Good grief, i can speak it! Preliminary experiments in audio restaurant reviews

In this paper, we introduce a new envisioned application for speech which allows users to enter restaurant reviews orally via their mobile device, and, at a later time, update a shared and growing database of consumer-provided information about restaurants. During the intervening period, a speech recognition and NLP based system has analyzed their audio recording both to extract key descriptive phrases and to compute sentiment ratings based on the evidence provided in the audio clip. We report here on our preliminary work moving towards this goal. Our experiments demonstrate that multi-aspect sentiment ranking works surprisingly well on speech output, even in the presence of recognition errors. We also present initial experiments on integrated sentence boundary detection and key phrase extraction from recognition output

Salvage of a failed open gastrocutaneous fistula repair with an endoscopic over-the-scope clip

AbstractOnce enteral access via gastrostomy tube (G-tube) is no longer indicated, the tube is typically removed in clinic with a high probability of spontaneous closure. When spontaneous closure is not achieved, the formation of a gastrocutaneous fistula (GCF) is possible. The incidence of GCF is directly related with the length of time the tube has been placed. When conservative management fails, surgical intervention is the standard treatment. Endoscopic techniques have been described for primary closure of GCF in adults including banding and cauterizing of the fistula tract with placement of a standard endoscopic clip. Over-the-scope clips (OTSC) have recently been reported in primary GCF closure in children (Wright et al., 2015). In patients with skin irritation surrounding a GCF making surgical repair difficult, endoscopic OTSC closure provides particular benefit. It is our belief that this is the first case report of endoscopically salvaging a leak from a failed open GCF repair

Varying Weed Densities Alter the Corn Transcriptome, Highlighting a Core Set of Weed-Induced Genes and Processes with Potential for Manipulating Weed Tolerance

The phenological responses of corn (Zea mays L.) to competition with increasing densities of winter canola (Brassica napus L.) as the weedy competitor were investigated. Changes in the corn transcriptome resulting from varying weed densities were used to identify genes and processes responsive to competition under controlled conditions where light, nutrients, and water were not limited. Increasing densities of weeds resulted in decreased corn growth and development and increased the number and expression intensity of competition-responsive genes. The physiological processes identified in corn that were consistently induced by competition with weeds included protein synthesis and various transport functions. Likewise, numerous genes involved in these processes, as well as several genes implicated in phytochrome signaling and defense responses, were noted as differentially expressed. The results obtained in this study, conducted under controlled (greenhouse) conditions, were compared with a previously published study where the response of corn to competition with other species was evaluated under field conditions. Approximately one-third of the genes were differentially expressed in response to competition under both field and controlled conditions. These competition-responsive genes represent a resource for investigating the signaling processes by which corn recognizes and responds to competition. These results also highlight specific physiological processes that might be targets for mitigating the response of crops to weeds or other competitive plants under field conditions

Sustained microglial depletion with CSF1R inhibitor impairs parenchymal plaque development in an Alzheimer's disease model.

Many risk genes for the development of Alzheimer's disease (AD) are exclusively or highly expressed in myeloid cells. Microglia are dependent on colony-stimulating factor 1 receptor (CSF1R) signaling for their survival. We designed and synthesized a highly selective brain-penetrant CSF1R inhibitor (PLX5622) allowing for extended and specific microglial elimination, preceding and during pathology development. We find that in the 5xFAD mouse model of AD, plaques fail to form in the parenchymal space following microglial depletion, except in areas containing surviving microglia. Instead, Aβ deposits in cortical blood vessels reminiscent of cerebral amyloid angiopathy. Altered gene expression in the 5xFAD hippocampus is also reversed by the absence of microglia. Transcriptional analyses of the residual plaque-forming microglia show they exhibit a disease-associated microglia profile. Collectively, we describe the structure, formulation, and efficacy of PLX5622, which allows for sustained microglial depletion and identify roles of microglia in initiating plaque pathogenesis

Calcium/calmodulin-dependent kinase kinase 2 regulates hematopoietic stem and progenitor cell regeneration

Hematopoietic stem and progenitor cells (HSPCs) are predominantly quiescent in adults, but proliferate in response to bone marrow (BM) injury. Here, we show that deletion of Ca2+/calmodulin (CaM)-dependent protein kinase kinase 2 (CaMKK2) promotes HSPC regeneration and hematopoietic recovery following radiation injury. Using Camkk2-enhanced green fluorescent protein (EGFP) reporter mice, we found that Camkk2 expression is developmentally regulated in HSPC. Deletion of Camkk2 in HSPC results in a significant downregulation of genes affiliated with the quiescent signature. Accordingly, HSPC from Camkk2 null mice have a high proliferative capability when stimulated in vitro in the presence of BM-derived endothelial cells. In addition, Camkk2 null mice are more resistant to radiation injury and show accelerated hematopoietic recovery, enhanced HSPC regeneration and ultimately a prolonged survival following sublethal or lethal total body irradiation. Mechanistically, we propose that CaMKK2 regulates the HSPC response to hematopoietic damage by coupling radiation signaling to activation of the anti-proliferative AMP-activated protein kinase. Finally, we demonstrated that systemic administration of the small molecule CaMKK2 inhibitor, STO-609, to irradiated mice enhanced HSPC recovery and improved survival. These findings identify CaMKK2 as an important regulator of HSPC regeneration and demonstrate CaMKK2 inhibition is a novel approach to promoting hematopoietic recovery after BM injury

Diffuse Optical Monitoring of Hemodynamic Changes in Piglet Brain With Closed Head Injury

We used a nonimpact inertial rotational model of a closed head injury in neonatal piglets to simulate the conditions following traumatic brain injury in infants. Diffuse optical techniques, including diffuse reflectance spectroscopy and diffuse correlation spectroscopy (DCS), were used to measure cerebral blood oxygenation and blood flow continuously and noninvasively before injury and up to 6 h after the injury. The DCS measurements of relative cerebral blood flow were validated against the fluorescent microsphere method. A strong linear correlation was observed between the two techniques (R=0.89, p \u3c 0.00001). Injury-induced cerebral hemodynamic changes were quantified, and significant changes were found in oxy- and deoxy-hemoglobin concentrations, total hemoglobin concentration, blood oxygen saturation, and cerebral blood flow after the injury. The diffuse optical measurements were robust and also correlated well with recordings of vital physiological parameters over the 6-h monitoring period, such as mean arterial blood pressure, arterial oxygen saturation, and heart rate. Finally, the diffuse optical techniques demonstrated sensitivity to dynamic physiological events, such as apnea, cardiac arrest, and hypertonic saline infusion. In total, the investigation corraborates potential of the optical methods for bedside monitoring of pediatric and adult human patients in the neurointensive care unit

New PEO-IAA-Inspired Anti-Auxins: Synthesis, Biological Activity, and Possible Application in Hemp (Cannabis Sativa L.) Micropropagation

Auxins play an important role in plant physiology and are involved in numerous aspects of plant development, such as cell division, elongation and differentiation, fruit development, and phototropic response. In addition, through their antagonistic interaction with cytokinins, auxins play a key role in the regulation of root growth and apical dominance. Thanks to this capacity to determine plant architecture, natural and synthetic auxins have been successfully employed to obtain more economically advantageous plants. The crosstalk between auxins and cytokinins determines plant development and thus is of particular importance in the field of plant micropropagation, where the ratios between these two phytohormones need to be tightly controlled to achieve proper rooting and shoot generation. Previously reported anti-auxin PEO-IAA, which blocks auxin signalling through binding to TIR1 receptor and inhibiting the expression of auxin-responsive genes, has been successfully used to facilitate hemp micropropagation. Herein, we report a set of new PEO-IAA-inspired anti-auxins capable of antagonizing auxin responses in vivo. The capacity of these compounds to bind to the TIR1 receptor was confirmed in vitro by SPR analysis. Using DESI-MSI analysis, we evaluated the uptake and distribution of the compounds at the whole plant level. Finally, we characterized the effect of the compounds on the organogenesis of hemp explants, where they showed to be able to improve beneficial morphological traits, such as the balanced growth of all the produced shoots and enhanced bud proliferation

The melanocortin pathway and energy homeostasis: From discovery to obesity therapy.

BACKGROUND: Over the past 20 years, insights from human and mouse genetics have illuminated the central role of the brain leptin-melanocortin pathway in controlling mammalian food intake, with genetic disruption resulting in extreme obesity, and more subtle polymorphic variations influencing the population distribution of body weight. At the end of 2020, the U.S. Food and Drug Administration (FDA) approved setmelanotide, a melanocortin 4 receptor agonist, for use in individuals with severe obesity due to either pro-opiomelanocortin (POMC), proprotein convertase subtilisin/kexin type 1 (PCSK1), or leptin receptor (LEPR) deficiency. SCOPE OF REVIEW: Herein, we chart the melanocortin pathway's history, explore its pharmacology, genetics, and physiology, and describe how a neuropeptidergic circuit became an important druggable obesity target. MAJOR CONCLUSIONS: Unravelling the genetics of the subset of severe obesity has revealed the importance of the melanocortin pathway in appetitive control; coupling this with studying the molecular pharmacology of compounds that bind melanocortin receptors has brought a new obesity drug to the market. This process provides a drug discovery template for complex disorders, which for setmelanotide took 25 years to transform from a single gene into an approved drug

Contrasting prefrontal cortex contributions to episodic memory dysfunction in behavioural variant frontotemporal dementia and alzheimer's disease

Recent evidence has questioned the integrity of episodic memory in behavioural variant frontotemporal dementia (bvFTD), where recall performance is impaired to the same extent as in Alzheimer's disease (AD). While these deficits appear to be mediated by divergent patterns of brain atrophy, there is evidence to suggest that certain prefrontal regions are implicated across both patient groups. In this study we sought to further elucidate the dorsolateral (DLPFC) and ventromedial (VMPFC) prefrontal contributions to episodic memory impairment in bvFTD and AD. Performance on episodic memory tasks and neuropsychological measures typically tapping into either DLPFC or VMPFC functions was assessed in 22 bvFTD, 32 AD patients and 35 age- and education-matched controls. Behaviourally, patient groups did not differ on measures of episodic memory recall or DLPFC-mediated executive functions. BvFTD patients were significantly more impaired on measures of VMPFC-mediated executive functions. Composite measures of the recall, DLPFC and VMPFC task scores were covaried against the T1 MRI scans of all participants to identify regions of atrophy correlating with performance on these tasks. Imaging analysis showed that impaired recall performance is associated with divergent patterns of PFC atrophy in bvFTD and AD. Whereas in bvFTD, PFC atrophy covariates for recall encompassed both DLPFC and VMPFC regions, only the DLPFC was implicated in AD. Our results suggest that episodic memory deficits in bvFTD and AD are underpinned by divergent prefrontal mechanisms. Moreover, we argue that these differences are not adequately captured by existing neuropsychological measures