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Chrysophyllum albidum is a forest food tree species of the Sapotaceae family bearing large berries of nutrition, sanitary, and commercial value in many African countries. Because of its socioeconomic importance, C. albidum is threatened at least by human pressure. However, we do not know to what extent climate change can impact its distribution or whether it is possible to introduce the species in other tropical regions. To resolve our concerns, we decided to model the spatial distribution of the species. We then used the SDM package for data modeling in R to compare the predictive performances of algorithms among the most commonly used: three machine learning algorithms (MaxEnt, boosted regression trees, and random forests) and three regression algorithms (generalized linear model, generalized additive models, and multivariate adaptive regression spline). We performed model transfers in tropical Asia and Latin America. At the scale of Africa, predictions with respect to Maxent under Africlim (scenarios RCP 4.5 and RCP 8.5, horizon 2055) and MIROCES2L (scenarios SSP245 and SSP585, horizon 2060) showed that the suitable areas of C. albidum, within threshold values of the most contributing variables to the models, will extend mostly in West, East, Central, and Southern Africa as well as in East Madagascar. As opposed to Maxent, in Africa, the predictions for the future of BRT and RF were unrealistic with respect to the known ecology of C. albidum. All the algorithms except Maxent (for tropical Asia only), were consistent in predicting a successful introduction of C. albidum in Latin America and tropical Asia, both at present and in the future. We therefore recommend the introduction and cultivation of Chrysophyllum albidum in the predicted suitable areas of Latin America and tropical Asia, along with vegetation inventories in order to discover likely, sister or vicarious species of Chrysophyllum albidum that can be new to Science. Africlim is more successful than MIROCES2L in predicting realistic suitable areas of Chrysophyllum albidum in Africa. We therefore recommend to the authors of Africlim an update of Africlim models to comply with the sixth Assessment Report (AR6) of IPCC. [ABSTRACT FROM AUTHOR]

Coastal wetlands provide a range of important ecosystem services, yet they are under threat from a range of stressors including climate change. This is predominantly as a result of alterations to the hydroregime and associated edaphic factors. We used a three-year mesocosm experiment to assess changes in coastal plant community composition for three plant communities in response to altered water level and salinity scenarios. Species richness and abundance were calculated by year and abundance was plotted using rank abundance curves. The permutational multivariate analysis of variance with Bray–Curtis dissimilarity was used to examine differences among treatments in plant community composition. A Non-metric Multi-dimensional Scaling analysis (NMDS) was used to visualize the responses of communities to treatments by year. Results showed that all three plant communities responded differently to altered water levels and salinity. Species richness and abundance increased significantly in an Open Pioneer plant community while Lower and Upper Shore plant communities showed less change. Species abundances changed in all plant communities with shifts in species composition significantly influenced by temporal effects and treatment. The observed responses to experimentally altered conditions highlight the need for conservation of these important ecosystems in the face of predicted climate change, since these habitats are important for wading birds and livestock grazing. [ABSTRACT FROM AUTHOR]

Numerous bottom current-controlled depositional and erosional features, which together form Contourite Depositional Systems (CDS), have been recognized in deep-water settings over the past decade. Most of these systems are described based on two-dimensional (2D) seismic data, whereas only a few CDS have been characterised from high-resolution 3D data. Here we document a newly identified CDS that formed during the Paleocene within the Morondava Basin, offshore west Madagascar, through analysis of a depth-migrated 3D seismic survey, enhanced by the implementation of seismic attributes. Three seismic units (SU) mark the main evolutionary stages of the CDS: (a) the onset (SU1), (b) drift growth (SU2), and (c) burial (SU3) stages. The growth stage documents lateral upslope migration of a mounded drift and its associated moat. The increasing, long-term influence of bottom currents along the foot of the slope occurred simultaneously with plate tectonic, climatic and oceanographic changes. Evidence amassed from the CDS highly erosive bounding discontinuities, internal discontinuities, and moat architecture all indicate the intermittent behaviour of the currents over shorter time frames during its formation. Drift deposits form under the influence of weaker currents, while discontinuities appear to record the most vigorous currents, producing the large-scale morphology of the system. [ABSTRACT FROM AUTHOR]

Alcohol consumption is associated with a number of diseases and injuries, including cardiovascular diseases, cancers, mental and neurological disorders, as well as transport-related injuries. This article reports the alcohol-attributable burden of diseases and injuries at the regional and national levels in the Middle East and North Africa (MENA) region between 1990 and 2019, by sex, age, underlying cause, and Socio-demographic Index (SDI). The regional deaths and disability-adjusted life-years (DALYs) attributable to alcohol consumption were reported for the MENA region, between 1990 and 2019, using the methodological framework and analytical strategies adopted by the Global Burden of Disease (GBD) study 2019. The estimates were all reported as counts, population-attributable fractions, and age-standardised rates per 100,000 population, along with their corresponding 95% uncertainty intervals (UIs). Also, the average annual percentage changes were used to represent the trends of age-standardised rates. In 2019, there were an estimated 22.0 thousand deaths (95% UI: 16.1–29.4) and 1.1 million DALYs (0.8–1.3) attributable to alcohol consumption in the MENA region. The number of DALYs attributable to alcohol consumption were much higher in men (878.0 thousand, 691.4–1104.8) than among women (181.8, 138.6–232.0). The overall age-standardised death and DALY rates attributable to alcohol consumption decreased by 34.5% (13.2–48.3) and 31.9% (16.9–42.5), respectively, over the study period. Egypt (10.1 [5.7–16.6]) and Kuwait (1.1 [0.8–1.5]) had the highest and lowest age-standardised death rates attributable to alcohol consumption, respectively. In 2019, the number of deaths and DALYs in the MENA region were highest in those aged 60–64 and 50–54 years, respectively. A negative association was observed between a country's SDI and their corresponding age-standardised DALY rates over the period 1990 to 2019. Digestive diseases were the main contributor to the alcohol-attributable burden. Over 1990–2019, the regional deaths and DALYs of diseases and injuries attributable to alcohol consumption decreased with AAPC of − 1.45 (− 1.78 to − 1.12) and − 1.31 (− 1.46 to − 1.15), respectively. The death and DALY rates attributable to alcohol consumption in the MENA region have decreased over the past three decades. Further decreases can be facilitated by implementing country-level policies and increasing public awareness. [ABSTRACT FROM AUTHOR]

Inorganic metal oxides with the merits of high carrier transport capability, low cost and superior chemical stability have largely served as the hole transport layer (HTL) in perovskite solar cells (PSCs) in recent years. Among them, ternary metal oxides have gradually attracted attention because of the wide tenability of the two inequivalent cations in the lattice sites that offer interesting physicochemical properties. In this work, ZnCo2O4 nanoparticles (NPs) were prepared by a chemical precipitation method and served as the HTL in inverted PSCs. The device based on the ZnCo2O4 NPs HTL showed better efficiency of 12.31% and negligible hysteresis compared with the one using PEDOT:PSS film as the HTL. Moreover, the device sustained 85% of its initial efficiency after 240 h storage under a halogen lamps matrix exposure with an illumination intensity of 1000 W/m2, providing a powerful strategy to design long term stable PSCs for future production. [ABSTRACT FROM AUTHOR]

The article deals with the study of poorly graded sand samples of different grain content subjected to liquefaction. The research results show the V-shaped behavior of the AE parameters that correspond to the three-stage sand behavior: Phase A is associated with microfractures/displacements between sand grains caused by an increase in pore pressure before the liquefaction point. Phase B (the stage of AE silence just before the liquefaction point) reflects the equality between pore pressure and stress in the confining chamber. Phase C (the stage of increase in AE parameters' values) is explained by intense friction between sand grains during their movement caused by liquefaction. Our results show that the AE behavior before, at, and after the liquefaction point is significantly affected by the sand grain content. The change in the sand composition from the poorly graded dune sand to "extremely poorly graded sand" significantly increases the time for the creation of the liquefaction state while the coarser the sand grains become, the longer duration of vibration loading is required to reach the liquefaction state. [ABSTRACT FROM AUTHOR]

How to mitigate the spread of infectious diseases like COVID-19 in indoor environments remains an important research question. In this study, we propose an agent-based modeling framework to evaluate facility usage policies that aim to lower the probability of outbreaks. The proposed framework is individual-based, spatially-resolved with time resolution of up to 1 s, and takes into detailed account specific floor layouts, occupant schedules and movement. It enables decision makers to compute realistic contact networks and generate risk profiles of their facilities without relying on wearable devices, smartphone tagging or surveillance cameras. Our demonstrative modeling results indicate that not all facility occupants present the same risk of starting an outbreak, where the driver of outbreaks varies with facility layouts as well as individual occupant schedules. Therefore, generic mitigation strategies applied across all facilities should be considered inferior to tailored policies that take into account individual characteristics of the facilities of interest. The proposed modeling framework, implemented in Python and now available to the public in an open-source platform, enables such strategy evaluation. [ABSTRACT FROM AUTHOR]

The active cycling of carbon between soil organic matter and the atmosphere is of critical importance to global climate change. An extensive body of research exists documenting the capricious nature of soil organic matter (SOM) dynamics, which is symptomatic of an intricate network of interactions between diverse groups of heterotrophic microorganisms, complex organic substrates, and highly variable local environmental conditions. These attributes are consistent with elements of complex system theory and the temporal evolution of otherwise unpredictable patterns of behavior that emerge from long range dependency on initial conditions. Here we show that vertical depth profile of self-potential (SP) time series measurements responds in a quantitative manner to variations in soil moisture, SOM concentrations, and relative rates of microbial activity. Application of detrended fluctuation analysis (DFA) of self potential time series data is shown additionally to reveal the presence of long-range dependence and emergence of anomalous electrochemical diffusion behavior, both of which diminish with depth as SOM specific energy densities decline. [ABSTRACT FROM AUTHOR]

The changes in gastric microbiota following reconstruction after gastrectomy have not been reported. This study aimed to compare the gastric microbiota following Billroth I and Roux-en-Y reconstructions after distal gastrectomy. We enrolled 71 gastrectomized patients with gastric cancer; 31 and 40 underwent Billroth I and Roux-en-Y reconstructions, respectively. During upper gastrointestinal endoscopy, gastric fluid was collected immediately before and 6 months after distal gastrectomy. Deoxyribonucleic acid isolated from each sample was evaluated using 16S ribosomal ribonucleic acid metagenomic analysis. Analysis revealed that the gastric microbiota's species richness (expressed as the alpha diversity) was significantly lower after than before distal gastrectomy (operational taxonomic units, p = 0.001; Shannon index, p = 0.03). The interindividual diversity (beta diversity) was significantly different before and after distal gastrectomy (unweighted UniFrac distances, p = 0.04; weighted UniFrac distances, p = 0.001; Bray–Curtis, p = 0.001). Alpha and beta diversity were not significantly different between Billroth I and Roux-en-Y reconstructions (observed operational taxonomic units, p = 0.58; Shannon index, p = 0.95; unweighted UniFrac distances, p = 0.65; weighted UniFrac distances, p = 0.67; Bray–Curtis, p = 0.63). Our study demonstrated significant differences in gastric microbiota diversity, composition, and community before and after distal gastrectomy but no difference between Billroth I and Roux-en-Y reconstruction after distal gastrectomy. [ABSTRACT FROM AUTHOR]

Impaired diaphragm activation is common in many neuromuscular diseases. We hypothesized that expressing photoreceptors in diaphragm myofibers would enable light stimulation to evoke functional diaphragm activity, similar to endogenous bursts. In a mouse model, adeno-associated virus (AAV) encoding channelrhodopsin-2 (AAV9-CAG-ChR2-mVenus, 6.12 × 1011 vg dose) was delivered to the diaphragm using a minimally invasive method of microinjection to the intrapleural space. At 8–18 weeks following AAV injection, mice were anesthetized and studied during spontaneous breathing. We first showed that diaphragm electromyographic (EMG) potentials could be evoked with brief presentations of light, using a 473 nm high intensity LED. Evoked potential amplitude increased with intensity or duration of the light pulse. We next showed that in a paralyzed diaphragm, trains of light pulses evoked diaphragm EMG activity which resembled endogenous bursting, and this was sufficient to generate respiratory airflow. Light-evoked diaphragm EMG bursts showed no diminution after up to one hour of stimulation. Histological evaluation confirmed transgene expression in diaphragm myofibers. We conclude that intrapleural delivery of AAV9 can drive expression of ChR2 in the diaphragm and subsequent photostimulation can evoke graded compound diaphragm EMG activity similar to endogenous inspiratory bursting. [ABSTRACT FROM AUTHOR]

The greenhouse effect of SF6 increasingly limits its application in various gas insulated equipment. C6F12O combines the advantages of insulation resistance, safety and environmental protection. When mixed with buffer gas, C6F12O is considered to have potential application prospects in medium and low voltage equipment. In this paper, about the partial discharge characteristics of the mixed gas, an experimental study was carried out. The partial discharge initiation voltage and discharge extinction voltage of mixed gas under power frequency voltage are measured and compared with the breakdown voltage. The results show that the breakdown voltage is greatly improved after adding C6F12O, with the increase of mixing ratio, the partial discharge initiation voltage and extinction voltage of mixed gas gradually increase, and the effect of gas pressure on high mixing ratio is obvious. The difference between the partial discharge inception voltage and the breakdown voltage is larger than that of pure N2. The research in this paper can provide an important reference for the application, operation and protection of C6F12O mixed gas in medium and low voltage equipment. [ABSTRACT FROM AUTHOR]

To identify candidate disease genes of central nervous system (CNS) phenotypes, we created the Neurogenetic Systematic Correlation of Omics-Related Evidence (NeuroSCORE). We identified five genome-wide metrics highly associated with CNS phenotypes to score 19,601 protein-coding genes. Genes scored one point per metric (range: 0–5), identifying 8298 scored genes (scores ≥ 1) and 1601 "high scoring" genes (scores ≥ 3). Using logistic regression, we determined the odds ratio that genes with a NeuroSCORE from 1 to 5 would be associated with known CNS-related phenotypes compared to genes that scored zero. We tested NeuroSCORE using microarray copy number variants (CNVs) in case–control cohorts and aggregate mouse model data. High scoring genes are associated with CNS phenotypes (OR = 5.5, p < 2e-16), enriched in case CNVs, and mouse ortholog genes that cause behavioral and nervous system abnormalities. We identified 1058 high scoring genes with no disease association in OMIM. Transforming the logistic regression results indicates high scoring genes have an 84–92% chance of being associated with a CNS phenotype. Top scoring genes include GRIA1, MAP4K4, SF1, TNPO2, and ZSWIM8. Finally, we interrogated CNVs in the Clinical Genome Resource, finding the majority of clinically significant CNVs contain high scoring genes. These findings can direct future research and improve molecular diagnostics. [ABSTRACT FROM AUTHOR]

Although there is a growing interest in the role of gastric microbiome on the development of gastric cancer, the exact mechanism is largely unknown. We aimed to investigate the changes of gastric microbiome during gastric carcinogenesis, and to predict the functional potentials of the microbiome involved in the cancer development. The gastric microbiome was analyzed using gastric juice samples from 88 prospectively enrolled patients, who were classified into gastritis, gastric adenoma, or early/advanced gastric cancer group. Differences in microbial diversity and composition were analyzed with 16S rRNA gene profiling, using next-generation sequencing method. Metagenomic biomarkers were selected using logistic regression models, based on relative abundances at genus level. We used Tax4Fun to predict possible functional pathways of gastric microbiome involved in the carcinogenesis. The microbial diversity continuously decreased in its sequential process of gastric carcinogenesis, from gastritis to gastric cancer. The microbial composition was significantly different among the four groups of each disease status, as well as between the cancer group and non-cancer group. Gastritis group was differently enriched with genera Akkermansia and Lachnospiraceae NK4A136 Group, whereas the cancer group was enriched with Lactobacillus and Veillonella. Predictive analysis of the functional capacity of the microbiome suggested enrichment or depletion of several functional pathways related to carcinogenesis in the cancer group. There are significant changes in the diversity and composition of gastric microbiome during the gastric carcinogenesis process. Gastric cancer was characterized with microbial dysbiosis, along with functional changes potentially favoring carcinogenesis. [ABSTRACT FROM AUTHOR]

BDNF (brain-derived neurotrophic factor) is present in skeletal muscle, controlling muscular metabolism, strength and regeneration processes. However, there is no consensus on BDNF cellular source. Furthermore, while endothelial tissue expresses BDNF in large amount, whether endothelial cells inside muscle expressed BDNF has never been explored. The aim of the present study was to provide a comprehensive analysis of BDNF localization in rat skeletal muscle. Cellular localization of BDNF and activated Tropomyosin-related kinase B (TrkB) receptors was studied by immunohistochemical analysis on soleus (SOL) and gastrocnemius (GAS). BDNF and activated TrkB levels were also measured in muscle homogenates using Western blot analysis and/or Elisa tests. The results revealed BDNF immunostaining in all cell types examined with a prominent staining in endothelial cells and a stronger staining in type II than type I muscular fibers. Endothelial cells but not other cells displayed easily detectable activated TrkB receptor expression. Levels of BDNF and activated TrkB receptors were higher in SOL than GAS. In conclusion, endothelial cells are an important and still unexplored source of BDNF present in skeletal muscle. Endothelial BDNF expression likely explains why oxidative muscle exhibits higher BDNF levels than glycolytic muscle despite higher the BDNF expression by type II fibers. [ABSTRACT FROM AUTHOR]

River dolphins are a highly threatened polyphyletic group comprised of four odontocete families: Iniidae, Pontoporiidae, Lipotidae, and Platanistidae, the first two endemic to South America. To address the knowledge gap regarding infectious agents in this cetacean group, we surveyed the presence of herpesviruses by PCR in skin and/or blood samples of live-captured Amazon (Inia geoffrensis, n = 25) and Bolivian (Inia boliviensis, n = 22) river dolphins of the Amazon basin and in selected tissue samples of franciscanas (Pontoporia blainvillei, n = 27) stranded or bycaught in southeastern Brazil. Additionally, available franciscana tissue samples were examined by histopathology. Herpesvirus DNA was amplified in 13 Bolivian river dolphins (59.1%, 95% CI 38.5–79.6%) and 14 franciscanas (51.9%, 95% CI 33.0–70.7%). All Amazon river dolphins were herpesvirus-negative. Two different herpesviruses were found in Bolivian river dolphins: a previously known gammaherpesvirus detected in blood and/or skin samples of all positive individuals and a novel alphaherpesvirus in the skin of one animal. A new gammaherpesvirus was found in several franciscana samples—the first herpesvirus recorded in Pontoporiidae. Intranuclear inclusion bodies consistent with herpesvirus were observed in the lymph node of one franciscana. The high divergence among the obtained herpesviruses and those previously described can be explained by viral-host coevolution, and by the fact that these populations are fairly isolated. [ABSTRACT FROM AUTHOR]

Automatic pattern recognition using deep learning techniques has become increasingly important. Unfortunately, due to limited system memory, general preprocessing methods for high-resolution images in the spatial domain can lose important data information such as high-frequency information and the region of interest. To overcome these limitations, we propose an image segmentation approach in the compressed domain based on principal component analysis (PCA) and discrete wavelet transform (DWT). After inference for each tile using neural networks, a whole prediction image was reconstructed by wavelet weighted ensemble (WWE) based on inverse discrete wavelet transform (IDWT). The training and validation were performed using 351 colorectal biopsy specimens, which were pathologically confirmed by two pathologists. For 39 test datasets, the average Dice score, the pixel accuracy, and the Jaccard score were 0.804 ± 0.125, 0.957 ± 0.025, and 0.690 ± 0.174, respectively. We can train the networks for the high-resolution image with the large region of interest compared to the result in the low-resolution and the small region of interest in the spatial domain. The average Dice score, pixel accuracy, and Jaccard score are significantly increased by 2.7%, 0.9%, and 2.7%, respectively. We believe that our approach has great potential for accurate diagnosis. [ABSTRACT FROM AUTHOR]

After disasters, people are often forced to reconstruct or move to new residences. This study aimed to reveal the association between the types of reconstructed residences and psychosocial or psychiatric conditions among the population. A total of 1071 adult residents in a coastal town, whose houses were destroyed by the tsunami caused by the Great East Japan Earthquake, enrolled in the study five years after the disaster. The type of reconstructed post-disaster residences (reconstructed on the same site/disaster-recovery public condominium/mass-translocation to higher ground/privately moving to remote areas) and the current psychosocial indicators were investigated. The results revealed that individuals living in public condominiums showed significantly worse scores on the Lubben Social Network Scale-6 (p < 0.0001) and the Center for Epidemiologic Studies Depression Scale (p < 0.0001), and slightly worse scores on the Kessler Psychological Distress Scale (p = 0.035) and the Impact of Event Scale-Revised (p = 0.028). Lower psychosocial indicator scores in the public condominium group were more remarkable in younger adults aged < 65 years. Insomnia evaluated using the Athens Insomnia Scale was not different among the four residential types. In summary, residents moving into disaster-recovery public condominiums are likely to have less social interaction, be more depressed, and may need additional interventions. [ABSTRACT FROM AUTHOR]

The association between blood transfusions and thromboembolic events (VTE) following total joint arthroplasty (TJA) remains debatable. Using contemporary institutional data, this study aimed to determine whether blood transfusions increase the risk of VTE following primary and revision TJA. This was a single institution, retrospective cohort study. The clinical records of all patients (n = 34,824) undergoing primary and revision TJA between 2009 and 2020 were reviewed. Demographic variables, co-morbidities, type of chemoprophylaxis and intraoperative factors such as use of tranexamic acid were collected. Clinical notes, hospital orders, and discharge summaries were reviewed to determine if a patient received a blood transfusion. Comprehensive queries utilizing keywords for VTE were conducted in clinical notes, physician dictations, and patient-provider phone-call logs. Propensity score matching as well as adjusted mixed models were performed. After adjusting for various confounders, results from regression analysis showed a significant association between allogenic blood transfusions and risk for developing VTE following primary and revision TJA (OR 4.11, 95% CI 2.53–6.69 and OR 2.15, 95% CI 1.12–4.13, respectively). While this strong association remained significant for PE in both primary (p < 0.001) and revision (p < 0.001) matched cohorts, it was no longer statistically significant for DVT (p = 0.802 and p = 0.65, respectively). These findings suggest that the risk of VTE is increased by approximately three-folds when blood transfusions are prescribed. This association was mainly due to higher symptomatic PE events which makes it even more worrisome. Surgeons should be aware of this association, revisit criteria for blood transfusions and use all means available in the perioperative period to optimize the patients and avoid transfusion. [ABSTRACT FROM AUTHOR]

Thyroid disease, particularly hypothyroidism, has been reported in systemic sclerosis (SSc). Some clinical features of SSc can also present in hypothyroidism. Our aims were to determine the prevalence of, and describe clinical features associated with, hypothyroidism in SSc patients. We conducted a historical cohort study of adult SSc patients who underwent screening thyroid function tests at the Scleroderma Clinic, Khon Kaen University, Thailand, between 2009 and 2018. The patients who had any thyroid disorders before the onset of SSc and were diagnosed as an overlap syndrome were excluded. A total of 200 SSc were included according to sample size calculation, among whom the female to male ratio was 2:1. The majority of cases (137; 69.5%) were diffuse cutaneous SSc subset. The mean age was 55.8 ± 10.7 years and the median duration of disease 4.9 (IQR 1.6–9.9) years. Of the total, 9 had primary hypothyroidism (prevalence 4.5%; 95%CI 2.1–8.4) and 22 had subclinical hypothyroidism (prevalence 11%; 95%CI 7.0–16.2). Of the latter 22, 71% had dcSSc. Logistic regression analysis indicated that unexplained anemia was significantly associated with either subclinical hypothyroid or hypothyroidism (OR 2.74; 95% CI 1.17–6.47), whereas Raynaud's phenomenon had a negative association (OR 0.28; 95% CI 0.11–0.66). Neither severity of skin tightness nor internal organ involvement were associated with hypothyroidism among SSc patients. Clinical-subclinical hypothyroidism is uncommon among SSc patients, it is frequently associated with anemia, and less so Raynaud's phenomenon. Clinical-subclinical hypothyroidism should thus be considered in cases of unexplained anemia in SSc patients. [ABSTRACT FROM AUTHOR]

CuAl2O4 is a ternary oxide spinel with Cu2+ ions ( s = 1 / 2 ) primarily populating the A-site diamond sublattice. The compound is reported to display evidence of spin glass behavior but possess a non-frozen magnetic ground state below the transition temperature. On the other hand, the spinel CuGa2O4 displays spin glass behavior at ~ 2.5 K with Cu2+ ions more readily tending to the B-site pyrochlore sublattice. Therefore, we investigate the magnetic and structural properties of the solid solution CuAl2(1-x)Ga2xO4 examining the evolution of the magnetic behavior as Al3+ is replaced with a much larger Ga3+ ion. Our results show that the Cu2+ ions tend to migrate from tetrahedral to octahedral sites as the Ga3+ ion concentration increases, resulting in a concomitant change in the glassy magnetic properties of the solution. Results indicate glassy behavior for much of the solution with a general trend towards decreasing magnetic frustration as the Cu2+ ion shifts to the B-site. However, the x = 0.1 and 0.2 members of the system do not show glassy behavior down to our measurement limit (1.9 K) suggesting a delayed spin glass transition. We suggest that these two members are additional candidates for investigation to access highly frustrated exotic quantum states. [ABSTRACT FROM AUTHOR]

Fish chemosensory olfactory receptors allow them to detect a wide range of water-soluble chemicals, that mediate fundamental behaviours. Zebrafish possess a well-developed sense of smell which governs reproduction, appetite, and fear responses. The spatial organization of functional properties within the olfactory epithelium and bulb are comparable to those of mammals, making this species suitable for studies of olfactory differentiation and regeneration and neuronal representation of olfactory information. The advent of genomic techniques has been decisive for the discovery of specific olfactory cell types and the identification of cell populations expressing vomeronasal receptors. These advances have marched ahead of morphological and neurochemical studies. This study aims to fill the existing gap in specific histological, lectin-histochemical and immunohistochemical studies on the olfactory rosette and the olfactory bulb of the zebrafish. Tissue dissection and microdissection techniques were employed, followed by histological staining techniques, lectin-histochemical labelling (UEA, LEA, BSI-B4) and immunohistochemistry using antibodies against G proteins subunits αo and αi2, growth-associated protein-43, calbindin, calretinin, glial-fibrillary-acidic-protein and luteinizing-hormone-releasing-hormone. The results obtained enrich the available information on the neurochemical patterns of the zebrafish olfactory system, pointing to a greater complexity than the one currently considered, especially when taking into account the peculiarities of the nonsensory epithelium. [ABSTRACT FROM AUTHOR]

The effect of altered occlusal force on masticatory-related neuromuscular control, which projects from the anterior part of the cortical masticatory area (A-CMA), during growth remains unclear. This study sought to evaluate the effect of occlusal hypofunction on neuromuscular development of jaw muscle activities and cortically-induced rhythmic jaw movements (RJMs) in growing rats. Sixty-four 2-week-old male albino Wistar rats were divided into the control (fed normal diet) and experimental (fed soft diet) groups soon after weaning. Electromyographic activity was recorded at 5, 7, 9, and 11 weeks from the right masseter and anterior digastric along with RJMs. We found a significantly longer onset latency and smaller peak-to-peak amplitude in the experimental group than that in the control group. The RJMs showed an increase in gape size and lateral excursion until up to 9 weeks in both groups. However, both the average gape size and lateral excursion were significantly smaller in the experimental group than that in the control group after 9 weeks. The jaw movement pattern also showed a significant decrease at the maximum opening period in the experimental group. Our findings indicate that inadequate occlusal function during growth alters neuromuscular control of masticatory behaviors and impairs the pattern of RJMs. [ABSTRACT FROM AUTHOR]

To explore the epidemiological characteristics and prognosis of lung cancer in patients aged under 45 years old in northern China. The population-based database about lung cancer cases aged under 45y selected form the Hebei Provincial Cancer Registry Center from 2010–2015. Mortality data of young death from 1973 to 1975, 1990 to 1992, and 2004 to 2005 were extracted from the national retrospective survey of death. Mortality rates were calculated by the mortality database above in this analysis. Consecutive, 954 non-selected younger patients (< 45 years) and 2261 selected older patients (≥ 45 years) with pathologically diagnosed lung cancer treated at the Fourth Hospital of Hebei Medical University were included as the hospital-based database. Epidemiological, treatment outcomes and prognosis status from 2010 to 2017 were documented. A comparison with younger and older patients was also made. Multivariate analysis with young lung cancer patients was calculated by Cox regression model. The younger lung cancer mortality rate tended to slightly increase in Hebei Province, from 1.04 per100 000 in 1973 to 2.01 per 100 000 in 2015, but the PDR tended to decrease over the last 40 years. There were 954 younger and 2261 older lung cancer patients included in the hospital-based database. The proportions of patients who were female (50.84% vs 34.85%), family history of cancer (12.37% vs 6.32%), advanced stage at diagnosis (65.46% vs 60.77%) and adenocarcinoma (65.27% vs 61.11%) were relatively higher in the younger group than in the older group. The median OS were 23.0 months and 27.0 months between younger and older, the OS difference existed between the two groups (P = 0.001). In the younger patients, Cox regression showed that a family history of cancer, symptoms at diagnosis, pathology, stage at diagnosis and surgery were confirmed as independent factors affecting the prognosis. Mortality rates among younger lung cancer patients showed an increasing trend in northern China. The younger account for small but have unique characteristics, with higher proportions of female, family history of cancer, adenocarcinoma and advanced stages than the older group and had a trend of worse OS. [ABSTRACT FROM AUTHOR]

Floods are among the most common and impactful natural events. The hazard of a flood event depends on its peak (Q), volume (V) and duration (D), which are interconnected to each other. Here, we used a worldwide dataset of daily discharge, two statistics (Kendall's tau and Spearman's rho) and a conceptual hydrological rainfall-runoff model as model-dependent realism, to investigate the factors controlling and the origin of the dependence between each couple of flood characteristics, with the focus to rainfall-driven events. From the statistical analysis of worldwide dataset, we found that the catchment area is ineffective in controlling the dependence between Q and V, while the dependencies between Q and D, and V and D show an increasing behavior with the catchment area. From the modeling activity, on the U.S. subdataset, we obtained that the conceptual hydrological model is able to represent the observed dependencies between each couple of variables for rainfall-driven flood events, and for such events, the pairwise dependence of each couple is not causal, is of spurious kind, coming from the "Principle of Common Cause". [ABSTRACT FROM AUTHOR]

In the context of the current COVID-19 pandemic, households throughout the world have to cope with negative shocks. Previous research has shown that negative shocks impair cognitive function and change risk, time and social preferences. In this study, we analyze the results of a longitudinal multi-country survey conducted in Italy (N = 1652), Spain (N = 1660) and the United Kingdom (N = 1578). We measure cognitive function using the Cognitive Reflection Test and preferences traits (risk, time and social preferences) using an experimentally validated set of questions to assess the differences between people exposed to a shock compared to the rest of the sample. We measure four possible types of shocks: labor market shock, health shock, occurrence of stressful events, and mental health shock. Additionally, we randomly assign participants to groups with either a recall of negative events (more specifically, a mild reinforcement of stress or of fear/anxiety), or to a control group (to recall neutral or joyful memories), in order to assess whether or not stress and negative emotions drive a change in preferences. Results show that people affected by shocks performed worse in terms of cognitive functioning, are more risk loving, and are more prone to punish others (negative reciprocity). Data do not support the hypotheses that the result is driven by stress or by negative emotions. [ABSTRACT FROM AUTHOR]

In this study we report, the synthesis of ZnO and its doping with Transition Metal Oxides -TMO-, such as Cr2O3, MnO2, FeO, CoO, NiO, Cu2O and CuO. Various characterization techniques were employed to investigate the structural properties. The X-ray diffraction (XRD) data and Rietveld refinement confirmed the presence of TMO phases and that the ZnO structure was not affected by the doping with TMO which was corroborated using transmission Electron microscopy (TEM). Surface areas were low due to blockage of adsorption sites by particle aggregation. TMO doping concentration in the range of 3.7–5.1% was important to calculate the catalytic activity. The UV–Visible spectra showed the variation in the band gap of TMO/ZnO ranging from 3.45 to 2.46 eV. The surface catalyzed decomposition of H2O2 was used as the model reaction to examine the photocatalytic activity following the oxygen production and the systems were compared to bulk ZnO and commercial TiO2-degussa (Aeroxyde-P25). The results indicate that the introduction of TMO species increase significantly the photocatalytic activity. The sunlight photocatalytic performance in ZnO-doped was greater than bulk-ZnO and in the case of MnO2, CoO, Cu2O and CuO surpasses TiO2 (P25-Degussa). This report opens up a new pathway to the design of high-performance materials used in photocatalytic degradation under visible light irradiation. [ABSTRACT FROM AUTHOR]

The intergenerational sustainability dilemma (ISD) is a situation of whether or not a person sacrifices herself for future sustainability. To examine the individual behaviors, one-person ISD game (ISDG) is instituted with strategy method where a queue of individuals is organized as a generational sequence. In ISDG, each individual chooses unsustainable (or sustainable) option with her payoff of X ( X - D ) and an irreversible cost of D (zero cost) to future generations in 36 situations. Future ahead and back (FAB) mechanism is suggested as resolution for ISD by taking the perspective of future generation whereby each individual is first asked to take the next generation's standpoint and request what she wants the current generation to choose, and, second, to make the actual decision from the original position. Results show that individuals choose unsustainable option as previous generations do so or X D is low (i.e., sustainability is endangered). However, FAB prevents individuals from choosing unsustainable option in such endangered situations. Overall, the results suggest that some new institutions, such as FAB mechanisms, which induce people to take the perspective of future generations, may be necessary to avoid intergenerational unsustainability, especially when intergenerational sustainability is highly endangered. [ABSTRACT FROM AUTHOR]

Cervical spinal cord injury (SCI) results in permanent life-altering motor and respiratory deficits. Other than mechanical ventilation for respiratory insufficiency secondary to cervical SCI, effective treatments are lacking and the development of animal models to explore new therapeutic strategies are needed. The aim of this work was to demonstrate the feasibility of using a mouse model of partial cervical spinal hemisection at the second cervical metameric segment (C2) to investigate the impact of 6 weeks training on forced exercise wheel system on locomotor/respiratory plasticity muscles. To measure run capacity locomotor and respiratory functions, incremental exercise tests and diaphragmatic electromyography were done. In addition, muscle fiber type composition and capillary distribution were assessed at 51 days following chronic C2 injury in diaphragm, extensor digitorum communis (EDC), tibialis anterior (TA) and soleus (SOL) muscles. Six-week exercise training increased the running capacity of trained SCI mice. Fiber type composition in EDC, TA and SOL muscles was not modified by our protocol of exercise. The vascularization was increased in all muscle limbs in SCI trained group. No increase in diaphragmatic electromyography amplitude of the diaphragm muscle on the side of SCI was observed, while the contraction duration was significantly decreased in sedentary group compared to trained group. Cross-sectional area of type IIa myofiber in the contralateral diaphragm side of SCI was smaller in trained group. Fiber type distribution between contralateral and ipsilateral diaphragm in SCI sedentary group was affected, while no difference was observed in trained group. In addition, the vascularization of the diaphragm side contralateral to SCI was increased in trained group. All these results suggest an increase in fatigue resistance and a contribution to the running capacity in SCI trained group. Our exercise protocol could be a promising non-invasive strategy to sustain locomotor and respiratory muscle plasticity following SCI. [ABSTRACT FROM AUTHOR]

Mechanical ventilation is the standard treatment when volitional breathing is insufficient, but drawbacks include muscle atrophy, alveolar damage, and reduced mobility. Respiratory pacing is an alternative approach using electrical stimulation-induced diaphragm contraction to ventilate the lung. Oxygenation and acid–base homeostasis are maintained by matching ventilation to metabolic needs; however, current pacing technology requires manual tuning and does not respond to dynamic user-specific metabolic demand, thus requiring re-tuning of stimulation parameters as physiological changes occur. Here, we describe respiratory pacing using a closed-loop adaptive controller that can self-adjust in real-time to meet metabolic needs. The controller uses an adaptive Pattern Generator Pattern Shaper (PG/PS) architecture that autonomously generates a desired ventilatory pattern in response to dynamic changes in arterial CO2 levels and, based on a learning algorithm, modulates stimulation intensity and respiratory cycle duration to evoke this ventilatory pattern. In vivo experiments in rats with respiratory depression and in those with a paralyzed hemidiaphragm confirmed that the controller can adapt and control ventilation to ameliorate hypoventilation and restore normocapnia regardless of the cause of respiratory dysfunction. This novel closed-loop bioelectronic controller advances the state-of-art in respiratory pacing by demonstrating the ability to automatically personalize stimulation patterns and adapt to achieve adequate ventilation. [ABSTRACT FROM AUTHOR]

The molecular and serological methods available for Discrete Typing Units (DTU)-specific diagnosis of Trypanosoma cruzi in chronic Chagas disease present limitations. The study evaluated the performance of Human Chagas-Flow ATE-IgG1 for universal and DTU-specific diagnosis of Chagas disease. A total of 102 sera from Chagas disease patients (CH) chronically infected with TcI, TcVI or TcII DTUs were tested for IgG1 reactivity to amastigote/(A), trypomastigote/(T) and epimastigote/(E) antigens along the titration curve (1:250–1:32,000). The results demonstrated that "AI 250/40%", "EVI 250/30%", "AII 250/40%", "TII 250/40%" and "EII 250/30%" have outstanding accuracy (100%) to segregate CH from non-infected controls. The attributes "TI 4,000/50%", "EI 2,000/50%", "AVI 8,000/60%" and "TVI 4,000/50%" were selected for DTU-specific serotyping of Chagas disease. The isolated use of "EI 2,000/50%" provided the highest co-positivity for TcI patients (91%). The combined decision tree algorithms using the pre-defined sets of attributes showed outstanding full accuracy (92% and 97%) to discriminate "TcI vs TcVI vs TcII" and "TcI vs TcII" prototypes, respectively. The elevated performance of Human Chagas-Flow ATE-IgG1 qualifies its use for universal and TcI/TcVI/TcII-specific diagnosis of Chagas disease. These findings further support the application of this method in epidemiological surveys, post-therapeutic monitoring and clinical outcome follow-ups for Chagas disease. [ABSTRACT FROM AUTHOR]

The name PM10 refers to small particles with a diameter of less than 10 microns. The present research analyses different models capable of predicting PM10 concentration using the previous values of PM10, SO2, NO, NO2, CO and O3 as input variables. The information for model training uses data from January 2010 to December 2017. The models trained were autoregressive integrated moving average (ARIMA), vector autoregressive moving average (VARMA), multilayer perceptron neural networks (MLP), support vector machines as regressor (SVMR) and multivariate adaptive regression splines. Predictions were performed from 1 to 6 months in advance. The performance of the different models was measured in terms of root mean squared errors (RMSE). For forecasting 1 month ahead, the best results were obtained with the help of a SVMR model of six variables that gave a RMSE of 4.2649, but MLP results were very close, with a RMSE value of 4.3402. In the case of forecasts 6 months in advance, the best results correspond to an MLP model of six variables with a RMSE of 6.0873 followed by a SVMR also with six variables that gave an RMSE result of 6.1010. For forecasts both 1 and 6 months ahead, ARIMA outperformed VARMA models. [ABSTRACT FROM AUTHOR]

Recent empirical studies have documented the importance of tropical mountainous rivers on global silicate weathering and suspended sediment transport. Such field studies are typically based on limited temporal data, leaving uncertainty in the strength of observed relationships with controlling parameters over the long term. A deficiency of long-term data also prevents determination of the impact that multi-year or decadal climate patterns, such as the El Niño Southern Oscillation (ENSO), might have on weathering fluxes. Here we analyze an 18-year hydrochemical dataset for eight sub-basins of the Panama Canal Watershed of high-temporal frequency collected between 1998 and 2015 to address these knowledge gaps. We identified a strongly positive covariance of both cation (Ca2+, Mg2+, K+, Na+) and suspended sediment yields with precipitation and extent of forest cover, whereas we observed negative relationships with temperature and mosaic landcover. We also confirmed a statistical relationship between seasonality, ENSO, and river discharge, with significantly higher values occurring during La Niña events. These findings emphasize the importance that long-term datasets have on identifying short-term influences on chemical and physical weathering rates, especially, in ENSO-influenced regions. [ABSTRACT FROM AUTHOR]

Tissue stem cell exhaustion is a key hallmark of aging, and in this study, we characterised its manifestation in the distal lung. We compared the lungs of 3- and 22-month old mice. We examined the gross morphological changes in these lungs, the density and function of epithelial progenitor populations and the epithelial gene expression profile. Bronchioles became smaller in their cross-sectional area and diameter. Using long-term EdU incorporation analysis and immunohistochemistry, we found that bronchiolar cell density remained stable with aging, but inferred rates of bronchiolar club progenitor cell self-renewal and differentiation were reduced, indicative of an overall slowdown in cellular turnover. Alveolar Type II progenitor cell density and self-renewal were maintained per unit tissue area with aging, but rates of inferred differentiation into Type I cells, and indeed overall density of Type I cells was reduced. Microarray analysis revealed age-related changes in multiple genes, including some with roles in proliferation and differentiation, and in IGF and TGFβ signalling pathways. By characterising how lung stem cell dynamics change with aging, this study will elucidate how they contribute to age-related loss of pulmonary function, and pathogenesis of common age-related pulmonary diseases. [ABSTRACT FROM AUTHOR]

Understanding the driving forces that control vole population dynamics requires identifying bacterial parasites hosted by the voles and describing their dynamics at the community level. To this end, we used high-throughput DNA sequencing to identify bacterial parasites in cyclic populations of montane water voles that exhibited a population outbreak and decline in 2014–2018. An unexpectedly large number of 155 Operational Taxonomic Units (OTUs) representing at least 13 genera in 11 families was detected. Individual bacterial richness was higher during declines, and vole body condition was lower. Richness as estimated by Chao2 at the local population scale did not exhibit clear seasonal or cycle phase-related patterns, but at the vole meta-population scale, exhibited seasonal and phase-related patterns. Moreover, bacterial OTUs that were detected in the low density phase were geographically widespread and detected earlier in the outbreak; some were associated with each other. Our results demonstrate the complexity of bacterial community patterns with regard to host density variations, and indicate that investigations about how parasites interact with host populations must be conducted at several temporal and spatial scales: multiple times per year over multiple years, and at both local and long-distance dispersal scales for the host(s) under consideration. [ABSTRACT FROM AUTHOR]

Reducing motorized transport and increasing active transport (i.e. transport by walking, cycling and other active modes) may reduce greenhouse gas (GHG) emissions and improve health. But, active modes of transport are not zero emitters. We aimed to quantify GHG emissions from food production required to fuel extra physical activity for walking and cycling. We estimate the emissions (in kgCO2e) per kilometre travelled for walking and cycling from energy intake required to compensate for increased energy expenditure, and data on food-related GHG emissions. We assume that persons who shift from passive modes of transport (e.g. driving) have increased energy expenditure that may be compensated with increased food consumption. The GHG emissions associated with food intake required to fuel a kilometre of walking range between 0.05 kgCO2e/km in the least economically developed countries to 0.26 kgCO2e/km in the most economically developed countries. Emissions for cycling are approximately half those of walking. Emissions from food required for walking and cycling are not negligible in economically developed countries which have high dietary-related emissions. There is high uncertainty about the actual emissions associated with walking and cycling, and high variability based on country economic development. Our study highlights the need to consider emissions from other sectors when estimating net-emissions impacts from transport interventions. [ABSTRACT FROM AUTHOR]

In microbial ecosystems, species not only compete for common resources but may also display mutualistic interactions as a result from metabolic cross-feeding. Such mutualism can lead to bistability. Depending on the initial population sizes, species will either survive or go extinct. Various phenomenological models have been suggested to describe bistability in mutualistic systems. However, these models do not account for interaction mediators such as nutrients. In contrast, nutrient-explicit models do not provide an intuitive understanding of what causes bistability. Here, we reduce a theoretical nutrient-explicit model of two mutualistic cross-feeders in a chemostat, uncovering an explicit relation to a growth model with an Allee effect. We show that the dilution rate in the chemostat leads to bistability by turning a weak Allee effect into a strong Allee effect. This happens as long as there is more production than consumption of cross-fed nutrients. Thanks to the explicit relationship of the reduced model with the underlying experimental parameters, these results allow to predict the biological conditions that sustain or prevent the survival of mutualistic species. [ABSTRACT FROM AUTHOR]

In recent years, ozone (O3) pollution in China has shown a worsening trend. Due to the vast territory of China, O3 pollution is a widespread and complex problem. It is vital to understand the current spatiotemporal distribution of O3 pollution in China. In this study, we collected hourly data on O3 concentrations in 338 cities from January 1, 2016, to February 28, 2019, to analyze O3 pollution in China from a spatiotemporal perspective. The spatial analysis showed that the O3 concentrations exceeded the limit in seven geographical regions of China to some extent, with more serious pollution in North, East, and Central China. The O3 concentrations in the eastern areas were usually higher than those in the western areas. The temporal analysis showed seasonal variations in O3 concentration, with the highest O3 concentration in the summer and the lowest in the winter. The weekend effect, which occurs in other countries (such as the USA), was found only in some cities in China. We also found that the highest O3 concentration usually occurred in the afternoon and the lowest was in the early morning. The comprehensive analysis in this paper could improve our understanding of the severity of O3 pollution in China. [ABSTRACT FROM AUTHOR]

A number of antimalarial drugs interfere with the electron transport chain and heme-related reactions; however, the biosynthesis of heme derivatives in Plasmodium parasites has not been fully elucidated. Here, we characterized the steps that lead to the farnesylation of heme. After the identification of a gene encoding heme O synthase, we identified heme O synthesis in blood stage parasites through the incorporation of radioactive precursors. The presence of heme O synthesis in intraerythrocytic stages of Plasmodium falciparum was confirmed by mass spectrometry. Inabenfide and uniconazole–P appeared to interfere in heme synthesis, accordingly, parasite growth was also affected by the addition of these drugs. We conclude that heme O synthesis occurs in blood stage-P. falciparum and this pathway could be a potential target for antimalarial drugs. [ABSTRACT FROM AUTHOR]

Maximal inspiratory pressure (PIMAX) reflects inspiratory weakness in late-onset Pompe disease (LOPD). However, static pressure tests may not reveal specific respiratory muscle adaptations to disruptions in breathing. We hypothesized that dynamic respiratory muscle functional tests reflect distinct ventilatory compensations in LOPD. We evaluated LOPD (n = 7) and healthy controls (CON, n = 7) during pulmonary function tests, inspiratory endurance testing, dynamic kinematic MRI of the thorax, and ventilatory adjustments to single-breath inspiratory loads (inspiratory load compensation, ILC). We observed significantly lower static and dynamic respiratory function in LOPD. PIMAX, spirometry, endurance time, and maximal diaphragm descent were significantly correlated. During single-breath inspiratory loads, inspiratory time and airflow acceleration increased to preserve volume, and in LOPD, the response magnitudes correlated to maximal chest wall kinematics. The results indicate that changes in diaphragmatic motor function and strength among LOPD subjects could be detected through dynamic respiratory testing. We concluded that neuromuscular function significantly influenced breathing endurance, timing and loading compensations. [ABSTRACT FROM AUTHOR]

The combination of pyrimethamine and sulfadiazine is the standard care in cases of congenital toxoplasmosis. However, therapy with these drugs is associated with severe and sometimes life-threatening side effects. The investigation of phytotherapeutic alternatives to treat parasitic diseases without acute toxicity is essential for the advancement of current therapeutic practices. The present study investigates the antiparasitic effects of oleoresins from different species of Copaifera genus against T. gondii. Oleoresins from C. reticulata, C. duckei, C. paupera, and C. pubiflora were used to treat human trophoblastic cells (BeWo cells) and human villous explants infected with T. gondii. Our results demonstrated that oleoresins were able to reduce T. gondii intracellular proliferation, adhesion, and invasion. We observed an irreversible concentration-dependent antiparasitic action in infected BeWo cells, as well as parasite cell cycle arrest in the S/M phase. The oleoresins altered the host cell environment by modulation of ROS, IL-6, and MIF production in BeWo cells. Also, Copaifera oleoresins reduced parasite replication and TNF-α release in villous explants. Anti-T. gondii effects triggered by the oleoresins are associated with immunomodulation of the host cells, as well as, direct action on parasites.

Extreme climatic events are growing more severe and frequent, calling into question how prepared our infrastructure is to deal with these changes. Current infrastructure design is primarily based on precipitation Intensity-Duration-Frequency (IDF) curves with the so-called stationary assumption, meaning extremes will not vary significantly over time. However, climate change is expected to alter climatic extremes, a concept termed nonstationarity. Here we show that given nonstationarity, current IDF curves can substantially underestimate precipitation extremes and thus, they may not be suitable for infrastructure design in a changing climate. We show that a stationary climate assumption may lead to underestimation of extreme precipitation by as much as 60%, which increases the flood risk and failure risk in infrastructure systems. We then present a generalized framework for estimating nonstationary IDF curves and their uncertainties using Bayesian inference. The methodology can potentially be integrated in future design concepts. [ABSTRACT FROM AUTHOR]

Allogeneic stem cell transplantation is currently the only curative treatment option for myelodysplastic syndromes (MDS). Pre-transplant debulking treatment have been employed for advanced MDS and we previously reported that marrow response (blast ≤ 5%) following the bridging therapy with hypomethylating agent was an independent favorable factor for survival; however, it is still not clear which patients will respond to hypomethylating agent and which genomic features can predict the response. In this study, we performed RNAseq for 23 MDS patients among which 14 (61%) and 9 (39%) patients showed marrow complete remission and primary resistance to azacitidine, respectively. Differential expression-based analyses of treatment-naive, baseline gene expression profiles revealed that molecular functions representing mitochondria and apoptosis were up-regulated in responders. In contrast, we identified genes involved in the Wnt pathway were relatively up-regulated in non-responders. In independent validation cohorts of MDS patients, the expression of gene sets specific to non-responders and responders distinguished the patients with favorable prognosis and those responded to azacitidine highlighting the prognostic and predictive implication. In addition, a systems biology approach identified genes involved in ubiquitination, such as UBC and PFDN2, which may be key players in the regulation of differential gene expression in treatment responders and non-responders. Taken together, identifying the gene expression signature may advance our understanding of the molecular mechanisms of azacitidine and may also serve to predict patient responses to drug treatment. [ABSTRACT FROM AUTHOR]

Pediatric cancer treatment often involves chemotherapy and radiation, where off-target effects can include skeletal muscle decline. The effect of such treatments on juvenile skeletal muscle growth has yet to be investigated. We employed a small animal irradiator to administer fractionated hindlimb irradiation to juvenile mice bearing implanted rhabdomyosarcoma (RMS) tumors. Hindlimb-targeted irradiation (3 × 8.2 Gy) of 4-week-old mice successfully eliminated RMS tumors implanted one week prior. After establishment of this preclinical model, a cohort of tumor-bearing mice were injected with the chemotherapeutic drug, vincristine, alone or in combination with fractionated irradiation (5 × 4.8 Gy). Single myofiber analysis of fast-contracting extensor digitorum longus (EDL) and slow-contracting soleus (SOL) muscles was conducted 3 weeks post-treatment. Although a reduction in myofiber size was apparent, EDL and SOL myonuclear number were differentially affected by juvenile irradiation and/or vincristine treatment. In contrast, a decrease in myonuclear domain (myofiber volume/myonucleus) was observed regardless of muscle or treatment. Thus, inhibition of myofiber hypertrophic growth is a consistent feature of pediatric cancer treatment. [ABSTRACT FROM AUTHOR]

Randomness and frustration are believed to be two crucial criteria for the formation of spin glass state. However, the spin freezing occurs in some well-ordered crystals below the related temperature Tf due to the instability of each spin state, which induces the variation of either magnetic moment value or exchange energy. Here we explore the new mechanism of the in-site originated disorder in antiferromagnets Gd0.73La0.27B6 and GdB6, which is caused by the random mutual shifts of Gd3+ spins from the centrally symmetrical positions in the regular cubic lattice. The universal scaling of ESR linewidth temperature dependencies to the power law ΔH(T) ~ ((T − TD)/TD)α with α = − 1.1 ± 0.05 in the paramagnetic phase of both compounds demonstrates the identity of the origin of magnetic randomness. In Gd0.73La0.27B6 the resulting random spin configurations freeze at Tf ≈ 10.5 K where the maximum of magnetization is observed. Below Tf the splitting of ZFC and FC magnetization curves takes place as well as the magnetic state depends on the antecedent sample history. In the case of GdB6 the coherent displacement of Gd ions compete with these random shifts forming an antiferromagnetic (AFM) phase at TN = 15.5 K, which prevails over the spin freezing at Tf ≈ 13 K, expected from the ESR data. The observation of the hysteresis of the ESR spectrum in the AFM phase suggests that its properties may be determined by the competition of two types of AFM orders, which results in formation of stable magnetic domains with nonequivalent positions of AFM Gd pairs at T < 10 K. [ABSTRACT FROM AUTHOR]

Aim: The aim of the study was to discover the metabolomic changes in plasma that occur during human Ischemia-Reperfusion (I/R) injury and to evaluate the diagnostic utility of plasma metabolomic biomarkers for determination of myocardial injury. Deciphering the details of plasma metabolome in ST-segment elevation myocardial infarction (STEMI) patients before and after primary percutaneous coronary interventions (PPCI) would allow for better understanding of the mechanisms involved during acute myocardial ischemia and reperfusion in humans. We performed a detailed non-targeted metabolomic analysis of plasma from 27 STEMI patients who had undergone PPCI in the first 48 hrs employing a LC-MS approach. Plasma metabolome at ischemic condition was compared to multiple time points after PPCI which allowed us to focus on changes in the reperfusion phase. Classification of the differential metabolites based on chemical taxonomy identified a major role for lipids and lipid-derived molecules. Biochemical pathway analysis identified valine, leucine and isoleucine biosynthesis, vitamin B6 metabolism and glutathione metabolism as the most significant metabolic pathways representing early response to I/R injury. We also identified phenyl alanine, tyrosine, linoleic acid and glycerophospholipid metabolism as the most significant pathways representing late response to I/R injury. A panel of three metabolites pentadecanoic acid, linoleoyl carnitine and 1-linoleoylglycerophosphocholine was discovered to have diagnostic value in determining the extent of I/R injury based on cardiac biomarkers. Using a non-targeted LC-MS approach, we have successfully generated the most comprehensive data to date on significant changes in the plasma metabolome in STEMI patients who had undergone PPCI in the first 48 hrs showing that lipid metabolites represent the largest cohort of molecules undergoing significant change. [ABSTRACT FROM AUTHOR]

The respiratory rhythm generator is spectacular in its ability to support a wide range of activities and adapt to changing environmental conditions, yet its operating mechanisms remain elusive. We show how selective control of inspiration and expiration times can be achieved in a new representation of the neural system (called a Boolean network). The new framework enables us to predict the behavior of neural networks based on properties of neurons, not their values. Hence, it reveals the logic behind the neural mechanisms that control the breathing pattern. Our network mimics many features seen in the respiratory network such as the transition from a 3-phase to 2-phase to 1-phase rhythm, providing novel insights and new testable predictions. [ABSTRACT FROM AUTHOR]

The goal of this study was to investigate the effects of repetitive stimulation and the oxidant H2O2 on fatigue of diaphragm intact fibers and in myofibrils measured with different Ca2+ concentrations. Intact fibers were isolated from mice diaphragm, and twitch and tetanic contractions (500 ms duration) were performed at different frequencies of stimulation ranging from 15 Hz to 150 Hz to establish a force-frequency relation before and after a fatigue and recovery protocol, without or after a treatment with H2O2. Fatigue was induced with isometric contractions (500 ms, 40 Hz) evoked every 0.8 seconds, with a total of 625 tetani. After the fatigue, the force recovery was followed by invoking tetanic contractions (500 ms, 40 Hz) every 1 min, with a total duration of 30 min. Individual myofibrils were also isolated from the mouse diaphragm and were tested for isometric contractions before and after treatment with H2O2 and NAC. In a second series of experiments, myofibrils were activated at different pCa (pCa = −log10 [Ca2+]), before and after H2O2 treatment. After 15 minutes of H2O2 treatment, the myofibrillar force was decreased to 54 ± 12% of its control, maximal value, and a result that was reversed by NAC treatment. The force was also decreased after myofibrils were treated with H2O2 and activated in pCa ranging between 4.5 and 5.7. These results suggest that fatigue in diaphragm intact fibers and at the myofibrils level is caused partially by oxidation of the contractile proteins that may be responsible for changing the force in various levels of Ca2+ activation. [ABSTRACT FROM AUTHOR]

Interannual climate variability patterns associated with the El Niño-Southern Oscillation phenomenon result in climate and environmental anomaly conditions in specific regions worldwide that directly favor outbreaks and/or amplification of variety of diseases of public health concern including chikungunya, hantavirus, Rift Valley fever, cholera, plague, and Zika. We analyzed patterns of some disease outbreaks during the strong 2015-2016 El Niño event in relation to climate anomalies derived from satellite measurements. Disease outbreaks in multiple El Niño-connected regions worldwide (including Southeast Asia, Tanzania, western US, and Brazil) followed shifts in rainfall, temperature, and vegetation in which both drought and flooding occurred in excess (14-81% precipitation departures from normal). These shifts favored ecological conditions appropriate for pathogens and their vectors to emerge and propagate clusters of diseases activity in these regions. Our analysis indicates that intensity of disease activity in some ENSO-teleconnected regions were approximately 2.5-28% higher during years with El Niño events than those without. Plague in Colorado and New Mexico as well as cholera in Tanzania were significantly associated with above normal rainfall (p < 0.05); while dengue in Brazil and southeast Asia were significantly associated with above normal land surface temperature (p < 0.05). Routine and ongoing global satellite monitoring of key climate variable anomalies calibrated to specific regions could identify regions at risk for emergence and propagation of disease vectors. Such information can provide sufficient lead-time for outbreak prevention and potentially reduce the burden and spread of ecologically coupled diseases. [ABSTRACT FROM AUTHOR]