contents in water, sediments and diets, and also to animal biometric parameters. The PTE levels (mg kg-1 DM) obtained are as follows: in the head-As (3.52-6.11), Cd (0.02-0.10), Co (0.14-0.49) Cr (0.23-4.89), Cu (99.9--233.0), Ni (0.52-1.86), Pb (0.24-1.09), Zn (51.8-100.5) and Hg (µg kg-1 DM) (10.00-66.81); in the tail-(0.91-3.21), Cd (0.01-0.02), Co (0.01-0.43) Cr (0.01-6.52), Cu (20.0-72.44), Ni (0.15-2.03), Pb (0.01-0.69), Zn (31.2-66.1) and Hg (µg kg-1 DM) (10.00-67.18). The concentration of all the PTEs is generally lower than the limits set for seafood by European regulations, except for As in the cephalothorax (4.63 mg kg-1). Different behaviours for PTE accumulation in shrimps were found, which preferentially tend to accumulate in the cephalothorax, except for Hg (40.13 µg kg-1 DM), which accumulates in muscle (body) and is associated with contents of proteins, lipids and total shrimp weight. Nonetheless, the target hazard quotient (THQ) values for PTEs indicate that the consumption of shrimp muscles from Ecuador does not pose a human health risk because the values of these indices are below 1 in all cases.

Magnesium supplementation alleviates drought damage during vegetative stage of soybean plants.

Our working hypothesis was that magnesium (Mg) supplementation modulates plant performance under low water availability and improves drought tolerance in soybean genotypes. Plants of Bônus 8579, M8808 and TMG1180 genotypes were grown under field conditions and subjected to three water stress treatments (control, moderate and severe stress) and three Mg levels [0.9 (low), 1.3 (adequate) and 1.7 cmolc dm-³ (supplementation)]. After 28 days of drought imposition, the growth parameters, osmotic potential, relative water content, leaf succulence, Mg content and photosynthetic pigments were assessed. In general, drought drastically decreased the growth in all genotypes, and the reductions were intensified from moderate to severe stress. Under adequate Mg supply, TMG1180 was the most drought-tolerant genotype among the soybean plants, but Mg supplementation did not improve its tolerance. Conversely, although the M8808 genotype displayed inexpressive responses to drought under adequate Mg, the Mg-supplemented plants were found to have surprisingly better growth performance under stress compared to Bônus 8579 and TMG1180, irrespective of drought regime. The improved growth of high Mg-treated M8808-stressed plants correlated with low osmotic potential and increased relative water content, as well as shoot Mg accumulation, resulting in increased photosynthetic pigments and culminating in the highest drought tolerance. The results clearly indicate that Mg supplementation is a potential tool for alleviating water stress in M8808 soybean plants. Our findings suggest that the enhanced Mg-induced plant acclimation resulted from increased water content in plant tissues and strategic regulation of Mg content and photosynthetic pigments.

Insights into next generation sequencing guided antibody selection strategies.

Therapeutic antibody discovery often relies on in-vitro display methods to identify lead candidates. Assessing selected output diversity traditionally involves random colony picking and Sanger sequencing, which has limitations. Next-generation sequencing (NGS) offers a cost-effective solution with increased read depth, allowing a comprehensive understanding of diversity. Our study establishes NGS guidelines for antibody drug discovery, demonstrating its advantages in expanding the number of unique HCDR3 clusters, broadening the number of high affinity antibodies, expanding the total number of antibodies recognizing different epitopes, and improving lead prioritization. Surprisingly, our investigation into the correlation between NGS-derived frequencies of CDRs and affinity revealed a lack of association, although this limitation could be moderately mitigated by leveraging NGS clustering, enrichment and/or relative abundance across different regions to enhance lead prioritization. This study highlights NGS benefits, offering insights, recommendations, and the most effective approach to leverage NGS in therapeutic antibody discovery.

Regulation Transcriptional of Antibiotic Resistance Genes (ARGs) in Bacteria Isolated from WWTP.

The incidence of antibiotics and transcriptional regulation of ARGs in isolated bacteria from wastewater needs to be explored. By HPLC, in samples of untreated wastewater, ampicillin (49.74 ± 5.70 µg/mL), chloramphenicol (0.60 ± 0.03 µg/mL), tylosin (72.95 ± 2.03 µg/mL), and oxytetracycline (0.22 ± 0.01 µg/mL) was determined. Through metagenomic analysis identified 58 bacterial species belonging to 9 phyla and at least 14 species have shown resistance to a variety of antibiotics. Twenty-two bacterial isolates were proved to be resistant to fifteen antibiotics of new generation and used in medical research to combat infectious diseases. Fourteen strains were shown to harbor plasmids in size ranges of 2-5 Kb, 6-10 Kb and plasmids with size greater than 10 Kb. By quantitative PCR it was possible to identify genes sul, qnr, cat1, aadA1, and sat-1 gene were shown to be present in gDNA samples from treated and untreated samples of wastewater and by relative expression analysis, differential expression of cat1, ermB, act, and tetA genes was demonstrated in strains that showed identity with Escherichia coli, Bacteroides fragilis, and Salmonella thyphi, and that were stressed with different concentrations of antibiotics. The presence of ARGs in untreated water samples, as well as in bacterial isolates, was indicative that in these habitats there are microorganisms that can resist ß-lactams, aminoglycosides, tetracyclines, sulfonamides, and quinolones.

Weed-Hoeing Periods in Cowpea Cultivation under Direct and Conventional Systems.

Weed coexistence with an agricultural crop can negatively affect its growth, development, and yield. From this perspective, this study aimed to evaluate weed management strategies and their effect on the agronomic parameters of cowpea cultivation in direct (SPD) and conventional (SPC) planting systems. The experiment was set up in a completely randomized block design with a split-plot arrangement with four replications. The plots received a source of variation referring to the planting systems (direct and conventional planting), and the subplots corresponded to ten weed management strategies (manual hoeing 18 days after planting (DAP); at 36 DAP; at 54 DAP; at 18 and 36 DAP; at 18 and 54 DAP; at 18 and 72 DAP; at 36 and 54 DAP; at 36-72 DAP; at 18, 36, and 54 DAP; and a control with no hoeing). Density and dry mass evaluations of the cowpea plants were performed at harvest (72 DAP) by determining the number of pods per plant, pod length, number of grains per pod, 1000-grain mass, and yield. A total of 28 species distributed in 12 botanical families were identified in the two cultivation systems. The family Poaceae showed the highest frequency, with 25% of the species identified. At the end of the assay, treatment 20 had the highest positive influence and provided significant quantitative gains to the complex of traits related to cowpea production (SPD and hoeing at 18, 36, and 54 DAP). UPGMA cluster analysis and canonical discriminant analysis were performed and allowed a better classification of the evaluated treatments. It was observed that the first two canonical variables explained 90.8% of the total variance contained in the original variables. The use of SPD with weeding at 18, 36, and 54 days after planting provides greater weed control and significant quantitative gains for the complex of characteristics related to cowpea production. The results underscore the importance of choosing the correct cropping system and implementing effective weeding practices to optimize weed control and improve crop performance.

Coumaphos residue transfer to honey bee brood (Apis mellifera) in realistic scenarios.

Coumaphos is a veterinary treatment administered for the control of Varroa destructor in honey bee colonies. The detection of its residues, however, has been frequently reported in beeswax. This study is pioneer to investigate whether the honey bee brood is exposed to coumaphos via contact or by ingestion of food resources due to a residue transfer inside the bee hive. This field study addresses two scenarios: 1) after its administration according to the posology using strips inside the bee hives and, 2) placing contaminated wax containing coumaphos at 10 mg/Kg into the bee hives (simulating the use of recycled wax). In bee bread, the average concentrations of residues (mean ± s.d.) were 246.66 ± 772.29 ng/g and 192.55 ± 320.19 ng/g in scenario 1 and 2, respectively. In honey, residue concentration was 1.98 ± 5.41 ng/g and 1.93 ± 6.59 ng/g. In scenario 2, exposure has led to residue detection in all larval stages at concentrations ranging from 51.93 to 383.42 ng/g (larvae), 42.20-58.54 ng/g (prepupae), 18.35-26.24 ng/g (pupae) to 21.92-35.92 ng/g (born bee). This study shows that there is a high risk for the bee brood (larvae) by ingestion of bee bread when the residue concentration is >251.31 ng/g. Residue levels in larvae or in prepupae >42.20 ng/g give rise to a moderate risk.

Cell Count Differentials by Cytomorphology and Next-Generation Flow Cytometry in Bone Marrow Aspirate: An Evidence-Based Approach.

Despite a lack of evidence, a bone marrow aspirate differential of 500 cells is commonly used in the clinical setting. We aimed to test the performance of 200-cell counts for daily hematological workup. In total, 660 consecutive samples were analyzed recording differentials at 200 and 500 cells. Additionally, immunophenotype results and preanalytical issues were also evaluated. Clinical and statistical differences between both cutoffs and both methods were checked. An independent control group of 122 patients was included. All comparisons between both cutoffs and both methods for all relevant types of cells did not show statistically significant differences. No significant diagnostic discrepancies were demonstrated in the contingency table analysis. This is a real-life study, and some limitations may be pointed out, such as a different sample sizes according to the type of cell in the immunophenotype analysis, the lack of standardization of some preanalytical events, and the relatively small sample size of the control group. The comparisons of differentials by morphology on 200 and 500 cells, as well as by morphology (both cutoffs) and by immunophenotype, are equivalent from the clinical and statistical point of view. The preanalytical issues play a critical role in the assessment of bone marrow aspirate samples.

Occupational Sun Exposure Among Physical Education Teachers in Primary and Secondary Schools in Andalusia, Spain.

Chronic sun exposure and sunburns are the main preventable causes of skin cancer. Due to the nature of their work, physical education teachers are at high risk for occupational skin cancer. This descriptive, cross-sectional study analyzes primary and secondary physical education teachers in Andalusia, Spain. All participants were invited to monitor their ultraviolet (UV) radiation exposure using individual biologic dosimeters and record their photoprotection practices over 3 workdays. The teachers spent an average of 2.7 h outdoors and the mean personal UV radiation exposure was 309.9 J/m2 per day, a value three times higher than international recommendations. Based on the photoprotection diary, it was determined that classes held outdoors were not scheduled outside the hours with the highest UV index and that the percentage of participants who followed the photoprotective practices of remaining in the shade or wearing a hat during outdoor lessons were less than 20% and 60%, respectively. The results on sun exposure and photoprotection practices show a need for organizational and educational intervention strategies to mitigate sun exposure and increase compliance with photoprotection measures to reduce skin cancer risk among these workers and promote early diagnosis of the disease.

Lymphovascular Invasion at the Time of Radical Prostatectomy Adversely Impacts Oncological Outcomes.

Lymphovascular invasion, whereby tumour cells or cell clusters are identified in the lumen of lymphatic or blood vessels, is thought to be an essential step in disease dissemination. It has been established as an independent negative prognostic indicator in a range of cancers. We therefore aimed to assess the impact of lymphovascular invasion at the time of prostatectomy on oncological outcomes. We performed a multicentre, retrospective cohort study of 3495 men who underwent radical prostatectomy for localised prostate cancer. Only men with negative preoperative staging were included. We assessed the relationship between lymphovascular invasion and adverse pathological features using multivariable logistic regression models. Kaplan-Meier curves and Cox proportional hazard models were created to evaluate the impact of lymphovascular invasion on oncological outcomes. Lymphovascular invasion was identified in 19% (n = 653) of men undergoing prostatectomy. There was an increased incidence of lymphovascular invasion-positive disease in men with high International Society of Urological Pathology (ISUP) grade and non-organ-confined disease (p < 0.01). The presence of lymphovascular invasion significantly increased the likelihood of pathological node-positive disease on multivariable logistic regression analysis (OR 15, 95%CI 9.7-23.6). The presence of lymphovascular invasion at radical prostatectomy significantly increased the risk of biochemical recurrence (HR 2.0, 95%CI 1.6-2.4). Furthermore, lymphovascular invasion significantly increased the risk of metastasis in the whole cohort (HR 2.2, 95%CI 1.6-3.0). The same relationship was seen across D'Amico risk groups. The presence of lymphovascular invasion at the time of radical prostatectomy is associated with aggressive prostate cancer disease features and is an indicator of poor oncological prognosis.

New dating of the Matalascañas footprints provides new evidence of the Middle Pleistocene (MIS 9-8) hominin paleoecology in southern Europe.

Hominin footprints were recently discovered at Matalascañas (Huelva; South of Iberian Peninsula). They were dated thanks to a previous study in deposits of the Asperillo cliff to 106 ± 19 ka, Upper Pleistocene, making Neandertals the most likely track-makers. In this paper, we report new Optically Stimulated Luminescence dating that places the hominin footprints surface in the range of 295.8 ± 17 ka (MIS 9-MIS 8 transition, Middle Pleistocene). This new age implies that the possible track-makers are individuals more likely from the Neandertal evolutionary lineage. Regardless of the taxon attributed to the Matalascañas footprints, they supplement the existing partial fossil record for the European Middle Pleistocene Hominins being notably the first palaeoanthropological evidence (hominin skeleton or footprints) from the MIS 9 and MIS 8 transition discovered in the Iberian Peninsula, a moment of climatic evolution from warm to cool. Thus, the Matalascañas footprints represent a crucial record for understanding human occupations in Europe in the Pleistocene.

Risk factors for equine trypanosomosis and hematological analysis of horses in Paraguay.

Animal trypanosomosis, caused by Trypanozoon trypanosomes (Trypanosoma evansi and T. equiperdum), and Trypanosoma vivax, is endemic to South American countries and has a negative impact on the livestock industry. However, the risk factors for trypanosomosis in Paraguay remain unknown. This study aimed to determine the risk factors for equine trypanosomosis in Paraguay based on a PCR-based molecular survey and individual horse sampling data. In this study, 739 blood samples were collected from horses in 16 departments of Paraguay between August 2019 and November 2020. To elucidate the risk factors for trypanosome infection, the relationship between trypanosome infection status detected by PCR and the location, sex, age, breed of horses, and season of sample collection was analyzed. There were no significant differences in trypanosome prevalence in horses between the eastern and western regions, ages, or breeds of horses in Paraguay. Sex and season were identified as risk factors for trypanosome infection in horses in Paraguay in the current study. These results suggest that the rainy-summer season, when vectors increase in number and their blood-sucking activity, could be the most important risk factor for trypanosome infection in Paraguay horses. Preventive measures and treatments should be developed to address these factors.

Evidence of recent Epstein-Barr virus reactivation in individuals experiencing Long COVID

The presence and reactivation of chronic viral infections such as Epstein-Barr virus (EBV), cytomegalovirus (CMV) and human immunodeficiency virus (HIV) have been proposed as potential contributors to Long COVID (LC), but studies in well-characterized post-acute cohorts of individuals with COVID-19 over a longer time course consistent with current case definitions of LC are limited. In a cohort of 280 adults with prior SARS-CoV-2 infection, we observed that LC symptoms such as fatigue and neurocognitive dysfunction at a median of 4 months following initial diagnosis were independently associated with serological evidence of recent EBV reactivation (early antigen-D [EA-D] IgG positivity) or high nuclear antigen IgG levels, but not with ongoing EBV viremia. Evidence of EBV reactivation (EA-D IgG) was most strongly associated with fatigue (OR 2.12). Underlying HIV infection was also independently associated with neurocognitive LC (OR 2.5). Interestingly, participants who had serologic evidence of prior CMV infection were less likely to develop neurocognitive LC (OR 0.52) and tended to have less severe (>5 symptoms reported) LC (OR 0.44). Overall, these findings suggest differential effects of chronic viral co-infections on the likelihood of developing LC and predicted distinct syndromic patterns. Further assessment during the acute phase of COVID-19 is warranted. SUMMARYThe authors found that Long COVID symptoms in a post-acute cohort were associated with serological evidence of recent EBV reactivation and pre-existing HIV infection when adjusted for participant factors, sample timing, comorbid conditions and prior hospitalization, whereas underlying CMV infection was associated with a decreased risk of Long COVID.

Ultrasound-guided vascular access in the neonatal intensive care unit: a nationwide survey.

Ultrasound-guided vascular access (USG-VA) is recommended by international practice guidelines but information regarding its use in the neonatal intensive care unit (NICU) is lacking. Our objective was to assess neonatologist's perceptions and current implementation of USG-VA in Spain. This was a nationwide online survey. The survey was composed of 37 questions divided in 4 domains: (1) neonatologist's background, (2) NICU characteristics, (3) personal perspectives about USG-VA, and (4) clinical experience in USG-VA. One-hundred and eighty survey responses from 59 NICUs (62% of Spanish NICUs) were analyzed. Most neonatologists (81%) perceive that competence in USG-VA is indispensable or very useful in clinical practice. However, 64 (35.5%) have never used USG-VA in real patients. Among neonatologists with some experience in USG-VA most perform less than 5 procedures per year (59% in venous access and 80% in arterial access) and a 38% and 60% have never used USG for venous and arterial access, respectively, in very low birth weight infants (VLBWI). More than a half of neonatologists (55.5%) use US to check catheter tip location but a 46.6% always perform a radiography for confirmation. Spanish neonatologists report that resident/fellow training in USG-VA is absent (52.2%) or unstructured (32%) in their units. The lack of adequate training is identified by a 60% of neonatologists as the most important barrier for implementation of USG-VA and 87% would recommend that future neonatologists receive formal training. CONCLUSION: Spanish neonatologists perceive that USG-VA is important in clinical practice but currently, these techniques are largely underused. Our results indicate that specific training in USG-VA should be implemented in the NICU. WHAT IS KNOWN: • Ultrasound-guided vascular access is recommended as the preferred method for central venous access and arterial line placement in children and adults. • The degree of current implementation of ultrasound for vascular access in the NICU and the perceptions of neonatologist about its use are largely unknown. WHAT IS NEW: • Most neonatologists consider that competence in ultrasound-guided vascular access is an indispensable aid for clinical practice. • However, most neonatologists are not adequately trained in ultrasound-guided vascular access and the technique is largely underused.

HMGA1 chromatin regulators induce transcriptional networks involved in GATA2 and proliferation during MPN progression.

Myeloproliferative neoplasms (MPNs) transform to myelofibrosis (MF) and highly lethal acute myeloid leukemia (AML), although the actionable mechanisms driving progression remain elusive. Here, we elucidate the role of the high mobility group A1 (HMGA1) chromatin regulator as a novel driver of MPN progression. HMGA1 is upregulated in MPN, with highest levels after transformation to MF or AML. To define HMGA1 function, we disrupted gene expression via CRISPR/Cas9, short hairpin RNA, or genetic deletion in MPN models. HMGA1 depletion in JAK2V617F AML cell lines disrupts proliferation, clonogenicity, and leukemic engraftment. Surprisingly, loss of just a single Hmga1 allele prevents progression to MF in JAK2V617F mice, decreasing erythrocytosis, thrombocytosis, megakaryocyte hyperplasia, and expansion of stem and progenitors, while preventing splenomegaly and fibrosis within the spleen and BM. RNA-sequencing and chromatin immunoprecipitation sequencing revealed HMGA1 transcriptional networks and chromatin occupancy at genes that govern proliferation (E2F, G2M, mitotic spindle) and cell fate, including the GATA2 master regulatory gene. Silencing GATA2 recapitulates most phenotypes observed with HMGA1 depletion, whereas GATA2 re-expression partially rescues leukemogenesis. HMGA1 transactivates GATA2 through sequences near the developmental enhancer (+9.5), increasing chromatin accessibility and recruiting active histone marks. Further, HMGA1 transcriptional networks, including proliferation pathways and GATA2, are activated in human MF and MPN leukemic transformation. Importantly, HMGA1 depletion enhances responses to the JAK2 inhibitor, ruxolitinib, preventing MF and prolonging survival in murine models of JAK2V617F AML. These findings illuminate HMGA1 as a key epigenetic switch involved in MPN transformation and a promising therapeutic target to treat or prevent disease progression.

One Hundred Years of Coat Colour Influences on Genetic Diversity in the Process of Development of a Composite Horse Breed.

Genetic diversity and demographic parameters were computed to evaluate the historic effects of coat colour segregation in the process of configuration of the Hispano-Arabian horse (Há). Pedigree records from 207,100 individuals born between 1884 and 2019 were used. Although coat colour is not a determinant for the admission of Hispano-Arabian individuals as apt for breeding, it may provide a representative visual insight into the gene contribution of Spanish Purebred horses (PRE), given many of the dilution genes described in Há are not present in the Arabian Purebred breed (PRá). The lack of consideration of coat colour inheritance patterns by the entities in charge of individual registration and the dodging behaviour of breeders towards the historic banning policies, may have acted as a buffer for diversity loss (lower than 8%). Inbreeding levels ranged from 1.81% in smokey cream horses to 8.80 for white horses. Contextually, crossbred breeding may increase the likelihood for double dilute combinations to occur as denoted by the increased number of Há horses displaying Pearl coats (53 Há against 3 PRE and 0 PRá). Bans against certain coat colours and patterns may have prevented an appropriate registration of genealogical information from the 4th generation onwards for decades. This may have brought about the elongation of generation intervals. Breeder tastes may have returned to the formerly officially-recognised coat colours (Grey and Bay) and Chestnut/Sorrel. However, coat colour conditioning effects must be evaluated timely for relatively short specific periods, as these may describe cyclic patterns already described in owners' and breeders' tastes over the centuries.