Miracle-dz/UniFAR-FTUs huggingface dataset:
Intracellular Ca2+ stores control in vivo neuronal hyperactivity in a mouse model of Alzheimer’s disease

Significance Although both patients with Alzheimer’s disease (AD) and mouse models of the disease suffer from a profound neuronal hyperactivity mediating an impairment of memory and cognition, the underlying mechanisms remain elusive. Here, we show that neuronal hyperactivity is a hallmark of healthy aging but is further aggravated by AD-related mutations in presenilin 1 protein. AD-mediated enhancement of neuronal hyperactivity occurred even in the absence of amyloid plaques and neuroinflammation, mainly due to a presenilin-mediated dysfunction of intracellular Ca2+ stores in presynaptic boutons, likely causing more frequent activation of synaptic NMDA receptors. Emptying the stores normalized neuronal network activity in mutant mice, thus identifying presynaptic Ca2+ stores as a key element controlling AD-related neuronal hyperactivity and as a target for disease-modifying treatments. Neuronal hyperactivity is the emerging functional hallmark of Alzheimer’s disease (AD) in both humans and different mouse models, mediating an impairment of memory and cognition. The mechanisms underlying neuronal hyperactivity remain, however, elusive. In vivo Ca2+ imaging of somatic, dendritic, and axonal activity patterns of cortical neurons revealed that both healthy aging and AD-related mutations augment neuronal hyperactivity. The AD-related enhancement occurred even without amyloid deposition and neuroinflammation, mainly due to presenilin-mediated dysfunction of intracellular Ca2+ stores in presynaptic boutons, likely causing more frequent activation of synaptic NMDA receptors. In mutant but not wild-type mice, store emptying reduced both the frequency and amplitude of presynaptic Ca2+ transients and, most importantly, normalized neuronal network activity. Postsynaptically, the store dysfunction was minor and largely restricted to hyperactive cells. These findings identify presynaptic Ca2+ stores as a key element controlling AD-related neuronal hyperactivity and as a target for disease-modifying treatments.
Responses of East Asian summer monsoon to natural and anthropogenic forcings in the 17 latest CMIP5 models

In this study, we examined the responses of East Asian summer monsoon (EASM) to natural (solar variability and volcanic aerosols) and anthropogenic (greenhouse gasses and aerosols) forcings simulated in the 17 latest Coupled Model Intercomparison Program phase 5 models with 105 realizations. The observed weakening trend of low‐level EASM circulation during 1958–2001 is partly reproduced under all‐forcing runs. A comparison of separate forcing experiments reveals that the aerosol forcing plays a primary role in driving the weakened low‐level monsoon circulation. The preferential cooling over continental East Asia caused by aerosol affects the monsoon circulation through reducing the land‐sea thermal contrast and results in higher sea level pressure over northern China. In the upper level, both natural forcing and aerosol forcing contribute to the observed southward shift of East Asian subtropical jet through changing the meridional temperature gradient.
The influence of procedural volume and proficiency gain on mortality from upper GI endoscopic mucosal resection

Objective Endoscopic mucosal resection (EMR) is established for the management of benign and early malignant upper GI disease. The aim of this observational study was to establish the effect of endoscopist procedural volume on mortality. Design Patients undergoing upper GI EMR between 1997 and 2012 were identified from the Hospital Episode Statistics database. The primary outcome was 30-day mortality and secondary outcomes were 90-day mortality, requirement for emergency intervention and elective cancer re-intervention. Risk-adjusted cumulative sum (RA-CUSUM) analysis was used to assess patient mortality risk during initial stage of endoscopist proficiency gain and the effect of endoscopist and hospital volume. Mortality was compared before and after the change point or threshold in the RA-CUSUM curve. Results 11 051 patients underwent upper GI EMR. Endoscopist procedure volume was an independent predictor of 30-day mortality. Fifty-eight per cent of EMR procedures were performed by endoscopists with annual volume of 2 cases or less, and had a higher 30-day and 90-day mortality rate for patients with cancer, 6.1% vs 0.4% (p<0.001) and 12% vs 2.1% (p<0.001), respectively. The requirement for emergency intervention after EMR for cancer was also greater with low volume endoscopists (1.8% vs 0.1%, p=0.002). In patients with cancer, the RA-CUSUM curve change points for 30-day mortality and elective re-intervention were 4 cases and 43 cases, respectively. Conclusions EMR performed by high volume endoscopists is associated with reduced adverse outcomes. In order to reach proficiency, appropriate training and procedural volume accreditation training programmes are needed nationally.
Muscle Synergies Control during Hand-Reaching Tasks in Multiple Directions Post-stroke

Purpose: A muscle synergies model was suggested to represent a simplifying motor control mechanism by the brainstem and spinal cord. The aim of the study was to investigate the feasibility of such control mechanisms in the rehabilitation of post-stroke individuals during the execution of hand-reaching movements in multiple directions, compared to non-stroke individuals. Methods: Twelve non-stroke and 13 post-stroke individuals participated in the study. Muscle synergies were extracted from EMG data that was recorded during hand reaching tasks, using the NMF algorithm. The optimal number of synergies was evaluated in both groups using the Variance Accounted For (VAF) and the Mean Squared Error (MSE). A cross validation procedure was carried out to define a representative set of synergies. The similarity index and the K-means algorithm were applied to validate the existence of such a set of synergies, but also to compare the modulation properties of synergies for different movement directions between groups. The similarity index and hierarchical cluster analysis were also applied to compare between group synergies. Results: Four synergies were chosen to optimally capture the variances in the EMG data, with mean VAF of 0.917 ± 0.034 and 0.883 ± 0.046 of the data variances, with respective MSE of 0.007 and 0.016, in the control and study groups, respectively. The representative set of synergies was set to be extracted from movement to the center of the reaching space. Two synergies had different muscle activation balance between groups. Seven and 17 clusters partitioned the muscle synergies of the control and study groups. The control group exhibited a gradual change in the activation in the amplitude in the time domain (modulation) of synergies, as reflected by the similarity index, whereas the study group exhibited consistently significant differences between all movement directions and the representative set of synergies. The study findings support the existence of a representative set of synergies, which are modulated to execute movements in different directions. Conclusions: Post-stroke individuals differently modulate the activation of synergies to different movement directions than do non-stroke individuals. The conclusion was supported by different muscle activation balances, similarity values and different classifications of synergies among groups.
Preparation of Fish Skin Gelatin-Based Nanofibers Incorporating Cinnamaldehyde by Solution Blow Spinning

Cinnamaldehyde, a natural preservative that can non-specifically deactivate foodborne pathogens, was successfully incorporated into fish skin gelatin (FSG) solutions and blow spun into uniform nanofibers. The effects of cinnamaldehyde ratios (5–30%, w/w FSG) on physicochemical properties of fiber-forming emulsions (FFEs) and their nanofibers were investigated. Higher ratios resulted in higher values in particle size and viscosity of FFEs, as well as higher values in diameter of nanofibers. Loss of cinnamaldehyde was observed during solution blow spinning (SBS) process and cinnamaldehyde was mainly located on the surface of resultant nanofibers. Nanofibers all showed antibacterial activity by direct diffusion and vapor release against Escherichia coli O157:H7, Salmonella typhimurium, and Listeria monocytogenes. Inhibition zones increased as cinnamaldehyde ratio increased. Nanofibers showed larger inhibition effects than films prepared by casting method when S. typhimurium was exposed to the released cinnamaldehyde vapor, although films had higher remaining cinnamaldehyde than nanofibers after preparation. Lower temperature was favorable for cinnamaldehyde retention, and nanofibers added with 10% cinnamaldehyde ratio showed the highest retention over eight-weeks of storage. Results suggest that FSG nanofibers can be prepared by SBS as carriers for antimicrobials.
Pfirsch–Schlüter impurity transport in stellarators

The Pfirsch–Schluter transport of impurities is calculated for stellarator geometry. Contrary to the tokamak case, where the only contribution to the particle flux arises from friction between different species, in a stellarator there is another source of impurity transport due to pressure anisotropy. However, the pressure anisotropy term is usually smaller than the friction term, so that the impurity particle flux is comparable to that in a tokamak. The pressure anisotropy is nonetheless important as it causes the transport to be nonambipolar and thereby determines the radial electric field. The presence of impurities therefore affects the radial electric field in a stellarator. The heat flux is also affected qualitatively by impurities.
Social cognitive and clinical factors associated with HPV vaccine initiation among urban, economically disadvantaged women.

OBJECTIVE To learn more about human papilloma virus (HPV) knowledge and vaccination among teens and young women age 13 to 26 years from an economically disadvantaged, urban community. Our aim was to identify common beliefs about HPV vaccine initiation and describe the relationship between attitudes, norms, perceived control, and intention to receive HPV vaccine, drawing from the theory of planned behavior (TPB). DESIGN Mixed method, descriptive design. Guided by the TPB, HPV vaccine beliefs were assessed through focus groups. Intention to receive the vaccine, demographic and clinical factors, and theoretical predictor variables (attitudes, norms, and control) were assessed through questionnaires. SETTING After recruitment, focus groups were held at a convenient date and time for our participants in a small university conference room. PARTICIPANTS Participants were economically disadvantaged young women, age 13 to 26 (N = 34). METHODS Specific behavioral, normative, and control beliefs were elicited in focus groups and analyzed using content analysis. Simple and multivariate general linear modeling with adjustment for prognostic demographic and clinical factors was completed to assess the influence of the theoretical predictor variables on the outcome of HPV vaccine initiation. RESULTS Influential beliefs toward vaccination were identified. Analysis indicated attitudes, norms, and perceived control toward HPV vaccine initiation were highly significant predictors of intent, as was tobacco use; all p's < . 001. CONCLUSION Barriers to HPV vaccine initiation were identified, and strong preliminary evidence supports use of the TPB to guide programs to promote urban, economically disadvantaged young women's intent to begin the HPV vaccine.
SCIB1, a huIgG1 antibody DNA vaccination, combined with PD-1 blockade induced efficient therapy of poorly immunogenic tumors

Purpose We have previously shown that supraoptimal signaling of high avidity T cells leads to high expression of PD-1 and inhibition of proliferation. This study was designed to see if this effect could be mitigated by combining a vaccine that stimulates high avidity T cells with PD-1 blockade. Experimental Design We investigated the anti-tumor effect of a huIgG1 antibody DNA vaccine (SCIB1) and PD-1 blockade. Results Vaccination of HLA-DR4 transgenic mice with SCIB1 induced high frequency and avidity T cell responses that resulted in survival (40%) of mice with established B16F1-DR4 tumors. SCIB1 vaccination was associated with increased infiltration of CD4 and CD8 T cells within the tumor but was also associated with upregulation of PD-L1 within the tumor environment. PD-1 blockade also resulted in increased CD8 T cell infiltration and an anti-tumor response with 50% of mice showing long term survival. In line with our hypothesis that PD-1/PD-L1 signaling results in inhibition of proliferation of high avidity T cells at the tumor site, the combination of PD-1 blockade with vaccination, enhanced the number and proliferation of the CD8 tumor infiltrate. This resulted in a potent anti-tumor response with 80% survival of the mice. Conclusions There is a benefit in combining PD-1 blockade with vaccines that induce high avidity T cell responses and in particular with SCIB1.
Estimating the need for palliative care at the population level: A cross-national study in 12 countries

Background: To implement the appropriate services and develop adequate interventions, detailed estimates of the needs for palliative care in the population are needed. Aim: To estimate the proportion of decedents potentially in need of palliative care across 12 European and non-European countries. Design: This is a cross-sectional study using death certificate data. Setting/participants: All adults (⩾18 years) who died in 2008 in Belgium, Czech Republic, France, Hungary, Italy, Spain (Andalusia, 2010), Sweden, Canada, the United States (2007), Korea, Mexico, and New Zealand (N = 4,908,114). Underlying causes of death were used to apply three estimation methods developed by Rosenwax et al., the French National Observatory on End-of-Life Care, and Murtagh et al., respectively. Results: The proportion of individuals who died from diseases that indicate palliative care needs at the end of life ranged from 38% to 74%. We found important cross-country variation: the population potentially in need of palliative care was lower in Mexico (24%–58%) than in the United States (41%–76%) and varied from 31%–83% in Hungary to 42%–79% in Spain. Irrespective of the estimation methods, female sex and higher age were independently associated with the likelihood of being in need of palliative care near the end of life. Home and nursing home were the two places of deaths with the highest prevalence of palliative care needs. Conclusion: These estimations of the size of the population potentially in need of palliative care provide robust indications of the challenge countries are facing if they want to seriously address palliative care needs at the population level.
Variation in the Distribution of Putative Virulence and Colonization Factors in Shiga Toxin-Producing Escherichia coli Isolated from Different Categories of Cattle

Shiga toxin-producing Escherichia coli (STEC) are pathogens of significant public health concern. Several studies have confirmed that cattle are the main reservoir of STEC in Argentina and other countries. Although Shiga toxins represent the primary virulence factors of STEC, the adherence and colonization of the gut are also important in the pathogenesis of the bacteria. The aim of this study was to analyze and to compare the presence of putative virulence factors codified in plasmid -katP, espP, subA, stcE- and adhesins involved in colonization of cattle -efa1, iha- in 255 native STEC strains isolated from different categories of cattle from different production systems. The most prevalent gene in all strains was espP, and the less prevalent was stcE. katP was highly detected in strains isolated from young and rearing calves (33.3%), while subA was predominant in those isolated from adults (71.21%). Strains from young calves showed the highest percentage of efa1 (72.46%), while iha showed a high distribution in strains from rearing calves and adults (87.04 and 98.48% respectively). It was observed that espP and iha were widely distributed throughout all strains, whereas katP, stcE, and efa1 were more associated with the presence of eae and subA with the eae-negative strains. A great proportion of eae-negative strains were isolated from adults -dairy and grazing farms- and from rearing calves -dairy and feedlot-, while mostly of the eae-positive strains were isolated from dairy young calves. Data exposed indicate a correlation between the category of the animal and the production systems with the presence or absence of several genes implicated in adherence and virulence of STEC.
NMDA receptor agonist and antagonists alter retinal ganglion cell arbor structure in the developing frog retinotectal projection

The development of sensory maps is thought to require an activity- dependent structural rearrangement of afferent terminal arbors within the CNS which recreates the topographic relations of sensory somata present in the periphery. In the frog retinotectal projection, activation of the NMDA receptor plays a role in this structural plasticity. Exposure of the optic tectum of tadpoles to NMDA receptor antagonists results in a rearrangement of retinal ganglion cell arbors so that their organization into a topographic projection and eye- specific stripes is disrupted (Cline et al., 1987; Cline and Constantine-Paton, 1989). Exposure of the optic tectum to the receptor agonist, NMDA, increases the eye-specific segregation of these arbors (Cline et al., 1987). We examined the projection of the supernumerary retina and the morphology of individual retinal afferent arbors of untreated, NMDA-treated, APV-treated, MK801-treated, and MK801/NMDA- treated 3-eyed tadpoles and young postmetamorphic frogs in an effort to understand how NMDA receptor activation is involved in the growth and ordering of retinal arbors. Treatments with MK801 in combination with NMDA resulted in a desegregation of eye-specific stripes, whereas treatments with MK801 or NMDA alone did not. As reported previously, APV treatment resulted in stripe desegregation without increasing the tangential area (measured from 2-dimensional drawings) of the terminal arbors. However, a detailed analysis revealed that the APV-treated tadpole arbors have 35% reduction in branch density (branch tips/area) compared to untreated 3-eyed tadpole arbors. We treated the optic tectum with a range of concentrations of NMDA prepared in the slow- release plastic Elvax. NMDA at 10(-4) M in Elvax was the optimal concentration to produce the sharpening of stripe borders. Exposure of the tectum to NMDA at 10(-6) M in Elvax produced no change in the stripe pattern, while 10(-2) M NMDA in Elvax resulted in beading of the arbors. At the optimal concentration NMDA treatment results in a 75% reduction in the number of axons crossing from a stripe to an interstripe zone. Drawings of individual HRP-labeled, NMDA-treated arbors demonstrate that they have fewer branch points and fewer branch tips. NMDA treatment reduced arbor density by approximately 50%. Arbors drawn from untreated postmetamorphic frogs have twice the branch density of arbors from untreated tadpoles. NMDA treatment in these animals reduced the branch density by 55%, comparable to the reduction seen in tadpole branch density. Our data support a specific hypothesis for NMDA receptor involvement in the activity-dependent structural refinement process within the developing retinotectal projection. (ABSTRACT TRUNCATED AT 400 WORDS)
A Dependable Localization Algorithm for Survivable Belt-Type Sensor Networks

As the key element, sensor networks are widely investigated by the Internet of Things (IoT) community. When massive numbers of devices are well connected, malicious attackers may deliberately propagate fake position information to confuse the ordinary users and lower the network survivability in belt-type situation. However, most existing positioning solutions only focus on the algorithm accuracy and do not consider any security aspects. In this paper, we propose a comprehensive scheme for node localization protection, which aims to improve the energy-efficient, reliability and accuracy. To handle the unbalanced resource consumption, a node deployment mechanism is presented to satisfy the energy balancing strategy in resource-constrained scenarios. According to cooperation localization theory and network connection property, the parameter estimation model is established. To achieve reliable estimations and eliminate large errors, an improved localization algorithm is created based on modified average hop distances. In order to further improve the algorithms, the node positioning accuracy is enhanced by using the steepest descent method. The experimental simulations illustrate the performance of new scheme can meet the previous targets. The results also demonstrate that it improves the belt-type sensor networks’ survivability, in terms of anti-interference, network energy saving, etc.
ChatPainter: Improving Text to Image Generation using Dialogue

Synthesizing realistic images from text descriptions on a dataset like Microsoft Common Objects in Context (MS COCO), where each image can contain several objects, is a challenging task. Prior work has used text captions to generate images. However, captions might not be informative enough to capture the entire image and insufficient for the model to be able to understand which objects in the images correspond to which words in the captions. We show that adding a dialogue that further describes the scene leads to significant improvement in the inception score and in the quality of generated images on the MS COCO dataset.
Distinct clusters of stunted children in India: An observational study

Abstract Childhood stunting is often conceptualised as a singular concept (i.e., stunted or not), and such an approach implies similarity in the experiences of children who are stunted. Furthermore, risk factors for stunting are often treated in isolation, and limited research has examined how multiple risk factors interact together. Our aim was to examine whether there are subgroups among stunted children, and if parental characteristics influence the likelihood of these subgroups among children. Children who were stunted were identified from the 2005–2006 Indian National Family Health Survey (n = 12,417). Latent class analysis was used to explore the existence of subgroups among stunted children by their social, demographic, and health characteristics. We examined whether parental characteristics predicted the likelihood of a child belonging to each latent class using a multinomial logit regression model. We found there to be 5 distinct groups of stunted children; “poor, older, and poor health‐related outcomes,” “poor, young, and poorest health‐related outcomes,” “poor with mixed health‐related outcomes,” “wealthy and good health‐related outcomes,” and “typical traits. ” Both mother and father's educational attainment, body mass index, and height were important predictors of class membership. Our findings demonstrate evidence that there is heterogeneity of the risk factors and behaviours among children who are stunted. It suggests that stunting is not a singular concept; rather, there are multiple experiences represented by our “types” of stunting. Adopting a multidimensional approach to conceptualising stunting may be important for improving the design and targeting of interventions for managing stunting.